Differential Diagnosis Mnemonics

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Differential Diagnosis � Mnemonics

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Differential Diagnosis Mnemonics Thomas J. Donnelly, MD Pulmonary and Critical Care Consultants Dayton, Ohio

Christopher C. Giza, MD Assistant Researcher Division of Neurosurgery University of California Los Angeles, California

HANLEY & BELFUS, INC. / Philadelphia

Publisher

HANLEY & BELFUS, INC . Medical Publishers 2 1 0 South 1 3th Street Ph i ladelphia , PA 1 9 1 07 ( 2 1 5) 546-7293; 800-962- 1 892 FAX (2 1 5 ) 790-9 3 3 0 Web site: http : //www. han leya ndbelfus.com

Note to the reader: Although the i nformation in this book has been carefully re­ viewed for correctness of dosage and ind ications, neither the authors nor the ed­ itors nor the publ isher can accept any legal responsibil ity for any errors or om issions that may be made. Neither the publ isher nor the ed itors make any warranty, expressed or i m pl ied , with respect to the material conta i ned here i n . Before prescribing a n y drug, the reader m ust review the manufacturer's current product i nformation (package i nserts) for accepted ind ications, absolute dosage recom mendations, and other i nformation perti nent to the safe and effective use of the product described .

library of Congress Cotolog ing-in-Publ icotion Dota Donnelly, T homos J, 1962Differential Diognosis Mnemonics / Thomas J. Donnelly, Christopher C. Gizo. p. ; cm. Includes bibliographical references and index. ISBN 1-56053-31 1·0 lalk paper) 1. Diagnosis, Differential. 2. Mnemonics. I. Giza, Christopher c., 1965II. Title. [DNlM: 1. Diagnosis, Differential-Term inology-English. 2. Association Learning-Terminology-English. WB 15 D685d 2000J RC71.5.D66 2001 616 07'5'014-dc21 99-088120

Differential Diagnosis Mnemonics

ISBN 1-5605 3-3 1 1 -0

© 200 1 by Hanley & Belfus, Inc. All rights reserved . No part of this book may

be reproduced , reused, republished , or transmitted in any form, or stored in a data base or retrieval system , without written permission of the publ isher.

Last digit is the print n umber: 9 8 7 6 5 4 3 2 1

CO NTENTS . . . . . . . : . . . . . . . . . . . . .

1 2 2 4 8

II. Pulmonary and Critical Care . . . . . . . . . . . . . . . . . . . . . . . . . .

1 1

I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

How to Use This Book . . . . . . . . . . . . . . General Approach to Differential Diagnosis Thi n king About Differential Diagnoses . . . . Presenting and Discussing Cases . . . . . . .

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General Considerations General Approach to Pulmonary Med icine . . General Approach to Critical Care Med icine Chest X-Ray Interpretation . . . . . . . . . . . . . . Clinical Symptoms and Sig ns Chronic Cough . . . . . . . . . . . . . . . . . . . . Clubbing . . . . . . . . . . . . . . . . . . . . . . . . Dyspnea . . . . . . . . . . . . . . . . . . . . . . . . . Hemoptysis . . . . . . . . . . . . . . . . . . . . . . . Stridor Wheezing . . . . . . . . . . . . . . . . . . . . . . . Clinica l Conditions or Diagnoses ARDS - Diffuse Pulmonary Infiltrates . . . . . . . Acute Respi ratory Failure . . . . . Bronchiectasis . . . . . . . . . . . . . . . . . . . . . Cavitary and Cystic Lung Disease . . . . . . . . Interstitial Lung Disease . . . . . . . . . . . . . . . Mediastinal Mass . . . . Pleural Effusion . Pneumothorax . . . . . . . . ' . Pulmonary Hypertension . . . . . . . . . . . . . . Pulmonary I nfiltrate . . . . . . . . . . . . . . . . . . Pulmonary Nod ule . . . . . . , . . . Refractory Hypotension . . . . . . Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . .

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III. HematolOgy and Oncology . . . . . . . . . . . . . . . . . . . . . . . . . .

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Genera.l Considerations Clinical Symptoms and Signs Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1 1 13 14 16 18 19 21 23 24 27 29 30 31 33 . 36 38 42 ; 43 46 ! 48 50 52 55 56

Contents.

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Bleed ing Diatheses . . . . . . Splenomegaly . . . . . . Clinical Conditions or Diagnoses Eosinophilia . . E ryth rocytosis . . . . . . . . . . . Hypercoagula ble States Lymphopenia Monocytosis . . . . . . . . . . . . . . . . . Neutropenia Neutrophilia . . . . . . Pa ncytopenia . . . . . . . . . . Throm botic Thrombocytopenic Throm bocytopenia . . . . . . . Thrombocytosis .. . . . . . . . . Tra nsfusion Reactions

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60 61

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63 65 66 68 70 71 73 75 76 77 80 81

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IV. Infectious Disease Clin ical Symptoms and Signs Fever of Un known Origin . . . . . Infections Causing Splenomegaly . . . Temperature/Pulse Dissociation . . Clinical Conditions or Diagnoses Acute Men ing itis . . . . AI DS/ Human I m m unodeficiency Virus Immu nodeficiency States Rheumatic Fever . . . . . . . . . . . Sexually Tra nsmitted Diseases .

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V. Cardiology Clinical Symptoms and Signs Syncope . . . . . . . . . . . . . . . . . Clinical Conditions or Diagnoses Arrhyth mia Atrial Fi bril lation . . Congestive Heart Failure Hypotension Pericarditis . . . Restrictive Cardiac Disease VI. Endocrinology . . . . . . . . General Considerations Pituitary/Hypotha lamus Cli nical Symptoms and Signs Amenorrhea . . . . . . . . . . . . Gynecomastia Hirsutism . . . . . . . . . . vi •

Contents

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87 89 91 92 93

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97 97 100 10 1 1 02 1 04 1 05 1 07 1 09 109 11 1 113 114

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Cli nica l Conditions or Diagnoses Adrenal I nsufficiency . . . . . . . . . . . . Carcinoid Tumors .' . . . Hypercalcemia . . . . . . . . . . . . . . . Hyperphosphatemia Hyperprolacti nemia . . . . .. . . . . . . Hyperthyroidism . . . . . . . Hypoca lcemia Hypoglycemia . . . . . . . . . . . . . . . . Hypophosphatemia . . . . . . . Syndrome of I nappropriate Antidiuretic .

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VI I . Nephrology . . . . . . . General Considerations Cli nical Symptoms and Signs Edema . . . . . . . . . Hematuria . Hypertension . . . . . . . . . . Clinical Conditions or Diag noses Hyperka lemia . . Hypernatremia . Hypoka lemia . . . . . . . . . . Hyponatremia . . . . . . . . Neph rotic Syndrome . Renal Fa ilure . . . . . . Renal Stones

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1 33 1 34 136

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VI I I . Acid-Base General Considerations Arterial Blood Gas Interpretation . . . . . . . . . . . . . Clinical Conditions and Diagnoses Meta bolic Acidosis with a High Anioll Gap . . . Meta bolic Acidosis with a Normal Anion Gap . . . . . . . Low Anion Gap . . Meta bolic Alkalosis . . . . . . . . . . . . . . . . . . . . . Respi ratory Acidosis Respiratory Alkalosis .

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1 38 1 40 1 43 1 46 1 49 1 50 152 1 55 1 55

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IX. Gastroenterology .

Clinical Symptoms and Signs Abdom inal Pa in . . . . Dia rrhea . . . . . . Dysphagia . . . . . . . . . Hepatomega ly . . . Jaundice . . Nausea and Vom iting . .

1 16 1 17 1 19 1 20 1 21 1 22 1 24 1 25 1 27 129

1 60 1 63 165 166 167 1 68 1 69

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]69 1 73 1 76 178 179 18 1 • vii

Clinical Conditions or Diagnoses Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 83 .

X. Rheumatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Clinical Symptoms and Signs Acute Monoarthritis . . . . . . . . . . . . . . . . . . . . . . . Inflammatory Polyarth ritis . . . . . . . . . . . . . . . . . . . Clinical Conditions or Diagnoses Calcium Pyrophosphate Di hydrate Deposition Disease CREST Syndrome . . . . . . . . . . . . . . . . . . . . . . . . Osteoa rthritis . . . Rheumatoid Arthritis . . . . . . . . System ic Sclerosis (Scleroderma) . . . . . . . . . . . . . . Systemic Lupus E rythematosus . . . . . . . . . . . . . . . . Vasculitis . Wegener's Granulomatosis . . . . . . .

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XI. Neurology . . . . . . . . . . . .

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XII. Appendix . . . . . . . . . . . . . . . . . . . Acronym Dictionary viii •

Contents

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1 87

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191 1 92 1 93 1 95 1 97 1 98 1 99 20 1 203

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General Considerations How To Make a Broad Differential Diagnosis How To Make a "Working" Differential Diagnosis How To Do a Good Neurologic Exam ination . . Neurologic Exam ination Summa ry . Clinical Symptoms and Signs Altered Mental Status . . . . Ataxia . Autonomic Disorders Di plopia . . . . . . . Dizziness . . . . . . . . . . . . . . . . . . . . . . . . . . Headache . . . . . . . . Loss of Consciousness . Monocular Visual Loss Ptosis . . . . . . . Rig idity Tremor . . Weakness . . . . . . . . . Cl inical Conditions or Diagnoses Dementia . . . . Myelopathy . . . Neuropathy . . . . . . . . . . . . . . . . . . . . . . Seizure . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stroke . . . . . . . . . . . . . Neurology Glossary . . . . . .

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203 204 207 213

215 218 222 . . . . . . . . . . 223 . . . . . . . . .. . . 226 229 . 233 237 239 24 1 243 246 .

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249 25 1 253 259 262 267 271

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PREFACE Generating a useful and complete differential diag nosis is a keystone of clinical medicine. Many texts exist which provide exhaustive lists of possible diagnoses for a particu lar com plaint. It is refining such lists into useful d ifferentials that is part of the "art" of med icine. Memorizi ng lists of diagnoses can be a daunting task, and a d ry one at that. By using mnemon ics as a framework, we wish to make learning differential d iagnoses more palatable and even enjoya ble. In ad. dition, we present an organizational a pproach to differential d iag nosis that is practical and easily learned . The mnemon ics presented here range from concise lists that may be committed to memory aher the first read, to more lengthy, com­ prehensive listings that can be looked up when needed . In al most all cases, the mnemonics themselves spell out something that refers to the symptom or diagno­ sis, increasing the l i kelihood of remembering it. Throughout a student's medical education, he or she receives countless little tips or "pearls" that a re of im mense practical worth but are ohen difficult to look up in the Iypical medical textbook . After each m nemon ic, we have i ncluded many pearls that refer to the symptom or condition descri bed . Some of these tips are j ust one-l i ners; others are small tables or outl i nes that help organ ize com­ monly referenced i nformation . We hope you find this to be a useful handbook that provides a sound organ­ i zational framework for a pproa c h i n g d i fferential d ia g noses. The m nemonic . format necessa rily led to some creative listi ngs, which should be easily remem­ bered as well as amusing . We welcome any suggestions or new m nemonics from our readers. Tom Don nelly Chris Giza

Preface.

ix

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INTRODUCTION The purpose of this book is to help med ical students and clinicians form com pre­ hensive d ifferential d i a g noses for common i nternal med icine a nd neurology problems. It is an aid for organ izing diag nostic poss ibil ities qu ickly and effec­ tively in clinical situations. A number of excellent references provide comprehensive l ists of d ifferential diagnoses. This book was created with a similar pu rpose in mind, but we pre­ sent an a pproach based on mnemonics. The mnemonics are i ntended to pro­ vide simple fra meworks on which to construct differentia l diag noses . They a re not i ntended to be the sole source of i nformation, and pri mary texts should be read to fully understand d isease pathogenesis. It is doubtful that anyone can re­ mem ber every mnemonic i n this book. We hope that those for commonly en­ countered problems will be reta i ned ; the others can be referenced shou l d a particular problem a rise. Most students and residents are fa miliar with nu merous disease processes, but have difficu lty g iving an exhaustive d ifferential diagnosis from memory for a particular clinical entity. This problem often stems from the lack of a n organiza­ tiona l framework. Once d ifferential d iagnoses a re considered in terms of "cate­ gories" of i l l ness, they a re much easier to com plete . We have attem pted to identi fy a wide variety of clin ical scenarios and organize a d ifferential d iagno­ sis for each. Some entities a re common, such as anemia or renal failure, while others are more specialized, such as refractory hypotension. Having a complete list of possible diagnoses at the outset will lead to the correct diagnosis even in the most complex cases. Th is a pp roach encourages thorough ness i n eva l ua­ tions, so that d iag noses a re not missed . The mnemon ics range in length depending on the clin ical entity. Sometimes more than one has been included for brevity or organizational reasons. The best m nemon ics a re concise, perti nent words or ph rases constructed to reflect the pathogenesis of the problem. Others a re no more than sim ple words that help in remembering a list of possibilities . An explanatory section is included with each mnemonic to review pathogenesis or provide helpful i nformation . Some com­ monly used m nemon ics (a uthors generally u n known) are i ncl uded in deference to their history or for lack of a better replacement. F i nally, please forgive a ny "artistic" license taken in the creation of these m nemonics.

Introduction •

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H ow to Use This Book The chapters are divided by organ system and presented with a common organi­ zational theme. A "General Considerations" section starts some chapters to pro­ vide an overview of differential diagnosis and clinical assessment pertinent to that particular system . Specific mnemonics, which are divided i nto two sections, follow. The first section , "Clinica l Symptoms and Sig ns, " l ists mnemon ics that refer to specific clinical complaints by the patient (e. g . , cough, headache), or to particular clinical signs detectable on careful physical exami nation (e. g . , jaundice, ataxia) . The second mnemonic section, "Clinical Cond itions and Diagnoses," lists d iffer­ ential diagnoses for clin icol conditions detected through the use of various d iag­ nostic tests (such as thrombocytopenia, hypernatremia), general mnemonics for broad diagnoses (e.g . , sexually transm itted disease, pneumothorax), and specific mnemonics that refer to a pa rticular d isorder (such as rheumatoid arthritis, AIDS). Thus, the first section is i ntended to help i n making a differential diagnosis list based primarily on the chief complaint or a significant clinical sign, aher the initial history and physica l . The second section is a i med at generati ng more specific differentials based u pon initial diagnostic testi ng and careful consideration of the overall clinical syndrome. Each section is listed alphabetically for ease of reference.

G eneral Approach to Differential Diag noses The d ifferential diagnosis for any medical problem can be thought of i n terms of categories of d isegse. The mnemon ic "MEDICINE DOC" may be used as a general a pproach to a ny patient: Meta bolic disease (e. g . , nutritional deficiency, dysli pidemias, porphyria) Endocrine disease (thyroid disease, diabetes) Drugs/ med ici nes (iatrogenic, accidental, self-administered) I n fections (e . g . , bacteria l , viral, fu ngal, mycobacterial, protozoa l , hel mi nthic) Congen ital a bnormalities (inherited a natom ic, immunologic and metabol ic disorders) Immunologic disease (collagen vascular diseases, asthma, acqui red immunodeficiency) Neoplasms (e. g . , primary, metastatic, paraneoplastic) Exotic ( "strange" diseases of unknown etiology such as sarcoid, histiocytosis X) Degenerative processes (e. g . , Alzheimer's, a myotrophic lateral sclerosis) Occu pational!envi ronmental exposures (e.g . , asbestos, hypersensitivity, trauma) Cardiovascular d iseases (e.g . , arrhythmias, atherosclerosis, pulmonary em­ bolus, congestive heart failure) 2 • Introduction

This list includes the primary etiologies for most medical problems. There is, of course, some overlap between categories: atherosclerosis i s both a cardio­ vascular and metabolic disease; both i nfections and collagen vascular diseases may cause ca rdiovascular disease; many of the "exotic diseases" may have an i m m u nolog ic basis, a n d many i m m unologic di seases are exotic. The redun­ dancy is necessary, however, si nce some entities a re difficult to classify or may be forgotten if a framework based solely on pathogenesis is used. For exam ple; where does one classify arrhyth mias or pulmonary embolus? Both a re common entities that have many causes. The cardiovascula� category helps you to re­ member these com mon problems in u nusual presentations. When faced with any clinical problem, you can use either the MEDICINE DOC m nemonic or another, more specific m nemonic to develop a differential diagnosis. For exa m ple, if a patient has renal fa ilure, you can construct a differ­ ential based on the categories in MEDICINE DOC or use the specific "I C HASE A RISING BUN," which lists specific ca uses of renal fa ilure: Pre-renal Intravascular vol ume depletion (dehydration, th ird spacing) Cardiac ca uses (CHF, MI, tamponade) Hepatorenal syndrome Arterial disease ( renal artery stenosis) Shock 'Eclampsia/obstetrical compl ications Pre-renal/Renal Acute tubular necrosis ( "ATN" in a sense, both " pre-" and "renal" in etiology) Renal Radiographic contrast and other toxi ns (drugs, rhabdomyolysis, hemolysis) I ntrarenal emboli (cholesterol, DIC) Scleroderma Interstitial nephritis Necrotizing vascul itis (polyarteritis nodosa , Wegener's) Glomerulonephritis Post-renal Bladder obstruction (usually prostatism, sometimes blood, pus, calcul i ) Ureteral obstruction (calcul i , retroperitoneal fi brosis, cancer) Necrosis of renal pa p i l lae (dia betes, sickle cell a nemia, NSAID a buse, i nfection) The two approaches provide fairly comprehensive lists of possibil ities, and there a re strengths and weaknesses for both . MEDICIN E DOC a l lows broad classification of disease processes, while I C HASE A RISING BUN l i sts spe­ cific causes of rena l fa ilure a n d organ izes them in p re-rena l , ren a l , a n d post­ renal categories . It is helpful to look at medical problems using both types of approach .

Introduction • 3

� inking About Differential Diagnoses Two thought processes are helpful in a pproaching differential d iag noses 1 . What is the most l i kely d iagnosis? This "gestalt" approach involves look­ ing at the entire picture first and form ulati ng a hypothesis to explain it. After re­ viewing a l l the data for a case, decide which d i agnosis is most l i kely. The th inking process from this point focuses on proving or disproving the hypothesis. This a pproach is helpful for more simple cases, although most clin icians use it to some extent i n all cases. Pay careful attention to a ny aspects that are i nconsis­ tent with the presum ptive diagnosis and be able to account for them . Avoid be­

coming fix,ated on a diagnosis and ignoring data that do not support it,

2 . What are the patient's problems? This a pproach focuses on the "pa rts" or individual aspects of the case. list all of the patient's problems and consider a d if­ ferential d iagnosis for each. Then, attempt to formulate a u nifying diag nosis that explains the data, creating a whole from the parts. This techn ique is helpful when faced with complex cases featuring multiple symptoms and large amounts of data. The m nemonic a pproach to differential diagnosis em phasizes sta rting with a com plete list of possibilities. Certain entities on the l ist wi l l be very uncommon and unl ikely in most circumstances, Common entities a re considered in the i n itial d ifferential diag nosis of a problem , but other aspects of 'a particu lar patient's case may di rect the work-up to more unusual entities. This approach is appropri­ ate as long as you do not ignore features that may be i nconsistent with the pre­ sumed diagnosis. Another a pproach to defi ning a long list of d iag nostic possibi l ities is to de­ velop a second or perhaps even a third list based on a second sign or symptom of the patient. If you assu me that the man ifestations of the d isease in question are secondary to one process, then you can limit the number of possibi lities by only pursu ing diag noses that a re on both l ists. Be careful using this a pproach, because patients may have more than one disease process at work, and impor­ tant diagnostic considerations may be eli m i nated prematurely. Aga i n , it is criti­ cal to always refer back to the com plete list of differential d iagnostic possibilities when all the features of a case do not add up to a coherent picture. Sources of Error in Differential Diagnosis

Decision ana lysis is a process that attempts to classify errors in medical rea­ soning, with the goal of i mproving the accuracy of differential diag nosis and en­ suring that a critical diag nosis is not m i ssed , Althoug h controversy exists i n a pplying decision analysis to clinical settings, i t i s worthwh ile to understa nd the sources of error. One a pproach focuses on fi rst outlin ing the basic steps in ar­ riving at a presum ptive diag nosis a nd then classifyi ng errors accord i n g to where they occur in those basic steps. The basic steps are: 1 , Triggering determ ining a d iagnostic possibil ity based on patient i nfor­ mation . -

4

• Introduction

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2. Framing-establish ing the context within which the problem will be solved . 3 . Gathering a n d processi ng - reviewi ng a n d i nterpreting d iag nostic data ; selecting and d iscarding possible diagnoses 4 . Verifi cation - reaching a final diagnosis, the one that best fits all of the data . Errors occur at each of these steps: Triggeri ng errors may result from a lack of knowledge and associations . Consider the exa mple of a renal fa i lu re patient in whom hypotension develops shortly after beginning dialysis. Some clinicians may consider sepsis or hemor­ rhage (which a re plausi ble) , but most neph rolog ists would i m med iately th i n k of a perica rd. ial effusion and tamponade as being m uch more likely Triggering is an associative process that comes with experience . Framing errors occur when you do not th ink broadly enough i n considering the cause of a patient's problem . For exa mple, a patient with recurrent a bdomi­ nal pa in secondary to hyperca lcemia may undergo a n extensive gastroi ntesti nal work-up because the d ifferential d iag nosis of a bdominal discomfort was not framed broadly enough to i nclude metabolic or systemic disorders . This type of error demonstrates the importance of having a com plete list of diagnostic possibili­ ties prior to embarking on an extensive work-up. It also shows the value of framing the differential diagnosis i n two or more contexts (i e . , MEDIC I N E DOC and a mnemonic for a bdominal pa i n ) and then looking at the " i ntersection" of the sets . Broad framing and framing in mu ltiple contexts may decrease framing errors. Gathering and processing errors result from m isi nterpreting test results, not understanding the sensitivity or specificity of a test, or not knowing a particu lar disease preva lence or li kelihood i n a given patient. For exam ple, a slightly ele­ vated u rinary catechola m i ne in a 75-year-old patient with severe hypertension may lead a clinician to pursue a diagnosis of pheochromocytoma , even though this is a rare disease. It is much more l i kely that the catechola mine result is false positive, and the test probably should not have been ordered in the initial evalu­ ation of this patient. I ntrinsic renal d isease or renovascular d isease should be i n­ vestigated fi rst in this type of patient before looking for more un usual diag noses. (See "Other Sources of Diag nostic Error�' on the next page for additional d iscus­ sion of proba bil istic thinking . ) Verifi cation errors occur when some data supporting a particular diag nosis are obtai ned , and the patient is then assumed to have that diagnosis, even when other, contradictory data subsequently become available. Failing to account for all aspects of a case and inappropriately adhering to a presum ptive diagnOSis re­ sults i n premature closure. Consider a woman with fever, rash , anem ia, renal i n­ sufficiency, and a positive antin uclea r anti body test suggesting the diagnosis of systemic l upus erythematosus (SLE) If this patient also had a heart murmur and a negative double-stranded DNA test, these features are less easily explained by a simple d iagnosis of SLE (although not impossible). Presumptive immunosuppressive therapy of this patient for a d iag nosis of SLE cou ld be hazardous if the patient rea lly has subacute bacterial endocard itis as the cause of her m ultiple problems. There also a re "no-fault" errors. These occur when the patient's findings are highly atypical for the underlying disease, or the disease is extremely uncommon. Introduction • 5

An example of this type of error occurred when a young woman on birth con­ trol pills presented with dyspnea, chest pa i n , and a h i g h-probability V /Q sca n . Most clin icians would proba bly i n itiate a nticoagulation , as was done i n

this case, given this constellation o f findings. Subsequently, however, the pa­ tie nt develo ped card i ac ta m ponade d ue to hemorrh a g i c perica rd itis ( h e r actual problem) and h a d a prolonged i ntensive care course as a result o f the a n ticoagulation . An a rteriog ra m demonstrated a congenitally stenosed pul­ monary a rtery su bseg ment, which expla i ned the h ig h-proba bility V/Q sca n . This type of error i s unfortunate but, i n some cases, u navoida ble . N o matter how well we perform our duties, errors will occu r. This exa mple points to the fact that you must continue to be vigilant even when a diagnosis seems as­ sured. Note that p remature closure, a lthoug h u ndersta nd a b le in this case, was to the patient's detriment. The Importance of Probability in Differential Diagnosis

When evaluating the data as they apply to a list of diagnostic possibilities, it is helpful to consider probabilities. Always question : 1. How common is the diseaseq 2 . How common is the d isease in the relevant population , i . e. in the par­ ticu lar patient being eval uated2 3 . How com mon is a pa rticular symptom, sign, or la boratory result in the disease bei ng consideredq As you prog ress in medical education and gain fa miliarity with different dis­ eases, these questions become easier to answer. Baye's theorem is a mathemat­ ical relationship that can be helpful in assessing the proba bil ity of one disease versus another, g iven a particular find ing. Probabil ities can be calculated based on Baye's rule, which states that the l i keli hood of a disease in a patient with a g iven set of findings can be esti mated as the proportion of patients with the same findi ngs who also have the d isease. For example, the likeli hood of pneu­ monia in a person with fever, cough, and sputum is estimated by d ivid ing the n umber of people with fever, coug h , sputum , and pneumonia by the num ber of people with fever, coug h , and sputu m . The actual mathematica l calculation is complex, and there a re many criticisms of this type of ana lytical approach, but a few simple and useful poi nts can be offered : • Have a general idea of the prevalence a nd common symptoms of a particular disease. For exa mple, a young woman with fever, sweating, anxiety, tachycard ia, and hypertension may have a pheochromocytoma , but hyperthy­ roidism also is possible . The above symptoms are characteristic of both disorders; however, hyperthyroidism is much more likely to be the cause because it is more commo n . The find ing of exophthal mos may be seen in Grave's disease, but would not be cha racteristic of pheoch romocytoma , aga in pointing toward hy­ perthyroidism as the more likely cause. An evaluation a i med at hyperthyroidism, while keeping pheochromocytoma "on the back burner, " would be a ppropriate in this instance. Also, in the above setti ng, you should consider an anxiety disor­ der (even more common) as a possible cause of the patient's symptoms. 6 • Introduction

• The more specific a find ing is, the more helpful it wi ll be in establ ishing a l ist of l i kely diagnoses . Select one or two pivotal fi ndi ngs ( " pivots " ) of a pa­ tient's case for consideration of the differential diag nosis. Hypercalcemia, for ex­ a m pl e , is a good pivot because it has a fa i rly we l l-defi ned list of causes . Clubbing also might be helpful as its list of diag nostic possibil ities is rather l i m­ ited . Entities such as chest pa in or fatigue are more problematic because they are nonspecific and can occur in a large number of diseases . • When considering diagnostic possibilities, it is perhaps best to compare one symptom or finding (pivot) across multiple diseases, instead of seeking several sym ptoms or findi ngs for a single d isease This step-wise l i m itation of data analysis keeps the proba bil ities of a specific find ing in a specific d isease in the forefront. The difficu lty of this approach is the lack of specific data for the incidence and preva lence of signs and symptoms in specific d iseases. Also, the most proba ble d iagnosis based on one sym ptom may not be the most l i kely after all the data a re considered . The step-wise consideration of single pivots is mea nt to enhance, rather than replace, good cli nical judgment.

Other Sources of Diagnostic Error • Giving equal weight to pdsitive and negative findings. Often we focus on a positive la boratory test result and pursue a diagnosis based on it. Before giving too much weight to a positive resu lt, pay attention to a bsent su pportive el­ ements . This aspect of probabil istic reasoning often is neg lected . • Using the first informatian that comes to mind. This source of error has been termed the "availability heuristic . " An example is the i m mediate considera­ tion of myoca rdial infa rction as a possible diag nosis when a patient presents with ·chest pai n to the emergency room; pericarditis or pulmonary embolism may not come to mind as readily These latter d iag noses may not be considered ini­ tia lly, and the evaluation and treatment may be misd irected . • Laoking for evidence that supports an early worki ng hypothesis and ignoring contradictory data . An exam ple of this so-cal led confirmation bias is

seeking ischem ic changes on the EKG of a patient with chest pa in, while ignor­ ing more d iffuse cha nges which may be suggestive of perica rd itis.

• Believing in the chosen course of action and favoring evidence that supports it. Physicians may become too invested in a d iag nosis and conti nue

down the wrong pathway in pursuit because of overconfidence. Summary ofTypes of Errors

Triggering errors Framing errors Gathering and processing errors Verification errors No-fa ult errors Premature closure

Not giving equal weight to positive and negative findings The availability heuristic Confirmation bias Overconfidence/overreliance on a method or dogma

In troduction • 7

Ways to Avoid Errors

1. 2. 3 4.

Carefully compile information Pick one or two " pivots " Have a complete differential diagnosis for each pivot. Have at least a general sense of the prevalence of the disease in a g iven population and in the releva nt population for the patient being considered . 5 Have a general idea of the prevalence of a symptom in a particular disease. 6. Do not discard contradictory data when it becomes available. A careful accounting of unexplained aspects of the case is essentia l . 7 . Pay attention to what is not present, i . e , negative find ings . 8 . Know that differential d iag nosis is an im perfect science: You are fallible. The unexpected , unlikely, or atypical may occur.

f?e senting and Discussing Cases A few words a re i n order regarding case presentation and discussion . Case conferences a re inva lua ble teaching exercises. Lea rning to present cases in a concise and orderly man ner teaches the princi ples of differential d iag nosis. Case presentation em phasizes organ ization of data . Case discussion employs critical th inking and organization of diagnostic possibilities. Case Presentation

The key to case presentation is breVity. The traditional " H and P" (h istory and physica l) format is the best framework for discussion. Begin with a chief complaint (why the patient came for medical attention) and then proceed with an orga nized h istory and physica l exa m . The h istory should be d iscussed i n chronolog ical order to avoid confusion. Patients who have been il l for a long time or have been transferred from another hospital typically have extensive and complex his­ tories . It is the duty of the presenter to avoid overly long discussions of previous work-ups or presum ptive diagnoses. Focus on the essential features of the case. Tips on Presentation •

• •

•

Be brief and be thorough You shou ld be able to present most cases com­ pletely in 5 minutes or less. Even the most complex cases can be sum ma­ rized effectively in a brief presentation. Present the case in chronological order. Avoid cl uttering the h istory with laboratory resu lts, previous work-ups, or other physicians' presum ptive d iag noses. Follow the trad itional "H and P" format a . Chief complaint b. History of present ill ness

8 • In troduction

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c. Past med ical history d. Med ications e. Fam ily history 1. Social h istory g Review of systems (brief) h. Physical exam • Focus on pertinent positive and negative elements. It usually is best, for the sake of teach ing, to omit laboratory resu lts from the i n itial presentation . This om ission emphasizes the i m portance of a careful clini­ cal eva luation to guide the ordering of laboratory tests . Sometimes the incl usion of la boratory tests is unavoidable since it may be the reason for adm ission or re­ ferral (e . g . , anemia). I n most cases, however, it is best to fi rst consider diagnos­ tic possibil ities and then ana lyze appropriately focused diag nostic testi n g . Note that a thorough h istory a n d physical examination should be performed on every patient, and the presenter should be prepa red to prOVide any informa­ tion if it is requested . However, an exha ustive list of all negative findings is un­ necessary. Describing a Symptom

When considering the differential diagnosis of a patient's sym ptom or chief complaint, it is essential to obtain a thorough history and accurately describe the problem . Ma ny com plai nts , such as chest or abdom inal pa i n , have nu merous causes, and a more specific description is req u i red to d i rect the work-u p . Consider the m nemon ic "COMPLAINS" : Compla int-what is the problem? Onset -when did it begin? Magn itude- how severe is it? Pattern - episodic? crescendo, decrescendo? constant? Location -where is it? does it radiate? Associated symptoms - are any other symptoms tempora l ly related to the complai nt? Im provements - what makes it better? Negative sti mul i -what makes it worse2 Simila r episodes in the past - has it ever ha ppened before2 Obtain ing these descri ptive features may reveal the cause of a sympto m . Consider the complaint of chest pa in: Compla int- chest pa in Onset- began 2 hours ago Magn itude- 1O/ 1 0 Pattern -crescendo, crush ing Location -substernal location radiating to the jaw and left a rm Associated symptoms - shortness of breath, diaphoresis, anxiety Improvements - rest, nitroglycerin Negative sti m u l i - exertion Similar episodes in the past- 5 years ago before coronary artery bypass grah In troduction • 9

Chest pa in has myriad causes, but the above h istory strongly points to angina . Consider a different set of featu res for chest pain Compla int- chest pain Onset- began 6 hours ago Magnitude- 1 0/ 1 0 Pattern - constant, sharp Location - su bsterna I location, nonrad iati ng Associated symptoms - i nabil ity to take a deep breath Im provements -sitting-up, leaning forward Negative stimuli - lyi ng flat Similar episodes in the past- no prior history In this instance, the chest pa in features a re suggestive of pericardial pa i n , and a different l ist of diagnostic possibilities should be considered . Case Discussion

1. Beg i n with a summary statement. After l i stening to the case, g ive a one-sentence s u m m a ry of the case . For exa m ple: "The case concerns a 44yea r-old male with a h i story of poorly control led d ia betes and i ntrave nous d rug a buse who presents with a 2-day h i story of fever, ras h , a nd decreasing u rine output . " The summary statement is a "gestalt, " or overa l l i m pression , of the case . It is helpful because a presentation often suggests a l i kely d iagno. sis, and the d i scussion can focus on provi ng or dis proving this presu m ptive d iagnos is. 2. N ext, make a problem list of the major cu rrent and past problems. I n the above example, a problem l ist could include: Fever Rash Decreasing urine output History of dia betes History of intravenous drug abuse 3 . Construct the differential diagnosis framework based on the categories of disease or by using m nemonics for specific entities on the problem l ist. 4. Na rrow the d iagnostic possibilities based on the h istory and physical exa m . 5 . Request specific la boratory o r imaging tests t o further na rrow down the diag nostic possibilities. Specific m nemonics may be used to consider the differ­ ential d iag nosis for certain la boratory abnormal ities . When new data is not consistent with the diseases being considered, always return to the original, complete differential to reconsider diagnostic possibilities. 6. Summa rize the data and prioritize diagnostic possibil ities.

1 0 • In troduction

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III

PULMONARY AND CRITICAL CARE General Considerations

G eneral Approach to Pulmonary Disease Many d isorders have pulmona ry manifestations, and chest symptoms a re fre­ q uently the fi rst noticed by the patient (e . g . , cou g h , wheezi n g , shortness of breath) . The lung is a common "ta rget" organ for infection, drug toxicity, cardio­ vascular com promise, i m m u nologic disease, and neoplastic processes. I n ap­ proaching the patient with thoracic disease, think of the more common categories of illness, such as infection, neoplasm , toxic exposures, and cardiovascular dis­ ease. Also i m portant, but less common, a re the immunologic and "exotic" cate­ gories of disease, a mong which there is considerable overla p. Other categories of illness such as endocrine or metabolic diseases have less d i rect pul monary in­ volvement. We can apply the m nemonic "ME DICINE DOC": Metabolic (e.g . , a myloidosis, a lpha- l -antitrypsin deficiency) Endocrine (para neoplastic syndromes, neuroendocrine cell hyperplasia) Drugs/medici nes (e.g . , nitrofurantoi n , am iodarone, chemotherapy toxicity) Infection (e. g . , H IV-related , TB, bacterial pneumonia) Congenital (e . g . , bronchogenic cysts, Kartagener's, cystic fibrosis) I m munologic (e . g . , Goodpasture's, rheumatoid lung, asthma, BOOP, PIE) Neoplastic (primary lung, pleural and mediastinal tumors, metastatic disease) Exotic d i seases (e . g . , sarcoi d , eosi noph ilic g ra n u loma, LAM, interstitial d iseases) Degenerative (e.g . , COPD?, degenerative neuromuscular disease [ALS]) Occupational/environmental (e.g . , smoking, asbestosis, hypersensitivity) Cardiovascular (e . g . , PE, edema from CHF, VOD, pulmonary hypertension) Metabolic disorders cause multi-system disease, but the lung and chest usually a re not prominently i nvolved . Amyloidosis (also "exotic" and immunologic) may Pulmonary and Critical Care . 1 1

rarely present as parenchymal or vascular lung disease. Alpha- l -antitrypsin defi­ ciency ohen leads to em physema, especia lly in young smokers, and also cou ld be classified as an i nherited disorder. In addition, the lungs may be affected by ongoing metabol ic processes, such as pu lmonary edema from u remia or tachyp­ nea (Kussmaul breath ing) from diabetic ketoacidosis. The lung has little known endocrine function and so this category usually is not helpful i n formu lati ng d ifferential diag noses for chest disease. Lung cancer, pa rticula rly small cel l carcinoma, can cause para neoplastic syndromes such as SIADH and Cush ing's syndrome. Myxedema may be associated with pleural ef­ fusions. The rare entity of neu roendocrine cell hyperplasia may present as chronic obstructive lung disease. Drugs can cause hypersensitivity reactions. Exa mples include nitrofu rantoin and phenytoin . Also, certa i n chemothera peutic agents have wel l-known pul­ monary toxicities (methotrexate, cytoxa n , bleomyc i n , BC N U ) Amiodarone ca uses p u l monary fibrosis as well as other types of lung i n j u ry. I ntravenous d rug a b use and coca i n e a buse may ha ve a c ute a n d c h ron i c p u l m o n a ry manifestations . I n fectious processes of many types can involve the lungs - either prima rily, as in loba r bacterial pneumonia, or as part of a dissemi nated infection , such as asperg illosis in immunocomprom ised patients. Viruses, mycobacteria, hel minths, and other parasites ca n all cause pulmonary pathology. Certa i n infectious agents may be specifica l ly associated with chronic diseases, such as PC P in AIDS, or Bu rkholderia in cystic fibrosis. The category of congen ital lung d isorders i nc l udes a natomic, i m m u no­ logic, and metabolic abnormal ities. Anatomic disorders i nclude bronchogenic cysts, sequestration , and dysmotile cilia syndrome. Immu nodeficiency syndromes such as immunog lobulin deficiency or functional neutrophil disorders characteris­ tically present with recurrent si nopulmonary i nfections . Alpha-l-a ntitrypsin defi­ ciency pred isposes patients to panlobu lar em physem a . Cystic fi brosis is a com mon i n herited disease with prominent pulmonary involvement i ncluding bronchiectasis, chronic i nfections, and fi brotic changes . Immunologic disease may affect the lu ngs specifical ly, as in asthma, or pul­ mona ry i nvolvement may be only a part of a more widespread i m m u nologic process such as Goodpasture's or Wegener's. Virtually all collagen vascular dis­ eases can i nvolve the respiratory system. Exam ples include pulmonary fibrosis i n scleroderma, l u n g nodules in rheumatoid a rthritis, pleural effusions in SLE, a n d tracheal collapse in rela psing polychondritis. Neuroimmu nologic d isorders such as myasthen ia g ravis and Gu illa in-Ba rre may lead to respiratory muscle fa ilure. Tropical eosinoph ilia represents an immunolog ic response to the i nfectious agent filaria, and is treated with the a nti-fi larial agent d iethylca rbamazine. Allergic bronchopulmonary asperg il losis is another exa m ple of an infectious agent elicit­ ing an i ntense i nfla m matory response . Treatment is primari ly d i rected at modify­ ing the host response with steroids. Neoplastic disease may arise primarily in the lungs or metastasize from a d istant cancer. Neoplasms in other thoracic structures also can affect pulmonary function (e. g . , pleura l tumors, compression of a irways from lym ph nodes). 12 • Pulmonary and Critical Care

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N umerous exotic conditions affect the lungs, i ncluding h istiocytosis X, sar­ coidos is, Iymphang ioleiomyomatosis, and eosinophilic lung d isease. Many of these diseases are thought to have an immu nologic basis. Degenerative diseases may ca use pul monary symptomatology secondari ly, as is the case with neuromuscu lar d isorders such as ALS . These disorders can lead to swa l lowi ng dysfu nction and aspiration or respiratory fa i l u re . Severe kyphoscoliosis can lead to a restrictive ventilatory defect. Emphysema also could be considered degenerative. I n normal aging, lung function slowly decli nes and is thus degenerative. In the category of occupational and environmental exposures, smoki ng-re­ lated lung d isease is very common Other agents that can cause lung disease are leg ion and i n cl ude asbestos, s i l i ca, coa l d ust, and beryl l i u m . Hyper­ sensitivity reactions include farmer's lung, bird-fa ncier's lung, and nu merous other entities Tra uma may lead to hemorrhage, pneumothorax, lung contusion , o r ini ury to other i ntrathoracic structures. Cardiovascular diseases may i nvolve the lu ngs secondari ly, ca using pul­ monary infiltrates and pul monary hypertenSio n . Abnorma l ities of the heart and aorta are i m portant considerations i n thoracic d isease. The vascul itides (classi­ fied under i m m u nologic d isease) and pulmonary veno-occl usive d iseases a re more rare. Pul monary embolism is very com mon, u nderd iag nosed, and may be insidious. The presentations of pulmonary embolism are myriad, and the dis­

order should be considered in the d ifferential for most thoracic problems.

G eneral Approach to Cri t i c al Care Medicine The care of critica lly i l l patients i s complex a n d requires a n organ ized a pproach for managing m u lti-system disease . Consider the m nemonic "MICU'S LIFE GOALS " : Med ications/ prophylaxis Invasions Cardiovascular Uri ne/renal Ski n/decubitis care Lu ngs Infectious disease F l uids/electrolytes/ nutrition Endocrine Gastroi ntestina l/l iver Oncolog ic/hematolog ic Analgesia/ neurologic Long-term prognosis Social/family Pulmonary and Critical Care • 13

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Many of these patients are on numerous medications which may cause side effects such os fever, rash, and cytopenias Carefully review the patient's medi­ ci nes dai ly, with an eye towa rd disconti nuing unnecessa ry agents. Consider all hospitalized patients for some type of DVT prophylaxis, especial ly ICU patients. Many patients should be considered for stress ulcer/gastritis prophylaxis, as wel l . I nvasive procedures and i n-dwel l i ng l i nes and catheters a re common i n the ICU. These i nvasions, while often necessary, a re sou rces of iatrogenic compli­ cations, especially i nfection, and should be discontinued as soon as possi ble. A systematic approach i s then used to add ress the patie nt's problems : cardiac (e . g . , hemodyna m ics, d i u resis), u ri n a ry/renal (e . g . , fluid ba lance, BUN/c reati n i ne , dialysi s ) , skin (e . g . , ras h , decubitus care), l u ngs ( i ncluding ventilator management! , infectious disease (active or suspected i nfections, a n­ tibi otic thera py i n c l u d i n g treatment day!, fluids/electrolytes/nutrition ( IVFs, electrolyte disorders or replacement, enteral or parenteral nutrition!, endocrine (e . g . , diabetes, thyroid d isease, steroid thera py! , GI/liver (e.g . , gastroi ntestinal bleeding, d iarrhea/consti pation, ci rrhosis/hepatic dysfu nction , pancreatic dis­ ease!, oncologic/hematologic (e . g . , m a l i g n a ncies, cytopenias, coag ulopa­ thy! , and ana lgesia/anxiolysis/neurologic status (e . g . , pain ma nagement, coma, neurologic defiCits, psych iatric d isease). It is i m portant to reassess the long-term prognosis frequently so as to avoid futile care . Careful attention often is g iven to a patient's medical issues without consideration of the l i keli hood of surviva l or chance of mea n i ngful recovery. Along the same l i nes , socia l/fa m i l i a l issues a re of para mount i m po rta nce . Family mem bers often a re upset and concerned . They req u i re regular meeti ngs with the ICU physician to discuss med ical problems, treatment decisions, prog­ nosis, and end-of-life decisions.

C hest X-Ray Interpretati o n Reading a chest x-ray req u i res an organized a pproach and ca n be as easy as ABCDE F . . Common methods used em phasize sta rti ng on the outside and working in or starting i n the center and working out. The ABCDEF method * starts with a q u ick confi rmation of the fi l m 's qual itative aspects a nd then outli nes a checklist for interpretation . Initial review: AP or PA Body position Confi rm name Date Exposure Films for comparison * This mnemonic was adapted from one proposed by Robert Crauseman, MD. 1 4 • Pulmonary and Critical Care

•

Interpretation . Ai rway/Adenopathy Bones/Breast shadows Cardiac silhouette/Costophrenic angles Diaphragm/Digestive tract Edges/Extra-thoracic tissues Fields/Fa ilure Initia l ly, the reader should look at the film's projection (AP or PAl , then the body position (lordotic, rotated , etc ) , a nd then confirm the name of the pa­ tient, the date of the fi l m , and the type of exposure (over-penetrated or u nder­ penet rated) See if old films a re ava i la ble for a compa rison . Aga i n , using ABCDEF as your guide, review the releva nt structu res on the chest x-ray. Start by looking at the airway for width and focal narrowing . Then look for evidence of h i lar adenopathy or enlargement as m ight be seen with pulmonary artery hy­ pertension . Next, exa mine for breast shadows, which may affect the density in the lower lung fields, and ca refully review the bones for rib fractures or evi­ dence of lytic bone lesions. The cardiac silhouette as well as the costophrenic angles should be exam­ i ned for evidence of cardiac enlargement or pleu ra l effusions Look at the di­ aphragm to see if there is d iscrepancy in the height of the hemi-d iaphragms or evidence of free air under the diaphragm . The digestive tract then ca n be ana­ lyzed . With in the chest, look for evidence of esophageal enlargement or herni­ ation of the stomach as wel l as dilated loops of bowel below the diaphrag m . Look at the edges and extra-thoracic tissues. Particula rly, look a t the a pices for fibrosis or a pical d isease as wel l as pneumothoraces, which may occur a long the edges a pica lly, lateral ly, or at the base of the l u n g . Pleura l thickening or plaq ues may be present. Next, exa m i ne the extra-thoracic soft tissues on both the anterior and lateral projections. Final ly, assess the lung fields for evidence of a lveolar filling or interstitial processes. Evidence of cardiac fa i l u re may be seen i f there is a lveolar a i r space d isease with promi nent vascularity with o r without evidence o f pleural effusions.

,

Pulmonary and Critical Care •

15

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C l inical Sym ptoms and Signs

CHRONIC COUGH GASPS AND COU G H

Gastroesophageal reflux disease Asthma Smoking/chronic bronchitis Post-infection Sinusitis/post-nasal drip Ace-inhibitor Neoplasm/l ower airway lesion Diverticulum (esophageal) Congestive heart failure Outer ear U pper airway obstruction G I - airway fistula Hypersensiti v ity/allergy N otes

I

1 . Cough is one of the most common complaints encountered by physicians. It is most often related to upper respiratory tract infections and/or smoki ng. A per­ sistent cough lasting longer than 2 weeks may ind icate a more serious disease. The above d ifferential for chronic cough refers to cases lasting severa l weeks i n which chest radiographs a re norma l . 2 . I n a smoker, a chronic cough may i ndicate chron ic bronchitis o r i t may herald the development of ca ncer, particularly when it involves an ai rway. Any change

i n the nature of a chronic cough i n a smoker warrants i nvestigation for pos­ sible neoplasm .

3 . Infections, the most common causes of cough , may be d ue to viral or bacte­

I

I

ria l pathogens; viral agents are the usual culprits . In addition, a post-infectious cough may a rise d ue to a cycle of i rritation and coughing, which further irritates 16 • Pulmonary and Critical Care

the throat. A post-infectious cough may lost several weeks aher the resol ution of the acute infectious process . Treatment consists of cough su ppressa n ts , ipra­ tropri um, and, occasionally, a course of inhaled steroids 4. Both pulmonary parenchymal and pleural d isease may present as a cough with or without dyspnea . A chest x-ray usua lly is the first test obtai ned after the history and physical in evaluating a chronic cough ( i .e . , a cough lasting longer than 2 to 3 weeks) . If the chest x-roy is negative, consider a more l imited differ­ ential diagnosis, as outlined by the GASPS AND COUGH mnemon ic. 5. Certa in historica l featu res may poi nt to the etiology of a chronic cou g h . Symptoms of heart burn or worsening cough i n recu mbency (e. g . , night) may in­ d icate gastroesophageal reflux. A cough that is worse in the evenings o r a childhood history of reactive airways disease may suggest asthma. Smoking-in­ duced chronic bronch itis and post-infection coug h from chronic i rritation a re very common and should be suspected when there is a history of smoking or an­ tecedent infection Nosal congestion or sensation of post-nasal drip may indi­ cate sin usitis as the cause of a coug h . Ra rely, persistent clear rhi norrhea may be secondary to a CSF leak, which should be considered if nasal drai nage and cough don't respond to treatment. ACE inhibitors, such as ca ptopri l , a re a common ca use of cough in pa­ tients on anti hypertensive therapy. A neoplasm in the lower a irway, which is not visible on x-ray, may be made manifest by cough. An esophageal diverticulum (e.g . , Zen ker's d iverticulum) causes hal itosis, reg u rgitation , and cough associ­ ated with eating. Patients with congestive heart failure may have an exacerba­ tion of reactive a i rways disease with coug h a nd/or wheeZi ng, often worse at nig ht. The presence of ear pain or ear disease should prompt an investigation of the outer ear canal and the ear dru m , as irritation in those a reas by hair, wax, or a foreign body may lead to sti m ulation of the vagus nerve and cough . The ea r canal should be exa m i ned in a l l patients presenting with coug h , as e(] r problems may be asymptomatic. The presence of stridor on physical exa m i nation or a palpable neck mass may indicate an upper airway problem as a cause of chron ic coug h . A gas­ trOintestinal-a i rway fistula, usua l ly tracheoesophagea l , cha racteristically causes cough wh i le eati ng. And finally, the occurrence of the cough after work or worsen ing of the cough during the work week may suggest an occupational cause leading to a hypersensitivity pneumonitis or an allergy. 6. Stud ies have shown that patients with cough lasti ng longer than 3 weeks who come to a pulmona ry special ist for evaluation almost i nvariably have one of four ca uses of chronic cough : gastroesophageal reflux, asth ma, smoking-in­ duced chronic bronch itis, or sinusitis/post-nasa l drip. The authors of these stud­ ies have suggested that a work-up for these four possible entities and/or empiric treatment of them will lead to resol ution of the cough in the g reat majority of cases. Adding the common entity of post-infectious cough to these four entities creates the mnemonic GASPS, which is a good start for d iagnosing the cause of chronic cough.

Pulmonary and Critical Care • 1 7

7 . Occasiona l ly, patients with pulmona ry fi brosis present with coug h and a negative x-ray. These patients usually have fine, "velcro" crackles on chest aus­ cultation, and a CT scan will reveal the i nterstitial d isease. 8 . Finally, for patients in whom all other causes of cough a re ruled out, a psy­ chogenic etiol ogy is possi ble. This d iagnosis req u i res exclusion of the other aforementioned etiolog ies.

CLU B B I NG CLU B

Cancer Liver disease U lcerative colitis B ronchiectasis (especially cystic fibrosis) N ote Clubbing has been observed in association with lung diseases si nce antiqu ity; however, its cause is unknown . It may be seen associated with cancers, particu­ la rly pulmona ry neoplasms, and when such an association exists, there usually is evidence of hypertrophic pul mona ry osteoa rthropathy. Clubbing also is ob­ served i n some cases of chronic l iver disease, as well as in inflam matory bowel disease, especially with ulcerative col itis. Clubbing is a very common symptom in patients with cystic fi brosis and in other patients with bronch iectasis. Other l u ng d iseases that have been assoc iated with clubbing i nclude lung a bscess and asbestosis. Less commonly, it has been seen in association with sarcoidosis and eosi noph ilic g ra nu loma . Clubbing is less commonly associated with pul­ monary fibrosis. It is not associated with COPD, the presence of clubbing should prompt an i nvestigation for other d iag noses . Clubbing may regress with treat­ ment of the underlying disease.

18 • Pulmonary and Critical Care

-

DYS P N EA S H E PANTS

Stress/anxiety/deconditioning H eart disease Emboli Pulmonary disease A nemia Neuromuscular disease Trachea/upper airway obstruction Sleep disorder N otes 1 . Dyspnea is defined as an a bnorma l ly uncomforta ble awareness of breath­ ing and has diverse causes. Patients' own descriptions of symptoms may include fatigue, heavy breath ing, weakness, chest tightness, wheezing, and other com­ plai nts . There a re four primary a natomic areas that i nfluence the sensation of breathing: Pulmonary/a irway stretch receptors, Aortic/carotid chemoreceptors, Neuromedullary chemoreceptors and Thoracic muscle stretch receptors ( " PANT" ) . I n put from these sites i nfluences the breathing pattern. For exa m ple, an acute exacerbation of COPD leads to lung hyperinflation and chest wall ex­ pansion, which i n tu rn sti mu lates pul monary and thoracic m uscle stretch recep­ tors, ulti mately leading to the sensation of dyspnea . Neuromuscular disease causes hypoventilation, al lowing CO2 to rise and O2 to fa l l . H igh pC02 and low p02 sti m u late aortic , carotid, and medullary chemoreceptors and ca use dyspnea . Alternatively, hypoxia from pul monary emboli sti m u lates aortic, carotid, and medulla ry chemoreceptors and causes dyspnea . 2 . The onset of dyspnea (acute, subacute, chron ic/progressive) as well as ex­ acerbants should be establ ished . Note that some patients with slowly prog res­ sive processes may g radually adapt by decreasing thei r physical activity, but compla i n of more acute symptoms at rest. Positional complai nts of dyspnea may be elicited, such as orthopnea (worsening i n the supine position - card iac d is­ ease, u pper airway obstruction, diaphragmatic paralysis! platypnea (shortness ' of breath when ass u m i ng an u pright position - ci rrhosis patients with intra pul­ monary shunts, pneumonectomy patients with i ntra-atrial shunts, patients with de­ ficient abdom inal m usculature!, trepopnea (dyspnea occurring in the right or left Pulmonary and Critical Care • 1 9

..

lateral decubitus position - heart disease , uni lateral pul monary d isease) , and

paroxysmal nocturnal dyspnea ( most often related to left ventricular fa ilure, but

may be seen with obstructive lung disease or sleep-disordered breath ing). 3 . I n addition to exertional and positional preci pita nts , q uestion the patient a bout occupational or environmental exposures, animal exposures, inhalational agents, and seasonal worsening. 4 . Stress, anxiety, and decond ition ing a re com mon causes of dyspnea , but often req u i re a n extensive i nvestigation to rule out more l ife-th reatening etiolog ies. 5 . Suspect heart disease or cardiac ischemia in patients at risk for or with a his­ tory of cardiac disease. A history of exertional symptoms, orthopnea, paroxysmal nocturnal dyspnea, or chest pa in may be present, as well as physical exa m i na­ tion findi ngs of edema , jugu lovenous distension , or card iac murmurs/gallops. I ntraca rdiac shunts also cause hypoxemia, CHF, and dyspnea . 6. Pulmonary emboli may present with acute dyspnea , chest pai n , or wheez­ ing . . Chronic, recurrent pulmonary emboli may be relatively "si lent" in itially and present as slowly progressive dyspnea . Evidence of lower extrem ity venous ob­ struction may not be present. 7. The category of primary pulmonary disease i ncl udes a i rway, interstitial and infiltrative, pleura l , and pulmonary vascular diseases (embolic d isease is consid­ ered separately a bove ) . Wheezing, coug h , and a worsening of symptoms in the evening in a younger person suggest reactive ai rways disease, while g radu­ ally prog ressive dyspnea and "velcro" crackles in an older patient suggest inter­ stitial pul monary fibrosis. Pri mary pulmonary hypertenSion is often seen in young women and may present as gradua lly progressive dyspnea with a paucity of physical find i ngs. 8. Anemia should be considered i n you n g , m enstruati ng women a n d i n pa­ tients with gastrOintestinal disease, chronic renal disease, or maligna ncy. 9. Neuromuscular diseases include myopathies, neuropathies, and diaphrag­ matic dysfunction . 1 0. Obstruction of the trachea or upper airways, may be subtle, and wheez­ i n g may be attri buted incorrectly to asth ma or COPD. Tu mors of the upper a i rway and vocal cord dysfu nction a re poss i ble etiolog ies. The flow-volume loop may show a cha racteristic pattern of obstruction. 1 1 . Sleep-disordered breathing is com mon i n obese patients, the elderly, and Pl tients with chronic heart and lung d isease. Heavy snori ng, jerky l i m b move­ m� nts while asleep, morn ing headaches, daytime hypersom nolence, and sexual dysfunction a re clues to the diagnosis. It is important to obtain i nformation from fa m i ly members and sleep partners as well as the patient . Sleep d istu rba nce can cause fatigue, exercise intolerance, and complaints of dyspnea . 1 2 . One of the most common clinical conundru ms is the differentiation of car­ diac from pulmonary dyspnea . Many patients have both hea rt and lung dis­ ease, and the relative contribution of each may be d ifficult to d iscern . The i m portance of a careful physical exa mi nation can not be overstated . Look ca re­ fully for the signs of C H F, including an S3 or S4 ga llop, rales, jugulovenous dis­ tension UVD ) , and peri phera l edema . S i g ns of pulmonary l i m itation i n clude 2 0 • Pulmonary a n d Critical Car£!

wheezing or reduced a i r entry, increased lung volumes, and hyperresonance to percuss ion . Note that JVD and pedal edema may be seen with cor pul monale, and they a re not always indicative of left-sided cardiac dysfunction . In additio n to the physical exa mination , a few simple measu rements may be The peak expiratory flow (PEF) is an easily obtai ned measure of a i r flow pful hel lim itation . A reduction in PEF « 200 L/m in) i ndicates obstruction and a likely pul­ monary etiology. The Pa02 also tends to be lower in pu lmonary dyspnea , a l­ though there is considerable overlap One g roup of investigators has suggested using a combination of both measures, PEF X Pa02 / 1 000, to differentiate be­ tween cardiac and pulmonary dyspnea . They have named this q uantity the dys­ pnea d ifferentiation i ndex (DDI) and use a cut-off of 1 3 to disti nguish between pulmonary and cardiac etiologies. A DDI < 1 3 ind icates a probable pulmonary etiology; values > 1 3 are suggestive of a cardiac etiology. Be careful to obta in a room air Pa02 and an accurate PEF (often tachypneic patients can not perform this test in itia lly) if these parameters a re being used . Another sim ple bedside parameter is the blood pressure response to the Valsalva maneuver. The a rterial pressure response to the Va lsa lva maneuver is abnormal in either systolic or d iastol ic dysfunction (see Cha pter V, Cardiology) . Norma lly, there is a decrease in the pulse am plitude and a narrowing of pulse pressure in response to stra i ning. In CHF this response is blunted, prod ucing a "square wave response . " A normal arterial response to Va lsalva suggests a pul­ monary etiology for dyspnea .

H E M 0 PTYS I S CAV I TAT E S

Congestive heart failure Airway disease/bronchiectasis Vasculitis/vascular mal f ormations I nfection (e.g., tracheobronchitis, anaerobes, fungi, T 8 ) Trauma Anticoagulation Tumo r Emb olism Sto mach (G I or nasal source) 'Pulmonarv and Critical Care • 2 1

N otes 1 . When a patient complains of blood in the sputu m , fi rst determine if the source is the lungs or ai rways (hemoptysis) and not the mouth , nose, pha rynx, or GI tract. The next steps are to q uantitate the a mount of blood and then consider possi ble etiolog ies . The d isease processes caus i n g hemoptysis often cause tissue necrosis, and the lung cavitates. Cavities, cystic cha nges, bronchiectasis, or alveolar ai rspace fi l l i ng on chest x-ray may ind icate a source of bleed i n g . Diffuse infiltrates suggest a more l i m ited d ifferential (e.g . , vascul itis with diffuse a lveolar hemorrhage, coagulopa thy, m i tra l stenos is) . Although an a l a r m i n g symptom, hemoptysis is often secondary to a benign etiology. Gross o r massive hemoptysis is most com monly caused by cancer, TB, or bronch iectasis. 2. Congestive heart failure often causes pink, frothy sputum , but rarely fra n kly bloody sputu m . Mitral stenosis is specifically associated with hemoptysis; ra rely, m itral regurg itation may cause expectoration of fra n k blood . 3 . Diseases of the a irways often cause hemoptysis, with tracheobronchitis as the most common cause of blood-ti nged sputum . Chronic a irway inflammation leads to bronchiectasis, which commonly causes hemoptysis. 4. Vasculitides, such as Wegener's granulomatosis or Goodpasture's d isease, are often characterized by fever, acute illness, and evidence of systemic involve­ ment, often renal dysfu nction . Arteriovenous ma lformations may cause hemop­ tysis and should be ruled out before biopsies a re ta ken . 5 . Certa in infections, such as TB, fungi , and a naerobic lung a bscess, are more likely to cause hemoptysis. Hemoptysis in these diseases is often seen in associ­ ation with cystic or cavitary lung d isease. Staphylococcal infection following i n­ fluenza characteristica l ly causes " rusty" or bloody sputu m . Rarely, Serratia marcescens lung infection causes redd ish sputu m that appears bloody. 6 . Trauma from thoracic injuries, in halations, pu l monary artery catheters, or en­ dotracheal tubes may cause va ria ble a mounts of airway bleed i ng . 7. Anticoagulation with coumad i n or heparin, or a bleed ing diathesis such as thrombocytopenia may precipitate bleed ing from the respiratory tract. Aga i n , the presence of blood does not necessarily indicate a malignancy or specific in­ fectious etiology, but be suspicious, si nce a nticoagu lation can " u n m ask" an occult lesion . 8 . Suspect tumors of the airway or parenchyma in smokers or patients with a known malignancy. 9 . Pulmonary emboli may cause tissue infa rction and hemoptysis. Ra rely, pul­ monary emboli cause cavitation. 1 0. Be careful to d iscri m i nate hemoptysis from stomach or other gastrointesti­ nal bleed i n g . N asopharyngeal bleed i n g may cause cough and be m isi nter­ preted as hemoptysis. The pH of hemoptysis is usua lly a l kaline, while that from the stomach is acidic. 1 1 . The treatment of hemoptysis usually i nvolves observation and perhaps maintaini ng the bleed ing source in the dependent position . If the hemoptysis is 22 • Pulmonary and Critical Care

maSSive (arbitrarily defined as > 500 ml/24 hours) , i ntu bation with a double­ lumen endotracheal tube is often required , with an attempt to isolate the hemor­ rhaging lung and prevent "soi l i n g " of the non bleed ing lung . The sou rce of massive bleed ing is usually the bronch ial a rterial system , and hemostasis may be obtained bronchoscopically, surgical ly, or by invasive radiologic procedure. 1 2 . A more comprehensive list of causes of hemoptysis is outlined below:

TRAC H EAL

Tracheobronchitis, Trauma, Tuberculosis, Thrombotic thrombocytopenic purpura Rupture of pulmonary artery (Swan-Ganz), Resin/paint production (trimeliitic anhydride), Rasmussen 's aneurysm Aspirated foreign body, A Ilergic bronchopulmonary aspergillosis, A naerobic/necrotic pneumonia Cancer, Cardiac (especiall y mitral stenosis) ' Crack coca i ne Heparin, Hemosiderosis (idiopathic pulmonary), Helminths (paragonimus, echinococcus) E NT/esophagus (pseudo-hemoptysis), Embolism (pulmonary, septic), Endometriosis A rteriovenous malformation, A rteritis/vasculitis, Amyloid Lung abscess, Left atrial myxoma, Lithiasis (broncholith), Lymphangioleiomyomatosis Also.· penicillamine and arterial bronchial fistula

STR I DO R WE TRA C H O R TR EAT

Wegener 's E piglottitis/supraglottitis Pulmonary and Critical Care • 23

Tracheobronchitis Relapsing pol y chrondritis Aspirated foreign body Cancer (endotracheal, metastatic, extrinsic compression) Hereditary (web, Ehlers-Danlos, Williams-Campbell, Mounier-Kuhn) Obstructive lung disease/"dynamic" compression Reidel 's thyroiditis/Radiation (fibrosing mediastinitis) Trauma/T racheostomy R hinoscleroma E motion/anxiety (vocal cord dysfunction) Amyloidosis Tracheopathia osteoplastica WH EEZI NG AST H MA

Asthma S mall airways disease Tracheal obstruction/l a rge airways disease H eart failure Mastocytosis/carcinoid A naphylaxis/A Ilergy N otes 1 . "All that wheezes is not asth ma" (Osler) . The mnemonic ASTHMA em pha­ sizes the maior causes of wheezi ng . Wheezi ng is ca used by a i rway narrow­ ing. The narrowing may be in the u pper a i rway (e . g . , laryngeal tumors, vocal cord dysfunction) , the large ai rways (e . g . , lung cancer, aspirated foreign body), or the small a i rways (e.g . , bronchiolitis, asth ma ) . When there is upper a i rway compromise, the wheezi ng sound is hea rd best over the trachea and is referred 24 • Pulmonary and Critical Care

to as stridor. Extra-p u l monary d i sorders a lso may ca use bronchoc 30% change per day in airfl ow • Nocturnal asthma • High amount of beta-agon ist use ( more than two ca n isters per m onth) . • Associated psych iatric d isease. Other factors i ncluding age, degree of obstruction , and race also ca ll be signif­ icant ind icators of high-risk asth ma . 3 . Small airways diseases a re a group of poorly understood entiti es d i sti nct from asthm a . As the name indicates, they cause narrowing and ObStruction of the small a i rways and consequent wheeZing . A relatively com mon p hysical ex­ amination find ing is an end-inspi ratory "squeak, " which probably c O rresponds to late opening of d istal airways. 4. Tracheal disease and large airway obstruction usually cause stritJ or, which may be d ifficult to differentiate from wheeZi n g . U pper airway lesions �an be de­ tected by physical examination (stridor over the upper ai rways) or Ch\l racteristic flow volume loops. A pa rticula rly common cause of upper ai rway W h eezi ng is vocal cord dysfu nction . These patients, often young women , typically h ave exer­ tiona I or emotionally ind uced wheeZing and shortness of breath whi� h may be severe. Characteristical ly, the wheeZing occurs with inspiration . The fI()w volume loop may show variabili ty in the i nspiratory phase. These patients oftE! n are mis­ diagnosed and treated im properly (often with steroids) as refractory Ci sth matics. Speech therapy and education are helpfu l . 5 . Extra-pulmonary disorders can cause bronchoconstriction . Heart f� i l u re may be made man ifest by wheezing or it may exacerbate normally q u i�scen t a i r­ ways hyperreactivity in certa in patients. A few un usual diseases (ma�tocytosis, carci noid syndrome) can produce h ista m i nic compounds that caus ras h , hy­ potension, and wheezi ng . Carcinoid tumors can cause wheeZi ng by two mech­ anisms: ( 1 ) airway obstruction by a bronchial carcinoid, and ( 2 ) prod ucti on of 5-H IAA, a bronchoconstrictor, which usually only causes wheeZing when the tumor i nvolves the liver (see Cha pter VI, Endocrinology, the Carcinoid secti on). 6. Anaphylaxis and allergy can cause bronchospasm and wheeZin g . It i s crit­ ical to identify environmenta l precipitants of wheeZing, as such knOW ledge can be life-savi ng. Avoidance of precipitants obviates the need for medic(:] tion s . Pulmonary and Critical t:are • 25

7. Pulmonary function tests a re essential in the diagnos is of a i rway obstruction and assessing the response to therapy. Inspect the flow volume loop with both i n­ spiratory and expiratory limbs for evidence of a large a i rway obstruction . Obtain lung vo,lume measurements: a n obstructive lung disease should show normal or increased lung volumes. Then a n assessment of simple spi rometry IFEV I , FVC) determines if obstruction is present. Occasional ly, a provocative test for asthma ; � needed ( i . e . , methacholine challenge test) when the d iagnosis is u ncerta i n . 8 . Below i s a more comprehensive list of the causes o f wheezi ng:

T H E AST H MATICS

Toxic fumes Hypersensitivity pneumonitis Eosinophilic disease Asthma Small airways disease Tracheal obstruction/l a rge airways disease Heart failure Mastocytosis/carcinoid A na phylaxis/Allergy Thromboembolism I nfection/bronchitis Cystic fibrosis/bronchiectasis Smoking/COPD

26 • Pulmonary and Critical Care

C l inical Conditions or Diagnoses

A C U T E R E S P I R AT O R Y D I ST R E S S SYN D R O M E­ D I F F U S E P U L M O N A RY I N F I LT R AT E S ARDS

Acute onset Ratio PaOiFi02 � 2 0 0 Diffuse infiltration Swan-Ganz wedge 1 8 mmHg <

N otes 1 . The clinical definition of ARDS is: ( 1 ) acute onset, (2) ratio (Pa02/Fi02) of 200 or less (regardless of PEEP level) , (3) diffuse, bilateral i nfiltrates on frontal chest x-ray, (4) Swan-Ganz wedge pressure � 1 8 m m H g or no c l i n i ca l evidence of leh atrial hypertension . / 2 . The development of diffuse pulmonary i nfi ltrates may rapidly lead to respira­ tory failure. Decide whether the etiology is secondary to congestive heart fa ilure or due to capillary leak. Capillary leak leads to the acute respi ratory d istress synd rome. Diffuse pul monary infiltrates may be com posed of any of the previ­ ously mentioned etiologies u nder pulmonary i nfiltrate (see previous section ) . 3 . Both congestive heart failure a n d capillary leak syndromes cause fluid to accu­ mulate in the a lveola r space, but the physiolog ic mecha n isms a re d ifferent Leh heart failure causes an increase in capillary hydrostatic pressure, and fluid is extruded into the alveol i , while ARDS occurs secondary to a capillary leak phenomenon , in which fluid extra va sates i nto the alveol i . The physical exami nation in a patient in respiratory d istress or who is already on a ventilator may be lim ited, and other diagnostic tests may be needed to i ndicate the nature of the pulmonary i nfiltrates . Two useful tests are the echocardiogram, which can g ive an assessment of overall global card iac function as well as pulmonary pressures , and pulmonary Pulmonary and Critical Care • 2 7

artery catheterization (Swan-Ganz) . Although many paroa meters may be mea­

sure d with the Swa n-Ganz catheter, the most i m portant i n d ifferentiating be­ twee n card iogenic p u lmonary edema and noncardiogen i c pu l monary edema a re the wedge pressu re and pulmonary d iastolic pressures . I n card i ogenic pul­ monary edema, both the wedge and PA d iastolic are elevated typically > 20 m m H g . I n nonca rd iogen ic pulmona ry edema, the pulmo m o ry capillary wedge pressure is usually < 20 mmHg. 4 . The therapy of ARDS is supportive, with special emphCll s i s o n identifying and treati ng the cause. There has been a great deal of intereslt i n steroid therapy for ARDS, and current data suggests a role 1 -2 weeks aher onset, du ring the so­ called fi broproliferative phase. Most stuQ ies have showm no sa luta ry effect of steroids when they were started early in the course of ARDS. F u rther studies are needed to confirm benefit later i n the course. 5. Here is a more comprehensive m nemonic for the causes of ARDS:

CA R D S ? H O PE I T' S N O T A R D S e N S disorders Aspiration (especiall y gastric) Radiation Drugs (i.e., heroin, morphine, barbiturate-s, etc.) S moke/toxic gas inhalation Hypotension/shock O2 Toxicity Pancreatitis Emboli (i.e., pulmonary, fat, amniotic fluicrj) I nfection/sepsis Transfusion reaction S urgery (especiall y cardiac) Near drowning O bstetrical emergencies (e.g., eclampsia , HELLP) Thermal injury/burns A Ititude sickness Renal failure D iffuse intravascular coagulation Systemic lupus erythematosus

28 • Pulmonary and Critical Care

A C U T E R E S P I R AT O R Y FA I L U R E A P E H I T I N T U BAT E D

Aspiration " White " X-Ra ys Pus Edema Hemorrhage I mmunologic Tumor " Black " X-Ra ys I nfarcted right ventricle Neurologic disease (drug overdose, botulism, CVA, Guillain Barre Tension pneumothorax U pper airway obstruction (anaphylaxis, foreign body 'aspiration) B ronchospasm (COPD exacerbation, asthma) Arrhythmia Tamponade Embolus (pulmonary, air, amniotic fluid, tumor) Diaphragmatic weakness (surgery/trauma, neurologic disease) N otes 1 . This m nemonic i ndicates the ma ior causes of acute respi ratory fa ilure . The fi rst part of the mnemonic, A P E H IT, ind icates the same processes causing pul­ monary i nfi ltrates. These processes lead to opacifications on the chest x-ray. The second half of the m nemonic, I NTU BATED, i n d icates etiolog ies in which the chest x-ray often d oes not show any i nfi ltrates. I n these entities, air space d is­ ease is not the cause of respi ratory fa ilure, and you m ust consider other causes of hypoxemia (e . g . , neurologic i m pairment leading to hyperventilation , tension Pulmonary and Critical Care • 29

pneumothorax , upper and lower a i rway obstruct.on , a nd vascular obstruction ) . Therefore, a common way to d ivide u p the causes :Jf acute respiratory failure i s by those that have "wh ite x-rays " (opacificaf ons) ane those that have "black x-rays" (clea r lung fields) . 2 . There are six primary mechan isms of hy poxertia : • Hyooventi lation • Low inspired fraction of oxyge n , • DiFusion impairment such as occurs at high a ltitude • Low m ixed venous oxygen . • V/0 m ismatch • Shunt Of these ca uses , the m ost i m porta n t o n es a re V/0 m i s'll atc h , s h u nt, a n d hypoventilation . 3 . The indications for emergent endotrach eal intLbation are. • Hypoxem ic respi ratory failure ( p02 < 60 rrm H g on > 60% oxygen) • Hypercarbic respiratory failu re (res pi ratory acidosis with a pH < 7 . 3 ) • Airway protection • I ncreasing intracranial p ressure

B R O N C H I E C TA S I S A SICK AI RWA Y

A irway/lesion/chronic obstruction S equestration I mmunodeficiency syndrome (especiall y immunogl o bulin abnormalities) Cystic fibrosis Kartagener 's syndrome/dysmotile ciliary syndromes A lIergic bronchopulm onary aspergill osis (ABPA) I nfection/I nflammation (e.g., tuberculosis, post-viral, whooping cough, coll a gen-vascula r disease) R eflux (aspiration)/R ecurrent i njury (heroin, toxic gas inhalation) Williams-Campbell and other congenital diseases (e.g., Marfan's, Mounier-K u n) A Ipha-I antitrypsin deficiency Yellow nail syndrome, Young syndrome h '

30 • Pulmonary and Critical C.are

s

N otes 1 . Bronchiectasis, a di lation of the ai rways, is usually a result of chronic endo­ bronchial inflammation . 2 . Hemoptysis may be a frequent feature of chronic bronchiectasis. 3 . Bronch iectasis leads to d i lation of bronchial arteries and i ncreased blood flow, which predisposes patients to bleed ing. 4. "Dry" bronchiectasis refers to predom i nantly u pper lobe d isease ( i . e . , sec­ ondary to TB or h i stoplasmosis). which usually dra i ns effectively. The ca rd i nal sym ptom is hemoptys is "Wet" bronchiectasis refers to lower lobe d isease , which is characterized by chron ic cough and purulent sputum . Exceptions to this rough classification include cystic fibrosis, which has prom i nent u pper lobe dis­ ease and thick, tenacious secretions. 5. A few diseases commonly cause bronchiectasis with an upper lobe predom­ inance. These can be remem bered by the m nemonic " FACT" ( F u n g i , ABPA, Cystic fibroSiS, TBI 6 . Ai rway lesions include tumors (benign and mal igna nt!. foreign body aspi ra­ tion , and bronchol iths. These airway lesions may cause chronic atelectasis and, ultimately, bronch iectasis.

C AV I TA R Y A N D C Y S T I C L U N G D I S EAS E WEIRD HOLES

Wegener 's Emboli (pulmonary, septic) I nfection (e.g . , anaerobes, Pn eumocvs tis carin ii, T B ) R heumatoid arthritis (necrobiotic nodules) Developmental cysts (bronchogenic, sequestration) Histiocytosis X Oncologic (primary or metastatic cancer) Left atrial myxoma ( LA M ) Environmental/occupational (silicosis, trauma) Sarcoidosis Pulmonary and Critical Care . 3 1

N otes 1 . The presence of cavities or cystic cha nges on the chest x-ray may be caused by necrotizing processes such as i nfections, vasculitides, i nfarction from emboli, or maligna ncy. Also consider certain developmental a nomal ies, occupational exposures, and u nusual primary l u ng diseases. 2 . Pul monary cavities primarily result from six sections of the "MEDIC I N E DOC" m nemon i c : ( 1 ) I nfectious , ( 2 ) Congenita l , ( 3 ) I m m u nolog i c , ( 4 ) Neo­ plastic, (5) Exotic, (6) Occupational/environmental exposures 3 . Infectious etiologies i nclude mycobacterial disease, fungal disease, necro­ tizi ng bacteria l i nfections, parasitic infections, and septic pulmonary embol i . Tuberculous cavities typica l ly occur i n the upper lobes, but can present i n a ny lo­ cation . They a re part of a chron ic disease process, so prior fi lms are helpful i n analyzing the progression of the disease. I n the a bsence o f superinfection , a i r­ fluid levels are uncommon in tuberculous cavities. Sputum analysis often is posi­ tive in active cavitary tubercu losis, as the organism load is relatively high with i n the cavity. Fungal diseases, such a s coccidiomycosis, blastomycosis, a n d h isto­ plasmosis, also can produce cavities Asperg illosis may couse on acute necrotizing pneumonia in i mmunocom pro­ m ised patients, or it may colonize pre-existi ng cavities, producing a visible fungal boll on chest radiography. Because invasive aspergillosis characteristically i nvolves blood vessels, thrombosis, i nfarction , and cavity formation often ensue. The char­ acteristic "crescent" sign is produced by i nfa rcted tissue within the fu ngal cavity. Vi rtually all bacterial i nfections can cause a pneumonia that may produce cavitary lung changes . Cavita ry cha nges a re more typical of a naerobes and g ra m-negative org a n i s m s . However, Staphylococcus aureus, Streptococcus pneumonia, and Legionella species all can produce cavitary l u ng changes. A ra re com pl ication of bacterial pneumon ia is pulmonary ga ngrene. The rad i o­ logic a ppearance can be characteristic, with i nfa rcted lung tissue floati ng with i n a parenchymal cavity. Surgery often is required for resolution. Pa rasitic i nfections should be suspected i n i n d ividuals with a pp ropriate travel and exposure history. Paragonim iasis is secondary to a l iver fluke and is endemic to Southeast Asia . Echi nococcus is associated with exposure to sheep, dogs, or wild hosts such as caribou or rei ndeer. A characteristic rad iologic a p­ pearance, the "water-li ly" sign, is produced when the encysted organ isms' mem­ branes detach from the adventitia and float with i n a cavity. Finally, septic pulmonary emboli most commonly occur as a result of tricuspid endocard itis or a peri pheral source . Multiple cavita ry lesions may be present, often in the lower lung zones where the blood supply is greater. 4. Congenital anomalies i nclude developmental cysts (e . g . , bronchogen ic) as well as pulmonary sequestration, and should be suspected in young adults pre­ senti ng with asymptomatic cavitary lung lesions. 5. I m m u nolog ic processes i nclude the vasculid ities and rheumatoid a rthritis. Wegener's granulomatosis is the most common immunologic disease that presents 32 • Pulmonary and Critical Care

.... I

with pulmonary cavities. Rheumatoid arthritis ca n cause lung nodules that fea­ ture central necrosis a n d eventua l ly cavitate. Ankylosing spondylitis and polymyositis also may feature a pical bullous disease. 6. Oncolog ic processes can produce cavities by two mechanisms: ( 1 ) obstruc­ tion of a bronchus with d istal suppurative i nfection, or (2) cavitation of the tumor mass secondary to outgrowi ng of the blood supply. Squamous cell carci nomas have a particu lar propensity to outg row their blood su pply a n d cavitate . Angiocentric lymphoma (lymphomatoid granulo matosis) is a n u n usual mal ig­ nancy that can cause multi ple lung masses which may cavitate. 7. Exotic diseases causing cysts i nclude histiocytosis X, LAM, and sarcoidosis. Younger patients who present with multiple lung cysts should be suspected of haVing these diseases. Histiocytosis X, also called eosinophilic granuloma , is a disease of smokers. lANI is related to tuberous sclerosis and occurs in young females. 8. Envi ronmental or occupational exposures may lead to cystic lung d isease. A common occupational cause of cystic lung disease is sil icosis, which occurs in hard rock m i ners . Also, rarely, multiple trauma patients develop acute cavitary lung d i sease of uncerta i n etiology. Presumably, the trauma leads to vascular iniury, resulting in the cavitary changes on x-ray. 9 . As with most respiratory problems, emboli are a possible, albeit rare, cause of cystic or cavita ry changes . Both pulmonary and septic e m boli can cause necrosis, infarction, and subsequent cavitation .

I N T E R ST I T I A L L U N G D I S EAS E IS IT I PF?

I PF Sarcoidosis I nhalational (pneumoconioses) Treatment-related (e.g., medications, radiation, chemotherapy) I mmunologic (collagen-vascular diseases) Post-inflammatory (e.g., infection, A R D S ) Familial Pulmonary and Critical Care • 33

N otes 1 . The lung interstiti u m is the a rea between the gas-exchanging alveolar epithe­ lium and the capi llary membra ne. Norma lly this space is very th i n and allows for effective gas exchange. When d iseases or toxins damage the in�-:: ' -titiu m , it may become i nfi ltrated with inflammatory cells and, ultimately, scar tissue. These interstitial lung d i seases produce an i m pa i rment in the d iffusion of oxygen and lead to respiratory sym ptomatology The chest rad iograph characteristically shows what is often called a reticular or li near pattern of i nfiltration . The term " d i ffuse pa renchym a l lung disease" m ay be more a ppropriate since these d iseases may involve the a i rways and a i rspaces i n addition to the interstiti u m . The m nemonic " I S IT IPF?" summarizes the pri mary causes of i nter­ stitial d isease. 2 . One of the m ost commonly encountered i n terstitial lung diseases is id io­ pathic p u l m o n a r y fi brosis, I PF . Sarcoidosis is a lso very common and has myriad systemic manifestations . Immunologic/collagen-vascular diseases have well-descri bed systemic features and pulmonary i nvolvement. Lung disease is oc­ casion a l ly the i n i tial f i n d i n g i n patients with collagen-vascular d iseases . Treatment-related causes m ust be ca refully considered si nce removal of the of­ fending agenr is critica l . A complete occupational and environmental histary is mandatory to exclude in halational lung d i sease . Avoidance of the i nciting agent is mandatory for the patient, and other persons at risk may be identified . Pulmonary i nfections, ARDS, and other lung i njuries may result i n post-inflamma­ tory fibrosis and permanent parenchymal changes. Finally, a number of unusual familial d iseases have associated interstitial lung d isease. 3 . The history a n d clin ical exam i nation sometimes suggest an etiology for inter­ stitial disease, such as a n exposure or an u nderlying disease. The chest rad io­ g ra ph may show characteristic patterns which may also suggest a n etiology. For exa m ple, certa i n diseases more commonly have predom inantly upper lobe i n­ volvement, incl u d i n g Ankylosing spondyl itis, PIE (chronic eosi noph ilic pneumo­ n i a ) , Infections (TB, h istoplasmosis), Coa l worker's pneu mocon iosis/s i l icosis, Eosinophilic granuloma (h istiocytosis X), and Sarcoidosis/berylliosis ( "APICES"). A predom i nantly lower lobe pattern of disease is seen i n asbestosis, alveolar pro­ tei nosis, I PF, collagen-vascular diseases, and chronic hypersensitivity pneumonitis. Nodu les suggest sarcoidosis, Wegener's, inhalational exposures ( pneumoco­ nioses). rheumatoid a rthritis, or lymphomatoid granulomatosis ("SWIRL"). The pres­ ence of pleural disease is unusual in interstitial lung disease, but may be seen i n asbestosis, Iymphongitic carcinomatosis, a n d collagen vascular diseases. Normal or increased lung volumes and cystic changes are seen in only a few diseases. Finally, lymphadenopathy is also unusual in i nterstitial lung disease and may in­ dicate sarcoidosis, amyloidosis, Iymphangitic carcinomatosis, or berylliosis. 4. Diffuse pa renchymal lung d isease most often leads to i ncreased lung elastic­ ity and a reductio n in lung volumes. Pulmonary function tests usua lly reveal a re­ strictive ventilatory defect. Occasionally i nterstitial disease is seen i n a patient 34 • Pulmonary and Critical Care

with normal or i ncreased lung volumes, a n d this narrows the differential con­ s i derably. The causes of I nterstitial lung d isease with normal or increased lung volumes are summarized by the m nemonic LET'S BRONC H : LAM, Eosinoph ilic g ranuloma ( h istiocytosis XL Talc injection ( i ntravenous drug a busel, Sarcoidosis, B ronchiectatic d iseases (e. g . , cystic fi brosis), Respi ratory bronch iol itis, Obliter­ a tive bronch iolitis, Neurofibromatosis, COPD + ILD, Hypersensitivity pneumon itis. (This m nemonic is adapted from one i nvented by Robert Shpi ner, MD . ) I n con­ trast to other causes of i nterstitial lung d isease, these diseases feature obstruction on pul monary function tests. Exceptions a re hypersensitivity pneumon itis and eosinoph i l ic g ra nuloma, which most often show restriction on pulmonary func­ tion testing despite normal or i ncreased lung volumes . 5 . There are a pproximately 1 80 known i nd ividual diseases that m a y b e associ­ a ted with interstitial lung d isease . The most frequently encountered are I PF, sar­ coidosis, and interstitial lung disease associated with collagen vascular diseases . The following m nemonic l ists many of the causes of i nterstitial lung d isease:

I HAVE BRO N C H E D A N I NTERSTITIAL LUNG

I diopathic pulmonary fibrosis (I PF) H ermansky-Pudlak syndrome A R D S recovery Veno-occlusive disease E nd-stage liver disease B ronchocentric granulomatosis R heumatoid arthritis and other collagen vascular diseases O rganic and inorganic dusts (occupational/ environmental) N iemann-Pick and Gaucher's diseases Congestive heart failure H ypereosinophilic syndrome Eosinophilic lung diseases (PIE syndromes) D rug exposures (e,g" amiodarone, gold, antibiotics, chemotherapy) Amyloidosis N eoplastic (Iymphangitic carcinomatosis, post-radiation therapy) Pulmonary and Critical Care • 35

Idiopa ltt--. ic p u lmonar y he m os ider osis Neuro f ib ro m atosis Tuber (Q l..J S s c lerosis Eosin granulo ma/his ti ocytosis X Renal C::>f�P hiluil icre/uremia Sarcoi d Trans b le�ntsisa tion ( G V H D ) I nfect i S (r esidua act ive infe ction of any type) Toxic 'ioc hllem icals (ga se s, f um es , va pors, ae r os ols, par � q ua t, rad iati or) ) Idiopa pereosi nop h ilic synd rome A Iveo''tail... icprhy o teinosi Lymp� a. ng io leiomyos mat o si s ( L Lympth a cy tic di so rd er s (e .g . , A M ) Iym ph oc ytic interstitia l p n pse udolymphoma, U I ce r � t i v e c oli tis an d ot he r geum onitis) . Nec r Q,ti :Z i n g va sculit i s (Weg e as tro intes tin al diseases Iy m p h o m atoid granulo m a ne r 's, Ch u rg-S tra u ss , s) Goo d � a. st ur e's dis e as e an d tosi he fln a rrh ag e sy nd ro me s ot he r pu l m onary of

M E D I AST I N A L M AS S C H E ;g T A L A R Ms

Cysts ( bro n chia l, pe ricar d ia l) H erni � � (B o chdalek , Mo rg ag ni) Es oplJ a ge al div ert i c ulu m Sch geni c tu mor s Ts (TwlJ..aan noTm's:a/neuro ter ato ma , th Ym o n a, thy r oid , and ter ri. ble I Y � Pt'lO rn a) 4

36 • �u lrr, ona ry and Critical Car e

A neurysms (aortic and pulmonary) Lymph node enlargement Adipose tissue Renal (intrathoracic kidney) Metastatic disease S plenosis/extramedullary hematopoesis N otes 1 . One of the most common disorders of the mediastinum is a moss. The fi rst step in evaluation is to determ i ne the compartment of the med iastinum i n which the mass is located : a nterior, midd le, or posterior. The most common anterior masses are the 4 Ts : thymona , thyroid moss, teratoma, terrible lymphoma . The most common middle masses a re vascular mosses, lymph node enlargements, or cysts ( perica rd i a l , bronchogen ic) . Posterior masses i nclude neurogenic tumors, hiatal hernias, or esophageal diverticu l i . 2 . A CT scan , followed b y biopsy when appropriate, is the usual approach to diag nosis. 3 . Ca uses of a med iastinal mass, by compartment, a re summa rized by the m nemonic below. There is some overlap in the categories as some entities can be found in more than one mediastinal compartment.

N ERVES A N D CH EST PARTS Pos terior Media s tin um

Neurogenic tumors Esophageal enlargement or diverticulum Renal (intrathoracic kidney) Vascular (e.g., descending aortic aneurysm) Extramedullary hematopoesis/splenosis Skeletal /spinal (e.g., vertebral osteophyte, menin g ocel e ) Middle Media s tin um

Adipose tissue ("fat pad") Nodes Dilated aortic root

Pulmonary and Critical Care • 37

Cysts (pericardial, bronchogenic) Hematoma (e.g., after surgery or line placement) Enlarged pulmonary arteries Stomach (hiatal hernia) Tumor (metastatic, primary) A n terior Media s tinum

Parathyroid mass Aortic arch aneurysm R ight ventricular enlargement Ts (teratoma, thymona, thyroid, terrible lymphoma) Subclavian catheter hematoma PLE U RAL E F FU S I O N P E H I T ? D E C U B , TA P

Pus Edema H emorrhage I mmunologic Tumor D ial ysis (peritoneal) Esophagus (Boerhaave's ) Chyle U rine B ile Total parenteral nutrition Ascites Pancreatic

38 • Pulmonary and Critical Care

-

N otes 1 . There a re many d ifferent types of fluid that may enter the pleural space . Si m i lar to pulmonary i nfi ltrates, pleural fluid may consist of pus, edema, hemor­ rhage, i m munologic reactions, or tumor cells (PE H IT) These are the major causes of fluid i n the pleural space. However, other types also may gain access, such as dialysis fluid, i nflam matory fluid from a ruptured esophagus, chyle from i n j ury to the thoracic duct, urine, bile, total parenteral nutrition (TPN), ascitic fluid, or pancreatic fluid (DECUB TAP) There even have been cases of CSF ( pleuro-d u ro fistu la) and stool (fecothorax) in the pleu ra l space . As with pul­ monary i nfiltrates, pulmonary embolism must be considered i n the differential d i­ ag nosis of a pleural effusion . 2 . When a pleural effusion is discovered, decubitus films should be obtained to see if the fluid flows freely. Thoracentesis should then be performed without delay on freely flowing fluid. Thoracentesis is indicated i n virtually all newly d iagnosed , free-floWing pleural effusions. Exceptions to this rule are when the clinical diagnosis is certain (e.g . , CHF) or there is only a small amount of fluid in the pleural space. 3 . Pleura l effusions a re broadly cate g orized as tro nsudates or exudates . Tra nsudates occur when syste m ic factors that infl uence the formation and a b­ sorption of pleural fluid are altered . The most common causes are leN ventricular fai lure, pul monary embolus, and cirrhosis. Others i nclude nephrotic syndrome, peritoneal dialysis, myxedema, atelectasis, and uri nothorax. Urinothorax is the only cause of an acidic transudate. 4. Exudates occur when local factors that i nfluence the formation and absorp­ tion of pleural fluids are altered . The most com mon causes a re bacterial pneu­ monia, malignancy, viral i nfection, and pulmonary embolus. Pulmonary embolus may cause either a transudate or an exudate depending on whether i nfarction and hemorrhage occurs. Ca ncer and hypothyroidism also may cause either a transudate or exudate. 5 . Criteria for an exudate are: a. Pleural fluid protein/serum protein > 0.5 b. Pleural fluid LDH/serum LDH > 0 . 6 c . Pleural fluid LDH > 2/3 o f the normal upper limit for seru m . Transudates have none o f these features. 6. If the fluid is exudative, the follOWing tests should be ordered : glucose, amy­ lase, cell count and differential , cultures, cytology, gram sta i n , and pH. Two or three cytologi C samples will rule out a malignancy in most cases. 7. A possible para pneumonic effusion should be tapped i m med iately. It is said to be "compl icated" if any of the follOWing are present: a. Gross pus b. Organisms visi ble on gram stain c . Glucose < 50 d. pH < 7 . 0 Complicated effusions usually require chest tube drainage. Pulmonary and Critical Care • 39

� TB pleuritis usual ly requires a pleural biopsy for d iag nosis due to the scarcity

of orgon isms in the fluid The flu id ohen ( but not always) lacks mesothelial cells. Ma king the d iagnosis of primary tu berculous pleuritis m ay be d i fficult, but i t should b e pursued agg ressively a s there i s a h igh i ncidence of progression to pulmonary parenchymal d isease. The diagnosis may be elusive: several new d i­ ag nostic stud ies a re ava i la ble. There is evidence that a n elevated adenosine dea m i nase level may be helpful i n establishing a d iagnosis of tuberculous pleu­ ritis . A second promising diag nostic test is a polymerase chain reaction assay specific for mycobacterial d isease. This test may be applied to sputum samples and has been used for ana lysis of pleural and other body flu ids. It has a high degree of sensitivity, with probably a lesser degree of specificity. 9. A low g lucose is characteristic of rheumatoid arthritis effusions. Other entities that may have a very low g lucose i nclude empyema, malignancy, tuberculosis, SLE , and esophageal rupture. 1 0 . B loody fl uid may be seen in many conditions, but an RBC count g reater than 1 00 , 000 suggests trauma, maligna ncy, pul monary embolism , post car­ d iac i n j u ry synd rome, or asbestos pleuritis ( I T B LE D - I ntravenous catheter, Tra u m a , BAPE [ benign asbestos pleural effusion ] , Lung ca ncer, E m bolism , Dressler's synd rome). 1 1 . A pleural fluid a mylase level occasiona l ly is helpfu l . The mnemonic AMY­ LASE UP (Adenocarci noma , Mycobacteria, Yorking (esophageal rupture), Liver disease, Acute pa ncreatitis, Serum hypera mylase m i a , Ectopic pregna ncy, U reteral obstruction, Pseudocyst) can help you remember related d isorders . Hydronephrosis and other d isease states that lead to an elevated serum a mylase also increase the pleural fluid a mylase level. The highest levels are seen in pan­ creatic d isease, and usua lly a re g reater than 2 0 . In other causes i ncluding cancer the pleu ral fl uid/serum a mylase level is usua l ly a bout 1 0 . Pancreatic pseudocysts typically have the h i g hest a mylase levels, often g reater than 1 00 , 000. Amylase isozyme ana lysis may be hel pfu l in pinpoi nting the cause of a h i g h pleural fl uid a mylase . A h i g h sal ivary i sozyme l evel indicates malig­ nancy, whereas a high pancreatic isozyme level ind icates pancreatic disease. The most common malignancies causing a high pleural fluid amylase are lung or ova rian carcinoma . This fact can be helpful i n differentiating lung carci noma from mesothelioma , because mesotheliomas do not make a mylase. 1 2 . A high percentage of eosinophils in the pleural space usually i ndicates the presence of air or blood . Eosi noph ils may accumulate aher a pneumothorax or hemorrhage into the pleural space. Other causes of pleural fluid eosinophilia in­ clude certa in d rugs such as dantrolene, pulmonary emboli , parasitic i nfections, funga l i nfections, and malignancies . Ben ign asbestos pleural effusion ( BAPE) is a compl ication of asbestos exposure that may occur 1 0- 1 5 years after the ini­ tial exposure. Because the pleural effusion is bloody, a high eosinophil cou nt may be seen with BAPE as wel l . The m nemonic BAPE ( B lood , Air, Parasites, Emboli) summarizes the primary causes of pleural fluid eosi nophilia 1 3 . Suspect the presence of lymphatic fluid i n the pleural space (chylothorax) when effusions re-accumu late ra pidly or have a m i l ky color. The fl uid is not always rrl k'y however, and may be turbid or bloody Cond tions that c:ommonly 40 • Pulmonary and Cntlcal Care

lead to the accum u lation of lymphatic fluid (chyle) i nclude trauma, maligna ncy (especially lymphoma ), chest surgery, coughing, vomiting, or straining. A great number of other cond itions may be associated with a chylothorax as wel l , in­ cluding LAM; yel low nail synd rome; i nfections lead ing to thoracic lymphade­ nopa thy, i ncluding tu bercu losis and fu ngal infections; filariasis; aortic a n d pul monary aneu rysms; and certa i n congen ital syndromes, for example Down's syndrome, Noonan 's syndrome, and Turner's syndrome. Some major etiologies of chylothorax a re summa rized by the m nemonic CHYLES - Cough/stra in/vom iting, Hereditary diseases, Yellow nail syndrome, Lymphoma/LAM/lymph node enlargement, Elephantiasis, Surgery/trauma . All of these cond itions lead to obstruction of lymphatics and/or i njury to the thoracic duct. A pleural fluid triglyceride level > 1 1 0 establishes the d iagnosiS of chylo­ thorax. A level at 50-- 1 1 0 is intermediate and may be ind icative of chylothorax. When the level is i ntermed iate , the pleural fl uid should be subm itted for elec­ trophoresis to look for the presence of chylomicrons. When a chylothorax is diag­ nosed, establish NPO for the patient, and in itiate TPN . Do not attempt aggressive chest tube dra inage, as th is may lead to nutritional depletion. The thoracic duct may then spontaneously hea l ; if it does not," surgical ligation may be ind icated . 1 4 . If the cause of a pleural effusion is not determi ned after thoracentesis, then pleural biopsy is usually the next diagnostic step. If pleural biopsy fa ils to yield a diag nosis, then consider a n open surgical proced ure . Bronchoscopy may be helpful if there is another confirmed pulmonary lesion or hemoptySiS, but the yield is qu ite low for an undiagnosed pleural effusion with an otherwise normal x-ray. 1 5 . A small n u m ber of exudative effusions elude d iag nosis even after open pleural biopsy. Experience shows that about two-thirds of these do not recur, and no d iagnosis is established . They are presumed to be a result of infection or other i nfla m matory process that has resolved . The rema i n i ng one-third of cases a re eventually found to have a specific d iagnosis. Ma lignancy, usually lymphoma, is the most com mon cause . A few patients eventually a re diagnosed with colla­ gen vascular diseases or other m iscella neous d iag noses . I n teresting ly, in the la rgest publi shed series, none of the patients with u nd iag nosed exudative pleural effusions who had surgical biopsy were ever found to have tuberculosis. 1 6 . Here is a longer list of the causes of pleura l effusions:

U H , D O C I ' L L N E E D M Y T A P S TAT

U rinothorax Hypothyroidism o rugs (e.g., nitrofurantoin, amiodarone, procarbazine, dantrolene, methylsergide) Ovarian hyperstimulation syndrome Collagen vascular disease Pulmonary and Critical Care • 4 1

I nfection (pneumonia, parapneumonic effusion, emphysema, T B ) Left ventricular failure Lymphangioleiomyomatosis N ephrotic syndrome Esophageal rupture E mbolism ( P E ) Dial y sis (peritoneal) Malignancy (primary, metastatic, Meig's syndrome) Yellow nail syndrome Trauma (hemothorax) Ascites (hepatic or pancreatic) Post-surgical SVC obstruction (or other great veins) Trapped lung Asbestos ( BA P E ) T PN P N E U M OT H O R AX C H EST PAI NS

Cystic lung disease (e.g., cystic fibrosis, LA M , histiocytosis X, bullous emphysema) H ereditary connective tissue diseases (Marfan's, Ehlers-Danlos, pseudoxanthoma elasticum) E ndometriosis (catamenial) S pontaneous Trauma

42 • Pulmonary and Critical Care

--

Pneumonia, PCP A Ititude, A Iveolar microlithiasis Iatrogenic (thoracentesis, central line, ventilator, postoperati v e) Neoplasm (rare-osteogenic carcinoma metastases) Scleroderma, Sarcoidosis N otes 1 . Pri mary or "spontaneous" pneumothorax commonly occurs i n tall, thin i ndivid­ uals and is usua lly d ue to rupture of apica l blebs . Smokers a re at i ncreased risk. 2. Treatment of a large pneumothorax i n itially i nvolves aspiration , often fol­ lowed by chest tube re-expansion . Recurrent pneumothorax can be treated with sclerosing agents (tetracycline or bleomycin) or surgically. A small pneumothorax can be followed by serial chest x-rays, because it may resolve without medica­ tions or treatment. 3 . Tensian pneumothorax is life threatening and can lead to cardiac a rrest. It may be a compl ication of mechanical venti lation. It is treated emergently with a large-bore needle placed in the pleural space

P U L M O N A RY H Y P E RTE N S I O N LV E D P

Left-sided failure Vascular disease/obstruction Extrinsic compression D esatu ration/hypoxia Pulmonary parenchymal disease

Pulmonary and Critical Care • 43

PA HTNS

P ulmonary pare nchymal disease/primary pulmonary hypertension A pnea/A noxia H eart failure Thromboembolism N euro m uscularlskeletal disease Scleroderma/va sculitis N otes 1 . The differential diag nosis for pulmonary hypertension (PA HTNS) is a "plumb­ i n g " problem. The h istory, physical examination , and chest x-roy guide you i n deter m i n i n g where the " block" in the plumbing is located ( i . e . , aorta , aortic valve, left ventricl e , m i tral valve, left atrium, large pul monary vei ns, pulmonary venules, pulmonary ca pi llaries, pul monary arterioles, pul monary arteries) . Also consider pulmona ry valve disease, right ventricular dysfunction, tricuspid valve disease, right atria l d isease, a nd subclavian vei n thrombosis. 2. Left ventricular fa ilure is the most common couse of pulmonary hypertension . I n left-sided fa ilure, t h e left ventricular end-d iastolic pressure (LVEDP) i s elevated . Thus, on i mporta nt first step is to assess left ventricular function to ru le-out a cardiac couse of pulmonary hypertension . The physical exam ination may detect on S4 or pulmonary edema , suggesting left ventricular fa ilure . Physical findings ind icative of pul monary hypertenSion of any couse i nclude jugulovenous distension, a right ventricular h eave, a loud P2, and a systolic pul monary murmur. 3 . Ca uses of left-sided failure (post-pulmonary ca pillary) i nclude systolic and diastol ic CHF, congeni tal heart disease, valvular heart disease, and atrial tumors . Vascular causes of pu l monary hypertenSion i nclude chronic thromboembol i , pri­ mary pulmonary hypertenSion , intravenous drug a buse, collagen-vascular diseases such as scleroderma/CREST, schistosom iasis, diet/weight-loss pills, sickle cell anemia, and pulmonary hypertenSion associated with cirrhosis. Pulmonary venous d i sease is ra re and, a lthough vascular, it is a post-pulmonary capilla ry process that may look like C H F. Extrinsic processes causing pul monary hypertenSion i n­ clude kyphoscoliosis, neuromuscular disease, a nd fibrosing med iasti n itis. Periodic oxygen desaturation caused by obstructive sleep a pnea or hypoventi lation syn­ dromes eventually couse pulmonary hypertenSion . Chronic hypoxia of any cause leads to pulmonary vascu lar constriction a n d , u lti mately, hypertenSion . F i nal ly, pulmonary parenchymal diseases such as COPD and interstitial lung disease destroy the capillary bed, leading to pul monary hypertension . 44 • Pulmonary and Critical Care

4. An echocardiogram demonstrates both LV and RV function , valvular function, and an estimate of pulmonary a rtery pressures; it is a good i n itia l noni nvasive test. Defin itive local ization of the "block" may require pul monary artery catheter­ ization to measure the pul monary capillary wedge pressure ( PCWPl. a reflec­ tion of left atrial pressure, and an ind icator of LVEDP. Pul mon()ry a ngiog ra phy may be necessary to rule out chronic pul mona ry embol i or other vascular ob­ structions. The mnemonic below l ists the causes of pulmonary hypertension and i nd icates the helpful diag nostic i nformation provided by the PA catheter.

I C H E C K PCWPS A N D LV E D PS

I nterstitial lung disease Chronic obstructive pulmonary disease Hyperthyroidism Emboli (chronic pulmonary emboli, intravenous drug abuse) Collagen-vascular diseases Kyphoscoliosis Primary pulmonary hypertension (including pulmonary capillary hemangiomatosis) Congenital heart disease Worms (e.g., schistosomiasis) Pulmonary veno-occlusive disease Sleep apnea A trial disease Neuromuscular disease Diet pills (aminorex) Liver disease/cirrhosis Val v ular heart disease Extrinsic compression of pulmonary vasculature (e.g., fibrosing mediastinitis) Diastolic inhibition/equalization (tamponade, constrictive pericarditis) Primary cardiomyopathy (dilated, restrictive, infiltrative) Sickle cell anemia Pulmonary and Critical Care • 45

P U L M O N A R Y I N F I LT R AT E A PE H IT?

Aspiration Pus Edema Hemorrhage I mmunologic Tumor N otes 1 . A pulmonary i nfiltrate is a com mon med ical problem . Although the potential etiologies are many, the composition of infiltrates is limited . A pulmonary i nfiltrate may be composed of: ( 1 ) aspirated food or oil, (2) pus ( infection ), ( 3 ) pulmonary edema or vascular leak, (4) hemorrhage, (5) certa i n immunolog ic processes including collagen vascular diseases, eosi noph i l ic lung diseases, BOOP, and alveolar protei nosis, and (6) tumor i nfi ltration . As the m nemonic suggests, always consider pulmonary embolism in the differential diagnosis of a new i nfi ltrate, particularly when risk factors a re present or the cli nical picture is unclea r. 2 . A patient's specific presenting symptoms can indicate the nature of the infi ltrate. For exa mple, fever and productive coug h may i nd icate an infectious etiology. On the other hand, a patient with rales and a history of congestive heart fa ilure most likely has pul monary edema . Hemoptysis may indicate an underlying pul­ monary hemorrhage syndrome, while the presence of certa i n systemic sym ptoms may point toward an i m munologic cause of the lung disease. F i nally, risk of lung cancer or characteristic radiographs may lead to a consideration of neoplasm . Pulmonary neoplasms often block an a irway, leading to a post-obstructive pneu­ mon ia, which may be recurrent ar fa i l to clear after appropriate thera py. Less commonly, neoplasms primarily i nvolve the a irspaces and cause an infiltrate (see below) Neoplasms can have the same effect by bleed ing i nto the a i rspaces. 3 . Commun ity-acq u i red , bacterial pneumon ia (CAP) is the most common cause of a pulmonary i nfi ltrate. The typical presenting features a re fever, coug h with purulent sputum , and a loba r i nfi ltrate. Multi-lobar disease is more serious and less common. With ti mely and effective antim icrobial therapy, clin ical and radio­ graphic i mprovement a re evident. Of course, there are exceptions to these rules dependi ng on host-specific factors (e . g . , the elderly) and the particular pathogen (e . g . , Legionella l , but they provide valuable g uidel i nes in assessing response. 46 • Pulmonary and Critical Care

4. A common cli nical problem is differentiating between CAP and other causes of ai r-space disease. When faced with a pulmonary i nfi ltrate, there are four pri­ mary considerations: Cli nical presentation , Underlying d i seases/risks, Rad io­ graphic a ppearance, and Expected response to thera py (CURE). The clin ical presentation of CAP usua l ly includes acute onset of fever, cough, and purulent sputu m . The a bsence of these features ar the presence of less typical findings (e.g . , prolonged course, hemoptysis, lymphadenopathy, disproportionate hypox­ emia) should prompt consideration of other entities. A particular patient's under­ lying diseases or risk factors (e . g . , AIDS, known mal ignancy, smoki ng/COPD, i mmobil ity/hypercoagulability, medications/drug use) pred ispose to speci fic pathogens or cond itions other than CAP. The radiographic pattern of the i nfil­ trate may suggest a specific diagnosis (e. g . , volu me loss, peripheral pattern, re­ cu rrence i n the sa me a rea) And, finally, has the patient had the expected response to therapy, or has the i nfiltrate persisted or increased in size? An a lgorithm based on these principa l considerations beg i ns with empi ric therapy for CAP when the rad iograph and symptoms a re reasona bly sugges­ tive. If the patient responds to treatment and radiographic clea ring occurs, then no further investigation is needed. If atypiccil features a re present, progression or recurrence occurs, or there is no i mprovement, then consider other etiologies. 5. When a pulmonary infiltrate progresses or fa ils to resolve after specific ther­ a pies, consider the causes of chronic pul monary infiltrates summarized by the mnemonic ALVEOLAR LI ST: Alveolar cell carcinoma, Lym phoma, Vasculitis, Eosi noph i l ic pneumonia, Orga nizing pneu mon ia, li poid pneumon i a , Alveolar protei nosis, Reflux/aspi ration, LIP/DIP (lymphocytic and desquamative i n tersti­ tial pneumonitis), Infection (e. g . , TB, fungi), Sarcoidosis, and Tracheobronchial obstruction. This m nemon ic refers to the fact that the ma iority of these entities show an alveolar-fi lling pattern on chest x-rays A few other etiologies may rarely cause a chronic alveolar i nfi ltrate, including amyloidosis, alveolar m icro­ l ithiasis, and si lent m itral stenosis. 6 . The fol lowing mnemonic offers a more deta i led summary of the causes of pul monary infiltrates:

CA N IT B E A PE?

CHF (pulmonary edema) Aspiration (e.g., food, oil , G E R D ) Neoplasm (airway obstruction, bronchoalveolar cell carcinoma, Iymphoproliferative disorders) I nfection (bacterial, fungal, viral, mycobacterial, protozoal, helminthic) T -cells/B-cells (LI P, sarcoidosis, hypersensitivity pneumonitis) Pulmonary and Critical Care . 4 7

BOOP (organizing pneumonia) Eosinophils (PIE syndromes) Alveolar hemorrhage (e.g., vasculitis, coagulopathy, focal processes) Protein (al v eolar proteinosis) Embolus (e.g., thromboemboli, tumor emboli, septic emboli) P U L M O N A RY N O D U L E A NODULE

Age N icotine O ld Films Doubling time U nderlying diseases Lymph nodes Examinations N otes 1 . The find i ng of a solitary pulmonary nodule is cause for concern. The potential etiologies are many, and same major causes a re summarized i n note number 1 1 . Even th is long l ist is not comprehensive, a nd so a more practical approach to the solitary pulmonary nodule is outli ned by the m nemonic A NODULE. 2. The most critical q uestions to answer a re whether or not the nodule repre­ sents a malignancy and if su rgery is i nd icated . Severa l historical elements i n­ crease the cha nce of a malignancy, and a stepwise approach also is outli ned by the m nemonic a bove. 3 . A.J1 age g reater than 35 i ncreases the cha nce of malignancy. Therefore, a more aggressive diag nostic strategy may be u ndertaken i n an older patient. 4. N icotine addicts (smokers) have a g reatly i ncreased i ncidence of broncho­ gen ic carcinoma . A smoking history mandates a more aggressive approach. 4 8 • Pulmonary and Critical Care

5 . One of the fi rst thi ngs to find out is whether or not old films a re available, to determine if the nodule is a new find i n g . A lesion that was present on an old fil m is much less likely to be malignant. 6 . The doubling time of a nodule may indicate whether or not it is l i kely to be malignant. Ma lignancies usually dou ble in size after 20 days but before 450 days. Benign lesions may g reatly i ncrease i n size i n less than 20 days and often are due to i nfections. Also, a ny lesion that does not double i n 450 days is much less likely to be malignant. 7. Consider the patient's underlying diseases. Is this patient a smoker with em­ physema and at i ncreased risk for cancer2 Does the patient have a known ma­ ligna ncy? Evidence of pneu monia a n d i n fecti o n ? Evidence of a collagen vascular disease or an i m munodeficiency syndrome? Ma ny h istorical features are ind icative of specific etiology for the nodule. 8 . Physical exam ination may reveal lymphadenopathy i ndicative of malignancy or i nfection . Also, if a lymph node is detected , th i s should be the fi rst site of biopsy. It will be easier to biopsy tha n the lung lesion and will esta bl ish stagi n g . 9 . F i nally, diag nostic examinations should b e undertaken . T h e choice o f tests depends, of course, on the patient and the a bove-mentioned risk factors, which will determine how aggressive the physician can be i n trying to identify whether or not the lesion is malig nant. Exam i nations i nclude CT scans, fine needle aspi­ ration of the lesion , bronchoscopy with biopsy, thoracotomy with biopsy, or, i n some cases, mediasti noscopy. Recent evidence h a s shown that PET sca n n i n g may b e a ble t o differentiate mal ig nant from ben ign lesions. 1 0. The finding of multi ple nodules ind icates different types of disease. The cat­ egories of disease to be considered i nclude developmental a bnormalities, infec­ tious d i seases, i m m u nolog ic d i seases, m etastatic neoplasms, and tra u matic i n j u ry, as well as i d i opath ic causes . I n AIDS patients, m u ltiple nodu les may occur secondary to PCP, tuberculosis, cryptococosis, CMV, Kaposi's sarcoma , lymphoma, and pyogenic organ isms (staph, strep) . 1 1 . Here is a partial list of causes of pulmonary nodules:

LEAVE T H AT C H EST A LO N E P L EA S E

lung cancer Embolism Aspirated foreign body Vasculitis Echinococcus Tumor metastasis Heart worm Amyloidoma Tuberculosis Pulmollary and Critical Care • 49

Coccidioides and other fungal diseases Hamartoma Enlarged pulmonary artery Sarcoidosis Teratoma Arteriovenous mal f ormation Lymphoma Organizing pneumonia/BOOP Necrobiotic nodules (rheumatoid arthritis) Eosinophilic granuloma Pseudotumor Localized anthrosilicosis End ot h e l i a I tumor (hemangiopericytoma) A telectasis (round) Sequestration Erythrocytes (hematoma) R E F R AC TO RY H Y P OT E N S I O N CRAS H I N G

Cardiovascular Respiratory Addison's/Acidosis Sepsis/toxic Hypocalcemia I naccurate reading Neurologic G I bleed/internal bleeding N otes 1 . Although there o re many causes of hypotension , when refractory hypoten­ sion is encountered, you must consider a very specific list of possible etiologies . 50 • Pulmonary and Critical Care

Turn to this list when a patient's blood pressure fa i ls to i ncrease despite use of i n­ travenous fluids or pressor agents . Many of these causes of refractory hypoten­ sion a re emergencies and require u rgent treatment. 2 . A s i m ple system for remembering the causes of refractory hypotension is summarized by the m nemonic CRASH ING, or by the m nemonic TERMINAL­ Toxic/drugs, E ndocri ne/electrolytes, Respi ratory, Myoca rd ial/vascular, Infec­ tion/sepsis, Neurolog ic, Artifact, Losing blood . 3 . Cardiovascular causes include right ventricular i nfarction , pul mona ry em­ bol ism, cardiac ta m ponade, a rryth m i a , and massive leh ventricula r i nfarction . Respiratory causes ohen are seen in patients on the ventilator and i nclude ten­ sion pneumothorax and auto-PEEP, which occurs when patients are over-venti­ lated or have severe a i rway obstruction. E ndocrine causes i nclude Add ison's disease, and systemic acidosis may cause hypotension. Sepsis/toxic causes i n­ clude bacterial septic shock, toxic shock, a na phylaxis, a n d d ru g overdose . Hypocalcemia may cause hypotension si nce vascular tone and pressor agents are ca lcium dependent. I naccurate blood pressure readings may result from poor blood pressure cuff fit, peripheral vas.cular disease, and venous obstruction (e. g . , superior vena cava syndrome), leading to a false impression of refractory hypotension . Neurologic causes i nclude CVA, spinal cord injury, and epidural anesthesia. GI bleeding may be occult, or blood loss may occur i n the thorax, retroperitoneal area , or a bdomen . 4. The following m nemonic lists specific causes o f refractory hypotension :

ALAR M , B P THAT'S D R O P P I N G

A rti f act (poor cuff fit, peripheral vascular disease, superior vena cava syndrome) Liver failure Arrhythmia Right ventricular infarct Massive left ventricular infarct B lood transfusion Pulmonary embolism Tamponade Hypocalcemia Addison's Tension pneumothorax � epsis Pulmonary and Critical Care . 5 1

Drugs/toxins (anaphyl a xis, drug overdose, snake venom) Rewarming hypothermia Occult blood l o ss Pancreatitis P EEP/auto-PEEP I ntubation (usually transient) Neurogenic (spinal cord injury, epidural anesthesia, dysautonomia) Gastrointestinal bleeding SARCO I DO S I S H I LAR N O D E S *

Hepatosplenomegal y I nterstitial fibrosis, pulmonary Lymphadenopathy A rth ra Ig ia/a rth ritis Renal·(calcium metabolism abnormalit i e s, nephrolithiasis) Neurologic involvement (unilateral facial paralysis, chronic meningitis, mass lesion) Ophthalmologic (uveitis, conjunctival granulomas, sicca syndrome) Diabetes insipidus/other pituitary deficiency Erythema nodosum/other skin lesion Sali vary gland enlargement, bil a teral *

Clinical characteristics

52 • Pulmonary and Critical Care

-

SARC O I D BLU ES * *

S kin rash A rthropathy/arthralgias Respiratory Central nervous system O ptic (uveitis, iritis) I ncidental finding on chest x-ray Dysrhythmia/cardiac dysfunction Bone marrow/spleen Lofgren's syndrome (erythema nodosum, fever, malleolar, join pain, hilar adenopathy) Uveoparotid fever (e.g., Heerfordt's syndrome) Ear, nose, and throat Syste m i c symptoms (fever, chills, myalgias, hypercalcemia) * *

Possible presentations

N otes 1 . Sarcoidosis is a m u ltisystem d i sease . Vi rtually any organ system may be i nvolved . • Pu lmonary i nterstitial i nvolvement (up to 1 00%) • Lymphadenopathy, hi lar/mediasti nal (75-90%) • Arthra lgia/arthritis ( 25-50%) • Bone ma rrow ( 1 5-40%), but rarely symptomatic beyond m i ld anem i a , neutropenia, a n d eosi noph ilia • Hepatomegaly/liver enzyme elevation ( 20-30%) • Ophthal molog iC (25%): uveitis (75-95% of eye cases) • Erythema nodosum (25%), skin lesions • Upper respi ratory tract (up to 20%) • Sal ivary gland, parotid enlargement, bi lateral ( 1 0%) • Splenomegaly (5- 1 0%) • Neurolog ic i nvolvement (5%): u n i lateral facial paralysis (most common ) , papi lledema , hearing a bnormal, hypotha lam ic/pitu itary lesion , chronic meningitiS , mass lesion , seizure • Cardiac disease (5%) arrhyth m ias, heart block , pericorditis, CHF • Renal ca bum meta bolism a bnormal , nephrolithiasIs (rare , < 5%) • Diobetes i nsipidus or other pituitary deficiency Pulmonarv and Cntical Care • 53

2 . Pul mona ry, ocular, lym ph node, and ski n cha nges a re the m ost com mon, clinically important features. 3 . Many cases are found inCidental ly on chest x-ray. In fact, this is one of only a few diseases in which a patient may have a ma rkedly a bnormal chest x-ray, but a ppear q u ite healthy. . 4 . The disease pathogenesis may be related to exaggerated helper T-cell activity. 5 . Hyperca lcemia is d ue to an i ncrease in 1 , 2 5-hydroxylase activity i n the g ranulomas. It often responds to steroid thera py. 6 . Certa in factors are associated with progressive d isease i n sarcoidosis, the presence of which may be reason for more agg ressive i n itial thera py. These factors i nclude c h ronic uveitis, chronic bone d isease, neph roca lci nosis, skin plaq ues, lupus pern io, and pulmonary i nfiltrates without nodu les ( "type 3 " pul­ monary sarcoidosis) .

54 • Pulmonary and Critical Care

--

IDI

H EM ATO L O G Y General Considerati ons

The d i fferential diagnosis for a hematolog ic disorder can be developed using the MEDICINE DOC categories: Metabolic (e.g . , a myloidosis, B 1 2 and folate deficiencies) E ndocrine (e.g . , para neoplastic synd romes, adrenal i nsufficiency, hypothyroidism) Drugs/med icines (e. g . , anti biotics, alcohol, chemotherapy toxicity) Infection (e.g . , HIV-related, TB, systemic i nfections) Conge n i ta l (e . g . , Fanco n i 's, c h ronic granu lomatous d i sease, prote i n C deficiency) Immunologic ( e . g . , hemolytic anemia, ITP, autoimmune neutropenia)

Neoplastic (e.g . , leukemia, lymphoma, metastatic disease) Exotic diseases (e. g . , sarcoid, porphyria, Wegener's)

Degenerative (?myelodysplasia; also premalignantl Occupational/environmental (e. g . , radiation, hydrocarbons, heavy metal poisoning) Ca rd iovascular (e . g . , i ntracard iac shunt, hypercoagula ble states causing DVT/PE) Problems considered in the hematology section primari ly i nvolve the bone marrow and ohen a re made manifest by a decrease or i ncrease i n one of the primary blood cell types: RBCs, WBCs, and platelets. Also i ncluded are a bnor­ mal ities of the spleen and disorders of coagulation .

Hematology • 55 ,

C l i n i ca l Sym ptoms and S i g ns

AN E M IA M CVS

pro blem M arrow ption/ de struct ion Cons um increase (hemodilution) Volume Stool/m e nstrual / occult losses N otes 1 . Anem i a is defi ned as a d rop in the hemoglobi n conce ntration . The fou r basic mech anisms a re l isted a bove. Exa m i nation o f the peri pheral smear and red cell indi ces ( i . e , mean cell volume [MCV] , RBC distribution width) is the first step in eval uation of a nemia . The MCV is the most helpful vrde\ to guide the & work-up . The m nemonic "MCVS" helps to na rrow down the ffer� ntial by clas­ sifyi ng an a nemia as microcytic, normocytic, or macrocytic . 2 . Marrow problems are characterized by a decrease i n production of RBCs. There may be a defiCiency in com ponents needed for normal RBC synthesis; the ma rrow may be i nvaded and replaced by an i nfiltrative process such as a ma­ lignancy ( " myelophthisic process"); or there may be primary marrow dysfunction (" myelodysplasia" ) . Marrow problems may be m icrocytic ( i . e . , processes that per­ turb hemogl obin production, such as i ron deficiency), narmocytic ( i . e . , myelo­ dysplasia), or macrocytic (i . e . , processes that i n terfere with R BC maturation , such as B 1 2 deficiency). 3 . Consum ption/destruction of eryth rocytes occurs in patients with a utoi m­ m u n e or neoplastic d i seases (hemolytic anem i a ) , m ec h a n i ca l heart valves, severe systemic ill nesses such as sepsis (DIC), or thrombotic thrombocytopenic purpura (TI P) RBCs are destroyed either by antibodies (autoi m mune disorders) or a n i ntravascular cause ( mecha n ical heart valve or blood vessel process) . I ntravascul ar i n j u ry i s called " microangiopathic, " and the periphera l smear fea­ tures damaged RBCs called "schistocytes . " Consum ptive/destructive processes are accompan ied by increased bone marrow activity and more reticulocytes i n t h e peripheral smear. S i nce the reticulocyte is a you n g , la rge RBC , there is a n

56 • Hema tology

i ncrease i n the Mev. Thus these processes usually are macrocytic, u nless there is concomitant marrow fa ilure l i . e . , iron deficiency from chronic hemolysis). 4. Volume increase causes hemod i lution and a decrease in hemoglobi n con­ centration . This situation is' encountered when dehydrated patients receive i ntra­ venous flu ids. Also, in acute blood loss, i ntravenous fluids may make the blood loss man ifest si nce the i n itial hemog lobin may be norma l . The MeV is u naf­ fected by volume increase and is usua lly normocytic. 5. Stool/menstrual/occult blood losses frequently are accompan ied by iron deficiency and a re com mon causes of m icrocytic a nem i a . Young women are often a nemic because of monthly menstrual blood loss. The other common cause of blood loss is occult GI bleed i n g lead i n g to hemoccult positive stools. Less commonly, occult blood loss occurs from an i nternal source, such as a retroperi­ toneal bleed . Retroperitoneal bleeding may occur after an i nvasive procedure or as a compl ication of a nticoagulation. In add ition to a drop in the hemoglobin , the BUN i ncreases from a bsorbed heme metabolites. 6 . The m nemonic below d ivides the anem ias into categories accord ing to the MeV: m icrocytic, normocytic, or macrocytic. .

IT'S A N E M IA'S B RA N D

ron deficiency Thalassemia S ideroblastic anemia

Microcytic

I

Usually Normocytic

Anemia of chronic disease Nephrogenic anemia (uremia) E ndocrine disorders Myelophthisis (marrow infiltration) I V fluids A plastic anemia S ickle cell anemia

Usually Macrocytic

B 1 2 deficiency Reticulocytosis/hemolysis Alcohol/cirrhosis N utritional deficiency (folate) D rugs (D NA synthesis inhibitors, D ihydrofol a te reductase inhibitors) Hematology • 57

--

exfol iative ski n diseases, hemod ialysis), and malabsorption. Drugs that i n­ h i bit dihydrolate reductase (e. g . , methotrexate, triamterene) or DNA metab­ olism (e . g . , 5-FU, hydroxyu rea , azath iopri ne, AZT, acyclovir) a lso cause a macrocytic anem i a . 1 0. The work-up o f anemia i ncludes ruli ng out occult blood loss (usually stool or menstrua l!, exa m i nation of the peripheral smear, checking for deficiencies (iron, folate, or B 1 2! , a reticulocyte count to assess marrow activity, a hemolysis work­ up (bilirubin, LDH , ha ptoglobin, serum free hemoglobi n ! , and possibly a bone marrow biopsy. 1 1 . The reticu locyte count is a n i nd ication of the ma rrow's capaci ty to make RBCs. Here is a slightly different mnemon ic for anemia [still based on MCV) that emphasizes the importance of the reticulocyte count:

IT'S A R ETICS D E F ECT

I ron deficiency Thalassemia S ideroblastic anemia

Microc ytic

Usually Normocytic

Aplastic anemia Renal failure Endocrine disorders Tumor/myelophthisis Illness/I nflammation (chronic disease) Cirrhosis (may cause macrocytosis or spur cell anemia) Sickle cell anemia Usually Ma crocytic

D rugs (D NA synthesis inhibitors, D ihydrofolate reductase inhibitors) EtOH Fol a te Erythroleukemia (Di Guglielmo's ) Cobalamin deficiency ( 8 1 2 ) TTP/hemol y sis

Hematology • 59

7. Microcyti c anemi as are due to a deficiency of one of the three ma jor con­ stitue nts of hemoglobin : iron, globi n, and porphyrin . Hemoglobi n compri s�s. 90% of the protein in the RBC , so microcytic cells are small and pale. Iron deflc le �cy is seen in states of chronic- blood loss (stool , menstrual, occult) . RBC destruction ( he m olysis) , or nutritiona l deficiency (vegetari an d iet) . The thalassemi� s are a d iver se group of d iseases re sulti ng i n defecti ve globi n cha i n prod uction . The side robla stic a nemi as are characterized by " ringed sideroblasts" in the marrow and abnormal porphyrin syn theSi s . They may be hered itary ( rare, X-linked) . acquire d (alcohol, isoniazi , lead). or idi opathic ( premali gnant) . . . 8 : Normocytic anem i a IS seen in many d ise ase states . The a nem i a of chron� c d i sea se is seen whenever th ere i s long-standi ng i nflamma tion or syste m i c d i S­ ea se . It is characteri zed by low serum iron and total iron-bind ing capa c i ty, but an e l evated or normal serum ferriti n . N ephrog eni c a nem i a is caused by re­ d U ce d erythropoetin levels a n d can b e ameliorated by erythro poeti n repla ce­ m e n t therapy. E ndocri ne di sorde rs ohen feature a normocytiC anemia because an y hormones affect R BC proliferati on , inclu ng thyroxine, glucocorticoids, di e stOsterone, a nd growth . � or mo ne. Less commonly, hypot hyroidism .causes m a c ro cytosis . Myelophth i s I s i s m arrow i nfi ltration by neoplasm , i nfect i on , or m eta bolic isease ( neoplas m s can d ca use anemia by a variety of mechan isms, I n c l u di ng myelop hthisis, hem olyti C ane mia, occult blood loss, nutr itional defi­ C i e n cy, or the effects of che �atherapy)·. Myelophthisic processes cause a nor­ m Ocyti c anem ia, and the peri pheral smear may show immature eryth rOi d forms a n ? , o ccasion ally, ma rked n eutrophi l i a ( "leu kemoid reaction " ) . I ntravenous l f U i d s cause a d ilutional decrea se i n hemoglobin conce ntrat ion and may u n ma sk nemia after acute blood loss . Apl a st i c a nem ia may be a primary a a r r o w failure or secondary to d rug tox icity. S kl e ce ll a nemi a , a hemogloic I n o Pathy, features abnormally shaped cells, but the MCV i s usually normal . �. MacrocytiC anemi as are usually a result of an i m pai rment of DNA repl ica­ hon . Often the LDH level is very high due to accelerated turnover in the marrow or P �ri pherally. B 1 2 ( cobala m i n ) deficiency can occur in several settings, i �­ u d �I l n g gastroi ntestina l disea se, c h ron i C nitrou s ox ide use , and, rarely, nutn­ tl o n a l deficiency. Both B 1 2 and folate are important cofactors in DNA syntheSi S , a nd a deficiency in either r�sults i n large, abnormal R BCs . Macrocytosi S also occ u rs w ith R BC destrud on le .g . , h emolytic anemia, TIP) because of compen­ sato ry reticulocytosis (see above) . A l cohol depresses bone m a rrow R B C production, causi ng anem ia , often m ac r c O ytic . Alcoholics may ha ve pri ma ry macrocytosis (usua lly modest) o.r sec­ on d a r y macrocytosis from folate and /or B 1 2 defi Ciency. Anemia in cirrhoti C pa­ e nts lI may be mic rocytic, norm ocytic, or macrocytic beca use of thei r myriad p rob l e ms including blood loss, nutriti onal deficiency, and the effects of chron ic d l seo se . L ess commo nly, c i rr h oti cs have a hem ol ytic anem ia ca l led s pur cell m l a t hat is caused by the a bnorm al li poprotein balance present in advanced r d l s ase The d a gn s l s s IT\ de when a ci rrhotic patient has eVi d ence of l � ,� � he mo lys� c s t er ac pur cha cells i n the periphe ral smear. r � lS l l s w i th . ' N u t r i tional defic i ency of folate i s seen i n starvation , cond itions w i th I n­ cre a Se d requ irements ( pregna ncy, ma l i g n a n cy, ch ron ic hemolys i s , chron ic

�

�

�

�:

58 . Hematology

B L E E D I N G D I AT H E S E S A PTT

A natomic abnormality (e.g., AVM , peptic ulcer) Plasma protein abnormality T hrombocytopenia/qualitative platelet abnormality Trauma N otes 1 . A bleed ing problem is most commonly related to an anatomic abnormality. Congenital a bnormalities such as an arteriovenous malformation or acquired de­ fects such as peptic ulcer disease a re com mon . Plasma protein abnorma lities are less common and may be made manifest with unexpected hemorrhage asso­ ciated with a m inor surgical procedu re . Thrombocytopenia has many causes and is relatively common, but qualitative platelet abnormalities a re rare. Finally, trauma is a common cause of hemorrhage and usually obvious, but excessive bleedi ng or bru ising aher minor trauma may i ndicate an occult bleedi ng diathesis. 2. The APTI, PT, platelet count, and bleeding time a re the primary laboratory studies obtained when i nvestigating a possible plasma protein abnormality or quali­ tative platelet defect. Other tests i ncluding thrombin time, fibrinogen assay, clot solu­ bility and lysis, and factor assays may be helpful in identifying specific deficiencies. Pri mary Hemostatic ( Platel et) D i so rd e rs

Platelet adhesion defects:

Von Willebrand's disease Bernard-Soulier syndrome (absence, dysfunction of Gp l b/IX)

Platelet aggregation defects

Glanzmann's thrombasthenia (absence, dysfunction of Gp l l b/llla)

Platelet release defects •

Decreased cyclooxygenase activity Drugs-aspirin, nonsteroidal anti-inflammatory agents Congenital

Platelet coagulant defect Scott's syndrome

Gp

=

glycoprotein.

60 • Hematology

•

• •

Granule storage pool defects Congenital Acquired Uremia Platelet coating (e.g . , penicillin or para proteins)

Relatio n s h i p Between Secondary Hemostatic Disorders and Coagu lation Test Abnormal ities

Prolonged partial thromboplastin time (PTI) No clinical bleed ing - factors XII, HMWK, PK Mild or rare bleeding - factor XI Frequent, severe bleeding- factors VIII and IX Prolonged prothrombin time (PT) Factor VII deficiency Vitamin K deficiency -early Warfarin anticoagulant ingestion Prolonged PTI a nd PT Factor II, V, or X deficiency Vitamin K deficiency- late Warfarin anticoagulant ingestion Prolonged thrombin time (TI) Mild or rare bleed ing- afibrinogenemia Frequent, severe bleeding -dysfibrinogenemia Heparin-like inhibitors or heparin adm i nistration Prolonged PT and/or PTI not corrected with normal plasma Specific or nonspecific inhibitor syndromes Clot solubility in 5 M urea Factor XIII deficiency Inhibitors or defective cross-linking Rapid clot lysis Alpho2 plasmin inhibitor HMWK

=

high-molecular-weight kininogen; PK

=

prekallikrein .

Both tables fram Handin R I : Bleeding and thrombosi s . I n Isselbacher KJ , et a l (eds) : Harrison's Principles of Internal Medicine, 1 3th ed . New York, McGraw-Hi l l , Inc . , 1994 , pp 3 17-3 2 2 ; with permission.

S P L E N O M E G A LY BA N T I 'S

B lood flow problem Anemia/erythrocyte problem Neoplasm/infiltrative disease Thyrotoxicosis I nfection Sarcoid/Systemic lupus erythematosus Hematology . 6 1

,..

N otes 1 . Banti's syndrome is the eponym used to describe congestive splenomegaly with hypersplen ism . Using " BANTI ' S " as your g u ide, the ca uses of spleno· megaly can be classified in six categories . Blood flow problems cause spleno· megaly by increased splenic vei n pressures and consequent congestion . Splenic vei n thrombosis (often secondary to pancreatitis), portal vei n thrombosis or ex· tri nsic compression, ci rrhosis, hepatic vein thrombosis (Budd-C h i a ri synd rome), and CHF all cause congestive splenomegaly Anemias secondary to erythro­ cyte abnormalities (e . g . , thalassemias, sickle cell d isease, hereditary spherocy­ tosis) cause splenomegaly because there is hyperplasia of the reticuloendothelial system associated with the destruction of the a bnormal RBCs . These diseases also may cause splenic i nfarction (i e , sickle cell). Neoplasms and infiltrative diseases d i rectly involve the spleen and lead to its enlargement. I n myeloproliferative syndromes and myeloph thisic processes, because of marrow hypofu nction, there may be compensatory extra medu l la ry h e matopoiesis causing splenomega ly. Thyrotoxicosi s is associated with splenomega ly beca use of thyroid hormone-ind uced lym phoid hyperplasia . Numerous i n fections, usually chronic, may ca use splenomega ly. Disorders of i m m u ne reg u lation such as sarcoidosis and SLE may feature splen omega ly. Other examples i nclude rheumatoid arthritis ( Felty's syndrome), serum sickness, and immune hemolytic anemias. 2. The deg ree of splenomegaly va ries with the d isease entity. Massive splenomegaly occurs in chron ic myelocytic leukemia, myelofibrosis with myeloid meta plasia, ha i ry cell leuke m i a , Gaucher's and N iema n n·Pick diseases , sa r· coidosis, thalassemia major, chronic malaria, congenital syphilis, leishmaniasis, and some cases of portal vein obstruction. These are chronic d iseases in which the spleen slowly enlarges. Rupture of the spleen may be seen in acute infec­ tious processes such as EBV mononucleosis, malaria , and typhoid fever. 3 . Here is a more com prehensive listi ng of the causes of splenomegaly:

HIS BIG SPLENIC MASS

Hepatic vein obstruction (Budd-Chiari) Infection S plenic vein thrombosis (e.g., pancreatitis) Berylliosis Infiltrative diseases (e.g., Gaucher's , amyloid, eosinophilic granulomatosis) Grave's diseas.e/hyperthyroidism 62

• Hematology

S LE/collagen vascular diseases

Portal vein obstruction Liver disease (cirrhosis) E rythrocyte abnormality (e.g., spherocytosis, sickle cell, thalassemia) Neoplasm (lymphoma, myeloproliferative disease, metastatic) I ron deficiency C HF (congestive splenomegal y ) Myeloproliferative disease A utoimmune-hemolytic anemia Sarcoidosis Serum sickness/drug reaction 4 . Always consider an occult, i nfectious etiology for splenomegaly si nce these

diseases a re likely to respond to appropriate thera py. There a re numerous infec­ tions associated with splenomegaly, many of which a re I �sted in Chapter IV (see " I nfections Causing Splenomegaly" ) .

C linica l Conditions or Diagnoses

EOSI NOPH I LIA ALLERG I C

Addison's (adrenal insufficiency) Lymphoma/malignancy L-tryptophan Eczema/skin diseases Respiratory diseases (asthma, allergic bronchopulmonary aspergillosis, P I E syndromes) Gastroenteritis I nfections (helminths, coccidioides mycosis) Collagen vascular diseases Hematology • 63

N otes 1 . Eosi noph ilia is defi ned as > 500 eosinophils/m icroliter of blood . E osino­ philia has d iverse disease associations, but "ALLERGIC" reactions are probably the most com mon . Allergic reactions to drugs, pol lens, micro-organisms, and other antigens can sti m ulate eosi noph ilia. 2 . Addison's disease frequently features a moderate eosinophi lia that resolves with admin istration of corticosteroids . Lymphoma is the malig nancy most com· monly associated with eosi noph i l i a , although associations with m a ny sol id tumors have been described . Tumor-associated eosinoph ilia is probably a result of i n terleu kin-5 secretion a n d often ind icates a widely d isse m i nated tu mor. Eosinophilic leukem ia is a rare hematolog ic neoplasm with dra matically h i g h eosinophil counts. L-tryptophan preparations from a single source were i m pli­ cated in the eosinoph il ia-mya lgia syndrome, a potentia lly fatal , m u ltisystem dis­ ease. Eczema a nd several other skin diseases ( e . g . , pem ph igus , mycosis fungoides) may be associated with eosi noph ilia . Several respiratory diseases feature eosi noph ilia, i ncluding asthma and the PIE ( pu l monary infiltrates with eosi noph ilia) syndromes . The PIE syndromes i n­ clude acute eosinoph i l ic pneumonia, chronic eosi noph ilic pneumon ia, Churg­ Strauss vasculitis, parasitic infestation ( i . e . , "tropica l" pneumonia), and al lerg ic bronchopulmonary asperg illosis (ABPA) The hypereosinophilic syndrome, a m ul­ tisystem disease, may cause eosi noph i l ic i nfiltration of any organ including the lungs. Drugs also can cause eosi noph ilia with pulmonary i nfiltration . Eosinoph i l ic gastroenteritis is cha racterized by eosinophilic infiltration of any portion of the gastrOintesti nal tract, peripheral eosi noph i l ia (75% of cases), and inflam matory d ia rrhea . I n fections with hel m i nths typically ca use eos i no­ p h i l ia , and cocc idioides mycosis is u n i q ue a mong fungal i nfections in its propensity to elicit eosinophilia . Collagen vascular diseases such as rheuma­ toid arthritis, eosinoph ilic fasci itis, allerg ic angi itis, sarcoidosis, and Wegener's granulomatosis also a re associated with eosi noph ilia. 3. The eponym Loeffler's has been a ppl ied to PIE syndromes, the id iopathic hy­ pereosinoph i lic syndrome, and to eosinophilic endocard itis . Loeffler originally descri bed tra nsient pulmonary i nfiltrates with eosinop h i l i a , which m ay have been related to ascariasis i nfestation . Although it has no specific definition, the name is sti l l u sed in cases of i d iopath ic, ben i g n pul monary i nfi ltrates with eosinophilia. 4. The cytokine IL-5 is an i m portant sti m ulator of eosinoph ils and is probably i n­ tegral in many or a l l causes of eosinoph i l i a . The folloWi ng mnemonic, empha­ sizing the role of IL-5 , lists the causes of eosi noph ilia:

64 • Hematology

P LASMA I L- F I V E RAG E

Parasites L-tryptophan Addison's Sarcoidosis Malignancy (e.g., Hodgkin's, CML, gastric, ovarian, lung, pancreatic cancers) A Ilergy/A topy (e.g., drugs, serum sickness, hay fever) Idiopathic hypereosinophilic syndrome Lung diseases/Loeffler's Fungal (A B PA, coccidioides mycosis) I gE hypersecretion (Job's syndrome) Vasculitis/collagen vascular disease Eczema/skin diseases Recovery from bone marrow transplant Angiogram/Atheromatous emboli ("cholesterol emboli") Gastroenteritis E ndomyocardial E RYT H R O C YTO S I S H I RBCS

H ypoxia/hypoventilation I nappropriate erythropoietin Relative polycythemia (stress, dehydration) Bone marrow disorder Carboxyhemoglobin/congenital hemoglobinopathies . Steroids/androgens Hematology • 65

N otes 1 . Eryth rocytosis or polycythemia ind icates an i ncrease i n n u m ber of erythro­ cytes i n a sample of blood, which may or may not be a reflection of total body red cells. It is i m portant to disti ngu ish between absolute erythrocytosis, a true i n­ crease in total body red cell mass, and relative erythrocytosis, which occurs with dehydration (increase in RBC concentration ) and stress . 2 . The basic mechanisms of erythrocytosis a re summarized by "HI RBCS . "

H Y P E R C OAG U LA B L E S TAT E S PT I N R S

P latelets Trauma 1 m m obo I ization/stasis Neoplasm RBCs Serum clotting factors N otes 1 . Nu merous d isorders may predispose patients to thrombosis. Frequently, the history and physical examination reveal a likely etiology. Factors predisposing to thrombosis include obesity, varicose veins, trauma, general anesthesia, i mmobi­ lization, maligna ncy, CHF, oral contraceptives, infection , preg nancy, neph rotic syndrome, and blood protein defects. 2 . -Leiden factor 5, a mutation in which factor 5 is resistant to activated protein C, is the most common i n herited hypercoagulable condition known. Homozygous ind ividuals are at high risk for recurrent thromboembolic events. The risk for het­ erozygotes is less clear.

66 • Hema tology

3 . Protei n deficiencies may be difficult to identify. Current tests only identi fy 1 0-20% of the cases of familial thrombosis. Serum levels of proteins C and S will be affected by large thrombi and warfarin a nticoagulation . Deficiencies may be congenital or acquired . Antithrombin (ATI-1 II , protein C, and protein S are the most common congenital conditions. The most common acquired defects are AT-III and antiphospholipid antibodies. 4. The "lupus anticoagulant" is an anti phospholipid antibody that prolongs the PTI by interfering with phosphol ipid in the laboratory assay. It does not cause clinical bleedi ng, but rather predisposes to thrombosis and mid-trimester abortion. 5 . Urinary AT-I I I loss proba bly causes hypercoagulabi lily in patients with the nephrotic syndrome. These patients are pred isposed to renal vei n thrombosis and pulmonary embolism. 6. High levels of homocystine predispose patients to arterial as well as venous thrombosis. Homocysti ne also may be an important factor in the development of atherosclerosis. 7. An important drug-related cause of hypercoagulabil ily is hepari n-associated thrombocytopenia. The features are arterial thrombosis with falling platelet counts. Even low doses of subcutaneous heparin can cause this syndrome. A heparin-ag­ gregation study is avai lable for laboratory confirmation in suspected cases . 8 . Here is a more comprehensive list of hypercoagulable states:

D VT , P E A N D C L O T S

D rugs (e.g., tamoxifen, heparin) Venous catheter (central) Trauma (endothelial in j ury) Prosthetic valves Erythrocytosis (polycythemia) A nticardiolipin/A ntiphospholipid antibodies Nephrotic syndrome/N eoplasm Dysfunctional platelets/Dysfibrogenemia CHF/Collagen vascular disease (e.g., 8eh 285) ind icates the presence of osmotically active �.olutes such as ma n n itol or g l ucose . Glucose a nd m a n n itol a re osmotically :lctive solutes, which cause water movement out of cells and a d i lution of the plasma. Hyponatremia ensues but, si nce plasma osmolality is i ncreased, clinical manifestations of hypotonicity a re absent. The low serum sod ium is, in a sense, appropriate, si nce a normal sodium level would lead to an even h igher osmo­ lal ity. Th is scena rio is com monly encountered in patients with hyperglycemia, in whom correction of the high glucose levels with insulin is accompanied by a rise in serum sod i u m . An osmotic diuresis causes free water loss, and hypernatremia may result after clea ring the osmotica lly active solute. 3. A pathologic sod i u m disorder is defi ned by a low serum osmolal ity « 2 80), the causes of which may be d ivided i nto hypovolem ic, euvolem ic, and hypervolemic etiologies as listed on pages 1 48- 1 49. 4 . A normal serum osmola lity ( 2 80-2 85) suggests pseudohyponatremia d ue to a measurement error, which can occur i n severe hyperlipidemia or hyperpro­ tei nemia . Th is type of error is less com mon with newer laboratory techniques . 5 . Once pseudohyponatremia from measurement errors a nd accu mu lation of osmotically active solutes is ruled out, then a true, patholog ic sodium disorder is present. The patient's volume status is then used to elucidate the cause . Edematous states and profound volume depletion a re usua l ly obVious, but i n some cases it may be difficult to distinguish between moderate volume depletion, normovolemia , and modest volume expansion by physical exam ination a lone. 146 • Nephrology

6. Hypovolemic hyponatremia indicates salt losses in excess of water losses If a hyponatremic patient appears to be clin ically volume depleted, then it should be determi ned whether the losses are extra-renal (sequestration or skin ) or renal (osmotically active solutes, diuretic therapy, urina ry salt wasti ng , dopamine infu­ sion or m i neralocorticoid deficiency) . Measurement of the urinary sodium estab­ l ishes the cause, with a h i g h u ri ne sod i u m (> 20 m mol/L) i nd icati ng renal losses, and a low urine sodium « 1 0 m mol/L) i ndicati ng renal sod ium conser­ vation and extra-renal losses. 7. Euvolemic hyponatremia is essential ly a result of excessive free water i ntake (with inadequate solute intake), or excessive ADH activity. Excessive, surreptitious, free water intake occurs with psychiatric illnesses. This condition may be d ifficult to d istinguish from SIADH, si nce patients do not acknowledge the problem . Other forms of th is i ntake imbala nce are "beer potomania," an excessive intake of hypo­ tonic fluids with little d ietary solute, and the "tea and toast" syndrome, in which elderly patients i nadvertently have a similar d ietary imbalance. The latter problem may be made man ifest when a d iuretic is prescribed to an elderly patient with a poor d iet. E levated ADH levels i n hibit the kid ney from excreting free water. The result is modest volume expansion (ohen clin ically inappa rent) and hyponatremia. The key feature of SIADH is a n i na ppropriately concentrated u ri n e i n the face of serum hypo-osmolal ity a n d normovolem i a . There a re many causes of SIADH, i ncluding drugs, neoplasms, and C N S d isorders . Some other states such as pai n , emotion , and the postoperative state may also temporarily i mpa i r water excretion , probably a s a result of an ADH-mediated mechanism . ADH i s proba bly i m po rta nt i n endoc r i n e causes o f hyponatremia such a s hypothy­ roidism and pure cortisol deficiency (Addison's disease usua lly results in hypov­ olemia and features salt-wasting). In SIADH , urine sod i u m usual ly exceeds 20 m mol/L un less fluid i ntake has been restricted . 8 . An i m portant d istinction to make in neurosurgical patients is between SIADH and cerebra l salt wasting (a hypovolemic state ) . Cerebral salt wasting is rela­ tively rare a nd may be re lated to elevated levels of atrial natr i u retic peptide (AN P). The diagnosis depends on establishing a reduction i n blood vol ume and ina ppropriate natriuresis. Volume restriction (as is appropriate in SIADH) may be hazardous in cerebral salt wasting si nce it can lead to cerebral ischem ia from vasospasm . The proper treatment is to mai ntain i ntravascular volume and correct hyponatremia with norma l sa line i nfusion . Dopa m i ne a lso sti m u lates ANP re­ lease and promotes natriuresis. 9 . A less well understood euvolemic state is "essential" hyponatremia or the "sick cell" syndrome. It is hypothesized that these patients have a reset serum "osmostat" « 2 8 0 m mol/L) and mai ntain a lower serum sodium due to reesta blishing the "normal" range of osmolality. Alternatively, it may also represent a state of elevated ADH activity secondary to an un known nonosmotic sti mulus. When osmolal ity is lowered sufficiently, osmotic inh ibition of ADH overcomes the nonosmotic stimulus. 1 0 . Hypervolem i c hyponatre m i a occurs with edematous states . Mec h a n i s­ tically, these conditions a re similar to the hypovolemic states in that the effective c i rculating volume is reduced and the kid ney conserves sod i u m ( u ri ne sod i u m < 1 0 m mol/L) . CHF is the most common cause o f hypervolemic hyponatremia, Nephrology . 1 4 7

b

and hyponatremia is associated with a poor prognosis Loss of plasma proteins (albuminuria , protei n-losing enteropathy) causes th i rd spacing of fluids, intravas­ cular depletion, and hyponatremia End-stage l iver disease impa i rs circu lation and plasma protein synthesis with consequent edema and hyponatremia . Renal fa ilure impairs the abil ity to excrete a normal volume of dilute u rine and results in hyponatremia and edema . Early in the course of renal failure, the volume expan­ sion may be modest, and patients may a ppear to have euvolemic hyponatremia . 1 1 . Treatment: In genera l , only severe , symptomatic hyponatremia and hypo­ natremia developing over 24 hours or less ( e . g . , patients with psychogenic polyd i psia, surgical and obstetric patients) should be treated with hypertonic so­ lution and more prompt correction . In the majority of patients, rapid correction

of hyponatremia i s hazardous and may lead to centra l nervous system damage (i . e . , centra l ponti ne myel i nolysis) A sta nda rd ru le is that the serum sodium should not be raised by more than 0.5 to 1 . 0 m mol/L per hour and no more than 1 2 mmol/L over 2 4 hours . Another maxim of hyponatremia treat­

ment is that the time for correction should approxi mate the ti m e course of devel­ opment ( i . e , ra pidly occurring hyponatremia should be corrected ra pidly, and more chronic conditions should be corrected gradually) . 1 2 . The following m nemonic separates hyponatremic conditions i nto four cate­ gories: pseudohyponatremia, and hypovolemic, euvolemic, and hypervolemic (edematous) states:

A S O D I U M WAT E R CA P E R Ps eudoh ypona tremia

A rtifactu a l Hypovolemic

S eq u estra t i o n , S k i n l o s s e s ( b u rn s a n d sweat i n g ) O s motic d i u re s i s D i u re t i c s I ntest i n a l l os s e s ( d i a rr h e a , vo m it i n g ) U ri n a ry s a l t wast i n g M i n e ra l ocort i c o i d d ef i c i e n cy Euvolemic

W at e r i n toxi c a t i o n A D H exce ss ( S I A D H ) T e m porary i m pa i rm e n t of water exc r e t i o n ( pa i n , e mot i o n , d ru g s , post-o p e rat ive ) E n d o c ri n e ( hypothyro i d i s m , p u re c o rt i c o l d ef i c i e n cy) R es et o s m ostat ( " s i ck ce l l " ) 148 • Nephrology

Hypervo/emic

C o n g est i ve h e a rt fa i l u re A l b u m i n u ria P rote i n- l o s i n g e n te ro p a t hy E n d-st a g e l ive r d i s e a s e ( c i rr h o s i s ) R e n a l fa i l u re

N E P H R OT I C SY N D R O M E MAD NEPH ROTICS M ed i cat i o n s/tox i n s/d r u g s A my l o i d o s i s D i a betes N eo p l a s m E n d oca rd i t i s/i nfect i o n s P ri m a ry g l o m e ru l a r d i s e a s e H e re d ita ry d i se a s e s R e n a l ve i n t h ro m bos i s O be s ity ( m o rb i d ) T hy ro i d d i s e a s e ( myxe d e m a a n d thyro i d it i s ) I nterstitia I neph ritis C h ron i c ref l u x/o b s t ruct i o n S L E , c o l l a g e n va s c u l a r d i s e a s e s

N otes 1 . Neph rotic synd rome is cha racterized by a l bu m i n u ria (> 3 . 5 g/d ) , hypo­ album inemia, and edema . Urinary loss of critical plasma proteins predisposes patients to thromboembolic events ( renal vein thrombosis, pul monary embolus), hyperlipidemia and accelerated atherosclerosis, vitamin D deficiency, and pro­ tein mal nutrition , as well as drug toxicity from decreased plasma protein binding . 2 . The majority of cases a re due to glomerular d isease (75%), including mem­ bra nous (40%), m i n imal change d isease, focal g lomeru losclerosis, membrane proliferative glumeruloneph ritis (GN), and mesang ioproliferative GN. Nephrology .

lL

149

3 . Systemic diseases, including diabetes mellitus, SLE, amyloidosis, drug reac­ tions, thyrOid disease, infections, and maligna ncy, as wel l as obesity, account for about 25% of cases. 4. Ma l i g n a nci es that may be assoc iated with nephrosis i nclude myelom a , Hodgkin's a n d non-Hodgkin's lymphomas, leukemia, a n d breast a n d GI tract carcinomas. 5. Drugs that cause the nephrotic synd rome i ncl ude gold, herO i n , penicil­ lamine, proben icid , captopril, and N SAIDs. 6 . Infections associated with the nephrotic syndrome include endocard itis, hepa­ titis B, shunt i nfections, syph ilis, and mala ria . 7. Evaluation of nephrotic syndrome includes 24-hour urine for protein and cre­ atine, serum albu m i n , cholesterol, and com plement. Rule out dia betes and SLE , as well as d rug exposure, u nderlyi ng maligna ncy, and infection If no systemic disease or exposure can be discovered , then a renal biopsy is ind icated .

R E N A L FA I L U R E BIG BUNS B l ood f l ow p ro b l e m ( p re-re n a l ) I n t r i n s i c re n a l d i s e a s e ( re n a l ) G I/i n te r n a l b l ee d i n g ( m eta b o l i s m o f h e m e ) B l a d d e r o u t l et o b s t r u ct i o n ( post-re n a l ) U retera l/c o l l ect i n g syst e m obstruct i o n ( p o st-re n a l ) N e p h rotox i n s (e . g . , d ru g s , r h a b d o myo lys i s , u ri c a c i d ) S te ro i d s (cata b o l i c states)

N otes 1 . An elevated blood urea nitrogen (BUN) level may indicate renal insufficiency (reduced GFR) or may occur secondary to increased catabolism of proteins (e.g . , steroid therapy) o r with i ncreased metabolism of heme products (e.g . , GI or other internal bleed ing). " BIG BUNS" prOVides a quick list of causes of a rising B U N . When renal i nsufficiency i s the cause o f a rising B U N , it is helpful to categorize etiolog ies as pre-rena l , renal, or post-rena l . Pre-renal azotemia occurs when renal blood is reduced and, as a consequence, renal fi ltration (GFR). Prerenal causes include volume depletion , heart failure, vascular disease, and shock. Renal 150 • Nephrology

causes of low urine output result from damage or disease of the renal parenchyma, including the g lomeru l i , i n terstitiu m , and tubules. Toxins, vasculitides, i nterstitial diseases, and primary g lomerulonephritides a re a mong the causes . Post-renal conditions that lead to low urine output a re characterized by on anatomic obstruc­ tion to u ri ne output. The most com mon of these is prostate enlargement, a lthough papillary necrosis, bilateral ureteral obstruction, and bladder outlet obstruction are possible causes. There is, of cou rse, overlap in etiologies (e. g . , CHF may pre­ cipitate ATNl , but this classification is useful in organ izing diagnostic possibil ities. 2. The following m nemonic l ists most of the causes of renal fa ilure accord ing to pre-rena l , renal, and post-renal mechanisms:

I CHASE A RISING B U N Pre-renal

I n t rava s c u l a r vo l u m e d e p l e t i o n ( d e hyd rat i o n , t h i rd spacing)

C a rd i a c ca u s e s ( C H F, M I , t a m p o n a d e ) H epatore n a l syn d ro m e A rte r i a l d i s e a s e ( r e n a l a rtery ste n o s i s ) S h ock E cl a m ps i a/obstetri ca l c o m p l i cat i o n s

Pre-renallRenal A cute tubular necrosis Renal

R a d i o g ra p h i c c o n t ra st a n d oth e r toxi n s ( d r u g s , r h a bd o myo l ys i s , h e m o l ys i s ) n t ra re n a l e m bo l i (ch o l e s t e ro l , D I C) S c l e ro d e r m a I n t e rst i t i a l n e p h ri t i s N ec roti z i n g vas c u l i t i s ( po lya rte r i t i s , n od o s a , Weg e n e r 's) G l o m e ru l o n e p h ri t i s

I

Pos t-renal

B l a d d e r obstruct i o n ( u s u a l ly p rostat i s m , s o m et i m e s b l oo d , p u s , ca l c u l i ) U rete ra l obstruct i o n (ca l c u l i , retro p e ri to n e a l fi b ros i s , ca n c e r) N ec r o s i s of re n a l p a p i l l a e ( d i a bete s, s i c k l e ce l l a n e m i a , N SA I D a b u se , i nfect i o n ) Nephrology .

151

br

3 . The usual approach again depends on the history and physical evaluation .

Frequently, prerenal causes a re obvious, such as C H F and ci rrhosis. Post-renal causes can be excluded in a ppropriate patients by placement of a Foley catheter. BUN and creati nine may further help to identify the pathogenesis I n pre-renal causes, BUN rises d isproportionately t o creati n i ne (often in a ratio of 2 0 : 1 or g reater) , while i n renal causes, creatine elevation usually is more pro­ nounced . Pre-existi ng renal disease may confound these para meters and is a common factor in low urine output. 4. When the etiology is sti ll in question, a renal u ltrasound is helpful to evaluate the collecting system for presence of obstruction and to assess renal size. Small, shrunken kidneys indicate long-standing d isease that is unlikely to be reversible. Normal or large kidneys may be ind icative of more acute disease. Certa i n sero­ logic tests and renal biopsy may be appropriate. Prompt renal biopsy is espeCially i m portant in cases of prog ressive renal i nsufficiency when i m m u nosuppressive therapy may preserve renal function (e. g . , vasculitis) . 5 . Hypocom plementemic renal failu re : "COMPS" Cryoglobulinemia Occult infection (endocarditis, "sh unt" nephritis) Membranoproliferative glomerulonephritis Post-streptococcal g lomerulonephritis Systemic lupus erythematosus Low complement levels a re occasionally helpful in the d ifferential diag nosis of glomerulonephritis, sign ificantly na rrowi ng the list of diag nostic possibil ities . The role of complement in glomerular i n jury and progression of renal insufficiency is not clear. In id iopath ic mem branoproliferative g lomeruloneph ritis, an antibody cal led C 3. nephritic factor is capable of inducing C 3 cleavage and proba bly causes the persistent depression of C 3 levels. This entity often is seen in associa­. tion with hepatitis B infection.

R E N A L S TO N E S OUCHS O xa l ate U rate C yst i n e H yp e rca l c e m i a S t ruvite

1 52 • Nephrology

N otes 1 . Kidney stones are among the most pa inful of afflictions, hence the mnemonic OUCHS. 2. Oxa late is a common com ponent of kid ney stones . Hyperoxa l u ria can occur i n mala bsorptive gastroi ntesti nal disorders, such as Crohn's disease and ulcerative colitis. Normally, free oxalate is bound by calci u m i n the gut and is not absorbed . Mala bsorbed fat binds calci u m , lead ing to free luminal oxa late. Free oxa late is read ily a bsorbed and then excreted in the urine. H igh levels of oxalate in the u rine precipitate calcium oXGJlate stone formation . 3 . Uric acid stones occu r with low pH a n d su persatu ration o f the urine with und issoc iated u ric aci d . Myeloprol iferative disease, chemotherapy, and Lesch­ Nyhan syndrome couse massive production and excretion of uric acid . In gout, dehydration, and id iopathic u ric acid l ithiasis, urine pH is usually low. U ric acid fac i l i tates heterogenous n ucleation of ca lci u m oxa late; th us, hyperuricosuria causes calciu m oxalate stones. 4. Cystine stones a re rare and a re seen in patients with hereditary cystinosis. 5. Hypercalcemia (e . g . , hyperparathyroidism, neoplastic hyperca lcemia) in­ creases urinary calci um concentration and precipitates calci u m stone formation. Hyperca lciuria may be id iopath ic or result from renal tubular d isease. I n distal renal tu bular acidosis, on al kaline urine and low uri nary citrate levels favor for­ mation of calcium phosphate stones. 6. Struvite stones (Mg N H4P04) occur mai nly in women and result from u rinary tract infections with u rease-prod ucing organisms (usually Proteus) . Struvite stones may grow quite large and fill the renal pelvis ("staghorn calculus").

Nephrology .

1 53

mID

ACID- BASE Genera l Considerations

A rte ria l B lood G a s I nte rpretation The interpretation of on a rterial blood gas can be sim pl ified by the steps out­ l i ned in the m nemonic "ABG READ" : Accurate ABG? ( Henderson-Hassel balch) Basic or acidic? (primary disorder) Go p/delta gop (onion gop) Respi ratory or metabol ic? Extreme disturbance? Appropriate compensation? Double or triple d isorder? F i rst, determine if the gas is accurate by determining the hydrogen ion concen­ tration [H+] using the Henderson-Hasselbolch equation :

A sim ple way to recall this relationship is to remember that [H+] increases as the pC02 increases or [HC03-] decreases The [H+] for a given pH can be de­ termined by either of the following methods: ( 1 ) Remember that at pH 7. 2-7 . 5 , every 0 1 u n i t change in pH changes [H+] concentration by . 1 0 m Eq/L i n the opposite direction . So, if [H+] for pH 7.4 is 40 m Eq/L, then [H+] for pH 7.5 is 30 mEq/L and [H+] for pH 7 . 3 is 50 mEq/L (2) With every 0 1 unit rise i n p H , multiply the preced ing [ H + ] b y 0 . 8 (e. g . , for a change i n pH from 7 . 4 to 7 . 5 , 40 mEq/L x 0 . 8 3 2 m Eq/L) . Conversely, for every 0 . 1 unit fa ll i n pH, mu ltiply the preced ing [H+] by 1 . 25 (e . g . , for a cha nge in pH from 7.4 to 7. 3 , 40 mEq/L x 1 . 25 50). The second method is slig htly more accurate, but either m ethod is usu­ a l ly sufficient for con f i r m i n g a ccu racy The follow i n g l i sts the [ H + ] for a g iven p H : =

=

Acid-Base • 1 55 (

pH 7. 8 , [H+] 1 6 .4 pH 7 . 7, [H+] 20 5 pH 7.6, [H+] 2 5 . 6 pH 7.5, [ H + ] 3 2 pH 7 . 4 , [ H+] 4 0 pH 7 . 3 , [ H + ] 5 0 pH 7 . 2 , [ H + ] 6 2 . 5 p H 7. 1 , [ H+] 78 5 pH 7.0, [ H+] 97.7 pH 6.9, [ H+] 1 2 2 . 1 The com ponents of the bica rbonate/ca rbon ic acid system a re always i n equ i librium i n the blood, a n d so pH, pC02, and [ HC0 3-] measured by venous blood chemistry should adhere to the constra ints of Henderson-Hasselba lch . If there is disagreement, then a la boratory or col lection error has occurred and repeat determination should be obtained . To assess the accuracy of oxygenation , add the p02 a n d pC02 . I f the tota l is g reater than 1 40 TORR (at sea level), then the patient was on su pplementa l oxygen or a la boratory error was made. The oxygen level decreases with age, which can be estimated by subtracting 1 TOR R from 80 for every yea r of age a bove 60 . So, an 80-yea r-old patient should have a p02 no less than 60 at sea level. After establishing the consistency of the values for pH, pC02, and [HC0 3-], look at the pH to establ ish if the primary or dominant d i sorder is basic or acidic. Si nce there is no over-com pensation for an acid-base d isorder, t h e pri­ mary disturbance is determi ned by the pH . Occasional ly, a chronic respi ratory acidosis or alka losis may have a normal pH in the a bsence of a m ixed disorder. Next, the serum anion gap, [Na+] - ([CI-] + HC0 3-1, is calculated to look for the p resence of u n m easu red a n ions, as occ u rs with the add ition of a ny strong acid to body fluids The anion gap can be altered i n the a bsence of a n acid-base disorder. A low seru m albumin or an i ncrease in u nmeasured cation, such as occurs with lithium ingestion or when certa i n paraproteins a re present i n m u ltiple myeloma, m a y decrease the g a p (see Low Anion G a p section) . On the other hand, meta bolic al ka losis may modestly i ncrease the a n i on gap. An i n­ crease in the a n ion gap usually ind icates the presence of a metabolic acidosis, but the normal a n ion gap va ries widely, with an averag e va lue of 1 0- 1 2 m Eq/L. Given the large number of factors that can affect the a n ion gap, previous electrolytes measurements from the patient may be helpful for comparison . With a high anion gap metabolic acidosis, there should be a close reci pro­ cal relationsh i p between the rise i n a n ion g a p a n d the decrease of serum [ HC03-] , cal led the delta gap. The delta gap is defined as (an ion gap - 1 2 ) . I n simple gap acidosis, a red uction i n serum [HC0 3-] by 1 0 i s associated with an i ncrease in anion gap of 1 0 . Addition of the va lue for delta gap to the mea­ sured [ HC0 3-] allows you to determ i ne the [HC0 3-] level that existed prior to the development of the gap acidosis. Thus, if delta gap + [ H C0 3-] is in the normal ra nge for serum [ HC0 3 -], then a simple an ion gap acidosis is present =

=

=

=

=

=

=

=

=

=

156 • Acid-Base

.

( i e . , the added acid has caused the expected drop in [ HC03-]) . If the value is outside the normal range, then another d isorder must have been present prior to the development of the gap acidosis. The following rules su mmarize the use of delta gap after a high anion gap is detected : 28

�

delta gap

+

[ HC03-]

�

2 3 , sim ple high gap acidosis

Delta gap

+

[HC03-]

<

2 3 , a non-anion gap acidosis also is present.

Delta gap

+

[HC03-]

�

2 8 , a metabolic alkalosis also is present.

Next, determ ine the specific type of acidic or basic disorder. Acid-base dis­ orders can be classified as either respiratory or metabolic. Respi ratory d isor­ ders are i n itiated by a change in PaC02 while metabolic disorders a re i n itiated by a change in [HC03-] . These primary d isturbances initiate predictable com­ pensatory changes (see below). Look to see if there is an extreme cha nge i n pH, pC02, or [ HC03-], as this often ind icates an acute process or two processes that cause the pH to change in the same d i rection (e. g . , a m etabolic al ka losis and respi ratory a l ka losis as occu rs in a preg nant patient who has severe vom iting from hypereme � is . g ravida, or COPD with CO2 retention and hypoxia ca using lactic acidosis) Acid-base disturbances in which the response to a primary d isturbance is obvi­ ously inappropriate (e . g . , increase pC02 with meta bolic ac idosis) a re mixed and do not require the use of predictive formulas. Extreme disturbances require rapid therapy. If the cha nges i n pH, pC02, and [ HC03-] are not extreme and do not rep­ resent on inappropriate d i rection of compensation, then assess whether appro­ priate compensation has occurred by usi ng specific predictive formulae. These formulae are useful in pred icti ng the appropriate degree of response, but keep in m i nd that an a ppropriate venti latory response for a metabolic d istu rbance may toke 1 2 hours to occur, and adequate renal compensation for a respi ratory d isorder may take several days to occur. It is also im porta nt to u nderstand that the compensatory responses do not normalize the pH . Exception : occasionally, chronic respi ratory acidosis or alkalosis may have a normal pH. S u m m a ry o f t h e Pri m a ry D i sturba nces and Compen satory Responses for Acid-Base D i sorders

Disorder

CompenPrimary satory Disturbance Response

Respiratory Increased acidosis pC02

Increased HC03

Type Acute

Appropriate Response for a Single Disorder

Comments

pH is lower For each change in pC02 of than chronic 1 0 TORR Ifrom acidosis Uncompl icated normal pC02 of 40 TORR), acute respiratory acidosis expected change Table continued on next page. Acid-Base •

1 57

��

S u m ma ry of the Pri mary Disturbances and Compe nsatory Responses for Acid-Base D isorders (Con tinued)

. Disorder

Compensa tory Primary Disturbance Response

Respiratory Increased pC02 acidosis {cant } (conti

Type

Increased Acute {cont i HC03 {cont.}

Appropriate Response for a Single Disorder in pH is 0 . 08 units (patient with pC02 of 60 should have pH of 20/ 1 0 x 0.08 0 1 6, so predicted pH is 7.4 0. 1 6 7 24) HC03 increases 1 mmal/L for each 1 0 mmHg increase in pC02 =

-

will not elevate [HC03-] over 32 unless superimposed metabolic alkalosis is present

=

pH less than Chronic For each change in normal, but pC02 of 1 0 TORR may be normal . from normal pC02 Unusual for paof 4 0 TORR, extients with pected change in pH is 0.03 un its pC02 > 60 (patient with pC02 TORR to have normal pH. of 60 should have pH of 20/ 1 0 x 0 0 3 0 .06 so predicted pH is 7 . 4 0 . 06 7 34) HC03 increases 33.5 mmol/L for each 1 0 mmHg increase in pC02. .

,=

,

=

Respiratory Decreased pC02 alkalosis

Decreased Acute HC03

Same rule as acute pH is higher respiratory acidosis than chronic (patient with pC02 alkalosis of 20 should have pH of 7 56) HC03 decreases 2 mmal/L for each 1 0 mmHg decrease in pC02.

Chronic Same rule as chronic Unusual for respiratory acidosis HC03- to fall (patient with pC02 to less than 1 5 mEq/L in of 20 should have pH of 7 46) absence of Table continued on next page. 1 58 • Acid-Base

S u m ma ry of the Pri mary Disturbances and Compensatory Responses for Acid-Base D i sorders (Con tinued)

Disorder

Compensatory Primary Disturbance Response

Type

Appropriate Response for a Single Disorder

Respiratory Decreased pC02 alkalosis lcont.) Icont ) Metabolic acidosis

accompanying Decreased Chronic HC03 decreases 4-5 mmol/L for metabolic HC03 lcont.) each 1 0 mmHg acidosis. Icont.) decrease in pC02. The pH is often normal . pC02 [ 1 5(HC03) Full compensation Decreased Decreased (hyperventila+ 8) ± 2 (patient HC03 pC02 tion) may take with metabolic acidosis and HC03 1 2-24 hours of 1 0 should have pC02 of [ 1 .5( 1 0) + 8) ± 2 23 ± 2 2 1 -25 TORR. pC02 last 2 digits of pH x 1 00. =

=

=

=

Metabolic Increased HC03 alkalosis

Increased pC02

Compensation pC02 0.9* less consistent (HC03) + 9 than for meta(patient with metabolic acidosis. bolic alkalosis and HC03 of 40 pC02 > 45 occurs in 25% should have pC02 of 0 . 9 * (40) + of cases. Rare to see pC02 9 45 TORR) > 55 TORR except in severe * range 0.6-0.9 alkalosis or superimposed respiratory alkalosis. =

=

=

After checking for a ppropriate compensation , decide if the d i sorder is simple or if a double or triple d isturba nce is present. Types of m ixed d isorders and clues to their presence QTe as follows: 1 . Metabolic a lkalosis + respi ratory alkalosi s - Both processes i n­ crease the pH . A decreased pC02 is seen with i n c reased HC0 3 A very high pH is possible because the a l kaloses sum mate. There is a m i ld elevation of a nion gap. Hypokalemia freq uently is p resent. Exa m ple preg nancy with vom iti ng . 2 . Respiratory acidosis + metabolic alkalosis- Both processes increase the HC03. Often there is a normal pH and a very high HC0 3 pC02 is h ig her tha n predicted on the basis of metabolic alkalosis alone. Example: COPD + d i­ uretic therapy. \

Acid-Base •

1 59

3 . Metabolic acidosis + respiratory acidosis- Both processes decrease the pH . pH is very low because the acidoses sum mate. Example: decom pen­ sated COPD + lactic acidosis 4. Metabolic acidosis + metabolic alkalosis- The two processes change the HC03 and the pC02 in opposite directions. The pH may be increased, de­ creased , or norma l , depending on the relative severity of the two processes . Consider this d iagnosis when the anion gap is increased, but the HC03 is not decreased. Example: DKA + vomiti ng . 5 . Metabolic acidosis + respiratory alka losis Both processes decrease the HC03 . Consider this diag nosis when a metabolic acidosis is accompanied by a pC02 that is lower than predicted, or when respiratory alkalosis is associated with an HC03 measurement lower than predicted . Example: sal icylate overdose . 6. Triple acid-base disturbance- triple distu rbances occur when a m ixed metabolic acidosis + meta bolic alkalosis is compl icated by either a respiratory acidosis or a respiratory a l kalosis. While m ixtu res of meta bol i c distu rba nces may occur, m ixed respiratory disturbances ca nnot occur by definition, because a person can never concu rrently over- and u nder-excrete CO2. The d iagnosis of a triple d isturbance is generally made in a patient with metabolic alkalosis and res­ pi ratory acidosis or alkalosis i n whom the anion gap is found to be sign ificantly increased (> 1 6) . Example: DKA + vomiting + obtundation/hypoventilation . -

Cl inica l Conditions and Diagnoses

M E TA B O L I C A C I D O S I S WITH A H IG H AN ION GAP KLU ES I K et o a c i d o s e s

Lactic acidoses U re m ia ( o rg a n i c a c i d s ) E thyl e n e g lyco l a n d t h e a l co h o l s S a l icylates

160 • Acid-Base

-

N otes 1 . This m nemonic lists the primary conditions i n which the anion gap, {[Na+] ­ ( [CI] + [ HC03])}, i ncreases . Because of electroneutrality, unmeasured anions m ust i ncrease as bicarbonate fa lls, lead ing to a widen i n g of the an ion gap. " KLUES" to the cause of an i ncreased an ion gap come from the history and lab­ oratory tests, i ncluding BUN, creati n i ne, glucose, lactate, seru m ketones, serum osmolality, and a toxin screen. 2. Ketoacidosis occu rs i n three settings: d iabetes, alcoholism, and malnutri­ tion ("DAM ! " ) . In diabetic ketoacidosis, acetoacetic and beta-hydroxybutyric acids are produced more ra pidly than they can be metabolized . They accumu­ late, causing a d rop i n plasma bicarbonate a n d a rise i n the a n ion g a p . Alcoholics m a y have poor food i ntake and vom iting associated with h i g h ethanol intake, causing ketoacidosis and an elevated an ion gap. T h e ketoaci­ dosis may be missed because the n. itroprusside test for ketones only detects ace­ toacetic acid and not beta-hyd roxybutyric acid, which tends to pr·edomi nate. Ma ln utrition alone may cause a modest ketoacidosis. Red uced ca rbohydrate levels cause low i nsul i n and high gl ucagon . These hormonal changes (also rele­ vant to DKA and alcoholic ketosis) favor glycolysis and ketogenesis. 3. Uremia is characterized by the accumulation of organic acids, which normally are excreted by the kidney. In acute renal failure, plasma bicarbonate falls by 1 to 2 mmol/L per day if impaired renal acid excretion is the sole cause of metabolic aci­ dosis. Greater rates of decline suggest the presence of an additional cause of acid production. In chronic renal failure, the bicarbonate tends to stabilize at levels of 1 2- 1 8 mmol/L and rarely falls below 1 0 m mol/L unless another disorder is present. 4. Lactic acidosis occurs when there is an i m balance between lactate produc­ tion and el i m i nation ("LACTIC") . During a naerobic conditions, glycolysis is ac­ celerated and pyruvate i ncreases . Pyruvate is in eq u i l ibrium with lactate; thus, lactate levels i ncrease. Si nce one proton is generated for each lactate molecule produced, acidosis is the result of lactate production . Because the l iver is the ma jor organ for meta bolizing lactate, severe liver d isease causes lactic acidosis. Lactate production is norma l , but meta bol ism is i mpa i red . With significant l iver dysfunction , the normal lactate load produced by the body is not metabolized , lactate accum ulates, and acidosis ensues . Selective dysfunction of m itochondria (e . g . , congenital disease, biguan ide toxicity) causes lactic acidosis i n the a bsence of other evidence of liver dysfunc­ tion. Lactate overproduction results from c;.i rcu latory fa i l u re . Tissue hypoxia, as occurs with cardiopulmonary grrest, �arbon monoxide poison ing and severe anem ia, leads to lactic acidosis. Vigorous exercise or muscular tetany as occurs with seizures may cause a tra n sient rise in lactate. System ic infection/sepsi s causes circulatory shock, org an hypoperfusion, a n d subsequent lactate produc­ tion . Lactic acidosis may complicate �ancers, such as leukemia and lymphoma, when tissue hypoxia is not i n evidence. Overproduction of lactate by the mal ig­ nant tissue may be a factor. Acid-Base . 1 6 1

Note that lactic acidosis a lso may contri bute to the severe acidosis seen with salicylate, methanol, or ethylene glycol poison ings. 5. Ethylene glycol and methanol a re converted to acidic m etabolites, which accumu late i n the bloe>d . An increase i n osmola r gap is characteristic, and prompt intervention is critical . Isopropyl alcohol causes a more modest increase in anion gap and serum osmolal ity. 6. Salicylates cause a characteristic in itial respiratory alkalosis by stimulating cen­ tral respi ration . The presence of respiratory alkalosis combined with an increased anion gap frequently occurs with sal icylate intoxication and should not be m issed . 7. Certain gastrOi ntestinal disorders have been reported to cause a gap acidosis secondary to accum ulation of D-Iactate. It is thought that certa in bacteria pro­ duce D-Iactate in the gut that is systemically a bsorbed . A special serum assay for D-Iactate is ava i lable, as it is not detected by the conventional assay. 8. Other drugs have been associated with a gap acidosis. Isoniazid causes re­ fractory seizu res and a subsequent lactic acidosis. Paraldehyde is rarely used , a nd its role i n ca using gap acidosis is not well documented , but it is remem­ bered beca use of the fa m i l i a r "MUD PILES" m nemonic ( m etha n oJ , u rem i a , DKA, paraldehyde, isopropyl a lcohol , lactic acid, ethylene g lycol , sal icylates). Propylene glycol, a d i luent used i n some intravenous medications (e. g . , nitro­ glyceri ne) , may rarely cause a secondary lactic acidosis. 9. When measured plasma osmolal ity exceeds the calculated osmolality [(2 x plasma No) + glucose/ 1 8 + BUN/2 .81, suspect ethylene g lycol or methanol toxicity. Ethanol intoxication and some cases of lactic acidosis or alcoholic keto­ sis also may feature a small "osmolal gap" (up to 1 0- 1 5 mOsm/kg ) .

DAM U LACT I C GAPS Ke toacidoses

D i a betic ketoa c i d o s e s A l c o h o l i c keto s i s M a l n utriti o n U re m ia

Organ ic acids

Lactic a cidoses

L ive r d i se a s e A rrest C a rbon m o n o x i d e p o i so n i n g T eta ny/s e i z u res ( rh a b d o myo l ys i s) I nfect i o n/s e p s i s C a ncer 1 62 • Acid-Base

b

O ther unmeas ured anions

G a stroi ntest i n a l d i s e a s e ( D- I a ctate) A l c o h o l s/a n t i-f reeze P ro py l e n e g lyco l/pa ra l d e hyde S a l icylates

M E TA B O L I C A C I D O S E S WITH A N O R MAL AN ION GAP GUT G a stroi ntesti n a l l o s s e s ( d i a r r h e a , pa n c re a t i c f i stu l a ) U ri n a ry l o s s e s T ota l p a r e n t e ra l n utrit i o n

N otes 1 . N ormal anion gap or hyperchloremic acidoses almost a lways result from

HC03 loss from the GI tract or from the kidney. As the a bove m nemon ic sug­

gests, GUT losses from d i a rrhea a re the most common cause. Uri nary losses from renal tubular disease a re less com mon . 2 . In both GI and renal disorders, sod i u m bica rbonate stores a re low, a nd sod ium chloride is reta i ned in excessive a mounts to preserve volume status. The urine net charge or u rinary anion gap, { ([Na] + [K] - [CI] }, is useful in d iffer­ entiating between renal and gastrointestinal causes of HC03 loss. Urinary acid­ ification results from the excretion of a m m o n i u m , N H4 + The p resence of the positive ion, N H4+, ind icates that other maior cations, [Na] + [K] , a re present in lower amounts when compa red to the maior anion, [Cl] . A negative u rine an ion gap i m pl ies the presence of N H4+ in the urine, ind icati ng appropriate rena l acid ification in response t o acidosis ( a s in GI losses) . A positive va lue ind icates a renal acidification defect (no N H4+ in the uri ne) . If the cause appears to be renal dysfu nction (positive urinary a n ion gap), then the serum potassium is help­ ful. Low potassium suggests an H+ secretion defect, whereas high values are consistent with deficient aldosterone action (Type IV renal tubular acido�i� rRTA] ) . Acid-Base • 1 63

bn

3 . I n rare cases, iatrogenic normal gap acidosis results fro m i ntravenous ad­

m i n i stration of TPN or acidic a m i no acid solutions, a m mon i u m ch loride or hy­ d rochloric acid . An apparent, normal gap acidosis is occasionally seen when a gap acidosis is accompanied by a pre-existing condition that lowers the anion gap, such as hypoalbuminemia or a cationic para protein (see Low Anion Gap section) 4. Respiratory alkalosis with reduced pC02 levels leads to a loss of bicar­ bonate. With rapid correction ( i . e , decreased respiratory rate), pC02 returns to norma l , but bica rbonate conservation and reclamation by the kidney takes 24 to 48 hours to return levels to norma l . A tra nsient non-gap acidosis occurs . 5 . In DKA, it is common to see a n incidental hyperchloremic acidosis i n the recovery phase. This phenomenon occurs because sodium ch loride is reta ined with vol u me repletion . The ketones (a source for regenerating bica rbonate) are lost i n the urine, and bicarbonate regeneration is slowed S i m i la rly, vigorous volume replacement in a dehyd rated patient suppresses aldosterone secretion . S i nce a ldosterone i ncreases bica rbonate regeneration a n d a bsorpti o n , the lower levels tend to mainta i n the hyperch loremic state. This "expa nsion acido­ sis" is the converse of the "contraction alkalosis" seen with vol ume depletion; the latter i s a h i g h a ldosterone state. The acidosis from vol u me replacement is rarely of cli nical sign ificance. 6 . A more comprehensive listing of causes of non-gap acidoses is listed below. The mnemonic em phasizes the i m portance of calculating the urine gap when the cause is u ncerta i n .

U R I N E G A P : N A + K-C L U retero s i g m o i do stomy R TA I ntest i n a l d i s e a s e ( d i a rr h e a ) N H 4+/T P N E a rl y re n a l fa i l u re G l u e s n i ff i n g (to l u e n e ) A I d osterone defi c i e n cy P a n c rea t i c f i stu l a N a C I i nf u s i o n ( "expa n s i o n " a c i do s i s ) A ft e r D KA o r res p i ratory a l ka l o s i s K+�s p a r i n g d i u reti cs C a rbon i c a n hyd ra s e i n h i bitors ( i m pa i rs u r i n e acid i f i cati o n ) L axative a b u se ( G I l o s s e s ) 1 64 • Acid-Base

L ow A N I O N G A P ALB U M I N A lb u m i n loss L ithium B ro m i n e U n m e a s u red cati o n s ( K, M g , C a l M ye l o m a (cati o n i c pa ra p rote i n ) I od i d e N a + u n d e resti m a t i o n/a rtifact

N otes 1 . A low seru m a l bu m i n is the most com mon cause of low a n ion gap The normal an ion gap is a pproximately 5- 1 2 . Because of this wide ra nge of normal and the many factors affecting the an ion gap, the clin ical usefulness of a low measured an ion gap has been questioned . Knowing the factors that affect the an ion gap is perhaps most useful when tryi ng to determine the sign ificance of modest changes in the anion gap (e.g . , an an ion gap of 1 6 may be sig nificant in a patient with a very low album i n ) . A reduction in the anion gap may also be due to laboratory error. 2 . A lower serum a n ion gap may be observed in conditions with an i ncrease in unmeasured cations, such as occurs with hyperkalem ia , hypercalcem ia , or hypermagnesemia . It may also be seen when there is an increase in unmeasured cations that are not normally present, such as with multiple myeloma, polyclonal g a m mopathy, or lith i u m . A l ow gap is seen with a decrease i n un measured anions (usually hypoalbuminemia). Sodium underestimation is much less likely to occur g iven new d i rect ion-selective techniques (a low gap was more common previously i n cases of hyperviscosity and severe hypernatremia). Chloride overes­ timation was formally seen i n cases of hypertriglyceridemia, but this also is less of a problem now. However, bromine and iodide may lead to ch loride overesti­ mation and thus reduce the anion gap. Bromine and iodide have slightly lower renal clearances than chloride. Electrolyte measurements do not disti nguish be­ tween brom ine or iodide and chloride, so a rise in brom ine or iodide is falsely measured as an ever g reater rise in ch loride. Other rarely reported causes of a low serum anion gap include renal transplantation and hyponatremia . 3 . Clea rly, there are many considerations i n calculating the a nion gap- partic­ ularly in a patient with m ultiple med ical problems. Take all of these factors into account when interpreting the a n ion gap. Acid-Base • 1 65

M E TA B O L I C A L K A L O S I S ALOOS A l d oste ro n e Lasix D e hyd rati o n O ve r-ve n ti l a t i o n S t 6 m a c h l os s e s

N otes 1 . Metabolic alkalosis is not a specific d isease; it is usually a response to NaCI and K+ deficit. Understanding the hormone aldosterone is the key to understanding most cases of meta bolic a l kalosis; hence, the m nemonic ALDOS . Aldosterone promotes renal acidification and concom itant bicarbonate regeneration and a b­ sorption . Pri mary hyperaldosteronism and other hypermi nera locorticoid states cause metabolic alkalosis. Simi larly, volume depletion causes a secondary i n­ crease in aldosterone, a lso promoting metabol ic al kalosis. With volu m e con­

traction, there is an increase in sod i um avidity due to aldosterone activity. Because of electroneutrality, anions must be reabsorbed with sodium; therefore, chloride is maximally reabsorbed , leaving very little chloride in the urine . For this reason, the measurement of urine chloride (see mnemonic next page) is helpful in determining the cause of metabolic alkalosis. 2 . The majority of m etabolic a lkalosis cases a re due to extracel lular fluid volume contraction and respond to saline admin istration . These so-called sali ne­ sensitive types com monly result from vom iting and d i u retic use. I n these i n­

stances, volume loss leads to renal sod ium conservation, necessitating maximal reabsorption of ch loride as an obligate an ion . Urine chloride is usua lly less than 1 0 mmoles/L in sali ne-sensitive metabolic alkalosis. Replacement of the volume deficit corrects the alkalosis. 3. Hyperminera locorticoidism (primary, Cush ing's syndrome, renal artery stenosis, malignant hypertension, J-G cell tumor, Bartter's syndrome, and licorice gluttony) is the other major mechan ism that can mai ntain metabolic alka losis. These condi­ tions a re sa l i ne-sensitive and typically have a urine ch loride concentration > 20 m moles/L. The patient's volume status helps to differentiate between a sa line-sen­ s itive cause (low volu me) and a saline-i nsensitive cause ( normal or increased vol u me) . Rarely, patients with extracellular fluid vol ume depletion have other causes for metabolic alkalosis ( mag nesium depletion, Bartter's syndrome). liddle's syndrome is a rare disorder in which patients appear to have hyperaldosteronism, 1 66 • Acid-Base

JI

but aldosterone levels are low. It is probably due to an i ntri nsic tubular defect and can be treated with trai mterene or amiloride, but not spi ronolactone. 4. The following m nemonic lists the specific causes of metabolic alkalosis :

R E N A L C L- E VA L R e covery from hype rca p n i a , orga n i c a c i d o s i s E mesis N a s o g a s t r i c s u ct i o n A l d oste ro n i s m L a s i x/ l o o p d i u re t i cs C ys t i c f i b r o s i s L ow K + , M g + + E xsa n g u i n a t i o n/m a s s ive t ra n sf u s io n ( c i t rate) V o l u m e d e p l et i o n A l ka l a i i n t a ke ( I V b i ca rb, m i l k-a l ka l a i ) L i d d l e's syn d ro m e

R E S P I R AT O R Y A C I D O S I S COPOS C a rd i a c a rrest o btu n dati o n P u l m o n a ry d i se a s e/a i r way obstruct i o n D ru g s/ove r d o s e S ke l eta l/n e u ro m u s c u l a r d i s e a s e

N otes 1 . Respi ratory acidosis represents a fa il u re of venti lation. Obstructive lung dis­ ease is the most common cause of both acute and chronic respi ratory acidosis, hence the mnemonic COPDS . Acid-Base • 1 67

2 . Common causes of hypoventi lation and subsequent respiratory acidosis in­ clude card iac arrest, obtu ndation, pul monary d isease or la rge a i rway obstruc­ tion, C N S-depress ing d rugs/overdose, and skeleta l /neuromuscular disease (e.g , ALS, myasthenia g ravis, advanced kyphoscoliosis).

R E S P I R AT O R Y A L K A L O S I S peo2 V E N TS P re g n a n cy C i rr h o s i s O 2 d ef i c i t

V e nt i l a t o r E mbolus N e u ro l og i c d i s e a s e T e m p e ratu re (fev e r, h ea t ) S a l i cylates/d ru g s

N otes 1 . I n contrast to respiratory acidosis, respi ratory alka losis is seconda ry t o hy­ perventi lation . Over-excretion of carbon d ioxide, PC02 V E NTS, accounts for the alkalosis. 2. Respi ratory center sti m u lation in pregnancy is due to increased production of progesterone, while in cirrhosis there probably is decreased meta bolism of substances that stim ulate the respiratory center. Hypoxia (02 deficit) also causes hyperventilation. Patients on mecha nical ventilators may have respiratory alka­ losis when the minute ventilation is i nappropriately high. Tachypnea and respira­ tory alkalosis is a very sensitive albeit nonspecific sign of pulmonary embolus. CNS injury or neurologic diseases also may cause hyperventilation . Temper­ ature elevations with fever or heat exhaustion sti mulate breath ing, and respira­ tory alkalosis is the initial acid-base a bnormality in salicylate overdose.

1 68 • Acid-Base

113

G ASTRO ENT EROLOGY Clinica l Sy m ptoms and Signs

A B D O M I N A L PA I N M EAN G U T M eta b o l i c E n d o c ri n e A bd o m i n a l N e u ro g e n i c G yn e c o l o g i c/g e n ita l ia U ri n a ry/r e n a l system T h o ra c i c

N otes 1 . "MEAN GUT" provides a simple outline for a pproaching abdomi nal pa i n . The most i m portant in itial decision i s whether u rgent surgical intervention o r d i­ ag nostic testi ng is ind icated . The history and physical exa m i nation and a few simple tests gUide the decision-making . It is essential to exclude extra-abdominal causes of pa i n ( i . e . , meta bolic, endocri nolog ic, neurolog ic, gynecolog ic, uro­ log ic, and thoracic) before embarking on expensive and invasive testi ng . 2 . Metabolic causes of a bdom inal pain include u remia , porphyria, C 1 esterase deficiency, Fami lial Mediterra nea n Fever, and poisons (e g . , heavy metals, en­ venomation, chemotherapy) . Endocrine causes include adrenal insufficiency, hy­ percalcemia , and diabetic ketoacidosis. Most of the i ntra-abdo m i na l etiologies Gastroenterology . 1 69

of pa i n a re listed i n the "PREP FOR SURGICAL APPE NDECTOMY?" m nemonic on page 1 72 . Neurogenic ca uses of pa i n incl ude herpes zoster, tabes dor­ salis, psychogenic pa i n , functional bowel d isease, a n d spinal rad i c u l itis. Gynecologic causes of pa i n - i mportant i n any female patient and especia lly those of menstruating age - a nd urologic causes of pai n , such as renal stones, pyelonephritis, and u rinary retention, also a re i ncluded in the differential for ap­ pend icitis . Finally, pa i n may be referred from thoracic problems such as pneu­ monia and myoca rd ial ischemia . Esophagea l d i sease usually causes chest d iscomfort, although patients may complain of a bdom inal symptoms. 3 . The in itial d iag nostic eva luation of a patient with acute a bdominal pa i n often includes CBC, urinalysis, a mylase a nd/or lipase, liver enzymes, a n d a b­ dominal x-rays, taken with the patient in the u pright position to eva luate for d i­ lated loops of bowel or free a i r. Other tests may be appropriate i n selected patients, such as serum electrolytes, BUN, creati n i ne, calcium, cosyntropin stim­ u lation testing for adrenal i nsufficiency, or a chest radiograph. 4 . Important tips for internists:

a. Be careful to exclude meta bolic derangements, systemic d i seases a n d extra-a bdominal processes, which m a y present with a bdom i nal pa i n . b. Rule out ectopic pregnancy i n a n y female o f menstruating age. Pelvic ex­ a m ination should be performed on virtually a l l women with acute a bdom i na l pa i n . Every woman o f reproductive a g e must have a pregnancy test. c. E lderly patients with acute a bdom i na l processes may have atypical pre­ sentations and should be ma naged with g reater caution. Mesenteric ischem ia, for example, may present with severe pai n and an unimpressive physical exam­ i nation ( i . e . , pa i n out of proportion to the clinical findi ngs) . Also, patients on cor­ ticosteroid therapy may have atypical presentations, as steroids may mask ( clinical findings . 5 . The location , d u ration, progression, and onset of pa i n (see ta ble) can be helpful in d ifferentiating between causes of a bdom inal pai n . There is consider­ a ble overlap, but a general time cou rse is often helpful in d iscerning the cause of abdom inal pai n . Relieving and aggravating factors a re helpful in local izing the source. For exa m ple, pa in relieved by the passage of bowel movements suggests the colon as a l i kely source. Pa i n i n itiated by swallowing implicates the esophagus, wh i le pain aggravated by a ny action that moves the abdomen sug­ gests periton itis (the patient usually prefers ta lie sti l l ) . On the other hand, with obstruction of a hollow viscus, patients usually move about in an attempt to seek relief, and movement does not make the pain worse.

1 70 • Gastroenterology

Pa i n Accordi n g to the Acuity of Onset

Abrupt-Gnset Pain ( instant) Gastrointestinal Causes

Nongastrointestinal Causes

Perforated ulcer Ruptured abscess or hematoma Intestinal infarct Ruptured esophagus

Ruptured or dissecti ng aneurysm Ruptured ectopic pregnancy Pneumothorax Myocardial infarction Pulmonary infarction Dissecting aneurysm

Rapid-Onset Pa in (minutes) Nongastrointestinal Causes

Gastrointestinal Causes

Ureteral colic Perforated viscus Strangulated viscus Renal colic EctopiC pregnancy Volvulus Pancreatitis Biliary colic Mesenteric infarct Diverticulitis Penetrating peptic ulcer H igh intesti nal obstruction Appendicitis (gradual onset more common) Gradual-Gnset Pain (hours) Gastrointestinal Causes

Nongastrointestinal Causes

Appendicitis Strangulated hernia Low intesti nal obstruction Cholecystitis Pancreatitis Gastritis Peptic ulcer Colonic d iverticulitis Meckel's diverticulitis Crohn's disease Ulcerative colitis Mesenteric lymphadenitis Abscess Intestinal infarct Mesenteric cyst

Cystitis Pyelitis Salpingitis Prostatitis Threatened abortion U rinary retention Pneumonitis

Gastroenterology . 1 7 1

b

6. Here is a m nemonic delineating the d ifferential diag nosis for a ppendicitis:

P R E P F O R S U R G I CA L A P P E N D ECTOMY? P ye l o n e p h r i t i s R e n a l sto n e E ctop i c p re g n a n cy P e lv i c i nf l a m matory d i s e a s e F o l l i c l e ru ptu re ( m i tt e l s ch m e rz ) O va r. i a n cyst t o rs i o n R u pt u re of c o r p u s l ut e a l cyst S p l e n i c ru ptu re U ri n a ry rete n t i o n R u ptu red a n e u rysm G a st r o e n t e r i t i s I nfarcted/i sch e m i c g ut Cro h n 's/u l c e rat ive co l i t i s A bs c e s s L ive r c a ps u l e d i st e n s i o n/i rrita t i o n A ppendicitis P a n creatit i s P e rforated u l c e r E s o p h a g e a I ru ptu re N o disease D i vert i c u l it i s E ndometriosis C h o l ecys t i t i s T wi sted bow e l O bs t ru cted bowel M ecke l 's d ive rt i c u l u m Y e rs i n ia/lym p h a d e n it i s

1 72 • Gastroenterology

D IA R R H EA SOILING S ec retory O s m ot i c I n f l a m matory L a xa t i ves (fact i t i o u s ) I sch e m i c N e u ro g e n i c G a st ro i ntesti n a l b l e e d i n g

N otes 1 . The pri mary mechan isms of d iarrhea (or apparent d iarrhea ) a re summa rized by the m nemonic SOI LING. Dia rrhea is defined as an i ncrease in daily stool weight above 200 grams per day. Si nce this is not a very easily obta ined mea­ sure, dia rrhea is here defined from the patient's perspective : an i ncrease in stool frequency and/or liqu idity. This defi nition includes hyperdefecation, which is an increase i n frequency without a n increase i n stool weig ht as occurs i n i rritable bowel syndrome, hyperthyroidism, and fecal i nconti nence. Also i ncluded is gas­ trointesti nal bleeding causing melena, which patients may describe as d ia rrhea . 2 . Secretory (watery) diarrhea is characterized by volu m i nous feca l output not necessa rily related to food inta ke, which fa i ls to i mprove with fasting. There is perturbation of normal fluid and electrolyte transport in the gut, and the result is watery stools with normal electrolyte concentrations and no increase in stool os­ molal ity. The classic exa m ples of secretory d ia rrheas are hormona l , including ca rci noid syndrome, Zol l i n ger-E l l ison , VIPoma, medullary thyroid carcinoma, and systemic mastocytosis. An exception is somatistati noma , in which the diar­ rhea is osmotic with steatorrhea secondary to inhi bition of pancreatic secretions and gall bladder motil ity. Bile salts stimulate colonic secretion, and processes that i ncrease bile salt delivery to the colon also cause secretory d iarrhea . Examples include: ileal bypass or resection ( reduced reabsorption), tru nca l vagotomy (ab­ normal transit), and after cholecystectomy (reduced storage capacity ) . 3 . Osmotic dia rrheas (such as pa ncreatitis, sprue, bacterial overgrowth , and Whi pple's d isease) a re cha racterized by bulky, g reasy, foul-smel l i n g stools, weight loss, and i mprovement i n diarrhea with fasti ng . This form of diarrhea re­ sults from an ingested solute that is not a bsorbed by the sma ll intestine /The un­ absorbed solute exerts an osmotic force and draws fluid i nto the i ntestinal lumen . The resultant i ncreased stool volume exceeds the colon's reabsorptive capacity, Gastroenterology .

tb

1 73

po;

a nd dia rrhea ensues. Stool analysis shows a gap between electrolyte concen­ trations and total stool osmolal ity d ue to the unabsorbed solute. 4. Inflammatory causes (infla m matory bowel disease, rad iation enterocolitis, eosinophilic gastroentereitis and certai n AI DS-associated infections) a re charac­ terized by fever, a bdominal pa i n , and blood and/or leukocytes in the stool. In these d i sorders there is i nfla mmation and i n j u ry to the i ntesti nal mucosa . The mechanism of dia rrhea may include mala bsorption or secretion due to disrup­ tion of normal mucosal functions. 5. Factitious dia rrhea from laxative abuse is osmotic and should be suspected in women with chronic dia rrhea , hypokalemia, and a h istory of psychiatric i l l­ ness . Certa i n prescri bed medications also can cause d i a rrhea , such as antacids, theophyl li ne, colch icine, digita lis, and antibiotics. 6 . Ischemia is not a common cause of d iarrhea , and the clin ical picture de­ pends on the deg ree of vascular comprom ise. Acute, fulminant ischemic colitis is due to complete vessel occlusion and features severe abdominal pa i n , bloody d ia rrhea , and rapid decompensation . Nonocclusive ischemia has a less severe course and usua lly resolves without intervention . Patients with nonocclusive is­ chemia have lesser deg rees of pain and bleed i ng , occ u rring over a longer period of time. Anorexia, vomiting, and diarrhea may be the primary complaints. 7. Neurogenic d isorders a re d isturbances of intestinal motility that often cause hyperdefecation or i nconti nence as o pposed to true d i a rrhea . The i rrita ble bowel syndrome (IBS) is a common a nd increasingly recog nized form of neuro­ genic diarrhea . IBS is characterized by alternating constipation and d iarrhea , as wel l as d iffuse a bdom inal pai n . I B S beg ins by early adulthood a n d should not be accepted as a diagnosis in a n older patient with recent-onset diarrhea . Other neurologic diseases (diabetes, cauda-equina syndrome, Shy-Drager) also can cause altered intestinal moti lity a nd diarrhea . 8. Gastrointestinal bleeding, when subacute, may cause frequent loose, black stools. Although not strictly d i a rrhea , patients may interpret it as such . Also, some of the other mechanisms of diarrhea may feature bleed ing, especially the infla mmatory etiologies and ischemia . 9 . The majority of cases of acute diarrhea « 7- 1 4 days in d u ration) a re i n­ fectious, the d iagnosis of which ca n be suspected by a history of recent travel, ingestion of unusual food (raw seafood or undercooked poultry products or ham. burgeri, or recent contact with people who have been sick. Infections by inva­ sive bacteria ( Campylobacter, Shigella, Salmonella, Aeromonas, certa i n Escherichia coli) a re often associated with bloody diarrhea . It is i m portant to ex­ clude other causes of bloody dia rrhea such as mesenteric ischemia and inflam­ matory bowel disease. Infections by noninvasive bacteria a nd protozoa ( Vibrio cholerae, enterotoxigenic E. coli, Klebsiella, Giardia, Cryptosporidia) typically produce watery diarrhea without blood . C. difficile rarely causes bloody diar­ rhea . Yersinia, which commonly infects the term inal i leum and cecum, often pre­ sents with watery d i a rrhea and right lower quadrant pa i n , which ca n m i m ic a ppend icitis and Crohn 's d isease. 1 0. A more comprehensive list of the causes of chronic diarrhea, organ ized pathophysiolog ically, follows: 1 74 • Gastroenterology

b

d

I RACE TO PASS LOTS O F WI LD 8 M , FI N D A CURE ! Isch emia

I sch e m i a

Secre tory

R ecta l v i l l o u s a d e n o m a A fte r c h o l ecystectomy (ch o l e rr h e i c ) C o l l a g e n o u s c o l i t i s ( l y m p h ocyt i c o r m i c ro s c o pi c co l it i s ) E n d oc r i n e (Zo l l i n g e r- E l l i s o n , V I Po m a , ca rc i n o i d , m e d u l l a ry t h y r o i d ca rc i n o m a , m a s tocyto s i s ) T ru n ca l va g otomy O be s i ty s u rg e ry ( i l e a l bypa s s o r resect i o n ) Osmo tic

P a n crea t i t i s (ch ro n i c p a n c r e a t i t i s w i t h steato r r h e a ) A beta l i p o p rote i n e m i a S o m atostati n o m a S h o rt-bowe l syn d ro m e L y m p h a n g i ecta s i a O ve rg rowth o f bacte r i a T ro p i c a l s p r u e S p r u e ( g l u te n -se n s itive)

o l es t ra/d i etet i c foods

F ru its/ca n d y (fru ctos e , s o r b i ta l )

W h i p p l e 's d i s e a s e I nfect i o n s ca u s i n g stea t o r r h e a ( I s o s p o ra , G i a rd i a , S t ro n g y l o i de s ) L a ctose i nt o l e r a n c e o r u g s ca u s i n g steato r r h e a (e . g . , c o l ch i c i n e , n eomyc i n ) Factitious o r "pseudo " diarrh ea

B leeding (melena) M u n ch a u s e n 's/ma l i n g e r i n g ( l a xa tive a b u s e )

Gastroenterology . 1 75

Ne urogenic or altered m o tility

F eca l i n c o n t i n e n c e o r i m pacti o n ( o b st i pati o n ) I rrita b l e bowe l N e u ro l og i c d i se a s e s (e . g . , a uto n o m i c n e u ropat. h i es , ca u d a e q u i n a syn d ro m e ) D i a betes m e l l it u s In flammatory

A I DS-a s so c i a t e d i nfect i o n s (ch ro n i c i nfecti o n s ) C ro h n 's d i s e a s e U l ce ra tive co l it i s R a d i a t i o n e nteroco l i t i s E os i n o p h i l i c g a stroente r i t i s

DYS P H AG I A BITES B l ocked e s o p h a g e a l l u m e n I n t r i n s i c n a rrow i n g o f t h e e s o p h a g u s T h roat/m o u t h d i se a s e ( o ro p h a ry n g e a l dys p h a g i a) E xt r i n s i c c o m p res s i o n of t h e e s o p h a g u s S m o ot h/S t r i a t e d m u s c l e d i s o rd e rs

N otes 1 . There are five primary mechanisms of dysphagia. Blockage of the esopha­ geal lumen results from i m pacted foreign bod ies and swa l lowing too large a food bolus. Processes that cause i ntrinsic narrowing of the esophagus i nclude

herpes virus and other opportu n istic i nfections, esophageal webs and rings, peptic strictures and caustic burns, ben ign and malignant tumors, and Croh n 's disease. Abnormal ities of the throat and mouth cause oropharyngeal dysphagia and i nclude pharyngeal weakness from stroke, lack of saliva from Sjogren's syn­ d rome and lesions affecting the tongue. Extrinsic compression of the esophagus may be caused by a thyroid mass, Zenker's diverticu lum, vascular a nomal ies, or 7 76 • Gastroenterology

mediasti nal tumors. Hiatal hernias predispose patients to both i ntrinsic narrow­ i n g (strictures from G E RD) a n d extri nsic com pression ( i ncarceration of a paraesophageal or sliding hernia). Disorders of smooth muscle (scleroderm a , achalasia, Chagas' disease, diffuse esophageal spasm o r " n utcracker" esopha­ gus) and striated muscle (neurom uscular d iseases, rabies, teta nus) cause motor dysphagia. 2. The symptom of dysphagia may be oropha ryngeal or esophagea l . Oro­ pharyngeal dysphag ia (throat and mouth etiologies) is suggested by a history of other oropharyngeal symptoms including nasal regurgitation , coughing on at­ tempting to swallow and concomitant speech d isturbances Patients with recent stroke are particularly likely to have oropharyngeal dysphagia . 3 . Esophageal dysphag ia is caused by the other fou r etiolog ica l g roups ( blockage, i ntri nsic, extri nsic, and smooth/striated m uscle) Blockage of the esophagea l l u me n , intrinsic narrowi ng, and extri nsic com pression cause me­ chanical obstruction, while diseases of smooth and striated muscle cause neuro­ muscular dysphag i a . Mecha nical and neuromuscular types of dysphagia can usually be d isti ngUished by a brief, but ca refu l , h istory focusing on the type of food i nd ucing dysphagia (solids, liquids) , the pattern of dysphagia ( i nterm ittent, constant and/or progressive), and whether heartburn is present 3 . Dysphagia for solid foods only: This sym ptom sug gests mecha n ical ob­ struction, as fluids a re a ble to traverse the partial ly obstructed esophagus more easily than solids If dysphagia for solid food is i nterm ittent, it may be due to a n esophageal (Schatzki) ring . With esophageal rings, the obstruction is m i l d , and only la rge food bol uses a re obstructed ; hence the intermittent nature of sym p­ toms. Prog ressive dysphagia with a h istory of heartburn suggests peptic esophag itis with or without a peptic stricture. ProgreSSive dysphagia for sol ids without a history of heartburn is characteristic of esophageal tumors. 5. Dysphagia for both solids and liquids: This symptom is cha racteristic of neu rom usc u l a r dys phagia ( m oti l i ty d i sorder), o r adva nced mecha nical ob­ struction preventing fluids from passi ng . ProgreSSive moti lity-type dysphagia is usua lly due to achalasia . Pseudoachalasia , due to tumor i nfi ltrating the myen­ teric plexus, is a rare cause of this symptom . I ntermittent, episodic moti lity-type dysphagia w i th a ssoc i a ted c h est pa i n may i n d i ca te d i ffuse esophageal spasm . In patients from South America , chagasic achalasia should be consid­ ered . Progressive dysphagia with severe associated hea rtburn is seen with scleroderm a . 6 . Physical examination should i nclude a search for cervical a n d supraclaVicu­ lar lym ph nodes and features of con nective tissue d isease . A barium esopha­ gram typically is the fi rst diagnostic test obta i ned . If a motil ity disorder is l i kely, esophageal manometry is obtained and, possi bly, an upper GI endoscopy to rule out pseudoachalasia . If mechan ical obstruction is seen on the barium study, an upper GI endoscopy with biopsy is ind icated . Thoracic CT is useful for d iag­ nosi ng the cause of extri nsic compression of the esophagus. 7>. Here is a comprehensive list of the causes of dysphagia :

Gastroenterology . 1 77

--

O H WH E N EATI N G BITES O ro p h a ry n g e a l dys p h a g i a (stroke, Sjog re n's, to n g u e p a r a l y s i s/i nj u ry) H e rp e s s i m p l ex/o p p o rt u n i st i c i nfect i o n s ( C M V, Ca n d i d a ) Web H i a t a l h e r n i a ( i n c a rc e rated) E so p h a g e a l s p a s m N ut c ra cke r e s o p h a g u s E xt r i' n s i c co m p re s s i o n (thyro i d m a s s , Z e n ke r 's d ive rti c u l u m , a n e u ry s m ) A ch a l a s i a T rypa n a s o m i a s i s ( C h a g a s ' d i se a s e ) I n f l a m m a t o ry bowel d i s e a s e ( C ro h n 's) N e u ro m u sc u l a r d i se a s e s ( myasth e n ia g ra v i s , p o l i o mye l i t i s , A LS, p o l y myo s i t i s ) G E R D /p e pt i c s t r i ct u re B u rn (ca u st i c i n g e s t i o n ) I m pa ct e d fore i g n body T u mo r E so p h a g e a l r i n g S c l e ro d e r m a

H E PAT O M E G A LY B I G H E PA T I C M A S S B u dd-C h i a ri syn d ro m e I nfect i o n s ( v i r a l h e p a t i t i s , E BV, We i l 's d i se a s e , T B , a m e b i c a bs c e s s , hyd a t i d cyst) G a u c h e r 's d i s e a s e/G I ycog e n stora g e d i s e a s e s

1 78 • Gastroenterology

,M

H epatic cysts ( p o l ycys t i c d i se a s e ) E xt ra m ed u l l a ry h e mato p o i e s i s ( i . e . , mye l o p ro l ife rative d iseases) P ri m a ry b i l i a ry c i rr h o s i s A my l o i d o s i s T oxi n s I ron ove r l o a d ( e . g . , h e m och romatos i s ) C o n g estive h e a rt fa i l u re M a l i g n a n cy (e . g . , h e pato m a , m etastat i c tu m o rs , I y m p h o p ro l i fe rat ive d i se a s e s , a d e n o m a ) A l co h o l S a rc o i d o s i s/g ra n u l o m at o u s h e p a t i t i s S ch i stoso m i a s i s (va s c u la r o bstru cti o n )

N otes 1 . A palpable l i ver, hepatomega ly, may i nd icate acute i nfection, toxic damage, infiltration , metabolic d isease, obstruction to bile d ra i nage, or vascu­ lar congestion/obstruction. A pa lpa ble liver may also be detected in patients with COPD where there is downwa rd d i splacement of the l iver and , rarely, when there is an a natomic anomaly (Riedel's lobe). 2. The evaluation of hepatomegaly depends upon the rapidity of enlargement and presenting historicol and clin ical features. In general, assess l iver enzymes, bilirubin, a nd hepatic synthetic function (prothrombin time, albumin), and follow up with i maging studies.

J�U N D I C E BILE B i l i a ry obstruct i o n I n h e rited d i so rd e rs o f b i l e meta b o l i s m L iver pa r e n c h ym a l d a m a g e ( i nfect i o n , tox i n s) E ryth ro cyte destruct i o n Gastroenterology .

&

1 79

N otes 1 . The pathophysiologic mechanisms of hyperbilirubinemia a re outli ned by the B I LE mnemonic ( 1 ) biliary obstruction (i e . , cholel ithiasis), ( 2 ) inherited disor­ ders of bile con i ugation or excretion ( i e , Gil bert's, Dubi n-Johnson , Crig ler­ Naiiar and Rotor syndrome), ( 3 ) liver parenchymal damage ( i nfection, toxins), and (4) erythrocyte destruction (hemolysis, ineffective erythropoiesis) . 2 . Jau nd ice results from hyperbi l i rubinemia and a ppears as yellowi ng of the skin and sclera . Other conditions may cause yellowing (carotenemia) or darken­ ing (Add ison's) of the ski n , but do not ca use scleral icterus. After obta i n i n g a serum bilirubin level and confi rming that skin pigmentation changes are due to iaund ice, the next step is to fractionate the bilirubin i n to unconi ugated ( " i ndi­ rect" )' and con iugated ("direct") fractions. 3. Uncon;ugafed hyperbilirubinemia rarely causes bilirubin levels g reater than 5 mg/d l ; order hemolysis labs (ha ptog lobi n , reticulocyte count, d i rect and indi­ rect a nti-globulin tests, etc . ) if a n other cause is not a pparent. Disorders that cause a predomi nantly unconi ugated hyperbil i rubinemia include eryth rocyte a b­ normalities, sepsis (decreased hepatic u ptake), C H F, and certain in herited con­ ditions (Gilbert's, Crigler-Naiiar types I and I I ) . 4. If t h e patient h a s a predomina ntly con;ugafed hyperbilirubinemia, the next step is to differentiate between liver parenchymal da mage and biliary obstruc­ tion . liver parenchymal i n i u ry ca uses very h i g h levels of tra nsa m i nases : AST (SGOT) and ALT (SGPT) Biliary obstruction has a lesser i ncrease iri transa m i­ nases and a more rema rka ble elevation of a l ka l i ne phosphatase (and 5 ' nu­ cleotidase, if obta i ned) If bil iary obstruction is suspected , then d ifferentiate between intra-hepatic and extra-hepatic biliary obstruction by i maging studies, often ultrasonography. Disorders that cause a predominantly coniugated hyper­ biliru binemia incl ude hepatocellular destruction ( i nfection , d rugs), bil iary obstruc­ tion (stones, anomal ies of the bile d uct, cancer, sclerosing cholangitis), and a few i nherited disorders of bile excretion (Dubinjohnson , Rotor) . 5 . Here is a more complete list of etiologies of iaundice :

I ' M P A G I N G M R S W H I P P L E S TA T I n fe c t i o n ( e . g . , v i ra l h e patit i s , s e p s i s , l e ptos p i ro s i s , Clonorchis, Ascariasis)

M ed i ca t i o n s/d r u g s P osto p e rat ive c h o l esta s i s A l p h a - 1 a n ti-tryps i n defi c i e n cy G a l l st o n e s 180 • Gastroenterology

b

I nj u ry/tra u m a ( h e m o b i l i a ) N eo p l a s m s ( e . g . , ch o l a n g i o c a rc i n o m a , p e r i a m p u l l a r y c a rc i n o m a , carc i n o m a h e a d o f pa n c r e a s ) G ra n u l o m a t o u s/i n f i l t ra t i ve d i s e a s e (e . g . , s a rc o i d o s i s ) M a l fo rm a t i o n o f t h e b i l ia r y t r e e (atre s i a , s t r i ct u re , c h o l e d o ch a l cyst, etc . ) R eye's syn d r o m e S c l e ros i n g ch o l a n g it i s W i l s o n 's d i s e a s e H e red i t a ry d i se a s e s ( G i l be rt 's , D u b i n-Jo h n s o n , R oto r syn d ro m e , C r i g l e r- N aj j a r) I ro n ove r l o a d P re g n a n cy-re l ated ( ch o l esta s i s of p reg n a n cy, p re-ec l a m ps i a , a c u te fatty l iver of preg n a n cy) P ri m a ry b i l ia ry c i rr h o s i s L a e n n e c 's c i r rh o s i s (a l co h o l i c ) . E ryth rocyte d e st r u ct i o n S ta rva t i o n/fa s t i n g TPN A u to i m m u n e h e patitis T oxi n s

N AU S EA A N D VO M I T I N G I VO M IT I n c re a s e d i nt r a c ra n ia l p r e s s u re/C N S d i se a s e Vascular O bstructive M et a b o l i c/tox i c I nfect i o u s T ra u m a t i c

Gastroenterology .

181

N otes 1 . Nausea and vom iting a re very common symptoms and may be associated with any of the causes of a bdominal pa in (see Abdominal Pa i n section ) . In fact, these symptoms often occu r together. When na usea and vom iting are the pri­ mary symptoms, however, a different prioritization of diag nostic possibil ities­ summa rized by the m nemonic I VOMIT (see a lso Pa n c reatitis section ) - is a ppropriate. Increased intracranial pressure, as occurs with intracerebral hem­ orrhage, can cause nausea and vom iting . Vascular etiolog ies i nclude mesen­ teric ischemia, myoca rd ial ischem i a , and m igraine headache. Obstruction of the GI tract (e.g . , adhesions, volvu lus, intussusception) and pseudo-obstruction (e. g . , scleroderma, gastroparesis) a re com mon causes of nausea and vom iti ng . Metabolic/toxic causes i n clude pregnancy, hyperca lce m i a , adrenal i nsuffi­ ciency, kid ney fai lure, d rugs, and diabetic ketoacidosis. Infectious etiologies in­ cl ude gastroenteritis, a ppendicitis, a bscess, Helicobacter pylori, sepsis, and mening itis. Finally, trauma to the abdomen, either extrinsic or related to surgery, a re easily recognized causes of nausea and vom iting . 2 . Seek a history of headaches or nE:uroiogical symptoms, as these may poi nt toward a eNS cause of nausea and vom iti n g . Abdom inal pa i n preceding the vom iting may help localize an i ntra-abdom inal i nflam matory process (e. g . , epi­ gastric pa i n with pancreatitis, right upper q uadrant pa i n with cholecystitis, right lower quadrant pain with append icitis). Undigested food in the vom itus may help localize the etiology to the stomach, but ca nnot d istinguish m echan ica l obstruction from gastroparesis. Fecu lent vom itus suggests bowel obstruction or fistula . 3 . In addition to perform ing a general physical examination, measure orthosta­ tic changes in pulse and blood pressure to estimate the degree of dehydration. Orthostatic changes may also be due to autonomic dysfunction in diabetic pa­ tients, or due to d rug therapy. 4 . Abdominal exam i nation should esta bl ish the presence or a bsence of d isten­ sion . An absence of bowel sounds on a uscultation may indicate an i leus or an i nfla mmatory condition with peritonitis. Pa l pation of the a bdomen helps d istin­ guish the two, as localized tenderness with guarding is present in i nflammatory cond itions. The local ization of pa i n a n d tenderness may i nd icate the organ system i nvolved .

OH GOD AM I SICK O bstet r i c a l ( p re g n a n cy, h y p e re m es i s g ra v i d a ) H yp e rca l ce m i a

1 82 • Gastroenterology

G a st r o e n t e r i t i s ( b a ct e ri a l a n d v i ra l ) O bstruct i o n ( a d h e s i o n s , vo l v u l u s , i nt u s s u scepti o n , peptic s t r i ct u r e s , tu m o rs ) D i a betes ( D KA, g a stropa res i s ) A d re n a l i n s uff i c i e n cy M ed i cati o n s ( o p i ates, a nt i b i ot i c s , N SA I D s , ch e m o t h e ra pe u t i c a g e n t s , a n t i a rrhyt h m i cs ) I n t ra-a b do m i n a l i n f l a m m a t o ry co n d it i o n s ( p a n crea t i t i s , ch o l ecysti t i s , a p p e n d i c i t i s , t ra u m a ) S c l e ro d e rma ( a n d oth e r p s e u d o-obst ru ct ive states) I sch e m i a ( m es e n t e r i c , myoca rd i a l ) e N S d i se a s e ( m i g ra i n e s , i n creased i nt r a c ra n i a l p re ss u re , m e n i n g i t i s , stroke) K id n ey fa i l u re

C l inica l Conditions or Diagnoses

P A N C R E AT I T I S VOMIT Vascular O bst ru ct ive M et a bo l i c/toxi c I nfect i o u s T ra u ma t i c

N otes 1 . The VOMIT m nemonic (see Nausea and Vomiting section) can be used to classify the causes of pancreatitis. Vosculor causes of pancreatitis include necrotizing Gastroen terologv . 1 83

-

vascul itis, atheroemboli, and TIP. Obstructive causes of pancreatitis incl ude bil­ iary disease/cholelithiasis, pancreas divisu m , ampullary malig na ncies . Crohn 's d isease, sphi ncter of Oddi dysfunction , Ascariasis infestation , duodenal divertic­ ulum and ( probably) cystic fibrosis. Metabolic/toxic processes causing pancre­ atitis include a lcohol, d rugs, renal fa ilure, acute fatty liver, scorpion sting, Reye's syndrome, hyperca lcemia, and hypertriglyceridem ia. Infectious causes of pan­ creatitis i nclude m u mps, other viral i nfections, Reye's syndrome (a lso a toxic/metabolic process) , Mycoplasma and Ascariasis (obstructs pancreatic out­ flow). Traumatic caus�s of pancreatitis include external trauma, ERCP, surgery, erosion of duodenal ulcer, and after renal transplantation (the latter a lso may be considered toxic/metabolic) . 2. The most com mon causes of acute pa ncreatitis a re ( 1 ) bil iary obstruction by gall stones, ( 2 ) alcohol toxicity (these fi rst two account for approximately 90% of cases), and ( 3 ) drugs, which account for a bout 5% of cases ( "BAD") . Other ia­ trogenic causes ( e . g . , ERCP, post-operative, and ca lcium a d m i n i stration) a re being increasingly recogn ized . 3 . An i m portant d iag nostic test is the a mylase level, a lthough a normal level does not rule out pancreatitis. The lipase level may have somewhat g reater sen­ sitivity and specificity in the diag nosis of acute pancreatitis. 4. Other non-pancreatic conditions wh ich cause an elevation of serum amylase include renal insufficiency, salivary gland disease, macroamylasemia, DKA, cer­ ta in tumors ( l u n g , esophagus, ova ri a n ) , bu rns, ectopic pregna ncy, and other intra-a bdominal disorders (perforated viscus, penetrati ng ulcer, peritonitis). 5. Serial measu res of serum amylase a re not helpful , and patients are best fol­ lowed clinical ly. Urine amylase esti mation is only helpful for making the diagno­ sis of macroamylasemia. In this cond ition , the a mylase com plex is too large to be filtered into the urine, and u rine levels a re low i n contrast to elevated serum levels. 6 . Ra nson's criteria for pa ncreatitis may be used for p rognosis. " H E LLO RANSON" lists these factors : Within 48 Hours On Admission Hyperglycemia Renal fa ilure (BUN i ncrease > 5 mg/dl) (Glucose > 200 mg/ dl) Anemia ( hematocrit d rop > 1 0 mg/dl) Elevated AST > 250 u/I No calciu m « 8 mg/dl) Leu kocytosis Sequestration (> 4 L fluid) (WBC > 1 6, 000/m m 3 ) LDH > 350 u/I Oxygen d rop ( P02 < 60 mmHg) No albumin « 3 . 2 g/d l) Older patients (Age > 55 years) Patients with only one of these factors have an i ncreased risk of complications; those with two risk factors may have a mortality rate as high as 2 0-30%; and those with six to seven risk factors have a nearly 1 00% morta lity rate. I n patients with gal lstone-assoc iated pancreatitis, the prog nosis is genera l ly better, a n d modified criteria have been proposed . Other ind icators o f poor prog nosis in­ cl ude acidosis (base deficit > 4 m mol/L), hypotension (BP < 90 mmHg), tachy­ cardia ( heart rate > 1 30), oliguria « 50 cc/hr) and hemorrhagic peritoneal fluid ("toxic broth"). An APACHE II score > 1 2 is a lso predictive of more severe disease, 184 • Gastroenterology

a lthough it is a com plex and seldom used calculation . The i m portance of risk stratification is that high-risk patients should be mon itored more closely and a re candidates for earlier interventional therapy (surgica l , radiolog ic, endoscopic) . 7. The treatment for pancreatitis is largely supportive , with fl u id resuscitation . and ana lgesia . The pancreas is rested by eli minating oral intake. Monitoring for complications ( i nfection , hemorrhage, hemodynamic collapse, respi ratory fa il­ ure, hypoca lcem ia, hyperglycem ia ) is critica l . There are no proven benefits for routine nasogastric suction, peritoneal lavage, administration of antibiotics, or therapy with other medications. In cases of gal lstone pancreatitis, i m med iate re­ mova l of stones in severely ill patients may improve outcome. Other invasive therapies a re reserved for severely ill patients with specific com plications (e . g . , a bscess, pseudocyst, phlegmon ) . 8 . The fo l lowi n g m n e m o n i c l i sts m o s t of t h e causes a n d a ssociations for pa ncreatiti s :

B A D PA N C R EATI T I S C RAS H ES H A R D B i l i a ry d i s e a s e (ch o l ed o ch o l it h i a s i s ) A lcohol D ru g s/tox i n s P a n c re a s d i vi s u m A m p u l l a ry m a l i g n a n cy ( a d e noca rc i n o m a o f t h e pa n c rea s , p r i m a ry a m p u l l a ry, etc . ) N ecrotiz i n g va s c u l it i s ( l u p u s , p o lya rte r i t i s n od o s a ) C ys t i c f i b ro s i s R eye's syn d r o m e E RC P A t h e ro e m b o l i T ra u ma I nfect i o n (vi ra l , p a r a s i t e s , bacte ria l ) TTP I d i o p at h i c/i n h e rited S u rg e ry ( posto p e rative pa n creati t i s , e s p e c i a l l y post card i o p u l m o n a ry bypa s s )

Gastroenterology . 1 85

--

C ro h n 's d i s e a s e R e n a l fa i l u re A c ute fatty l ive r of p re g n a n cy S co r p i o n st i n g H yp e rca l c e m i a E ros i o n o f d u o d e n a l u l c e r S p h i n ct e r of O d d i dysf u n c t i o n H y p e rt r i g lyce r i d e m i a A sca r i a s i s R e n a l t ra n s p l a n t D u o d e n a l d iv e rt i c u l u m

1 86 • Gastroenterology

13

R H EUMATOLOGY Clinical Sym ptoms and Signs

AC U T E M O N OA R T H R I T I S HIS G O UT FIT* H e m a rt h ro s i s ( c oa g u l o pathy, e . g . , h e m o p h i l i a ) I n fect i o n ( b a cteri a , [e . g . , g o n ococc u s ] , myc o b a cte r i a l , f u n g a l , Lym e d i s e a s e , v i ra l ) S ystem i c i l l n e s s ( R e i t e r 's , S L E , r h e u m a t o i d a rt h ri t i s , p s o ri a s i s , s a rc o i d , B e h ge t 's ) G o u t/ps e u do g o u t O steoa rt h r i t i s U l c e rative c o l i t i s/C ro h n's T ra u m a/fo re i g n body s y n ov i t i s F i b r i n d e p o s i t i o n ( pa l i n d ro m i c a rt h r i t i s ) I sch e m i c n ec ros i s T u m o r ( m et a s t a t i c , pri m a ry) *

Differential diagnosis

N otes 1 . Acute pa in and swelling i n a joint req u i res i m med iate eva l uation a n d , in almost all cases, im mediate arthrocentesis to rule out infection . Rheumatology .

1 87 .

2 . The age of the patient, history of other d isease or symptoms (gastroenteritis), fa m i ly h istory, and sexual h istory m ust be carefully evaluated . Physical exa m i na­ tion is performed to look for signs of infection (skin cha nges) o r evidence of other systemic ill ness. Consider cu lture of the throat, u rethra, and rectu m in indi­ viduals suspected of gonococcal infection 3. Examine joint fluid by g ram sta i n and polarized light i n itia lly, and send for a culture and cell count. Normal synovial fluid contains fewer than 1 1 0 cells/mm 3 , most of which a re mononuclea r. F l u id is cOhsidered " n o n i nflam matory" if i t conta ins less than 3000 cells/mm 3 As the cel l count increases, s o does the sus­ picion of i nfectio n . Effusions with more than 1 00 , 000 WBC/mm 3 a re con­ sidered septic, but there is a wide range of possible va lues . Careful exam i nation of fluid for crystals may esta blish a d iagnosis early and obviate the need for hos­ pital ization . The presence of crystals, however, does not exclude infection, and if there is sti ll a q uestion of infection , the patient should be adm itted for a ntibi­ otics until cu lture results a re ava i lable. (See ta ble i n I nfla m matory Polya rthritis section . ) 4 . A freq uent diag nostic dilemma i nvolves d ifferentiati ng i nfections from other acute i nfla m matory a rthritides . Patients should be admitted for i ntravenous anti bi­ otics while awa iting cu lture results. N SAIDs should be withheld initially to j udge the response to antibiotics alone.

I N F L A M M AT O R Y P O LYA R T H R I T I S A G G RAVAT E D S Y N OV I A L J T S * A d u lt Sti l l s ' d i s e a s e G o u t/ps e u d o g o u t G o n ococce m i a R h e u m a t o i d a rt h ri t i s A c u t e r h e u m a t i c feve r Vascu litis A my l o i d o s i s T u be rc u l o s i s E n d oca rd i t i s D e rmatomyo s i t i s/polymyo s i t i s

1 88 • Rheumatologv

b

S yste m i c l u p u s e ryt h e ma t o s u s Y e rs i n ia , Ca m py l o b a ct e r, S h i g e l l a ( Re i t e r 's) N o n-g o n ococca l u reth ritis ( R e ite r 's) O ve r l a p syn d ro m e s (e . g . , m i xed c o n n ective t i s s u e d i sease) V i ra l i nfe ct i o n s ( reactive) I n f l a m m a t o r y bowe l d i s e a s e A I DS Lyme d isease J uve n i l e r h e u m a t o i d a rt h r i t i s T re p o n e m a l i n fect i o n (syp h i l i s ) S a rc o i d o s i s Also: scleroderma, polymyalgia rheumatica, psoriasis, intestinal bypass surgery, hemochromatosis *

This m nemonic provides the differential diagnosis.

N otes 1 . A q U ick and easy etiolog ic way to look at i nfla m matory polyarthritis is as follows a . Infection - d irect infection of joint ( bacteria, syphilis, TB, etc . ) b. Crysta l-ind uced (gout, pseudogout) c. Immunologic ( RA, SLE, vasculitis, etc) d . Reactive - i n response to infection elsewhere in body (Reiter's synd rome, AIDS, etc . ) e . Id iopathic (ankylosing spondylitis) 2. Work-up of inflammatory polyarth ritis includes: a. Laboratory studies: CBC, E S R , C R P may help distinguish i nfla m ma tory from noninfla m matory conditions. b . Synovial fluid aspiration is a lways ind icated when either an i nfectious or crysta l-i nduced i nfla m matory a rthritis is being considered . Normal viscosi ty is such that when expressed from a syri nge, each d rop has a long ta i l or string attached . R BCs a re not generally seen i n synovial fl u id except i n a settinq of hemarthrosis or trauma.

Rheumatology . 1 89

Synovial F l u i d Characteristics

Noninflammatory Arthritis

Crystal-Induced Arthritis

Infectious Arthritis

Appearance W BC

Clear

Tu rbid, yel low 3000-50,000

Turbid, opaque > 50,000 cells/ml

Differential

Mostly mononuclear cells

Mostly PMNs

Mostly PMNs

Glucose

Normal (within 1 0- 1 5 mg/dl of serum values)

Normal or low

Low

Protein

Normal

Normal or high

High

Viscosity

Good , stri nging of fluid

Poor, no stri ng ing

Poor, no stringing

Crysta ls

No

Yes

No

Gram stain/ culture

Negative

Negative

Positive

<

3000

cells/ ml

cells/ml

c. Specific serologic tests seek RF, ANA, com plement levels, ASO titers, etc. only when a specific diag nosis is suggested ; these tests are not useful as screen­ ing tools. d. Rad iograph ic tests i nclude • X-rays are ind icated with history of trauma, suspected chronic i nfection, monoa rticular i nvolvement, or progressive disabi l i ty. For i nfla m matory disorders, findings i nclude primarily soft tissue swell i ng and periarticular dem i neral ization. I n chronic disease, ioint space na rrowi ng, calcifica­ tion , osteophyte formation, and subchondral cysts may be seen. • Radionucl ide scans may show increased uptake i n synovitis, i nfection, or maligna ncy. Osteonecrosis may be seen as decreased uptake .

. 1 90 • Rheuma tology

d

C linica l Conditions or Diagnoses

C A L C I U M P Y R O P H O S P H AT E D I H Y D R AT E D E P O S I T I O N D I S EAS E H OW I GOT BA D CPPD H yperparathyro i d i s m O steoa rt h ri t i s W i l so n's d i se a s e I ron ove r l o a d G out O ch ro n o s i s T hyro i d d i s e a s e ( hypoth y ro i d i s m ) B owe l d i se a s e ( C r o h n's, u l c e ra tive c o l i t i s ) A c ro m eg a l y D i a betes C o n g e n it a l hypoca l c i u r i c hyperca l c e m i a P a g et 's d i s e a s e P ost-tra u ma t i c D i s e a s e rese m b l i n g r h e u m ato i d a rt h r i t i s Also. amyloidosis, hypophosphatemia, hereditary calcium pyrophosphate dihy­ drate deposition (CPPD)

N otes 1 . There are numerous reported disease associations of CPPD (or pseudogoutl, but the importance of some is debatable, as rigorous, controlled studies are not

Rheumatology . 1 9 1

s

ava i la ble. However, i n patients with CPPD, consideration must be g iven to the possibi lity of an u nderlyi ng disease process. 2 . One characteristic feature of this disease is patellofemoral joint disease with a normal femoral/tibial joint. 3. Screening work-u p usual ly i ncludes TSH , calciu m , and gl ucose levels. Also consider ferritin and ceruloplasmin .

C R E ST SY N D R O M E CREST* C a l c i n o s i s c ut i s R ay n a u d 's s y n d r o m e E so p h a g e a l dys m ot i l ity S c l e rodactyly T e l a n g i e ct a s i a * The mnemonic presents clinicol characteristics.

N otes 1 . Anti-centromere antibodies are seen in a high percentage of patients with CREST, but few patients with scleroderma/systemic sclerosis. 2. Calci nosis cutis descri bes i rreg ular cuta neous papu les that a re f i rm a nd white . 3 . Raynaud's phenomenon involves episodic vasoconstriction o f the small ar­ teries and arterioles of the digits. Triggers i ncl ude cold , vibration, and stress . An i n itial vasoconstrictive event leads to whitish pallor i n affected areas associ­ ated with the sensation of coldness, ti ngling, or pa i n . A cyanotic ( blue) phase may occur, and the episode eventually ·resolves with a period of reactive hyper­ emia ( red) . 4. Esophageal dysmotility may man ifest as dysphag ia, heartbu rn, regurg ita­ tion, and/or a sensation of epigastric fullness. 5. Sclerodactyly i nvolves ta ut, thinned skin over the d ig its, which may often have a tapered appea rance. It eventually leads to dimin ished joint movement. 6. Telangiectasia features superficial cutaneous ca pillary malformations. 1 92 • Rheumatology

b

d

O ST E OA R T H R I T I S I G OT M R . PAI N , DOC* I d io pa t h i c p r i m a ry osteoa rt h r i t i s G o ut O cc u p a t i o n a l/s p o rts T ra u m a , a c u te/f ra ctu re M et a bo l i c ( h e m o ch ro ma tos i s , W i l so n's , G a u c h e r 's , och ro n o s i s ) R h e u ma t o i d a rt h r i t i s P so r i a t i c a rt h r i t i s A c r o m e g a l y/e n d o c r i n e (hype rpa rathyro i d i s m , D M , o b e s ity, hypothyro i d ) I nfect i o n N e u ropat h i c D eve l o p m e n t a l ( Leg g-Ca l ve-Pert h e s , co n g e n it a l h i p d i s l ocati o n , etc . ) O steopetro s i s/osteoc h o n d ri t i s C a lc i u m deposition d i sease *

Differential diagnosis

N otes Osteoa rth ritis (OA) is a disease or pathology of movable, synovial joi nts. It is synonymous with degenerative joint d isease Heberden's nodes a re bony enla rgements of the d istal interphalangeal joints . They are the most common form o f id iopathic osteoa rthritis. Bouchard's nodes a re bony enlargements of the proximal interphala ngea l joi nts. ,

1 . OA may be classified as primary or secondary. Prima ry OA occurs in the

absence of an identifiable underlying etiology. Secondary OA is due to an u n­ derlying condition or d isease. Rheumatologv . 193

...

2 . Locations of OA:

a. Interphalangeal ioi nts: Heberden's and Bouchard's nodes b. H i p : most cases are secondary and d ue to congenital or developmenta l defects. c. Knee : • Varus deformity (bow-legged) due to medial comportment OA • Valgus deformity (knock-kneed) due to lateral compartment OA • Chondroma lacia, a syndrome of knee pa in, usually occurs in younger patients and is not generally prog ressive to true OA . d . Spine • Spondylosis- degenerative disk disease • Diffuse id iopath ic skeletal hyperostosis-calcification and ossification of paraspinous ligaments • Osteoarth ritis of the spine - degeneration of mova ble, synovial-li ned spinal ioints 3 . Clinical signs and symptoms a. Pa i n has gradual onset, dull aching. joint tenderness and pa in occur with range of motion . b. Morn ing stiffness is not prom inent, as in infla mmatory rheumatic disease. c. Crepitus is a g rinding sound or sensation hea rd or felt as ioint is moved . d . joint enlargement may be due to soh tissue swelling/effusion or osteophytes. e. joint deformity, such as Heberden's and Bouchard 's nodes, varus or valgus angulation 4. Work-up of OA a . X-rays of affected ioi nts - may be normal, or show ioint space na rrowi ng, subchrondral sclerosis, subchondral cysts, and marginal osteophytes. b. Ro utine la boratory tests help identify causes of secondary OA, including ESR, CBC, seru m chem istries, u rina lysis. c. Synovial fl u i d : m i ld leukocytosis « 2 000 WBC/ml, < 25% PMNs), no crysta ls, good mucin clot. 5. Charcot ioi nts - secondary OA d ue to underlying neurologic disease.

R H E U M AT O I D A R T H R I T I S RF RISES R h e u m a t o i d facto r e l evated F i n g e r/ha n d j o i nts i nvo lved

1 94 • Rheumatology

R h e u m a t o i d n od u l e s I nvo lve m e n t of t h ree o r m o re j o i nts S tiff n e s s , m o r n i n g E ro s i o n s/d eca l c i f i cati o n s o n X-rays S y m m et r i c ( b i l a t e ra l ) a rt h r i t i s

N otes Rheumatoid a rthritis (RA) is a chronic multi-system disorder characterized by in­ flammatory joint disease, usua lly symmetric.

1 . Diag nostic criteria

a. Four of the seven criteria a bove are needed to d iag nose RA. b. Patients with two or more other clinical d iagnoses a re not excluded . 2 . Elevation of serum rheumatoid factor can be determ i ned by any method that has < 5% false positive rate . 3 . Finger/hand joint involvement incl udes arthritic changes in the wrist and the metacarpophalangeal (MCP) or proximal i nterphalangeal (PIP) joints. 4. Rheumatoid nodules a re fir m , round, subcutaneous nodules over the joints, extensor surfaces, or bony prominences. They a re seen i n 20-25% of patients. 5 . Multiple joint i nvolvement (of three or more) refers to soft tissue swelling or joint effUSions, not j ust osteophytes. Fourteen possi ble areas a re descri bed : right or left proxi mal i nterphalangea l , metacarpopha langea l , wrist, el bow, knee, ankle, and metatarsophalangeal joi nts. 6. Morning stiffness is defined as a joint stiffness upon awakening that persists 1 hour before maximal i mprovement. 7 . Radiographic findi ngs in hand and wrist x-rays must i nclude erosions or bony decalcification in or ad jacent to affected joi nts. 8. Symmetry means simultaneous involvement of the sa me joint bilatera lly. 9. Signs and symptoms: a. Joint man ifestations • Generalized : pa i n , joint swelling, effUSion, wa rmth , and lim ited range of motion . • Cervical spine: most serious is atla ntoaxial su bl uxatio n . May cause nerve root impi ngement, spinal cord symptoms, or even lower bra i n­ stem problems. • Cricoarytenoid joint: i m pairs voca l cord mobil ity, cause hoarseness. • Shoulder: synovitis and rotator cuff injury. • Elbow: rheumatoid nodules on extensor surface of forea rm lead to ole­ cranon bursitis. • Ha nd/wrist: typ ically d ista l interphala ngeal (DIP) joi nts a re spa red . Swan neck deformity is flexion at the DIP and MCP joints and hyper­ extension at the PIP joi nts . Boutonniere deformity is DIP hyperextension Rheumatology . 195

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with PIP flexion . Carpal tunnel syndrome is not uncom mon . Ulnar drift is a deformity characterized by PIP flexion and deviation of the fi nger­ tips toward the ulna • Hip: may manifest with g roin pa i n . Severe involvement is rare (5%) • Knee: very com mon . Boker's cyst is a posterior hern iation ' of synoviu m a n d fluid from the knee into the popliteal fossa . • Ankle/foot Common i n both a n kle a nd foot. Cock-up toe deform ity occurs at the metata rsophala ngea l l oint. b. Systemic man ifestations include weight loss, fatigue, achi ness, anorexia , malaise. c . Other organ involvement i . Rheumatoid nodu les: see number 4, previous page i i . Eye manifestations: Sicca complex is burning, gritty eye sensation; d ry mouth; and sal ivary gland enlargement. Episcleritis and scleritis may a lso occur. i i i . Card iac: rarely clinically sign ifica nt, but include pericard itis and in­ fla mmatory g ranulomas. iv. Pul monary: pleuritis, pleural effusions, i nterstitial fi b rosis and nodules. Coplon's syndrome consists of i nterstitial fi brosis and multiple nodules . v. Neu rologic: entra pment neuropath ies (carpal tunnel) , occasional vas­ cul itic com plications. vi . Hematolog ic: anemia, throm bocytosis (500-700 KI, m i ld leu kocyto­ sis. Felty's syndrome is a com bi nation of RA, throm bocytopenia, leukopenia, and splenomegaly. vi i . Vasculitis: cutaneous, neuropath ic, or visceral i nvolvement with is­ chemic com plications. 1 0 . Diag nostic work-up a . CBC - normochromic, normocytic anem ia. Also throm bocytosis, elevated ESR, i ncreased IgG, and even eosi noph ilia. b . Rheumatoid factor- pOSitive i n 70-8 0% . N onspecifi c . ANA positive ( 2 5% of patients) and VDRL false positive (5- 1 0%) c. Synovia l fluid - WBC 5000-2 5 , 000, mostly PMNs. Glucose low and complement levels low. No crystals. d. X-rays - approximate symmetric i nvolvement, osteopenia/deca lcification , soft tissue swelling, bony erosions, joint space na rrowi n g .

1 96 • Rheumatology

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SYST E M I C S C L E R O S I S (SCLE RO D E R MA) SCLERODERMA* S kin changes C a rd i a c i nvolve m e nt L u n g i nvo l ve m e n t E so p h a g e a l dysfu ncti o n R ay n a u d 's p h e n o m e n o n O bstruct i o n , p s e u d o­ D ry eyes/ m o u t h E n d o c r i n e ( hypothyro i d i s m ) R e n a l fa i l u re M yo p a thy/myos i t i s A rt h r i t i s *

Clinical characteristics

N otes 1 . Skin changes include early swel ling, particula rly of the fingers and hands. Later, skin becomes firm and thickened . Chron ical ly, skin becomes th in and at­ roph ic. Skin over the fi ngers become taut, and contractu res l i m i t movement. Other cutaneous man ifestations include telang iectasia, subcutaneous calcifica­ tions, sa lt-and-pepper pigmentary changes, abnormal nail bed capilla ries, and skin ulcers . 2 . Cardiac involvement i ncludes perica rditis, pericard ial effusion, hea rt fa il­ ure, and heart block!a rrhyth m i a . Myocard ial fibrosis ca using cardiomyopathy Occurs in < 1 0%. 3 . Lung involvement occurs in two-th i rds of patients and is often manifested by exertional dyspnea and d ry, nonproductive cough. Additional com pl ications in­ clude pulmonary fibrosis, aspiration pneu mon ia, decreased vital capacity, and decreased lung com pliance. Pulmonary hypertension in the a bsence of fibrosis can occur in < 1 0%. 4 . Gastrointestinal dysmotility is related to neuromuscu la r dysfu nction This may manifest as hea rtbu rn , dysphag i a , reflux/reg u rg itation , delayed gastric Rheumatology . 197

th

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emptying, bloati n g , a bdom inal pa i n , and pseudo-obstruction . Bacterial over­ growth can lead to mala bsorption syndrome. 5. Hypothyroidism may occur a nd is due to either antithyroid a nti bod ies or fibrosis. 6. Renal failure may occur i nsid iously or as a renal crisis . Renal crisis is char­ acterized by m a l i gnant hypertension, hypertensive encepha lopathy, severe headache, retinopathy, seizures and left ventricular fa ilure. This occurs due to overactivation of the ren in-angiotensin system. Renal fa ilure is the leading cause of death in systemic sclerosis. 7. Muscular effects of scleroderma include d isuse atrophy, myopathy without enzyme a bnormalities, and, rarely, a polymyositis-like syndrome. 8. Polya rthritis is manifested by pai n , swelling, and stiffness - particularly i n the hands, fingers, and knees in more than 50% of patients. Tendon sheath fibrosis may become a problem, and can lead to carpal tun nel syndrome when it occurs in the wrist.

SYST E M I C L u p u s E R Y T H E M AT O S U S ORDER H IS ANA O ra l u l c e rs R as h ( m a l a r) D i.s c o i d ras h E xa g g e rated p h otose n s itivity R e n a l d i se a s e H e m a to l o g i c a b n o rma l it i e s m m u n o l og i c a b n o r m a l i t i e s S e ro s i t i s

I

A rth ra l g i a s/a rth r i t i s ( n o n e ro s i ve) N e u ro l og i c d i se a s e A nti-n u c l e a r a n t i body

198 • Rheumatology

b

N otes 1 . The d iag nosis of SLE depends u pon the presence of fou r or more of the above 1 1 criteria . The d isease, however, may involve a ny organ syste m . 2. The findi ngs o f oral ulcers, m a l a r rash, d iscoid rash, exaggerated photosen­ sitivity, and a rthritis are obta i ned by history and physical exa m i nation . Neu ro­ log ic criteria include seizures and psychosis ( i n the a bsence of other d rugs or preCi pitants). Renal disease is defined as persistent proteinuria or cellular casts. Serositis may be manifested as pleuritis or pericard itis. Immunolog ic criteria for diag nosis include a positive LE cell prepa ration, anti-DNA antibodies, a nti-SM antibodies, or a false-positive serologic test for syph ilis. Hematologic criteria i n­ clude hemolytiC anemia, leukopenia, lym phopenia , or thrombocytopen ia . 3 . Other manifestations of SLE include fever, pancreatitis, hepatitis, retinal d isease, myocardial disease (myocarditis, endocarditis), gastrOintestinal disease, pulmonary disease (diffuse infi ltrates, vascul itis), and coagulopathy (lupus a nticoagulant) .

VA S C U L I T I S WHAM ! A N G I ITIS * W e g e n e r 's g ra n u l o ma to s i s H yp e rs e n s i tivity vasc u l it i s ( H e n och-Sch b n l e i n ) A ss o c iated with syste m i c d i s e a s e , r h e u m a t i c d i s e a s e , neoplasm M u cocuta n e o u s l y m p h n o d e syn d ro m e ( Kawa s a k i 's ) A l l e rg i c a n g i i t i s ( C h u rg-Stra u s s d i se a s e ) N od o s a , p o l ya rt e r i s G ia nt c e l l a rt e r i t i s (te m po ra l a rt e r i t i s ) I atro g e n i c/d rug-i n d u c e d I nfecti o n T a kaya s u 's a rt e r i t i s I so l ated C N S va s c u l it i s S erum s ickness *

Differential diagnosis

Rheumatology . 1 99

N otes Vascul itis is a disorder characterized by inflam mation and damage to blood ves­ sels, often resulting in ischemia to tissues supplied by affected vessels. It may occu r as a primary manifestation of disease or in combi nation with other patho­ logic processes, and may be limited to one organ or affect multiple organs.

1 . Wegener's g ranulomatosis vascu l itis usually affects small vessels and is classically associated with u pper and lower respiratory tract involvement and glomerulonephritis (see Wegener's section ) . 2 . Hypersensitivity vasculitis is a broad group of d isorders believed to b e d ue to a. reaction to a particu lar (endogenous or exogenous) a ntigen and involving small vessels. a. Henoch-Schon lein purpura - palpable purpura (usually on buttocks and lower extre m ities) , arthralgias, GI sym ptoms, and g lomerulonephriti s . More com mon in children. b. Associated with other primary diseases - often con nective tissue diseases (SLE, RA, S iogren's syndrome), malignancies ( lymphoid or reticuloendothelia l , hairy cell leukem ia), o r other ill nesses (cryoglobulinemia, pri mary biliary cirrhosis, alpha l antitrypsin deficiency, ulcerative colitis, and intesti nal bypass surgery) . c. latrogenic/drug-induced - penicillin and sulfa may ind uce a serum sick­ ness-like reaction. d. Infection subacute bacterial endoca rd itis, E pstein-Barr virus, hepatitis e. Serum sickness - fever, u rtica ria, a rth ra lg ias, a n d lym phadenopa thy 7- 1 0 days after primary exposure or 2-4 days after secondary exposure to for­ eign protein. 3 . Mucocutaneous lymph node syndrome ( Kawasaki 's) �acute; fever, cervi­ cal adenitis, con i u nctiva l edema , orol ingual a nd pa lmar erythemia , fingertip desq uamation; occu rs in c h i ld re n . Da nger is later development of coronary artery aneurysms. Treat with IV i m munoglobulin and aspiri n . 4 . Allergic angiitis (Churg-Strauss) i s characterized by hypereosi nophilia, aller­ gic rhinitis/asthma, and small-medium vessel vasculitis involVi ng two or more extra­ pulmonary sites . 5 . Polyarteritis nodosa ( PAN ) - small-medium vessel arteritis involving m ultiple organ systems, i ncluding renal (60%), m uscu loskeletal (64%), peripheral nervous system (5 1 %), GI tract (44%), skin (43%), card iac ( 36%�, gen itourinary ( 2 5%), and CNS (2 3%) . . 6. Giant cell arteritis (temporal a rteritis) - large vessel a rteritis associated with fever, anemia, headache, and elevated ESR. Usua lly in elderly patient. Da nger i is development of ama urosis fugax and retinal ischemia . Diagnosed clin ica l ly and confirmed by temporal a rtery biopsy. Treated with prednisone. · 7. Takayasu's arte r itis - medium-Ia rge vessel arteritis, more prevalent i n East Asia, and more l i kely in the aortic a rch or its d i rect branches. Manifestations are I usually ischemia in distribution of affected a rteries (i nclud ing cerebral infarction). I -

i

1 200 • Rheumatology

8 . Isolated eNS vasculitis- usually or/erioli/is, but any size vessel may be af­ fected Diag nosed by ang iogra phy and bra i n/meni ngeal biopsy. Associated with CMV, syph ilis, bacteria, varicel la-zoster virus, Hodgki n 's disease, and am­ phetam ine abuse.

WEGENER'S G R A N U L O M AT O S I S L U N G H EA O * L u n g/p u l m o n a ry va sc u l it i s U p p e r re s p i rato ry t ract d i s e a s e , s i n u s i t i s N e u ro p a thy, c ra n i a l o r p � r i p h e ra l G l o m e r u l o n e p h r i t i s/re n a l d i s e a s e H ea rt i nvo lve m e nt E ye i nvo l ve m e n t A rth r a I g i a s/a r t h r i t i s D e rmato l og i c l e s i o n s

*

Clin ical characteristics

N otes 1 . Classic clin ical presentation: a. U pper respi ratory tract i nvolvement-si nusitis, nasa l d rai nage b. Lower res p i ra to ry tract/ p u l monary i nvolvement- coug h , hemoptys is, dyspnea c. Renal i nvolvement- g lomerulonephritis, proteinuria, hematuria 2. Neurologic sig ns/symptoms occur in 22% of patients. Granu lomatous in­ volvement of cranial nerves or mononeuritis multi plex due to vascul itis may occur. Less likely is CNS vasculitis or cerebral granulom a . 3 . Cardiac manifestations ( 1 2% o f patients) include pericarditis, coronary vas­ culitis, or, rarely, cardiomyopathy.

Rheumatology . 201

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4. Ophthalmologic involvement is fairly common (60%) conjunctivitis, episcleri­ tis, scleritis, uveitis, vascul itis, and/or retro-orbital mass resulting in proptosis. 5. joi nt-related symptoms i nclude arth ralgias/joint pa i n (up to 50%) True syn­ ovitis is rare. 6. Cutaneous man ifestations of Wegener's a re seen in 45% of cases and i n­ clude papules, vesicles, purpura, ulcers, or subcutaneous nodules . 7. An i m porta nt d iag nostic d istinction is that between Wegener's and lym­ phomatous g ranulomatosis. Wh ile the former is a multisystem infla m matory vas­ cul itis, the latter is a diffuse infiltration of atypical Iymphocytoid cells which is seen in the lung, ski n , CNS, and kidney. Lymphomatosis evolves into malignant lym phoma in 50% of cases, while Wegener's does not.

202 • Rheumatology

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EU

NE UROLOGY The key to a good d ifferential d i agnosis is to start with a b road , a l l-inclusive differential based on the major points of the case and narrow it down logica lly to a smal ler, "worki ng" differential based on the specifics of the case. If the pa­ tient's signs/symptoms become atypica l , or new information becomes ava i l­ able, you can go back to the broad d ifferential; in this way, you will not miss u n usual presentations of disease . Consider a 50-year-old man with hyperten­ sion, diabetes, and hyperlipidemia presenti ng with stroke: the expanded differ­ ential should i nclude all causes of stroke, but the working d ifferential features atheroth rombotic d isease, hemorrhage, a nd embol ism as l i kely etiolog ies. If the CT scan shows a mass lesion, then you'd better return to the broad d iffer­ ential to include tumor and bra i n a bscess. If the patient develops a fever and is found to have a sed i mentation rate of 1 00 , then you should return to the ex­ panded differential and retrieve vasculitis and infection to add to you r worki ng differentia l . Without a com plete i n itial differential diagnosis, o r a return to . the in itial dif­ ferential when a typical case becomes atypica l, you wil l miss diagnoses.

General Considerations

H ow to M a ke a B road D ifferential Diagnosis Despite t h e stereotype o f neurology as a mysterious and a rcane " black box , " there a re severa l effective methods to help any physician make a complete dif­ ferential diagnosis for neurological d isease. Differential by Etiology

The M E D IC I N E DOC mnemonic is a useful sta rting place to develop a complete neurolog ic differential diag nosis. To review: Neurology • 203

Meta bol ic d i sease (e . g . , metabolic e ncepha lopa thy, leu kodystrophy, Wilson's disease) E ndocrine d isease ( e . g . , d i a betic neu ropathy, myxedema como, hypoglycemic seizures) Drugs/medicines (e.g . , iatrogenic, occidenta l , self-admin istered) Infections (e.g . , meningitis, herpes encephalitis, H IV dementia, neurosyph ilis) Congen ital abnormal ities (e.g . , spino bifida, Chiari ma lformations, muscular dystrophy) Immunologic disease (e . g . , vascul itis, myasthenia g ravis) Neoplasms (e.g , primary tumors, metastatic disease) Exotic ( "stra nge" d i seases of u ncerta i n etiology, e . g . , m u ltiple scleros is, Guillain-Barre) Degenerative processes (e. g . , Alzheimer's, Pa rki nson's) Occupational exposures (e.g . , environmental or occupational toxins, trauma) Cardiovascular (e . g . , infarction, hemorrhage, embol ism, aneurysm, a rteriovenous malformation) Diffe re n ti a l by Anatomy

A deta iled understanding of neuroa notomy, although useful in precisely lo­ calizing lesions, pinpointing d iag noses, a n d i m press i n g/bori ng col leag ues during rounds, is not required to make basic differentials. The sim plest method is to sta rt at the m uscle and work bock anatom ica l ly to the cerebral cortex. Exam ples of on anatomic d ifferential for "weakness" are i n parentheses: 1 . Muscle ( polymyositis) 2 . Neurom uscular j unction ( myasthenia g ravis) 3 . Peripheral nerve (Guilla i n-Barre) 4. Nerve plexus (brachial amyotrophy) 5 . N erve root (d isc herniation) 6. Meninges/subarachnoid space (arachnoid itis) 7 . Spinal cord (spinal cord tumor) 8. Brainstem ( pontine i nfarction) 9 . Subcortical structures - basal ganglia, thalamus ( lacunar infa rction - in­ ternal capsule) 1 0 . Cortica l structu res - cerebr u m , cerebe l l u m ( m i d d l e cerebral a rtery i nfarction)

H ow to M a ke a " Worki n g " D iffe rential D i a gn os i s Essential i n the development of a useful working d ifferential d iagnosis is ta ki ng clinical characteristics from the case in point and using them to narrow down the broad differentia l . Here i n l ies the a rt of d iagnosis: how do you know when a history of a lcohol a buse is helpful in making the d iagnosis of alcohol withdrawal 204 .

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Neurology

seizure, or simply a " red herring" distracti ng you from the correct diag nosis of mening itis? If things don't fit, go bock to the brood differential Make sure noth­ ing has been overlooked . Differential by Time Course

In many diseases, and pa rticula rly in neurologic diseases, the time cou rse of symptomatology is critical to intelligently narrowing down the differential. Different etiolog ies a re suggested by d ifferent time cou rses . I ntermittent sym ptoms with complete resolution between epi sodes invoke a different set of diag noses tha n chronic, g radually progressive sym ptoms. A history of headache with nausea and vom iting might be due to migraine in a patient with the first time course, but the second cou rse is more consistent with a bra in tumor. It a lso is possi ble for a history of episod ic symptoms to be g radually progressive (such as crescendo transient ischemic attacks). Take a careful history of the ti m i ng of the symptoms. A good history of the time cou rse incl udes not only whether the symptoms are i ntermittent or conti nuous, but a lso the fol lowi ng i nformatio n : whether the symptoms were maxi mal at onset, ra pidly progressive, or prog ressing in a step­ wise fashion; what factors exacerbate/precipitate symptoms and what factors ameliorate symptoms; if episod ic, the duration and frequency of the episodes; and if and in what order associated symptoms occur. Here is a general overview of the relationship between time cou rse and the onset of i n itial symptoms and etiology. HYPERACUTE (seconds-minutes) Hemorrhage Ischemia * Seizure* Trauma Infa rction Migrainous* Toxin Metabolic Infection Inflammatory

ACUTE (min utes-hours)

CHRONIC (weeks-months)

SUBACUTE (days-weeks)

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* Denotes etiologies that are particularly l i kely to cause intermittent symptoms with complete resolution of symptoms between episodes

Differential by Age of Patient

It is helpful and important to narrow the differential d iag nosis based on the age of the patient. An acute n eu rologic deficit has an entirely d ifferent list of likely etiologies in a 90-yea r-old than it does i n a 20-year-old . I n genera l , con­ genita l , tra u matic, m i g ra i nous, and infectious etiolog ies a re more frequent i n Neurology • 205

younger patients. Older patients are more likely to have symptoms related to is­ chem ic, neoplastic, chronic com pression; or degenerative d iseases. D ifferential by N e u ro a n ato m i c Loca l izat i o n

The most basic d istinction i n neuroanatomy is whether a lesion is located i n the central nervous system (the bra i n a n d spinal cord) o r the peripheral nervous system ( peri pheral nerves, nerve roots, neuromusc u l a r j u nction and muscle) . Some clin ical exa m i nation fi ndings a re useful i n making this distinctio n . In the example below d iagnoses suggested by a given combination of exam findi ngs and neurologic localization a re i n parentheses. Factors Disting u i s h i n g Location of I nj u ry

CNS (brain/spinal cord)

PNS (nerves/ roots/NMJ/ muscle)

Visual loss

Field cut (occipital infarct)

Optic disc

Normal or bilateral abnormality (increased intracran ial pressure) Forehead spared (frontal infarct)

Monocular loss (retinal artery occlusion) May be abnormal on one side only (optic neuritis)

Exam Finding •

Cranial Nerve Exam

Facial weakness •

Motor Exam

Muscle tone

Atrophy Fasciculations Deep tendon reflexes Bobinski Clonus

Acutely decreased , later increased Absent Absent Acutely hypoactive , later hyperactive May be present May be present (multiple sclerosis, cerebral infarct, intracranial bleed , brain tumor, spinal cord injury)

Forehead weak ( Bell's palsy)

Decreased Acutely absent, later present Acutely absent , later present Hypoactive Absent Absent (radiculopathy, neuropathy, myopathy, myasthenia)

Both upper and lower (amytrophic lateral sclerosis motor neuron signs [ALS], cervical stenosis) D ifferential by R i s k Factors a n d Coexist i n g M ed i ca l C o n d itions

Ma king d differentia l d ia g nosis solely on the basis of risk factors is fool­ hardy, to say the least. However, risk factors such as environmental exposures, medications, d rugs/a lcohol, and coexisting medical cond itions are helpful i n 206 • Neurology

narrowing down to a good working differential . For example, diabetes, hyper­ tension , atrial fibril lation , and smoking are all risk factors associated with cere­ bra l infa rction. Pre-existi ng cancer m ight suggest severa l risk factors, including metastatic d isease, i m m u nosu ppress ion , a nd exposu re to chemothera peutic drugs and/or rad iation, each of which will mold the d ifferential i n a slightly dif­ ferent way. Immunosuppressed status by itself suggests a whole host of infections which would not norma l ly be considered in an i m m u nocom petent patient. I ntravenous drug abuse i ncreases the possibil ity of bacterial endocarditis, spinal epidura l a bscess, and bra i n a bscess, as wel l as H I V U re m i a can l ead to encephalopathy, seizures, myoclonus, and neu ropathy. Organ tra nspla ntation has a whole host of d isorders associated with dysfu nction of the transplanted organ, immunosuppression, and side effects of m ultiple med ications. Use these factors as h i nts and suggestions, but do not rely on them to make the d iag nosis. For example, the a lcoholic who iust seized and now has a hem i­ paresis may have had an a lcohol withdrawa l seizure with a post-ictal Todd 's paralysis, but don't m iss the subdural hematoma he got falling down the stairs, which is the real reason he seized and is hem i paretic. If you i u m p to the conclu­ sion that he has had " i ust" an alcohol withdrawa l seizure, then you may find yourself u nhappily awakened to see him herniating in the m iddle of the night.

H ow to Do a G ood N e u ro l o g i c Exa m i nation There a re several aspects of the neurological work-up that are unique and must be considered when evaluating a patient with neurological disease. The history is critical . The h istory is where you w i l l get i n formation regarding the exact symptoms the patient experiences or experienced and the time course of these symptoms. In many cases, the history ma kes the diagnosis, and the exam i nation serves merely as a confirmation of your historical d iagnosis. Rea l ize, however, that the sym ptoms the pati ent reports can sometimes (often?) be vague and difficult to interpret: It is in these cases that the exa m i na­ tion plays a key role. A patient may com pla i n of visual loss in the len eye, but on exa m i nation , it becomes clear that the patient actually has a left homonymous hemianopia . This d isti nction is of g reat value, for monocular visual loss ind icates d isease in the eye or the blood supply to the reti na (from the ca rotid a rtery), while a left visual field cut suggests pathology i n the right OCCi pital lobe or its blood supply (from the vertebral-basilar arteries) The work-up and treatment thus a re significantly altered by the exa m findings, which help to clarify the patient's interpretation of h is/her neurologic deficit. If something is found on exam that is inconsistent with the patient's h istory, this does not necessa rily i mply mali ngeri ng, but rather a d ifficu lty in accu rately describing symptoms. Always be sure you understand what the patient is tryi ng to describe. Some patients compla in of weakness, when they rea lly mean numb­ ness, and vice versa . A patient may compla i n of an acute or subacute onset of Neurology • 207

wea kness , but exa m i nation shows severe atrophy. Atrophy is a sign of lower . motor neuron disease, but it is not present acutely. In this case, further question­ ing would be necessary to try to elicit a more chronic (and perhaps subtle) h is­ tory of weakness (a nother possibility is a pre-existi ng chronic weakness with a superim posed new, acute insult) . From these exa mples you can see that the neurologic history and exa mina­ tion are interrelated and that, while the history ohen suggests the diagnosis, it is im­ portant to synthesize the information from both to come up with the correct answer. In addition , rea lize that if a basic neurologic function is impa i red , it is not easy to rel ia bly test higher neurologic functions; i . e . , if a patient's arm is paralyzed or paretic, then fine motor coordination is difficult to assess; likewise, it would be unfair to label a patient as having severely impaired memory if the patient is aphasic. The M e ntal Statu s Exa m i nation

A good mental status exa mi nation leaves no doubt about the patient's level of arousal for the next exa m i ner. Terms l i ke "sleepy, " " leth a rg i c , " "stuporous"

may mean slig htly different thi ngs to different examiners . The best mental status exam Simply states what the patient can or ca nnot do. For exa m ple, "The pa­ tient was awake, watching television , and spea king normal ly, " or "The patient was asleep, arousa ble to tacti le sti m ulation" but would fa ll back to sleep if u n­ stimulated . " Remember to check basic a n d objective information . I s the patient oriented to person, place , and time? Assess the patient's attention . This is most easily done by having the patient repeat a series of ra ndom n u m bers, starti ng with th ree numbers in 3 seconds and working up until the patient is no longer able to correctly repeat them (normal is five to seven numbers in as many seconds) . This is known as the digit span. If a patient's attention is impaired, as demonstrated by a digit span of less tha n 5 , then more com plicated menta l status testing may be difficult to interpret. For instance, a patient with a digit span of 3 is not likely to be a ble to remember three objects in 5 minutes, but this does not necessa rily i m ply a pri mary memory problem and may just represent poor attention to the exa m i ner. I mpa i red attention may mean Simply that the patient is preoccupied or anxious or may signi fy an acute confusional state or encephalopathy. Speech is i m porta nt to assess for both fluency ( language output) and com­ prehension (language i n put) . An i m pa i rment of smooth a n d fluent output sug­ gests dysfunction of the dominant ( usually left) frontal lobe ( Broca's a real, while fluent output with an inability to understa nd spoken language indicates damage to the dominant parietal-tem poral a rea (Wernicke's area ) . Difficulty with both flu­ ency and comprehension is usua lly the result of a more extensive dominant hemi­ sphere lesion (such as a m iddle cerebral artery infarct) . C ra n i a l N e rve Exa m i nation

Objective assessment of many of the cranial nerves (eNs) is possible, and thus brainstem function may be assessed even in comatose or otherwise uncooperative 208 • Neurologv

patients . Abnormalities i n the cranial nerve exa m usually suggest u n derlyi ng brainstem pathology. eN I : Sense of smell usua lly is not tested , but may be by asking the patient to identify a characteristic a roma with eyes closed (e.g . , coffee, flowers). eN I I : Check visual fields to confrontation (Can patient see movement in all fields? Can patient count fingers in all fields?) and look for consensual pupil/ary reactivity. eN III, IV, VI: Have the patient follow the movement of l ight in all directions . Dol/'s eye maneuver (oculocepha l ic ) - This is most useful i n patients whose consciousness is impaired . A normal or positive response occurs when vigorously rotating the patient's head to one side, a nd the eyes deviate to the opposite side. An a bnormal or negative response is when the eyes do not move in the orbits regardless of head position - the doll's eyes are absent. A fully conscious patient may be a ble to voluntarily override th is reflex, resulting in a "false" nega­ tive result. Cold calorics (ocu lovesti bula r) - ea r canals a re inspected for a clear view of the eardrums, the patient's head is hyperextended a bout 30°, a nd ice-cold water is i rrigated i nto one ear canal .. A normal or positive response in an awake patient is deviation of the eyes toward the irrigated ea r and nystagmus beating away from the i rrigated ear. (Si nce awake patients ca n volu ntarily move thei r eyes, and since cold calorics can be qu ite nauseati ng, calorics are seldom indi­ cated in awake patients . ) A normal or positive response in a comatose patient is deviation of the eyes toward the irrigated ea r, with no nystagmus. An a bnormal or negative response shows no eye deviatio n . After 5 m i n utes, repeat the test with the opposite ear. eN V: Ask the patient to close his/her eyes, touch (or use a pin to prick) the patient's face on the forehead, cheek, and chin on either side, and have the pa­ tient identify specifically or point to the place touched . eN VII : Ask the patient to close his/her eyes tightly and look for the ability to "bury the eyelashes" symmetrical ly. Look for a symmetric smile. Ask the patient to "puff out his/her cheeks" and try to gently push the air out of the cheeks with your fingers. Ask the patient to clench his/her teeth together and look for sym­ metric contraction of the platysma m uscle (stretches from the ch i n/jaw to the clavicles) eN V/VII : Corneal test-A light wisp of cotton or tissue is brushed gently agai nst the cornea, approaching from the side ( not from the front). A positive re­ sponse is eye closure/bl inking. This should be done on one eye, then the other. Cornea Is may be a bsent in patients with a history of contact lens use . This test is not routinely performed in awake patients. eN VII I : Whisper numbers (or letters) into the patient's ear from a distance of about 1 foot and note if the patient ca n repeat the numbers . eN IX/X: Gog test- Using a Q-tip or tongue depressor, touch the back of the oropharynx on one side, then the other, and look for a gag with symmetric palate elevation . If the patient is intubated, a Q-tip can sti ll be used . Pulling on the endotrachea l tube is n ot recom mended as a method for testing the gag reflex. A decreased or a bsent gag someti mes can be fou n d i n otherwise Neurology • 209

...

normal patients , but a n asym metric gag usua l ly is i nd ica tive of b ra i nstem pathology. . C N X I : Aga i nst resistance, have the patient shrug h is/her shoulders u p (trapezius) a n d turn h is/her head to one side (sternocleidomastoid). Remember, difficulty turn ing the head to the right i ndicates a weak left sternocleidomastoid, and vice versa . CN XII: Ask the patient to stick out h is/her tongue. The tongue will deviate toward the weak side. M otor Exa m i nation

Although the motor exa m i nation as typically discussed relies significantly on patient cooperation, there is a lot of obiective i nformation that can be elicited by a skilled exa m i ner. . Muscle bulk is very obiective, and focal atrophy or fasciculations a re a sign of chron ic lower motor neuron disease (ALS, neu ropathy, rad iculopathy, some­ ti mes myopathy) . Muscle tone can be assessed by passively moving a ioint throu g h its full ra nge of motion . Flaccid tone offers little or no resista nce, and the movement will seem limp. This demonstrates either an acute upper motor neuron lesion or a lower motor neuron lesion . Spastic tone offers more resista nce the faster the movement. Spasticity is seen with subacute or chronic upper motor neuron i n iury (spinal cord iniury, cerebral i nfarct, bra i n tumor, multi ple sclerosis, ALS) . Rigidity shows equal resistance throughout the entire range, regardless of the velocity of the movement. Occasionally rigidity has a ratchety qual ity, which is referred to as cogwheeling ( Pa rkinsonism, other basal ganglia d isease) . Experience aids greatly i n the accurate evaluation of m uscle tone. Pronator drift is an excellent m ethod of testi ng for su btle corticos p i n a l wea kness . The patient is asked t o h o l d both a rms fu lly extended i n front of h i m/herself with the pa lms u p . The palms should be level a n d not touch i n g each other. The patient must then mai nta i n this position with the eyes closed . A positive drift (and hence, evidence of corticospinal weakness) is cha racterized by not only a downward movement of the affected side, but also pronation of that extremity. Su btle lower extrem i ty weakness is suggested by external rotation of the hip at rest. Di rect strength testi ng of i nd ividual m uscles is g raded on the fol lowi ng scale: o No movement 1 Twitch or fa int movement 2 Movement but not against g ravity 3 Full movement against g ravity but not against resistance 4 Movement agai nst partial resistance Movement agai nst full resistance 5 I A "+" or sign often is used to denote smaller va riations of strength ( e . g . , I slight weakness against full resistance would be 5-. Paralysis or plegia means "_,,

210 • Neurology

that there is no observa ble movement. Paresis mea ns there is weakness but still observa ble movement. Another part of the motor exam that assesses strength without d i rect one­ on-one m uscle testing is functional testing . Can the patient easily rise from a sitting position to a standing position without push ing up with the a rms? An i n­ ability to do this suggests proxi mal lower extrem ity weakness. Can the patient wa l k up steps? Sta nd on one leg? Hop on one leg? Bei ng able to sta nd on one's tip toes i m pl ies at least 4 to 4+ power i n the gastrocnemius. Being a ble to sta nd on one's heels suggests at least the same degree of power in the a n­ terior tibialis. Does the patient have a resting tremor ( Pa rkinsonism)? Does the patient have a tremor when forced to m a i nta i n posture, such as when the hands a re outstretched? This is cal led a postural tremor and is ohen physiologic, but may be fa milial (essential tremor) . C e re b e l l a r Exa m i nation

Ca n the patient ra pidly a n d alternately pat the pa l m of the hand and the dorsum of the hand on a surface? This is the rapid alternating movement test, which assesses the cerebellum 's abi lity to coord inate agonists and antagonists. Impa irment of this is termed dysdiadochokinesis. An intention tremor is a tremor that worsens with motion toward a particular poi nt. It is checked for by havi ng the patient ra pidly a l ternate po inting (and touching) the exa miner's outstretched finger and the patient's nose (finger-nose­

fi nger test). The heel-knee-shin test involves touching one heel to the opposite knee and

smoothly moving the heel down the opposite shin to the ankle and back up to the knee. Normally this is a steady movement, but patients with ataxia wobble the moving leg from side to side. An inabil ity to perform any of these tests (in the absence of sig nificant motor weakness) suggests i psi lateral cerebellar dysfunction. Gait and Stance Exa m i nation

Ga it and stance may be observed casually when the patient is wa lking to the exa m i n ing area . Normal gait has a narrow sta nce, fluid movement, and symmetric arm swi nging. Normal stance is steady with feet side by side and no swaying . Specific ma neuvers can be tested later in the exa m . Tandem g a i t i s tested by haVing the patient wa l k heel to toe in a stra i g ht l i ne, and a d ifficulty with this (ataxic -ga it) suggests m id l i ne cerebellar dysfunc­ tion. Obese and elderly patients may have some difficulty with tandem gait with­ out specific cerebellar disease. Ataxic g a it is cha racterized by u nstead i ness, swaying, wa lking with the feet widely apa rt, and an inability to perform tandem gait. Hemiparetic gait demonstrates decreased movement of the weak side, with he patient having to lea n away from the paretic leg and swing it back to front Neurology . 2 1 1

(circumduction ) . The arm swi ng usually is decreased on the affected side, and the arm may be held i n a flexed posture. Parkinsonian gait classically has a stooped forward posture with small sh uffl ing steps and a tendency to fa ll over backward ( retropu lsion ) . Tu rns a re not made with a smooth rotation , but usually consist of a series of small steps (en-bloc turn i n g ) . Parki nsonian patients may have difficu lty getting started wa lk­ ing, but once sta rted may actually walk faster and faster and be unable to stop (festi nation ) . Steppage gait is associated with a foot d rop, and this involves simply step­ ping h igher with the affected leg so that the foot, which is hanging down, can clea r the g round. These patients often g ive a history of stu mbli ng/tri pping over their toes on the weak side. Scissor gait is seen in patients with a spastic paraparesis (spinal cord injury, cerebral palsy) and shows increased tone in the thigh adductors, such that when­ ever a step forward is attem pted , the legs actually cross ( hence the name scissor) . S e ns o ry Exa m i nation

It is not necessary to memorize every poss ible com bination of peripheral nerve or dermatomal sensory loss; however, some general guidelines a re help­ ful . A pin (or a toothpick) is more accurate than a finger at mapping out a reas of sensory loss. Dermatomes to Remember

Root

Sensory Distribution

C6 C7 C8 T4 T1 0 L5 Sl

Thumb Middle finger Pinky Nipple Umbil icus Big toe Sole of foot Peripheral Nerves to Remember

Nerve

Sensory Distribution

Radial Ulnar Median Lateral femoral cutaneous Peroneal

Dorsum of hand Pinky side of hand Pajm of hand Lateral aspect of thigh Lateral aspect of leg and dorsum of foot

If spinal cord compression is suspected, be certa i n to check for a sensory level on the trunk. Perianal sensation is i m portant to check in patients with sus­ pected cauda equ i na lesions. 212 • Neurology

Dissociated sensory loss, i . e . , loss of pain and temperature on � ne side of the body and loss of vibration and proprioception on the other, is characteristic of a hem i-spi nal lesion i psi latera l to the vibratory/proprioceptive loss ( B rown­ Sequard syndrome) . D e e p Te ndon Reflexes

An easy way to remember roughly which nerve roots serve which tendon re­ flexes is to start at the a nkles and move up: Count

Reflex

Root

1 -2 3-4

Ankle Knee B iceps Triceps

S l -S2 L3-L4

5-6 7-8

C5-C6 C7-C8

Grading of reflexes is as follows: o Absent trace Fl icker of muscle contraction 1+ Hypoactive (moy be normal, especiolly in muscular or obese patients) 2+ Normal Hyperactive, usually shows spread of reflex (may be normo l , especially 3+ i n th i n or anxious potients) 4+ Hyperactive, clonus (always abnormal)

Spread of a reflex refers to when one reflex is bei ng checked and muscle contraction occurs in another reflex. Clonus refers to repetitive reflex contractions after a single stimulus (usually elicited by abrupt dorsiflexion of the a n kle by the examiner) . Plantar response is elicited by a qu ick, noxious sti mulus (scratching with a key or other i m plement) to the latera l planta r aspect of the foot. A flexor re­ sponse is when the great toe flexes and is the normal response of adu lts a nd older children . An extensor response (positive Babinski) is when the g reat toe ex­ tends (dorsiflexes) and the other toes spread apa rt. This is usually a sign of upper motor neuron disease (cerebral i nfarct, spinal cord com pression, tu mor), but ca n be normal in i nfants.

N e u rolOgiC Exa m i nation S u m ma ry Mental Status Level of a rousa l : description Orientation: to self, place, time, situation r Attention : digit spa n (normal 5-7) • Speech: fluent? comprehension? •

•

Neurology . 2 1 3

Cranial Nerves • •

•

•

• • • •

I I - visual fields; consensual pupillary response III, IV, VI - pupillary reactivity/an isocoria ; extraocular movements. doll's eyes - positive=eyes deviate in opposite di rection of head turn . cold ca lorics- pos itive=eyes deviate ton ically toward i rrigated ea r ; with or without nystagmus away from i rrigated ear. V - facial sensation ; cornea l reflex (sensory) - eyebl i n k when cornea touched with cotton wisp. VI I - facial expression - if forehead movement is spared , lesion is above the facial nucleus (central); if forehead is weak, lesion is peripheral (Bell's palsy) . VIII - hearing IX, X - palate symmetry, gag XI - head turn (sternocleidomastoid); shoulder shrug (trapezius) XII - tongue protrusion - deviates toward weak side

Motor Exam • • •

•

•

Bulk: check for symmetry; atrophy, fasciculations Tone: check for symmetry; is tone flaccid, spastic, rig id (cogwheeling)? Strength/power: 0 No movement Trace/flicker of movement 1 2 Movement but not against g ravity 3 Movement agai nst g ravity but not against resistance 4 Movement agai nst partial resistance 5 Movement against fu ll resistance F u nctional tests: Pronator drift - arms outstretched with pa lms u p . Also, can patient rise from cha i r without pushing u p with arms? stand on tip­ toeS"? stand on heels? hop? hop on one foot? Tremor: resting tremor, postural or essential tremor

Cerebellar Examination • • •

Rapid alternation movements (dysdiadochokinesis) F i nger-nose-finger ( i ntention tremor) Heel-knee-shin.

Gait and Stance Examination •

• •

Casual gait: observe as patient wa lks i nto room and during formal neuro exam Tandem gait: walk stra ight line heel to toe. Specific Ga its : ataxic - lurching, u nsteady, swaying, wide stance; hemi­ paretic - decreased movement on weak side, circumduction of leg , de­ creased arm swi n g ; parki nson i a n - stooped , sh u ffl i n g , retropu lsion , en-bloc turns, festi nation ; steppage - foot d rop, wa l ks with high step on weak foot; scissor- legs cross when stepping forward .

Sensory Examination •

•

Modalities to test: l ig h t touch, pi nprick, temperature; vi bration , proprio­ ception . Sensory leve l : check with p i n up a n d down trunk when suspicious of spinal cord lesion .

2 14 • Neurology

•

Perianal sensation : check with suspicion of lower cord or cauda equina lesion

Deep Tendon Reflexes •

Root S 1 -S2 L3-L4 C5-C6 C7-C8

•

Reflex Ankle Knee Biceps Triceps

•

Grading of Reflexes Absent trace Flicker of muscle contraction 1+ Hypoactive 2+ Normal 3+ Hyperactive; may show spread 4+ Hyperactive; pathologic; clonus

o

Clinical Sym ptoms a nd Sig ns

A LT E R E D M E � TA L S TAT U S I WA T C H D E A T H I nfect i o n W it h d rawa l A c ute m et a bo l i c d e ra n g e m e nt T ra u m a e N S p a t h o l ogy H ypoxia D ef i c i e n cy E ndocri ne A c ute va sc u l a r T oxi n s/d r u g s H eavy meta l s

Neurology . 2 1 5

CT, LP, A N D E E G H I M C e re b rova sc u l a r a c c i d e n t ( b ra i n st e m i s ch e m ia/i nfa rct) T ra u m a L ow b l o o d p re s s u re/hypote n s i o n P sych i a t r i c A n ox i a/hypoxia N eo p l a s m D ru g s/tox i n s/wi t h d rawa l E p i l e psy ( n o n convu l s i ve stat u s , post-ict a l ) E l evated b l oo d press u re ( h y p e rte n s ive e n ce p h a l op a t hy) G l u co s e l a ck/hypog lyce m i a H emorrhage/bleed (i ntracra n i a l , especi a l ly posterior fossa) I nfect i o n ( m e n i n g i t i s/e n c e p h a l i t i s/s e p s i s ) M et a b o l i c/e n d o c r i n e The fi rst m nemonic i s shorter but less comprehensive. The second m nemonic is more com plete, and it pokes fun at a nonspecific a pproach to these patients. The CT, LP, and EEG a re not requi red for all patients. The following describes o n organ ized approach to this common problem .

N otes Altered mental status refers to any acute or su bacute change i n the level of con­ sciousness, ra nging from m ild confusion to deep com o . Chronic problems such as dementia or mental retardation a re not considered in this d iscussion .

1 . Initial treatment of como or unconsciousness is ai med at rapidly identifyi ng and treating any reversi ble process . Protocol : a . ABC's (Ai rway, Breath i n g , C i rculation), vital signs, s u pplemental O2 if necessary, pulse oximetry and ABG, ECG. b. IV l i ne with normal sa l i n e . Send blood for CBC with d ifferential a n d platelets, electrolytes, BUN, creatine, glucose, Co, Mg , PT, PH Other tests to be considered i nclude toxicology screen, liver enzymes, a m monia, blood cul­ tures, urinalysis. • F i ngerstick glucose, then 1 00 mg th iamine, then 5 0 m l 50% dextrose . solution IV • Rapid assessment of clinical situation , exami nation . Consider head CT sca n . Emergent treatments i nclude the following : 2 1 6 • Neurology

If opiate overdose suspected , Naloxone 0 0 1 mg/kg IV If seizure activity noted , Larazepam 2 mg IV If infection suspected , begin IV anti biotics, then proceed qU ickly with CT and LP. If herniation detected , i ntubate, hyperventilate, mann itol 1 g/kg IV, CT, ca ll neu rosurgery. • Defin itive treatment will depend on the cause of the coma. 2 . The exami nation of the comatose patient can be both q U ick and hel pful in determining the etiology of the coma (see " H ow To Do a Good Neurolog ic Exami nation , " page 207) . a . Mental status: Use specific descri ptive terms; avoid vag ue terms l i ke "sleepy" or " letharg i c . " To what level of sti m u l u s does the patient respond? verba l, touch, pain? b . Cranial nerves: C heck pupils, eye movements (dol l 's eyes) , cornea Is, facial symmetry, and gag (see page 209 for specifics on how to perform these tests). Cranial nerve abnormalities suggest brainstem dysfunction. c . Motor/sensory: Observe the patient's movements . Note any obvious asym metries . Passively m ove the patien t's l i m bs to assess for asym metry of muscle tone. Does the patient move spontaneously? Is the movement pu rpose­ ful? Does the patient move to command? Does the patient move to noxious sti muli? When assessing the patient's reaction to noxious sti muli, note what sort of motor response is obta i ned . Purposeful withdrawal mea ns movi ng the l i m b away from t h e sti m ulus and i m pl ies integrity o f t h e cerebral cortex. Decorticate posturing is described as a flexion response i n the u pper extremity and exten­ sion in the lower, and suggests cortical dysfuf)ction . Decerebrate posturing i n­ volves extension of both upper a nd lower extremities i n response to a noxious sti mulus, and this i m pl ies bra instem dysfu nction . No motor response suggests severe bra instem dysfunction or peri pheral paralysis (Guillain-Ba rre synd rome, iatrogenic paralysis ) . d . Reflexes: Look for asym metry o f deep tendon reflexes. Check for clonus and Babinski responses. 3. There a re three mecha nisms of coma/depressed mental status. a. Bi lateral cerebral hemisphere dysfunction (e . g . , bilatera l infarcts, bi lateral subdu rals, hydrocephalus, men i n g itis, subarach noid hemorrhage, general ized seizure activity) b. Bra i nstem dysfunction only • Direct bra instem i n j ury ( bra instem infarction, tumors or bleeds) • Bra i nstem compression/displacement by su pratentorial lesion ( hern ia­ tion secondary to supratentorial tumor, edema or bleed) c . Diffuse cerebral and brainstem dysfunction (e.g . , hypoxia , hypoglycemia, drug intoxications, uremia, hepatic encepha lopathy, meningitis, suba rachnoid hemorrhage) Unilateral cerebral dysfunction alone does not cause coma ( i . e . , a uni lateral i n­ farct or tumor does not explain com a , u n less herniation a n d com pression of brainstem structures has occurred .

Neurology • 2 1 7

4. Approach to the differential diagnosis of coma: Be aware that brainstem lesions do not a lways show up clearly on CT scans, so if bra instem pathology is strongly suspected and the CT scan is "normal , " con­ sider neurologic consultation and MRI scanning. COMATOSE PATIENT

t t Broinstem exomination/reflexes � ABCs, Como PROTOCOL

r-

Intact

Abnormal

I

I

r--- CT Abnormal

t

Bilateral subdurals Hydrocephalus Bilateral infarcts Multiple contusions Subarachnoid bleed Meningitis/encephalitis Cerebral edema/Reye's Epidural bleed Neoplasm(s) Abscess(es) Vasculitis (infarcts) Sinus thrombasis Metabolic insult superimposed on old focal lesion

r--- CT ------, Normal

Abnormal

Normal

Meningitis/encephalitis Toxic encephalopothy Metabalic encepha· Iopathy Drug-induced Hypoxic/anoxic Acute bilateral infarct Seizure Hypotension/shock Hypertensive encephalopothy Sinus thrombosis

Brainstem hemorrhage Brainstem neoplasm Brainstem infarction Subarachnoid bleed Supratentorial mass with herniation Brainstem/cerebellar abscess

Acute brainstem imarct Toxic encephalopothy MetaboliC encephalopathy Meningitis/encephalitis Drug-induced Hypoxic/anoxic Basilar migraine

t

t

ATA X I A C a n 't Sta n d V e ry W e l l C e re b e l l a r a t a x i a S e n so r y a t a x i a V esti b u l a r a t a x i a Weakness

2 1 8 • Neurologv

t

A C U T E ATA X I A U N A B L E T O S TA N D U n d e rlyi n g wea kn ess ( may m i m i c a t a x i a ) N ut r i t i o n a l n e u ropathy (vita m i n B 1 2 defi c i e n cy) A rte ri t i s/va s c u l it i s B a s i l a r m i g ra i n e L a by r i n t h i t i s/vesti b u l a r n e u ro n i t i s E n c e p h a l i t i s/i nfect i o n T ra u ma ( postco n c u s s ive) O th e r ( ra re meta bo l i c or g e n e t i c d i s e a s e s ) S tro ke ( i s ch e m i a o r h e m o r r h a g e ) T ox i n s ( d r u g s , to l u e n e , m e rc u ry) A I c o h o l i ntox i ca t i o n N e o p l a s m/pa ra n eo p l a s t i c syn q ro m e s D e mye l i na t i o n ( M i l l e r F i s h e r, G u i l l a i n B a rre, M S)

C H R O N I C ATA X I A CA N 'T STA N D C on g e n it a l m a l fo rm a t i o n/C h i a ri A utosom a l recess ive a t a x i a s N ut r it i o n a l (vita m i n B 1 2 defi c i e n cy) T ra u ma ( postcon c u s s i ve ) S t roke s e q u e l a e T ox i n s ( d r u g s , to l u e n e , a l co h o l ) A utoso m a l d o m i n a n t a t a x i a s N eo p l a s m/pa ra n eo p l a s t i c syn d ro m e s D e mye l i n a t i o n ( M S)

Neurology

Ii

219

--

N otes Ataxia is the subjective com pla int or objective finding of i m paired coord ination, usua lly manifested as an impa i rment of gait or dexterity in the absence of sign if­ icant muscular weakness. Dysdiadochokinesis is an i mpairment of the ability to perform ra pid alter­ nating movements . Dysmetria is i m pa i rment in the normal acceleration and deceleration of di­ rected movements. Usua lly eva luated by finger-nose-fi nger and heel-knee-shin tests . Intention tremor is an exaggerated oscillation of a limb, most pronounced as it is approaching a target, and essentially absent at rest or at the beg i n n ing of a movement. Intention tremor is a man ifestation of dysmetria . Titubation is a moderate frequency head tremor, usually anteroposterior.

1 . The time course ot ataxia helps narrow the d ifferential d iag nosis. Acute ataxias usually are due to acute bra i n i n j ury (trauma, i nfarct, bleed ) , i n toxica­ tion, infection, inflam mation/a utoi m mune reactions (vascul itis, para neoplastic), or migraine. Ch ronic ataxias usua l ly are caused by congen ita l ma lformations, sequelae of bra i n i njury ( post-stroke, cerebral palsy, trauma!, multi ple sclerosis, bra i n tumors, or genetic diseases ( Friedreich's, ataxia-telangiectasia). 2. Evaluation of ataxia includes coordi nation testing and sensory testi ng. a. F i nger-nose-finger: The patient is asked to use the i ndex finger to alter­ nately touch his/her nose and the exa m i ner's outstretched fi nger� b . Heel- knee-s h i n : The patient is asked to touch one heel to the opposite knee and then move the heel down the shin to the foot. c. Rapid a lternating movements : The patient is to a lternately pronate and supinate either hand, usually patting on the thigh or another horizontal surface. In the lower extrem ities, this may be tested by having the patient tap either foot on the floor. d . Proprioceptio n : Position sense is tested by havi ng the patient identify whether a digit is being moved up or down at a joint (usua l ly interphalangeal finger or toe) with the eyes closed . At least one joint on each limb is tested sev­ eral ti mes . If a deficit is detected d istally, continue testi ng proximally u ntil the pa­ tient is able to identify movements correctly ( i . e . , if position sense is i m paired i n t h e fingers, follow with testing at the wrist, elbow or even shoulder to determi ne the extent of the deficit) . e. Romberg sig n : This is tested by havi ng the patient assume a comfortable stance with the eyes open and the feet as close as possible, then closing his/her eyes . Conti n ued sta bi l i ty is a negative Romberg , a n d i ns tabil ity/fa l l i ng with eyes closed is a positive Romberg . A positive Romberg is i ndicative of i mpai red proprioceptive i n put. Romberg testing is not useful in patients unable to stand steadily with their eyes open .

220 • Neurologv

b

3 . Ataxia may be divided into four categories that often can be disti nguished

by careful h i story and exa m i na tion . Some d i sorders may be associated with more than one type o� ataxia ( i n particular, cerebellar a n d vestibular ataxia often occur together) . a . Cerebellar ataxia is c h a racte rized by dysmetria , dysd iadochokine· sis, hypoto n i a , a n d u nsteady g a i t i n the a bsence of s i g n ificant motor wea k­ ness, na usea , o r vom iti n g . Nysta g m us may be p resent. Cerebellar ataxia may be u n i latera l or bi latera l . U n i lateral cerebellar ataxia suggests a focal lesion ( tumor, infarct, bleed, multiple sclerosis) , while b i late ra l cerebe l l a r a t a x i a i s m o re l i kely d u e t o d i ffuse c a u ses ( a lcohol, drug intoxication, paraneoplastic) . b. Sensory ataxia is caused by impaired position sense and not by cerebel­ lar pathology. Findings consistent with sensory ataxia i nclude i m pa i red sensa­ tion, particularly p ropriocepti on and vi brati o n . Na usea , vom iting, a n d nysta g m us a re not seen with sensory ataxia . Etiolog ies i nclude neu ropath i es and spinal cord dorsa l col u m n pathology (e. g . , vitamin 8 / 2 deficiency, neu. rosyphilis/tabes dorsalis) . c . Vestibular ataxia typically is associated with vertigo, nausea and vom it­ ing. Impa i red coordination , d i m i n ished hearing, nystagmus, and gait i nstabil ity also may occur. Vestibular causes of ataxia include labyrinthitis/vestibular neu­ ronitis, brainstem ischemia, and multiple sclerosis, among others. d. Weakness due to hemiparesis may man ifest by falling or gait d isturbance and is not true ataxia. In the setting of sign ificant motor weakness, it is d ifficult to assess coordi nation separately. Sig nificant focal weak.ness should raise the pos­ sibility of a foca l cerebral lesion ( tumor, infarct, bleed, abscess) . 4 . Intoxication is a common cause of acute ataxia . Offendi ng agents include many anticonvulsants (e . g . , phenytoin, carbamazepine) and alcohol . 5 . A good family history is essential in the evaluation of chron ic or recu rrent ataxia . Migra i nes often occur in persons with a positive fa m i ly history of m i­ g ra ine headaches (aura , photophobia, nausea, vom iti ng). Metabol ic diseases presenting with recurrent or progressive ataxia often have a utosomal recessive i nheritance ( maple syrup urine d isease, ataxia telangiectasia, Friedreich ataxia ) . Autosomal dominant forms o f ataxia i nclude von H i ppel-lindau disease (cere­ bellar hema ngioblastoma) , oIivopontocerebeliar atrophy, and Machadojoseph disease. 6. Work-up for ataxia depends on the d ifferential diagnosis. Neuroi mag i ng (CT acutely, but MRI is better for chronic symptoms) is necessary if a foca l lesion is suspected . Acute, nonfocal ataxia warrants testi ng for alcohol and d rug intox­ kation . I n patients with known malignancy, work-up for metastases (CT/MRI) and paraneoplastic syndromes (autoanti bodies) should be considered . Lum bar puncture should be performed i n cases where C N S i n fection is l i kely (fever, meningismus). Patients with primarily sensory ataxia should be eva l uated for ca uses of sensory neu ropathy a n d d orsa l col u m n pathology by checking ' VDRL/RPR, g lucose, and vita m i n 8 1 2 .

Neurology . 22 1

"

.....

A U TO N O M I C D I S O R D E R S A BP DROP, I G U ESS A my l o i d o s i s B otu l i s m P a rk i n so n 's d i se a s e D i a betes R i l ey-Day syn d ro m e/fa m i l i a l dysa uto n o m ia o n c o l o g i c/pa ra n eo p l a st i c P o rphyria I d i o pa t h i c/I a t rog e n i c G u i l l a i n- B a rre syn d ro m e U re m i a E t h a n o l/a l co h o l i s m S hy-D ra g e r sy n d ro m e S p i n a l c o r d d i s o rd e rs

N otes Autonomic d isorders constitute a wide range of neu rolog ic derangements, which man ifest prima rily through symptoms of a utonomic dysfunction, including but not l i mited to orthostatic hypotension/syncope, cardiac arrhyth m ias, altered lacrimation, i m pa i red temperature reg u lation, dia phoresis/anhidrosis, sexua l dysfunction, and bowel/bladder problems. 1 . Autonomic dysfunction can occur d ue to impairment of the a utonomic nervous , system in the bra i n (Shy-Drager syndrome, hypothalamic tumor, Parkinson 's dis­ ease) , spinal cord ( tumor, myelitis, multiple sclerosis) , a utonomic nerves ( dia­ be/es, Gull/ain-Barre syndrome, amyloidosis) or neuromuscular j unction (botulism) . Systemic diseases (peripheral vascular disease, connective tissue disease, prosta: tism) may manifest with autonomic symptoms. Autonomic impairment becomes more i pronounced with advancing age, prolonged bed rest, and various medications. ' 2 . Autonomic symptoms are rarely the sole manifestation of an u nderlying i l � ness, a n d the diagnosis often i s made based on the combinatio� of autonomic

i

1 222 I

• Neurology

impairment and other cardinal signs/symptoms. For exa m ple, the following diag noses feature autonomic sym ptoms in combi nation with others: a. Parkinson 's, Shy-Drager- bradykinesia, rigid ity, postura l instabil ity ( resting tremor in Parkinsons) b Guillain Barre - su bacute onset, ascending pa ralysis, a reflexia, auto­ nomic instabil ity c. Peripheral vascular disease, diabetes - orthostatic hypotension, i m paired di sta l circulation, poor wound h eo l i n g i n extremities (hyperg lycemia i n dia­ betes) . 3 . Management of autonomic disorders ahen is symptomotic, once the underly­ ing condition has been diagnosed and is being treated. a . Orthostatic hypotension - mai ntain good hydration and sodium, g radual postura l changes, disconti nue hypotension medications, avoid prolonged inac­ tivity. Fluorohydrocortisone may be helpful in patients with d ifficult to control or­ thostasis. b . Bladder dysfu nction - flaccid bladders may respond to bethanechol . Spastic bladders may be relaxed using propa nthe l i ne a nd/or oxybutyn i n . Intermittent self-catheterization often i s helpful i n preventing urinary incontinence in certa in patients ( multiple sclerosis, spinal cord disease) . c. Sexua l dysfu nction - pe n i l e i m pla nt, medication , endocrine a n d u ro­ logic/gynecologic evaluation .

DI PLOPIA H I N T : I S CT D O N E? Cen tral

H e m o r r h a g e , c e reb e l l a r I nfa rct/T I A N e o p l a s m ( b ra i n st e m t u m o r) T ox i c/meta bo l i c Periph eral

I nfe ct i o u s/me n i n g i t i s S u ba rach n o i d h e m o rr h a g e/a n e u rys m C a n c e r (ca rc i n o m a t o u s m e n i n g i t i s , cave r n o u s tu m o r) T hy r o i d o p h t h a l mopathy Neurology •

223

D ia betes O rb i t a l p rocess ( o rbita l f ra ctu re/ma ss) N e u ro m u s c u l a r j u n c t i o n d i se a s e ( myasth e n ia ) E ye p ro b l e m ( l e n s s u b l uxat i o n )

CT W H O M ? M O S T CT I M A G E D Cen tral

C VA/i sch e m i a , b ra i n st e m T ox i n s/d r u g s W e r n i cke's H e m orrh a g e , c e re b e l l a r O n co l og i c ( b ra i n st e m tu m o r) M u l t i p l e s c l e ro s i s Peripheral

M yast h e n i a g ra v i s O rb i t a l p rocess ( o r b i t a l f ractu re/ma ss) 5 u b a ra ch n o i d h e m o rr h a g e T ra u m a ( s h ea r i ng I nj u ry to c ra n i a l n e rve) C ave r n o u s s i n u s p ro c e s s T hy r o i d o p ht h a l m opathy I nfect i o n s ( h e rp e s zoste r o p h th a l m i c u s ) M a l i g n a n cy (ca rci n om a t o u s m e n i n g it i s ) A n e u l ys m a l co m p re s s i o n G ra n u l o m a to u s (sa rc o i d , To l o s a- H u nt) E ye p ro b l e m ( l e n s s u b l uxati o n ) D i a betes

.

Also under Peripheral: increased intracranial pressure (as i n pseudotumor cere­ bri) can cause cranial nerve (eN) VI palsy with resultant diplopia.

N otes I

Diplopia is the subjective symptom of double vision . Dysconj ugate gaze is the objectiv,e exa m i nation find i ng of eye rtlisalign­ ment; which may or may not be associated with symptoms of diplopia.

224

• Neurology

1 . Exa m i nation i ncludes d i rect observation of eye move ments i n a l l axes of movement. Does the patient report resolution of diplopia if one eye is covered ? Is the visual acu ity in both eyes eq ual? 2. Drugs and toxins a re a co m mon cause of d i plopia . Offending agents i n­ clude carbamazepine, phenytoin, and alcohol . 3 . Congenita l strabism us, if not corrected , leads to suppression of the visual i mage from one eye. Thus, it is possi ble for a patient with obViously dysconiu, gate gaze not to complain of d iplopia 4. Monocular d i plopia (di plopia with one eye covered) al most always is sec­ ondary to intraocu lar disease. 5 . A CN I I I palsy may be a cause of d i plopia . A com plete CN III pa lsy causes ptosis; inabil ity to move the eye up, down , or i nward; and a d ilated, un reactive pupi l . Many are incomplete. Compressive lesions of CN I I I (aneurysms, tumors) are most likely to cause pupillary i nvolvement and should be i maged . A patient with a ppropriate i m pa i rment of eye movement a nd no pupillary involvement most likely has a medical CN III palsy ( presumed to be a microi nfarction of the nerve fibers), especially if the patient has diabetes . Generally these patients do not need a brain CT, and palsy resolves over a few weeks . They should be fol­ lowed closely, however, to ensure that the pupil does not become i nvolved . 6. Diplopia can be a man ifestation of cavernous sinus disease. The cavernous sinus is an i ntracranial compartment located beh i nd the orbit and lateral to the pitu ita ry. The carotid artery, CNs I I I , IV, and VI, and the V 1 bra nch of V pass throug h this area . The V2 branch of CN V occupies the most inferior portion of the cavernous sinus. Whenever a combination of CN deficits i nvolVing I I I , IV, V l , V2, and/or VI is detected , a structural lesion in the cavernous sinus should be ruled out with an imaging study, preferentially a gadolinium-enhanced MRI. 7. Herniation is a condition where a supratentorial mass causes latera l dis­ placement of the b ra i n stem a nd can ca use a n i psilateral palsy i nvolving the pupi l . Patients who a re herniating have altered menta l status, and thus are not likely to be compla ining of anyth ing, let alone diplopia. The typical clin ica l pic­ ture i n which herniation is a concern is the comatose patient with a "blown" ( i . e . , fixed and di lated) pupil. Hern iation requ i res i mmediate treatment to reduce intracra n ia l pressure (hyperventi lation , man nitol) and prompt CT scann ing to de­ termine the ca use of the problem . Patients with a dilated pupil and a normal mental status are not herniating. ,8 , Central causes of diplopia l isted above involve primarily the bra instem and cerebellum . There' may be other evidence of bra instem or cerebellar dysfunction (other CN palsies, ataxia, hyperreflexia , u pgoing toes, hemipa resis). Imaging studies are indicated in patients with other focal nevrologic findings. 9, Peripheral causes of diplopia listed a bove involve the eye itself and cranial nerves ( I I I , IV, VI). A careful ophthalmolog ic exam i nation is warranted, particLl­ larly in cases of monocular d i plopia . Imaging studies of the brain generally are not needed for intraocular causes of diplopia, medical eN III palsy, or myas­ thenia gravis. However, when u n certa i n a bout exa m find i ngs, imag i ng may help to eliminate the more omi nous possibil ities.

Neurology • 225

D I ZZ I N ESS So Very D i zzy N ow S y n cope/presyncope V e rti g o D i se q u i l i b ri u m N o n s pe c i f i c

OLD SPI N NING MAMA O to l i t h ( be n i g n p o s it i o n a l ve rt i g o ) L ow b l ood s u g a r D e mye l i n a t i o n ( m u lt i p l e s c l e ro s i s ) S t ro ke/T I A/b l ee d P ost-tra u m a t i c I n t rava s c u l a r vo l u m e d e p l et i o n/hypot e n s i o n N e u ro m a/n e o p l a s m N e u ro n i t i s/l a byri n t h i t i s I ntox i ca t i o n ( Et O H , d ru g s , m e d i c a t i o n s ) N e u ropathy/mye l o pathy G I b l e ed/a n e m i a M u l tifacto r i a l/m i g ra i n e A m i n o g lyc o s i d e s/ototoxi c m e d i ca t i o n s M e n i ere's d i se a s e A nx i ety/h y p e rve n t i la t i o n

226 • Neurology

A HOBBLED MAN SPINS A n e m ia H ype rve nti l a t i o n/psych i a t r i c O th e r ( m u l tifacto r i a l , m i g ra i n e ) B e n i g n pos i t i o n a l ve rt i g o B l e e d/h e m o r r h a g e L a byri n t h i t i s/vesti b u l a r n e u ro n i t i s E n d ocri n e/met a bo l i c ( hypog l yc e m i a ) D e mye l i n a t i o n ( m u l t i p l e s c l e ro s i s ) M e n i e re's d i s e a s e A m i n o g lyco s i d e tox i c i ty N e u ropathy/mye l o pa t h y S yn cope/hypote n s i o n P ost-tra u ma t i c I ntox i ca t i o n ( Et O H , d ru g s , m e d i ca t i o n ) N e u ro m aln e o p l a s m S t ro ke/T I A

N otes 1 . A complaint of d izzi ness may mea n d ifferent things to different people. Try to historically determine which category 0f symptoms the patient has (these cate­ gories can be remembered by the m nemonic "So Very Dizzy Now. " a . Syncope/presyncope: lig htheaded ness, fa intness, postu ra l . DDx more l i kely to i nclude a rrhythm i a , decreased cardiac output, orthostasis, autonomic neuropathy, vasovagal reflex. b. Vertigo: I l lusion of movement of patient or surrou nd i ngs, often w ith na usea , vom i ti n g . DDx more l i kely to i nclude benign positional vertigo, labyrinth itis, Meniere's, MS, post-trau matic, vesti bular nerve neu roma . c . Disequilibiru m : u n steadi ness, feel ing "drunk, " clumsi ness, wobbly. DDx more l i kely to i ncl ude d rug i ntoxication , E tO H , a m inog lycoside ototoxicity, severe peripheral neuropathy, m ultifactorial. d . Nonspecific: Anxiety, weakness, vague, d ifficult to describe. DDx more l i kely to incl ude hyperventi lation, systemic disease (anemia, meta bolic!, m u lti­ factorial.

Neurology • 227

2 . When exa m i n i ng a patient with d izzi ness, try to reprod uce the patient's symptoms with a variety of ma neuvers. a. C heck for orthostasis by blood pressure and pulse (su pine and standing) and note any subiective com plai nts the patient has. b. Perform the Hall-Pi ke (Barany) maneuver (see 6 a ) to d iag nose benign positional vertigo. c. Hyperventilation may reproduce symptoms of d izziness associated with anxiety or pan ic attacks. d . Va lsalva maneuver may reproduce symptoms related to decreased car­ d iac output. A patient may compla in of some form of d izziness with more tha n one of these ma neuvers. It is most helpful if the patient can determine which ma neuver actu­ al ly reproduces the symptoms comprising the ch ief com plaint. 3. Vertebrobasilar ischem i a rarely causes isolated vertigo. I nvestigate thor­ oug hly for other evi dence of bra instem/ cerebellar dysfu nction (other c ra n i a l nerve palsies, ataxia, hyperreflexia , upgoing toes, hemiparesis) . 4. Meniere 's disease is associated with hearing loss. Benign positional vertigo and labyrinthitis/vestibular neuronitis are not. 5. In many cases of dizziness, no single foetor stands out as the causative one. A com bi nation of factors may conspire to make the patient more symptomatic than any one factor would alone. For exa mple, a patient may have m i ld dia­ betic neuropathy, cataracts, and a history of alcohol abuse. The combination of peripheral neu ropathy, decreased visual acuity, and diminished cerebel lar func­ tion , plus the possibil ity of a diabetic autonomic neuropathy, put this patient in the multifactorial category of this differential diagnosis. 6 . Benign positional vertigo (BPV) is cha racterized by attacks of vertigo follow­ ing a change in head position , most com monly rol ling over in bed or looking up It is most common in the elderly and is thought to be caused by free-floating calcifications (otoliths) in the posterior sem icircular conal . a . The Hallpike maneuver is used to diag nose this cond ition . The sta rti ng position is with the patient sitti ng, the exam i ner standing to the side, and faCing the patient, with the exa miner's hands supporting the patient's head . The patient may hold onto the exa miner's elbow. The final position is with the patient supine, eyes open, the neck extended 30° below the plane of the bed , and the head rotated 30° laterally toward the side being tested (the side the exam iner is on). The ma neuver involves ra pidly moving the patient from the first position to the second . The test is considered positive (diag nostic for benign positional vertigo) if, after a brief latency of 3-30 seconds, the patient develops a torsional nys­ tagmus in the direction of the side being tested . Upon sitting up, there often is a torsional nystagmus in the opposite d i rection. Each side is tested to determine which side is involved . Occasional ly, both sides a re affected . b . .Torsional nystagmus is the hallma rk of BPV The eye on the side of the af­ fected labyri nth demonstrates a mostly lateral nystagmus toward the affected side, while the opposite eye shows a more rotatory component, with the top of the globe rotating toward the affected side. 228 • Neurology

c . A va riation of the Hallpike known as Epley's maneuver may be used to d islodge the offending calcificati on . The Hallpike is performed to the sym pto­ matic side, then , without allowing the patient to sit up, the patient is rolled to the asymptomatic side into a lateral decubitus position . Fina lly, from this lateral decu­ bitus position , the patient is allowed to sit up. The patient should feel vertigi nous throughout the maneuver, burt aher it is completed , the vertigo should resolve . d . If Epley's maneuver is unsuccessful , the patient can be instructed in vesti bu­ lar exercises to desensitize the vesti bular apparatus . These consist of self-admin­ istered Hall pike maneuvers done two to three times a day, with five repetitions each time. e. Vestibular suppressants such as meclizine prolong the period of vesti bular desensitization and a re general ly less helpful , except in severe cases involving dehydration risk from nausea and vomiting.

H E A DAC H E CT S CA N M E ? C l u st e r Tension S i n u s i t i s/ot i t i s/m a sto i d i t i s C ravi n g ( d rug-s e e k i n g v s . rebo u n d ) A n e u rys m/a rte r i t i s N e u ra l g i a , t r i g e m i n a l M i g ra i n e E l evated i nt r a c ra n i a l p re s s u re ( s u bd u ra l h e m a t o m a , h e m o rr h a g e , AVM , t u m o r, p s e u dotu m o r, h y p e rte n s i o n , hyd roce p h a l u s ) Also: infection (meningitis/meningoencephalitis), metabolic, psychiatriC, post-LP, osteoarthritis, post-concussive, sinus thrombosis

Neurology • 229

l CA N 'T STOP H EA D PA I N S C l u st e r/m i g ra i n e A rteritis (te m po ra l , l u p u s ) N e u ra l g ia (tri g e m i n a l ) T e n s i o n h ea d a ch e

I

S i n u s t h ro m bos i s (ve n o u s) T ra u m a ( p ost-co n c u s s ive) o steoa rth r i t i s/m u s c u l o s ke l eta I P ost- L P

,

. H yd roce p h a l u s E l evated b l ood p r e s s u re I A n e u rysm/s u ba ra ch n ai d h e m o rr h a g e o ru g s ( o piate rebo u n d h ea d a c h e , ste ro i d wit h d rawa l , oral conva c e ptives) P se u d ot u m o r c e r e b ri A rt e r i ove n o u s m a lform a t i o n nfect i o n s ( m e n i n g it i s/m e n i n g o e n c e p h a l i t i s ) N eo p l a s m S i n u s it i s/oti t i s/ma stoi d it i s

I

Also: psychiatric, metabolic (hyperthyroid, Cushing 's, chronic lung disease with hypercapnia)

N otes Headache is a general term used to describe a ny pa i nful sensation i nvolving the structures of the cranium, face, and/or neck.

1 . H istory is all-important in the diagnosis of heaQache. Questions to ask i n­ clude the following: a. Precipitating factors - stress, trauma, certa i n foods, caffeine, alcohol, time of day, d rug use b. Prodromal symptoms -visual scotoma, focal weakness/numbness, aphasia c. Rapidity of onset-seconds, m i nutes, hours d. Lecation (uni- or bi latera l, tem pora l, OCCi pital, cervical) and nature (fh rob­ birig, stabbing, pressu re-l ike, lancinating) of pa i n e. Associated symptoms - n ausea, d i plopia, vertigo, vom iting, lacrimation , 230 • Neurology

fever, gait d isturbance, a ltered menta l status, seizures, photophobia , exacer­ bated by sta nd ing f. Duration - seconds, minutes, hours, days, dai ly/ch ronic g. Alleviating factors - qu iet, sleep, ana lgesics, darkness, prescription med­ ications h . Other pertinent med ica l history - cancer, hypertension, preg nancy, h istory of similar headaches, fam ily history of m ig ra i ne, medications, trauma 2. To scan or not to sca n? Worrisome complai nts such as new-onset severe

headache, seizures, recent change in pattern of a c h ronic headache, and/or focal neurologic deficits may ind icate the need for a n imaging study.

However, routine scanning of patients with symptoms of classic mig ra ine and a nonfocal neurologic exam has a very low yield of revea ling a treata ble intracra­ nial abnormal ity. Routi ne sca nning of patients with chronic headache com pla ints (migra i ne or nonmigra i ne) and a nonfocal neurologic exam a lso tends to have a low yield of demonstrating treatable i ntracranial disease. 3. Approach to diag nosis of chronic headache: see ta ble. Be aware of types of chronic headaches that don't fit well into these categories, i ncluding temporal a rteritis, l u pus, some pituitary tu mors, cluster headaches, hypercapnea sec­ onda ry to pulmona ry d isease, and some endocrinopath ies. Approach to D i a g nosis of C h ro n i c Headache

Headache Type Characteristics

Migraine

Tension

Elevated fep

Onset

Minutes

Hours-days

Days-weeks

Time course of pain

Maximal in 1 5-60 minutes,

Moderate, waxing

Gradually worsen­ ing over time

Duration Hours-(days)

Hours-weeks-

(Days)-weeks(months)

Location

Unilateral, but can be on either side

B ilateral, esp. frontal, OCCipital

Quality of pain

Throbbing, pulsatrle Achey, pressure-like, Pressure-like, dull muscle tension

Nausea, vomiting

Common with headache

No

Nocturnal , early

light and noise sensitivity

Common

No

No

normal between headaches

and waning, may be persistent

months Unilateral if focal lesion, otherwise bilateral

morning

(Table continued on next page.) Neurology • 231

Approach to Diagnosis of C h ro n i c H eadache (Con tinued) Headache Type

Elevated fep

Characteristics

Migraine

Tension

Focal neurologic signs

Stereotyped and transient, often

No

Gradual onset and progressive, sometimes di plopia

visual (scotoma) Seizures

Very rare

No

Occasional

Papilledema

No

No

Yes

4 . S u m m a ry of specific headache types: Symptoms

. Type Cluster

Uni lateral stabbing peri/retro-orbital pai n ; i psi lateral lacrimation, rhinorrhea Occurs i n "clusters" of daily attacks over a period of weeks, between clusters may be asymptomatic for weeks/months/years Duration usua l ly 1 5-30 m i n utes, may last 2-3 hours Unl ike migraine patients, may be agitated, generally do not sit sti ll

Migra i ne, common

Episodic, recurrent, throbbing , u ni- or bilateral pai n Associated with light and noise sensitivity, nausea a nd vomiting Duration usua l ly 2-4 hours, may last u p to 2-4 days Patients seek quiet, dark a reas and try to sleep a nd be stil l

Migra i ne, classic

S i m i l a r to common migraine but preceded b y focal neurologic disturbance (visual scotoma, n u m bness, a phasia, vertigo) and lasting a few m i nutes to an hour

Tem poral arteritis

Throbbing temporal or bitemporal pai n in elderly patient Associated with monocular visual loss, jaw claudication, tender temporal a rtery( ies) to pal pation

I ncreased intracra nial pressure With focal lesion

Without focal lesion Post-LP

Wakens from sleep Associated with early morning vomiting May have papilledema on funduscopic exami nation • Tumor - focal neurologic deficit, seizures, h/o systemic cancer • Abscess - focal neurologic deficit, seizures, may have fever, evidence of systemic emboli (check fund i , nailbeds, cardiac murmur) • AVM- focal neurologic deficit, seizures, head bruit • Pseudotumor cerebri -.may have visua l loss (decreased visual fields and/or decreased visual acuity), sixth nerve palsy/diplopia • Hydrocephalus- may have gait disturbance, decreased upgaze, i ncontinence Often positional, better when lying down Duration may last up to a week

(Table continued on next page. )

232 • Neurology

Type

Symptoms

Subarachnoid hemorrhage

Abrupt onset, may have initial loss of consciousness "Worst headache of my life" May have fever, stiff neck, altered mental status

Meningitis/ encephalitis

Associated with fever, stiff neck, altered mental status May have seizures (especially herpes encephalitis)

Tension

"Pressure-like" or " hat-ba nd" bifrontal or bioccipital pai n May b e associated with neck/shoulder/back pa in Often c h ronic

Rebound

Associated with worsening of headache as analgesics/na rcotics wear off Diagnosis of excl usion

5. Therapy for headache is dependent on the d iagnosis. Treatment with anal­ gesics/ na rcotics may tem pora r i ly a lleviate d iscomfort, but does not treat the cause of the headache. In general , beware of treating pain while leaving the underlying etiology untreated (e . g . , meningitis, hemorrhage) .

Loss OF CONSCIOUSNESS VA G A L S Y N C O P E V o l u m e l o s s/b l e ed i n g A o rt i c d i ss e ct i o n G l u cose d rop A uto n o m i c dysf u n ct i o n L ow ca rd i a c o ut p u t S e i z u re Y o u r m a m a 's v i s i t i n g/a n x i ety/psych o g e n i c N e u roca rd i og e n i c/ref l ex e VA/s u b a rach n o i d h e m o r r h a g e O rt h o s t a t i c hypote n s i o n P u l m o n a ry e m bo l i s m/pe r i p h e ra l va s c u l a r d i s e a s e E l evated b l ood p re s s u re Also� basilar migraine

Neurology • 233

A C LS ! I H A V E TO PA S S O U T A o rtic a n e u rysm/d i s s e c t i o n C o u g h/ m i ctu r i t i o n/re f l ex s y n c o p e L ow g l u co s e S i n u s hyperse n s i tivity, ca roti d I at rog e n i c/d ru g/m e d i ca t i o n H e m o rr h a g e , s u ba ra ch n o i d A uto n o m i c n e u ropathy V a sova g a l s y n c o p e E t h a n o l i n toxica t i o n T ra n s i e nt i s ch e m i c attack O rt h os t a t i c hypote n s i o n ( hypovo l e m i a , poor va s c u l a r tone) P sych og e n i c A systo l e/h e a rt b l ock S e i z u re S u bc l a v i a n stea l O ut f l ow obstru cti o n U n d e rp owe red h ea rt/ca r d i o myop a t hy T a chya r rhyt h m i a Also: basilar migraine

T H I S M A D E M E VA G A L T l A/c e r e b ra l i s ch e m i a H yp e rte n s i o n I n t ra c ra n ia l h e m o r r h a g e ( s u ba ra ch n o i d ) S e i z u re M yo ca r d i a l i nfa rct i o n A o rt i c d i ssecti o n D ru g s/a l co h o l E m oti o n s/psych i a t r i c 234 • Neurology

M i g ra i n e E m b o l i s m , p u l m o n a ry V o l u me loss A rrhyt h m i a G l u co s e d rop A uto n o m i c L ow ca rd i a c o ut p u t ( c o n gest ive h e a rt fa i l u re , a o rt i c ste n o s i s , p u l m o n a ry hype rt e n s i o n Also: neurocardiogenic/reflex syncope

N otes Syncope ( i e , fa inting) is defined as a transient loss of consciousness and pos­ tura l tone d ue to impaired cerebral blood flow. 1 . A description of the spell is crucial tQ appropriate worku p and d iagnosis. The patient as well as any eyewitnesses should be q uestioned . I mportant histori­ cal i nformation can be d ivided into three time periods: a. Prior to the event- postural cha nges (e . g . , patient stands up), precipitat­ ing factors (ski pped meals, physical exertion, severe stress, cough, m ictu rition ) , symptoms (headache, dizziness, chest pa in, shortness o f breath, heart pa lpita­ tion, fa intness, focal neurologic symptoms, nausea ) , and eyewitness descriptions (altered behavior/mentation, pa llor, excessive sweating) . b . During the event (usually from the eyewitness) - rapid ity of onset, duration of episode/unresponsiveness, involuntary motor activity, a pnea , overt seizu re activity, inj ury to the patient, loss of continence. c. After the event- orientation/responsiveness, a m nesia, rapidity of recov­ ery to baseline mental state, recurrent episodes. In addition, pertinent information about pre-existing med ical cond itions, cu rrent medications, recent a lcohol!d rug i ngestion, a nd fa m i ly h istory of fa inting or seizures should be sought. 2. Cond itions that may mimic syncope incl ude seizure, drug/alcohol intoxica­ tion, subarachnoid hemorrhage and basilar migraine. Conditions associated with faintness but in which complete loss of consciousness is rare i nclude hypo­ glycemia, anemia, hyperventilation, panic disorder, and hysteria. 3 . The differential for syncope can be thoug ht of in four major categories: a. Neurocardiogenic- reflex inhi bition of heart via autonomic nervous system • I ncl udes vasovagal attock, carotid sinus syndrome, m ictu rition, cough, valsalva, emotional stress. • Disti nguished by the presence of preci pitating event and a bsence of cardiac and peripheral vascular pathology. Usually in younger persons. Neurology • 235

b. Orthosta ti c - drop in blood pressure due to inability to mai ntain vascular tone • Med ications, postu ral change, neu ropath ies (especially a utono m i c ) , neurodegenerative disease, peripheral vascula r d isease, hypovolemia . • Disti ngu ished by orthostatic tachycardia/hypotension ol'l exa m , a n d history o f spells correlating with postura l change. c. Card i oge n i c - di rect card iac pathology • Cardiomyopathy, aortic valve disease, tachyarrhyth m i a , bradyarrhyth­ mia/asystole. • Disti ngu ished by ca rd iac sym ptomatology ( e . g . , chest pa i n , pa lpita­ tions), known cardiac d isease, and ECG abnormal i ties during spell. d . Other- miscellaneous • Hypog lyce m i a , cerebral ischemia/i nfa rct, i ntracra nial hemorrhage, basilar m ig raine, drug/a lcohol intoxication , pulmonary embolism (PEl, . aortic dissection . • SystemiC metabolic causes (hypoglycemia, intoxication) associated with "woozi ness , " more g radual onset . Vascu lar causes usually due to a sudden mechan ical obstruction of cerebral vasculature (infa rct, d issec­ tion ) . Catastrophic causes i nclude PE and intracranial bleed . 4. Reflex syncope is due to excessive vagal sti m ulation , which slows the heart rate a n d decreases cerebral blood flow, causing u nconsc i ousness . Carotid sinus syndrome is due to excessive pressure sensitivity of the carotid sinus. Tight collars o r other extel nal pressure on the neck can provoke syncope . Other known provocateurs of reflex syncope include m ictu rition , valsa lva maneuver, a n d cou g h i ng . Vasovagal syncope is a type of reflex syncope triggered by pa i n , fear, or other sudden emotional stress . It typica l ly occu rs in adolescents and young adu lts and may be more likely in the setting of prolonged standing, fatigue, and/or fasti ng. 5 . Med ications commonly i m plicated in orthostatic hypotension i nclude anti hy­ pertensive d rugs, diuretiCS, nitroglyceri n and other a rterial vasodi lators, tricyclic a ntidepressants, phenothiazines, lith i u m , calcium channel blockers , a nd beta blockers. 6. Cardiac causes of syncope can be revealed by physical exam and ECG. It may be necessary to monitor patients with card iac telemetry or a Holter monitor to detect a tra nsient a rrhyth m i a . Ec hocard iogra phy may demonstrate aortic valve disease or cardiomyopathy. 7. Initial workup for a transient loss of consciousness is fa i rly stra ightforwa rd : a . ABCs; if episode over, then proceed with further evaluation i ncluding h istory and exa m . b . ECG a n d blood pressure monitors. c. Accucheck, pulse oxi metry. d . Laboratory studies to be considered electrolytes, g l ucose, BUN/C r, CBC, etha nol , tox screen. 8. F u rther workup (and treatment) depends on the suspected cause of the episode. a. Seizure CT/MRI, EEG. 236 • Neurology

b . Card i a c cardiac telemetry/Holter mon itor, echocard iogra m , cardiac enzymes Pul monary embol ism -VQ scan , pulmonary ang iogra m c. Orthostatic some cases may need provocative testing such as tilt table d Neuroca rdiogenic if i n itia l workup negative a nd history suggestive of reflex syncope, general ly no further workup is requ ired . e. Cerebrovascular: Aortic d issection/aneurysm - chest x-ray/CT, ang iogra m S u ba rachnoid hemorrh age/cerebral a neu rys m - head CT MRI, Angiogra m , lumbar pu ncture Tra nsient ischem ic a ttack - head CT/MR I , ca rotic/vertebral doppler, a ng iogra m , coagulation lab studies f. Metabolic Hypoglycemia- check serum glucose, admin ister IV glucose I ntoxication - blood ethanol, seru m or urine tox screen

M O N O C U LA R V I S U A L L o s s BLI N D B l o o d vess e l s ( a rteriti s , h e m o r r h a g e , e m b o l i s m ) L e n s (cata ract) I nfect i o n N e rve (tu m o r, o p t i c n e u ri t i s , g la u c o ma-v i a p r e s s u re o n n e rve) D et a c h e d reti n a/ot h e r reti n a l d i se a s e

G RAVE V I S I O N E D G la ucoma R et i n a l/oc u l a r m i g ra i n e A rte r i t i s , te m po ra l V e n o u s t h ro m bo s i s ( c e n t ra l reti n a l ve i n o c c l u s i o n ) E m bo l i s m (ce n t ra l reti n a l a rt e r y o c c l u s i o n ) Neurologv • 237

paz

V a sc u l a r occ l u s io n (ca ro t i d ) I nfect i o n s ( C M V ret i n it i s ) S e n i l e cata ract I n t ra oc u l a r b l e e d O pt i c n e u ri t i s N eo p l a s m ( o p t i c n e rve g l i o m a ) E l evated s e r u m v i co s ity ( s i c k l e c e l l , po lycyt h e m i a ) D et a ch e d ret i n a

M O N O -VI S I O N E D M ig ra i n e , o c u l a r/reti n a l O cc l u s i o n , c e n t r a l ret i n a l a rtery N eo p l a s m O cc l u s i o n , ce n t ra l ret i n a l ve i n V a s c u l i t i s , t e m p o ra l ( g i a nt c e l l ) I nfect i o n S e n i l e cata racts I n t ra o c u l a r b l e e d O pt i c n e u ri t i s N ot m o n o c u l a r v i s u a l l o s s E l evated s e r u m v is c o s ity D et a ch e d reti n a Also: glaucoma

N otes Monocular visual loss is either a subjective report of tra nsient visual loss in one eye (as opposed to Ofle visual field) or a n objective finding of decreased visual acu ity in one eye. Pseudotumor cerebri and other causes of increased intracra­ nial pressure generally produce bi lateral signs/symptoms

1 . It is critical to distinguish between monocular visual loss and a visual field cut. With monocular visual loss, yisual acuity is diminished in one eye, a nd

the lesion is in the eye o� optic nerve. With a visual field cut, vision is i mpaired in a particular a rea of tbe visual field in both eyes, and the lesion is in the optit: tract 238 • Neurology

or the bra i n . This distinction ca n be made clear by testing visual acuity and visual fields one eye at a time. Sometimes, patients mistake a visual field cut for monocular visual loss on the same side ( " Doc, I ca n 't see out of my left eye. " I . On exam , however, the patient demonstrates a left visual field cut in both eyes . 2 . True monocular visual loss is ca used by a lesion i n the eye or optic nerve (anterior to the optic chiasm), a n d thus may be d ue to problems in the lens, retina , blood vessels, or the optic nerve itself. 3 . Amaurosis fugax is the sub iective compla i nt of tra nsient visual loss in one eye, often described as a veil or shade com ing over the eye. Th is is essentially a transie(lt ischemic attack of the reti na, and may be caused by emboli from the heart to the central reti nal a rtery, an ulcerated carotid plaque causing emboli or occlusion, or temporal mteritis i nvolvi ng the carotid a rtery. 4. It is critical not to miss the d iag nosis of tem poral arteritis because prompt treatment could prevent com plete infarction of the reti na. The classic clin ical pic­ ture is a person > age 65 , with uni lateral or bi lateral severe headache, tender temporal a rteries, low-g rade fever, a nemia , and elevated ESR. Amaurosis fugax, polymya lgia rheu matica , and iaw claudication may occu r. Treatment is with pred n isone 60- 1 00 mg/d and should not be delayed to obta i n tem pora l artery biopsy, but biopsy should be performed bilaterally within 3 days of initi­ ating steroids. ESR should be monitored and used to g uide therapy. In cases of acute retinal ischemia, IV methylprednisolone has been used . 5 . Ophthal moscopic exa m i nation is also of g reat i m porta n ce i n eva l uati ng monocular visual loss, since central reti nal a rtery occlusion , central retinal vei n occlusion , retinal detach ment, cataracts, infections/reti nitis, hemorrhage, a n d optic disc edema can b e detected .

P TO S I S LID DROP L i d i nf i l t ra t i o n ( by tu m o r o r i nf l a m m a t o r y t i s s u e ) I nfe c t i o n (zoster, botu l i s m ) D ia betes/thyro i d D ru g s . R eceptor q nt i b o d i e s ( myast h e n i a ) O cu losym patn e t i c p a l s y/oc u l o motor p a l sy P ropto s i s

Neurologv •

239

T E N S I LO N M E, DOC T h i rd n e rve pa l sy E ye d ro p s (ste ro i d ) N e u ro m u sc u l a r j u n c t i o n d i se a s e ( mya sth e n i a ) S u rgery I n fect i o n ( h e rp e s zoste r o p h t h a l m i c u s) L i d i n f i l t ra t i o n ( by t u m o r o r i nf l a m matory t i ss u e) O c u l o sy m p a t h e t i c pa l sy ( H o r n e r 's syn d ro m e) N e u rotox i n s ( botu l i s m ) M yopathy ( m u s c u l a r dystrop hy, myoto n i c dystrop hy) E n o p h th a l m os ( eyeba l l retra c t i o n i nto o r b i t) D i a betes/thyro i d d i s e a s e O p p o s i te l i d retra cti o n C l u s t e r h e a d a ch e !

Also: congenital ptosis

i

I N otes

I

Ptosis is a physical finding of one pa lpebral fissu re being sma ller than the other, i e , a d rooping eyel id .

1 . Ptosis may be the result of a partia l or complete thi rd nerve palsy (with asso­ ciated ophtha l moplegia and pupi llary dilation/unreactivity) . For a full descrip­ tion of third nerve palsy, see notes 5-9 under the heading Diplopia, page 225 . 2 . Ptosis is part of the oculosympathetic palsy or Horner's syndrome, which con­ sists of unilateral ptosis, m iosis (small pupil), and anhidrosis of the face (de­ creased sweating) .

The sympathetic pathways go down the spinal cord to the thoracic level, where they exit the cord and ascend the neck as the sympathetic trunk to the su­ perior cervical ganglion, then follow the i nternal carotid a rtery and, ultimately, the V l d ivision of cranial nerve V to the eye. Any lesion that interru pts the oculosym pathetic pathways can result i n Horner's syndrome, i ncluding tumor (lung, mediastinal, thyroid, pharyngeal , lym­ phoma, spinal cord ) , tra u m a , a nd congen ital causes, as well as ( less l i kely) carotid dissection/occlusion, cervical d isc or rib, mening itis, bra i nstem infarct, syrinx, polio, pneumothorax, and ALS . A significant proportion of Horner's cases are id iopath ic, with a high frequently of diabetes and hypertension in this idio­ pathic group 240 • Neurology

3 . Neuromuscular d isease , speci fica l ly myasthen ia g ravis, may present as

ptosis (often bilateral but asym metric) . This often is associated with fluctuati ng ocular palsies (diplopic:L facial weakness, weakness of speech and swa llow­ ing, and neck and shoulder g i rdle weakness. Not infrequently, the weakness af­ fects the m uscles of respiration . Characteristica l ly, muscles a re fati g uable if subjected to susta ined contractio n . Pupillary muscles, smooth m uscle, cardiac muscle, and sensation are unaffected The Tensilon (edrophonium) test is helpful in the diagnosis of myastheni a . Myasthenia i s caused by a utoa ntibod ies to the acetylchol ine (ACh) receptor. Norma lly, ACh crosses the synapse, binds to the receptor, and eventually is me­ tabol ized by acethylcholine esterase (ACh E ) In myasthenia, the ACh receptor is pa rtia lly blocked, and ACh is m eta bolized by ACh E betore it can bind the re­ ceptor. Edrophonium is an AChE inhi bitor, delaying the meta bolism of ACh and increasing the likeli hood of ACh binding to the partially blocked receptor. Thus, a d m i n i stration of ed rophon i u m to a myasthenic patient should i n crease the strength of involved muscles. 4. An eyelid may appear ptotic even when it is normal, if compared to a re­ tracted eyelid (e.g , proptosis) on the opposite side. likewise, a normal lid may look ptotic if the eyeball itself is retracted into the orbit due to loss of orbital tissue.

R I G I D I TY D O PAM I N E D ysto n i a o l ivo po ntoce r e be l l a r a t ro p hy ( O PCA) P a rk i n so n's A n ky l os i n g s p o n d y l i t i s M e n i n g i s m u s ( m e n i n g i t i s , s u ba ra ch n o i d h e m o r r h a g e ) I n c re a s e d t o n e/s p a s t i c i ty N e u ro l e pt i c m a l i g n a n t syn d ro m e E l evated i ntracra n ia l p r es s u re

N otes Rig idity is a conti nuous or intermittent i ncrease i n muscle tone throughout the full . . range of passive movement. Neurology • 24 1

p

Cogwheeling is a form of rigid ity charaGterized by rhythm ic, rachet-l i ke resistance throughout the range of motion . • Lead-p i pe is a form of rigid ity cha racterized by u n iform resi sta nce throughout the ra"nge of motion . Spasticity i s a n i ncrease i n m uscle tone that i s m i ld with slow movement and more pronounced with rapid movement. Classical ly, rapid passive movement is met with i ncreasing resistance until a point at wh ich the resistance breaks ( "clasp knife phenomenon " ) . •

1 . Rigid ity m a y be caused by:

a . Neurolog ic pathology • Extrapyra m idal/basal ganglia disorders (dystonia, oIivopontocerebel­ lar atrophy, Parkinson's, drug effects) • Corticospinal i nvolvement (spasticity, elevated intracranial pressure/her­ · n iation) . b. Men ingeal i rritation (men ingitis, suba rachnoid hemorrhage) c. Skeletal i m mobi lity (ankylosing spondylitis, severe spinal osteoarthritis) 2 . In genera l , i ncreases in m uscle tone may be due to corticospinal or ex­ trapyramidal pathology. The term rigid ity may be used to refer to hypertonus of extrapyra m ida l orig i n , and spasticity refers to i ncreased tone of corticospinal orig i n . Disti nguishing characteristics of" each a re summa rized i n the table. Extra­ pyra m idal syndromes of rigid ity a re not usually associated with hyperreflexia, Ba binski signs, or pa ra lysis, and are more often associated with other move­ ment disorders such as tremor, choreoathetosis, ataxia, and/or dystonia . Rigidity

Spasticity

I i Associated abnormal movements

Cogwheel or lead-pipe

Clasp-knife

Yes

No

Associated weakness/paralysis

No

Yes

Deep tendon reflex/plantar response

Normal

Increased/ upgoing

3. Acute general ized rigidity is often an emergent sign. I n itial treatment a i ms at maintain ing vital functions while rapidly determi n i ng the etiology. a . ABCs, vital signs, monitors, O2 b. Work-up by suspected d iagnosis: • Increased ICP/herniation: EMERGENCY. May requ i re i ntubation, hy­ perventilation, and/or mannitol . Diagnostic tests i nclude head CT /MR I . Diagnostic considerations i nclude mass lesion, i ntracranial bleed, C N S i nfection, head trauma. • Meni ngitis: EMERGENCY. Check CBC and differenti a l , electrolytes, B U N /C r, g l ucose, cu�ures, l u m ba r punctu re ( i f no evidence of i n- . creased i ntracran ial pressure) . , ' . Subarachnoid hemorrhage: EMERGENCY. Check C BC , platelets, PT/PTI ( I NRI. electrolytes, BUN/Cr, glucose, head CT. 242

• Neurology

Neuroleptic malignant syndrome: EMERGENCY. Rule out other causes of acute rigidity, obta i n medication h istory, check tox scree n , CBC, electrolytes, glucose, BUN/Cr. • Dystonia: U RGE NT. Rule out other causes of acute rigid ity, obta i n med­ ication h istory. c. Treatment is di rected toward the underlying process. 4. Chronic rigidity is more l i kely a permanent sequelae of neurolog i c in i u ry (spasticity) or a neu rodegenerative condition ( Pa rki nson 's , OPCAI, or due to skeletal lim itations (ankylosing spondylitis, severe spinal osteoa rthritiS) 5. Acute iatrogenic dystoniC reactions may occur in response to therapy with phenothiazines, haloperidol, an tiemetics, and other related drugs. Treatment with di phenhydra mine relieves the dystonia in most cases. •

TREMOR S HAKE IT U P S ta g e f r i g h t/e moti o n a l H yp e rt hyro i d/hypo g l yc e m ia A l co h o l w i t h d rawa l K i n e s og e n i c E ss e n t i a l/fa m i l ia l I nt e n t i o n T ox i n s/d r u g s/m e d icat i o n s U n d e rl y i n g m eta b o l i c c o n d i t i o n s ( u re m ia , h e p a t i c e n c e p h a l o pat hy, W i l so n 's) P a rk i n s o n's

H ELP, I 'M SHAKING H yp o g l yce m ia E ss e n t i a l L it h i u m/va l p roate/o t h e r m e d i c a t i o n s P a r k i n so n 's NeurologV • 243

I ntox i c a t i o n (e . g . , sti m u l a nts) M eta b o l i c/a ste r i x i s S ta g e f r i g h t/e m oti o n a l H yp e rt hy ro i d A l c o h o l wit h d rawa l K i n e s og e n i c I nt e n t i o n N o r m a l/phys i o l o g i c G e n et i c (e . g . , W i l so n 's , H u nt i ngto n 's d i s e a s e )

N otes Tremor is defined as an involu ntary rhythm ic oscillatory movement. Asterixis is a condition cha racterized by nonrhyth m ic, episod ic loss of m uscle tone . Max.; be confused with tremor.

1 . Tremor can be d isti nguished into th ree main types based on clin ica l featu res. a. Resting tremor is typica lly a coarse, relatively slow ( 3-5 hertz) tremor that

is maxi mal when the affected area is at rest. Usually associated with forms of parkinsonism . b. Intention tremor is a rhyth mic oscillation that becomes more pronounced as the affected a rea approaches a target, and is a bsent or m i n i mal at rest and at the beginn ing of motion . Etiologies include all forms of cerebellar d isease. c. Postural/action tremor is a rhyth m i c tremor present when the affected a reO is actively mainta i ned in a particular posture or during active movement, but a bsent at rest. Physiologic tremor, alcohol withd rawal, hyperthyroidism, and famil ial essential tremor a re all good exa mples. 2. Six cardinal signs of parkinsonism: resting tremor, rigid ity, bradyki nesia , flexed postu re, loss of postural reflexes, and "freezi ng . " For a defin ite diagnosis of pa rkinsonism , at least 2 of the 6 features must be present, and at least 1 of the 2 must be either resting tremor or bradyki nesia. 3. Pa rki nsonism may be d ivided into four maior syndromes. a. Idiopath ic: No known etiology- Pa rkinson's d isease. b. Symptomatic: Due to an identifiable insult- drug-i nduced ( phenoth iazine, ha loperidol), hyd rocephalus, hypoxic, postencepha litic, pa rathyroid dysfunc­ tio n , toxic ( manga nese, ca rbon monoxide, "designer" d rugs -MPTP, cya n ide), posttraumatic, tumor, infarction . c . Parki nson-plus< Pa rki nson i a n with additional sign ifica n t sym ptoms ­ Alzheimer's disease, multi ple system atrophy, progressive su pran uclear pa lsy. d . Genetic: I nherited forms of parkinsonism - Hallervorden-Spatz, H u nting­ ton's disease, Wi lson's disease. 244 • Neurology

4 . I ntention tremor is characterized by i m pa i red finger-nose-fi nger and heel­ knee-shin ma neuvers. These patients often have other evidence of cerebellar dys­ fu nction , such as nystagmus a nd gait i nstabil ity U n i lateral intention tremor is suggestive of focal cerebellar disease such as i nfa rct, bleed , or tumor, and should be evaluated with MRI (CT if acute) . . 5 . Postural or action tremor is not present at rest, and, although it is brought out by motor activity, is not greatly a m plified u pon approach to a target like i nten­ tion tremor. Postural tremor may be obvious s i m ply by hold ing the arms out­ stretched . 6. Two major types of action tremor i nclude the following : a . Physiolog ic: This tremor is simply an exaggeration of a normal phenome­ non ( usually 8- 1 4 hertz) . I t is precipitated by many sti m u l i , i ncluding anxiety/fear, hyperthyroidism, caffeine, l ith i u m , va lproic acid, alcohol/drug withd rawa l , exerci se, and e n ha nced adrenergic sti m ulation ( i n c l u d i n g pheochromocytoma) . b . Familial or essential tremor: Usua l ly 4-8 hertz shaking of the hands or head, often a ble to be suppressed by a lcohol , va riable in i ntensity. If there is a fa m i ly history ( usually a utosomal dom i nant), it is considered familial tremor; if fam ily history is not evident, it is termed essential tremor; and if it man ifests only late in l ife, it is called senile tremor. 7. Drugs associated with tremor i nclude adrenerg ic d rugs (al buterol, meta pro­ terenol ) , sti m u lants ( methylphen idate , coca ine, caffei ne, a m pheta m i ne), theo­ phyl line, pred nisone, va lproic acid , and lith i u m . 8. Management of tremor depends upon the type of tremor. a . Id iopath ic parki nson ian tremor may respond to ca rbidopa/levodopa , dopa m i ne agonists ( bromocri ptine, pergolide), or anticholi nerg i cs (tri­ hexyphenidyl, benztropine) . b. SymptomatiC parkinsonism also should be managed by treating the cause ( i . e . , discontinuing offending d ru g , identifying and e l i m inating toxi n exposure, relief of hydrocephalus, etc . ) c. Severely d isabl ing d rug-resistant parkinsonian and essential tremors have been successfully treated with stereotactic thalamotomy. d . Cerebellar tremor also may be treated depending on the cause ( i . e . , re­ moval of hemorrhage, excision of tumor, etc . ) e . Essential tremor i s effectively treated with either propranolol o r prim idone.

Neurology • 245

WEAKN ESS * M ISS GIMP M ye l opathy ( a c ute)/myo pathy I nfect i o n S tr o ke S yste m i c i l l n e s s G u i l l a i n- Ba rre s y n d r o m e I atrog e n i c/d r u g s M ya st h e n ia P a ra lyt i c tox i n s/p e r i o d i c p a r a l ys i s Note: MISS GIMP emphasizes the acute causes of motor weakness.

G , I ' M L I M P , CA N 'T S TA N D G u i l l a i n- B a rre syn d ro m e I atrog e n i c ( p a ra lyti c a g e n t s , a m i n og l yco s i de s , stero i d s ) M yo pa thy/myos i t i s L o u G e h ri g 's d i s e a s e (ALS, m ot o r n e u ro n d i s e a s eu s u a l l y g ra d u a l ) I nfect i o n ( p o l i o, botu l i s m ). M ye l o pathy ( a c u te ) P e ri o d i c pa ra l ys i s , p o r p h y ri a , pa ra p rote i n e m ia C u s h i n g 's A rt e r i t i s/va s c u l it i s/st ro ke N eo p l a st i c ( m e n i n g it i s , p a ra n eo p l a s t i c) T ox i n s ( l e a d , a rse n i c, p u ffe rf i s h , t i ck pa ra l y s i s ) *

Acute/subacute, bi lateral with minimal sensory involvement

246 • Neurology

S yste m i c i l l n e s s ( a n e m i a ) T hy r o i d A dd i s o n 's N e u ro m u sc u l a r j u n c t i o n d i s e a s e ( myast h e n i a ., La m b e rt-Eaton syn d ro m e ) D ia betic a myotrop hy

N otes Weakness is the reported symptom or demonstrable sign of decreased strength of m uscular contractio n . The cause of wea kness m ay be at any level of the motor u n it (bra i n , spinal cord, nerve root, peripheral nerve, neuromuscular j unc­ tion , or muscle). It a lso may occu r secondary to systemic or psychiatric illness.

1 . Localization of weakness can be determined from only a few qual ities of the patient's com plai nts/physical signs: sym metry, sensory i nvolve ment, a n d deep tendon reflexes/planta r responses. Lesion Location

Usually Symmetric

Prominent Sensory Loss

Central Brain

No

Often ipSilateral to weakness

Maybe

Yes, usually have sensory level

Maybe Yes

Spinal Cord

Peripheral Peripheral nerve Neuromuscular junction Muscle Both Motor neuron disease

DTRs

Toes Up?

Increased (decreased acutely) Increased (decreased acutely)

Yes

Yes No

Decreased Decreased

No No

Yes

No

Decreased

No

Maybe

No

Increased

Yes

Yes

DTRs deep tendon reflexes Muscle weakness due to brain lesions is discussed under "Stroke." Muscle weakness due to spinal cord lesions is discussed under "Myelopathy. " Muscle weakness due to peripheral nerve lesions is discussed under "Neuropathy. " =

2 . Amyotrophic lateral sclerosis (ALS; also called Lou Geh rig's d isease, motor neuron d isease) is unique in that it presents with chronic, progressive weakness,

Neurologv • 247

and on exam i nation has mixed u pper (increased tone, increased DTRs, u pgoing toes) and lower (atrophy, fasciculations) motor neuron signs. 3 . Acute/subacute weakness can be o n emergency, especially if the integ rity of the a i rway and respi ratory m uscles is comprom ised . Diag noses that merit careful mon itoring of respi ratory function i nclude: Guillain-Barre, periodic paral­ ysis, acute myelopathy (high cervical ) , and myasthen i a . Serial vital capacities are critical in the ma nagement of these patients. 4. In general, neuropathic causes of weakness will be weaker dista lly and will have some sensory involvement, and neurom uscu lar j u n ction and m uscular ca uses of weakness will be weaker proximally a nd have no sensory i nvolve­ ment. In addition, muscular causes of weakness may show elevated m uscle en­ zymes (CPK, aldolase). 5 . Guillain-Borre syndrome is a sing ular neuropathic couse of acute/subacute weakness in which sensory com pla ints are not often promi nent. It is cha racter­ ized by symmetric, d ista l-to-proximal, progressive motor paralysis with areflexia . Diagnosis is often mode clinically, but can be supported by delayed nerve con­ duction studies. Lumbar puncture may reveal elevated CSF protein without pleo­ cytosis Treatment is either plasmapheresis or i ntravenous i m m u noglobu l i n . Careful monitoring of respiratory function (by vital capacity) and autonomic function ( by vital signs) is necessary to determine when i nterventions such as i ntubation may be req uired . Other supportive care includes aspiration precautions ( if not i ntu­ bated ) , prophylaxis for deep venous thrombosis, decu bitus prophylaxis, bowel and bladder care, n utritional supplementation, and range of motion exercises to prevent contractures. 6. Myasthenia gravis can present with acute/subacute weakness and respi ra­ tory insufficiency. Typical clin ical cha racteristics i nclude waxing and wa n i n g symmetric proximal extremity a n d bulbar (cranial nerve) weakness with n o sen­ sory loss. Diagnosis is suggested by the clinical picture, and can be supported by a positive Tensilon test (see the Ptosis section) EMG also shows a cha racter­ istic decremental response to repetitive sti mu lation . Chest i maging may demon­ strate an associated thymoma . Acetylcholine receptor a ntibod ies may be detected in the seru m . Treatment acu tely i nvolves su pportive care m uch as outli ned a bove (for GUillain-Barre) with careful monitoring of vital capacity and i ntubation when nec­ essary. Plasma pheresis and a nticholi nesterase d rugs ( pyridostig m i ne , neostig­ m i ne) a re useful acutely. Thymectomy is indicated in all cases of thymic tumor, and may help i n many other cases because of non-neoplastic thymic hyperpla­ sia . Corticosteroids and other i m m u nosuppressants (azath iopri ne, cyclophos­ phamide) are used for long-term therapy. 7. Patients who undergo iatrogenic paralysis for management of a venti lator have been reported to remain para lyzed for a prolonged period of time (days to weeks) after disconti nuation of the paralytic agent, in spite of the (normally) short half-lives of these agents. The likeli hood of prolonged post-treatment paral­ ysis appears to increase with longer duration of therapeutic paralysis and with the severity of other systemic i l lnesses (especially renal fa ilure ) . 248 • Neurology

8 . Endocrinologic causes of weakness include the folloWing: Thyroid

Thyrotoxic-grodually progressive, especially in thig hs/pelvic m uscles, normal CPK Thyrotoxic periodic paralysis - attacks of symmetric wea kness, usually with low K Thyroid ophth a l mopathy - exophtha l m os a n d wea kness of extraocu lar muscles Myasthenia gravis-associated with dysthyroidism (either hyper­ or hypo·) Hypothyroidism - diffuse myalgias, stiffness, slowed contraction, and relaxation of muscles Addison's - genera lized weakness, fatigability, associated with Adrenal electrolyte i m bala nce Cush ing's - proximal weakness, also may be seen aher corticosteroid treatment 9. Systemic causes of nonspecific weakness may be secondary to a nemia, congestive heart fa ilure, malnutrition, deconditioning, cancer, etc. 1 0. Several paralytic i ntoxications may lead to acute weakness and even res­ pi ratory collapse. These i nclude botu lism, tick paralysis, pufferfish i ngestion, and paralytic shellfish poisoning.

C l inical Conditions or Diagnoses

D E M ENTIA DEMENTIA D eg e n e rat ive E t h a n o l/tox i n s/d r u g s (ch ro n i c) M u I t i -i nfa rct E n d o c ri n e/m et a b o l i c N o rma l p re s s u re hyd roc e p h a l u s T u m o r/t ra u m a I nfect i o n A l z h e i m e r 's Neurologv • 249

D E M E N TIA M I N D D egenerative ( Pa r k i n son's, P i ck's) E th a n o l M u lti-i nfa rct E n docri ne (thyro i d d i sease, C u s h i n g 's , Ad d iso n's) N o rmal pre s s u re hyd roce p h a l u s T u m or I nfecti on ( H I V, n e u rosyp h i l i s) A l z h e i m e r 's M eta l s a n d oth e r ch ro n i c i ntoxications I nj u ry (co ntu s i o n s , chro n i c s u b d u ra l s ) N utritiona l/m eta bol i c ( 8 1 2 def i c i e n cy, Korsa koff's) D ep ress ion/psych iatric (pseudode mentia)

N otes Dementia is an acquired condition characterized by chronic deterioration of i n­ tellectual function and associated with i m pa irment i n at least three of the follow­ ing areas: language, memory, visuospatial skills, personality, and cog nition . It is not associated with an acute confusional state.

1 . By defi n ition , it is not possible to make a clear diagnosis of dementia in a patient with an acute encephalopathy. Only after the encepha lopathy clears can the diagnosis of dementia be enterta ined . 2 . Sta ndard work-up for revers i ble causes of dementia i n cludes CT /MRI ( normal pressure hydrocephalus, neoplasm, m ulti-infarct), TSH ( dysthy­ roidism), VDRL/RPR ( neurosyph ilis) , B 1 2 , and folate. If the onset is su bacute or ra pidly p rog ress ive, an LP (subacute a n d chronic infections) should be strongly cons idered . 3 . Dementia must be d isti nguished from a num ber of other cond itions. a. Aphasia: This is purely an a bnormal ity of language expression/compre­ hension . With aphasia , it may be d ifficult to determine that the patient has intact memory and intellectual function. Aphasia may be a part of dementia, but by itself is suggestive of focal cerebral pathology. b. Depression/pseudodementia : Severe depression may man ifest as ex­ tremELpsychomotor retardation . Patients with pseudodementia have a primary psych iatric disorder, and the symptoms resolve upon successful treatment of this disorder. They tend to answer " I don't know" to di rect questions, and show no evidence of cortical dysfunction l i ke a phasia . This i s u s u a l ly a diag nosis of 250 • Neurology

",

s1

exclusion . It is important to realize that depression can accompany many de­ menting illnesses without being the cause of the dementia . . c . Acute confusional state/deliriu m : This is the most important disorder to distinguish from a dementia, because delirium requires urgent diagnosis and treatment of its underlying cause. Clinical features associated with delirium in-;; �Jude a waxing and waning course, abrupt onset, underlying medical disease, and hallucinations. It is possible for a demented patient to become delirious (i.e . , a patient with Alzheimer's d isease develops a cystitis or pneumonia and becomes more confused), but the diagnosis of dementia cannot be made for the first time in a delirious patient.

M Y E L O PAT H Y BAD STRA I N B leed/hemorrhage/a rteriovenous ma lformation A bscess, e p i d u ra l D e my� l i nating d i sease ( m u lt i p l e sclerosis) S pond ylosis/ste nosis T ra u m a

R adiation A rteriat occ l u s i on/vascu l i t i s/i nfa rction I nfection N eoplasm

IT'S S A V I N G T H E C O R D � diopath ic ' roxie/iatrogenic ( i nt r athecal ch emothera py) 'System i c l upus e ryth ematosus

Neurology • 251

•

S po n dy l o s i s/ste n o s i s ( d e g e n e rative s p i n e d i se a s e ) A ra ch n o i d i t i s V a sc u l a r/i sch e m i a I nfe c t i o n (tra n sverse mye l it i s , syp h i l i s , Pott's d i sea se/t u b e rc u l o s i s ) N utriti o n a l ( B 1 2 d ef i c i e n cy) G e n etic ( Fr i e d r e i ch's a t a x i a ) T ra u ma H e m o r r h a g e/a rte r i ove n o u s m a l f o r m a t i o n E p i d u ra l a bs c e s s C o n g e n i t a l (tet h e re d c o r d , C h ia ri m a lfo r m a t i o n , s y r i n x ) O nco l o g i c ( p ri m a ry s p i n a l t u m o rs , e p i d u ra l a n d b o n y m etasta s e s , c a rc i n o m a t o u s m e n i n g it i s ) R a d i at i o n D e mye l i n a t i o n ( m u lt i p l e s c l e ro s i s )

N otes Myelopathy is any pathologic process lead ing to spinal cord dysfunction .

1 . Clinical signs of a myelopathy i nclude weakness and sensory loss below the level of spinal cord injury. 2 . Although the classic motor findings of a myelopathy are upper motor neuron signs (spasticity, hyperreflexia, upgoi ng toes), upper motor neuron signs may be absent acutely; that is, acute motor find i ngs of a myelopathy a re often a flaccid paralysis. 3 . A classic sensory finding of spi nal cord dysfunction is a sensory level, i .e . , numbness or sensory loss o n the tru n k below a certai n dermatome. This is i n­ valuable in loca l izing the segment of cord i nvolved . 4 . Remember that the spinal cord ends at L H2. If the lower extremities show upper motor neuron signs, and the u pper extrem ities a re norma l, i mage the tho­ racic and u pper lumbar spine. If all four extremities a re i nvolved , i mage the cer­ vical spine. 5 . Acute myelopathy is a neurologic emergency. I ma g i n g is u rgent in a l l cases, a n d I V methylpred n isolone should b e administered i n cases o f myelopa­ thy resulting from trauma or neoplasm . Definitive acute therapy may i nclude sur­ g ical decompression/spine stabilization and, for neoplastic disease, rad iation. 6 . It is i m porta nt to obta i n any history of trauma, back/neck pai n , pre-existing cancer, multiple sclerosis, bowel/bladder dysfunction , and previous radiation to the spine. 252 • Neurology

b

N E U R O PAT H Y P R I M A R I LY M O T O R A TA D L I M P A myot ro p h i c l a t e ra l s c l e ro s i s T oxi n ( h exa n e , d a p s o n e ) A nti-G M 1 a n t i b od i e s D e mye l i n a t i o n ( G u i l l a i n- B a rre, ch ro n i c i nf l a m m a t o ry d e mye l i n a t i o n p o l y n e u ropathy [ e I D P ] ) Lymphoma I nfect i o n ( po l i o , d i p h t h e r i a , h e pat i t i s , H IV) M eta l , h eavy ( l ea d ) P orphyria

P R I M A R I LY S E N S O R Y G ET PAI N OR N U M B G e n et i c E n doc r i n e T ox i c P o l yc l o n a l/m o n o c l o n a l a n t i b o d i e s A my l o i d I nfect i o n N ut r i t i o n a l O cc u pati o n a l (ca r p a l t u n n e l ) Radiation Neurology • 253

•

N e o p l a s m/pa ra n eo p l a st i c U re m i a M ed i c a t i o n B rach i a l n e u ri t i s

M I X E D S E N S O R I M OT O R W EA K A N D T I N G L E W o r k-re l a te d/t ra u m a E l evated I g G ( p a r a p rote i n e m i a ) A uto i m m u n e vasc u l i t i s ( p o lya rte r i t i s , l u p u s ) K i d n ey fa i l u re/u r e m i a A l co h o l N utriti o n a l D e mye l i n a t i o n (C I D P) T ox i n ( m e rc u ry) I nfect i o n (H I V, Lym e d i s e a s e ) N e o p l a s m/pa ra n e o p la st i c G enetic L ive r d i s e a s e E n d o c r i n e ( d i a bete s , thyro i d )

N otes Neuropathy is any disorder that affects primarily peripheral nerves and is mani­ fested by symptoms of weakness or sensory d i stu rba nce or both . Some d i sor­ ders ca n mimic neuropathies by causing sim i lar symptoms, and are i ncluded i n the differential diagnoses a bove, even thoug h they involve more than just the pe­ ri pheral nerves (ALS, brachial neuritis). Paresthesia is a sensation of num bness or ting l i ng . Dysesthesia i s on uncomfortable sensation o f ti ngling, prickl i ng o r burn ing, often elicited by light ( normally nonpainful) touch . Hypesthesia/hypoesthesia is a sensation of n umbness; diminished sensation . 254 • Neurology

b

""

1 . Clin ically, the diagnosis of neuropathy can be a ided greatly by categorizing the symptoms i n two ways. Fi rst, by type of neuropathic d isturbance; that is, pri­ marily sensory, m ixed sensori motor, or primarily motor. Second, categorize the neuropathy by its onset/duratio n : acute (hours/days), subacute (weeks/months), or chronic ( months/years). Categorizing N e u ropathy Sym ptoms

Onset/ Duration

Type of Disturbance Primarily Motor

Mixed Sensorimotor

Primarily Sensory

Acute

Arsenic Guillain-Barre syndrome Poliomyelitis AI DS (Guillain-Barre-like) Neuromuscular blockade (myasthenia, drug·induced) Myopathy (periodic paralysisl

Herpes zoster

Subacute

Chronic inflammatory demyelinating neuropathy Toxins (hexanes , lead) Paraproteinemia Neuromuscular disease (myasthenia) Myopathy (polymyositis) Motor neuron disease (ALS)

Diabetes AIDS Uremia Alcohol-related Nutritional deficiency (e. g . , B 1 , B 1 2 , B6 ) Toxins (hexanes , arsenic) Medications Rheumatolog ic Sarcoid Vascular Para neoplastic Paraproteinemia Hypothyroidism Leprosy Critical illness polyneu ropathy

Amyloid Herpes zoster Lyme disease Medication Nutritional deficiency (e. g . , B 1 2 , B6 , E) Para neoplastic Post-radiation therapy Vitamin B6 toxicity

Chronic

Paraproteinemia Hereditary motor sensory neuropathy Neuromuscular disease (myasthenia) Myopathy (muscular dystrophy) Motor neuron disease (ALS , post-polio syndrome)

Diabetes AIDS Uremia Alcohol-related Nutritional deficiency (e .g. , B 1 , B 1 2 , B6) Toxins (hexanes, arsenic) Medications Rheumatolog ic Sarcoid Vascular Para neoplastic

Amyloid Hereditary sensory neuropathy Herpes zoster Lyme disease Medications Nutritional deficiency (e.g. , B 1 2 , B6 , E) Post-radiation therapy

(Table continued on next page.1 Neurology . 255

....

Categorizing Neu ropathy Sym ptoms (Con tinued)

Onset/ Duration

Type of Disturbance Primarily Motor

Primarily Sensory

Mixed Sensorimotor

Paraproteinemia Hypothyroid ism Leprosy Hereditary motor sensory neuropathy Critical illness polyneuropathy

Cnronic (cont )

2 . The d ifferentia l diag nosis for a primarily motor neuro pathy includes other conditions such as motor neuron disease, neuromuscular j unction ( NMJ ) dysfunc­ tion, and myopathies. Neu roanatomic local ization can be difhcult. Genera lly, the motor neuropathies cause decreased reflexes, while motor neuron d isease (ALS) has increased reflexes and u pgoing toes. Neuropathies and ALS tend to cause d ista l weakness, wh i le in NMJ diseases and myopathies, the weakness is more proximal. C l ues for the Differe ntial Diagnosis

Disorder Signs

Neuropathy

Myopathy/NMJ Disease

Motor Neuron Disease/ALS

Atrophy Reflexes Plantar response Distribution of weakness Fasciculations Sensory loss

Yes, if chronic Hypoactive Down Distal

Yes, if chronic Variable Down Proximal, bulbar

Yes, always chronic Hyperactive Up Distal, bulbar

Yes, if chronic Yes, sometimes small

No No -

Yes, always chronic No

3 . Acute weakness may be due to cerebral, neuropathic, neuromuscular, and

muscular d i sorders. For d i fferentia l diagnosis of genera l ized acute/subacute wea kness see Wea kness, page 246. For acute focal wea kness see Stroke, page 262 . 4. Chronic weakness i n the absence of sensory complaints merits workup for NMJ d i sease, ALS, and myopathy, in add i tion to the few primary motor neu­ ropath ies. Using the a bove chart, try to d isti nguish clin ica l ly where the pathol­ ogy is. Workup depends on the neuroanatomic loca lization and may i nclude EMG/NCV, cervical MRI, tensilon test, CPK, a ldolase, ESR, vita min B 1 2,. and uri ne/serum protei n electrophoresis. 5 . Most nonacute neuropathies fa ll i nto the category of sensori motor or pri­ marily sensory. There is a massive d iffe�ential d iagnosis for th is, and workup 256 • Neurology

should be a i med at the most common and the most treata ble neuropathies (not necessa rily the same) .

Diagnostic Tests

Diagnosis

Diabetic neuropathy Serum gl ucose, gl ucose tolerance test U remic neuropathy BUN, Cr Hypothyroidism , hyperthyroidism TSH Hepatic disease liver enzymes B l 2 deficiency Vitamin B l 2 AIDS H IV Polyarteritis nodosa, lupus, ESR, ANA, RF RA, etc . Urine/serum protein electrophoresis Anti-Hu , -Ri, -Yo; gu iac, CXR, Paraproteinemia mammogram Paraneoplastic neuropathy RPR, VDRL Syphilis Lyme titers Lyme disease Vitamin E deficiency Vitamin E Level Acromegalic neuropathy Growth hormone, pituita ry CT/MRI Be careful with the shotgun a pproach ! Don't order every test at once! Decide clinically which diagnoses are likely and test for those first. If no diagnosis is made and symptoms persist or worsen , conti nue the workup methodically. Also, don 't forget to look for risk factors for neuropathies (e. g . , alcohol, toxin exposure, family history, known malignancy, medications, known medical condition, IV drug use) . 6. Specific treatment of neuropathies is a imed at the underlying cause. I n addi­ tion , symptomatic ,elief may be helpful in cases of painful neuropathy. Here a re some suggested medications and their uses: Chronic pa i nful neu ropathies Amitri ptyl ine, other TCAs ( low-medium dose) Gabapentin Pai nful neuropathies, diabetic, post-zoster Capsa icin (topical) Diabetic, post-zoster Trigem inal neuralgia Phenytoin, carbamazepine Aspirin, ibuprofen, naproxen General nonnarcotic anti-inflam matories Codeine, oxycodone General na rcotic analgesics 7. In add ition to pharmacologic i ntervention, general supportive care may be beneficial, includ i n g : physica l thera py, range of motion exerc ises, padd i n g , skin care, orthotics, safety awareness. 8. Med ications known to cause neuropathy include:

Drug

Type of Neuropathy

Comments

Isoniazid Eth ionam ide Hydralazine N itrofu rantoin Disulfiram Vincristine C i:,platin

Initially sensory, then m ixed Similar to isoniazid Simila r to isoniazid I n itially sensory, then mixed I n itia lly sensory, then mixed I n itia lly sensory or m ixed Primarily sensory

Treat concomitantly with B6 Especially in urem ics Dose related Especially proprio­ ception/vibration

(Table continued an next page) Neurology • 257

Drug

Type of Neuropathy

Phenytoin

Mild m ixed sensorimotor

Metron idazole

Similar to phenytoin

Amitriptyline

Similar to phenytoin

Dapsone Amiodarone Neuromuscular blockers L-tryptophan

Primarily motor Mixed sensori motor Primarily motor

Chloramphenicol

Mild sensory

Comments

Associated with neuropathy Associated with (years) use Associated with (years) use Associated with (years) use

optic chronic chronic chronic

5% of patients aher months Prolonged ventilation/ICU

Mixed sensorimotor

Associated with impurities, results in eosinophi liamyalgia syndrome 9. Focal neuropath ies, rather tha n a general problem with a l l peri phera l nerves, i nvolve individual peripheral nerves a nd ohen are caused by local com­ pression . Common syndromes include: a. Carpal tunnel syndrome Clinical : pa in/numbness in digits 1 -4, worse at n ight, ra re weakness, positive Tinel's a nd/or Phalen's sign. Location: wrist. Diagnosis: NCY slow through carpa l tunnel; risk factors are repetitive motion, rheumatoid arthritis, acromega ly, hypothyroidism, a myloid. Treat: anti-inflamma­ tory drugs, wrist spli nts, proper adi ustment of workstation/posture. Surgery is someti mes necessary. b . Ulnar neuropathy Clinica l : pai n/numbness in digits 4-5, hand weak­ ness, claw-ha nd deformity. Diagnosis: NCY slOw along course of ulnar. Locations: several, especially elbow. Treat: symptomatic, surgery to relieve compression. c . Radial neuropathy Clinical : wrist drop, i mpa ired sensation on back of hand . Location: axilla or upper arm. Diagnosis: NCY; causes include crutch in axi lla, arm over back of chair or edge of bed ("Saturday N ight Pals/I, humeral fracture, lead toxicity. Treat: underlying cause. d . Meralgia paresthetica C l inical lateral thigh pa in/num bness, purely sensory. Location : i nguinal ligament. Diagnosis: clinica l; risk factors are obe­ sity, pregnancy, diabetes, tig ht/heavy workbelt/ha rness, backpacking. Treat: relieve compression . Benign. e. Peroneal palsy Cli n ica l : weak dorsiflexion of foot, top of foot n u m b­ ness, often weak fool--eversion . Location: head of fibula. Diagnosis : clin ica l , NCY; risk factors a re plaster cast, prolonged leg crossing while seated, tight knee boots, emaciation, fibula fracture, diabetes. Treat: underlying cause.

258 • Neurology

J

SEIZURE BITE TO N G U E B l eed/h e m o rr h a g e I nfect i o n T ra u m a E t h a n o l/d rug s/toxi n s T u mor O xyge n l ack/i sch e m i a/hypoxia N o n c o m p l i a n ce ( s u bt h e ra p e u t i c m ed s ) G l u cose l ack/hypog lyc e m ia U re m i a/meta b o l i c E c l a m ps i a

I CO NVU LS E B I G TI M E I nfec t i o n C oca i n e/d ru g s O xyg e n l a ck/i s ch e m i a/hypox i a N eoplasm Vascular ma lformatio n U re m ia L ytes (hypo N a , hypo M g , hypoCa) S i n u s t h ro m b o s i s E th a n o l w i t h d rawa l B l eed/h e m o r r h a g e I d i opath i c G l u cose l a ck/hypo g l yce m i a T ra u m a I n bo r n e rro r o f m eta b o l i s m M ed i cat i o n s (too m u ch , too l i tt l e ) E c l a m ps i a Neurology • 259

1

N otes A seizure is a clin ical man ifestation of excessive, a bnormal synchronous activity of neu rons in the cerebral cortex. It is usua l ly transient, and man ifestations in­ clude alterations of consciousness, involuntary movements, sudden loss of motor tone, and sensory disturba nces (especially olfactory or g ustatory) . Epilepsy is a term reserved for chronic, recurrent seizures . A single seizure does not make a diagnosis of epilepsy.

1 . The description of the seizure is helpful in diagnosis and treatment. A good description of a seizure includes any premonitory symptoms reported by the pa­ tient, any foca l motor activity noted during the seizure, whether the motor activity was rhyth mic and synchronous, the presence and d i rection of eye deviation, res­ pi ratory pattern, whether the patient was a ble to respond to verbal sti m u l us, whether the patient bit h is/her tongue or experienced i ncontinence, and the presence and duration of post-ictal confusion . 2 . Major types of seizures:

a. Absence - sta ring, blinking, very brief, preci pitated by hyperventilation , onset in chi ldhood , no post-ictal confusion . b . General ized ton ic-clon ic - a l l fou r extremities stiffen i n itially (ton ic!, then undergo rhyth m i c contraction and relaxation (clon ic); post-ictal confusion is a lways present (to some degree) ; may be assoc iated with cya nosis, tongue biti ng, and incontinence. May often start as a focal/partial seizure and be sec­ ondarily generalized, particularly in adults. c. Simple partial- may be motor (focal motor twitching) or sensory (foca l sen­ sory disturbance!, with no alteration i n level of consciousness during episode, no post-ictal confusion . May secondarily become generalized tonic-clonic. d. Complex partial - a lteration in consciousness, automatisms (lip-smacki ng, eye blinking, swallowi ng, picking at clothes!, preceded by aura (unusual smell, taste). May secondarily become generalized tonic-clonic. 3 . Treatment by seizure type

a . Treatment of a bsence seizure is primarily with ethosuximide or valproic acid . b. Treatment of primarily generalized seizures is usually with valproic acid . c . Trea'i ment of seconda rily general ized seizures is pri m a ri ly with ca rba­ , mazepine, phenytoin, or valproic acid . d . Treatment of partial seizures (simple or complex) is pri mari ly with carba­ . mazepine, phenytoin , or valproic acid . I Other med ications used to treat epilepsy i nclude ch lorazepate, clonazepa m , felbamate, gaba penti n , phenoba rbita l , prim idone, tiagabine, topira­ mate, and lamotrigine. 4 . It is i m porta nt to d i stinguish between seizure, syncope, and psychogenic seizure/ pseudoseizures. I a. Syncope is typically preceded by a lightheadedness, p recipitated by pos­ tural change, results in a fa ll/colla pse with loss of consciousness lasti ng only

I

1 260

• Neurology

seconds, and has no post-ictal confusion . Occasionally, a few myoclonic twilches may accompany syncope. Syncope is usually preci pitated by a vasovagal re­ action, but is also associated with arrhyth mia, orthostatic hypotension, low car­ diac output, and aortic valve disease. See the Loss of Consciousness section . b. A generalized tonic-clonic seizure may also present with a fal l/collapse, but is associated with grunting or apnea, occasional cyanosis, tonic then clon ic motor activity, sometimes tongue-biting and inconti nence, and a lways post-ictal confusion (usually lasti ng 5 m i n utes or longer) . The d uration of a general ized seizure is usua lly longer than a syncopal event, lasting seconds to minutes. c . Pseudoseizures may be d ifficult to d isti ngu ish from epi lepti c seizures; indeed , the two disorders frequently overlap. I n genera l , pseudoseizures occur in the presence of observers, are not stereotypic, have no post-ictal confusion , a n d a re not associated with self-in j u rious activity l i ke fa l l i n g or tongue-biting. Motor activity incl udes com pletely asynchronous limb movements, struggling agai nst restra ints or resisting eye open ing, and repeated side-to-side head m ove­ ments . None of these is d iagnostic, but carefu l observation helps avoid placing these patients on anticonvulsants or increasing dosages unnecessarily. ' 5 . The most common couse of a seizure in a patient with a known seizure dis­ order is subtheropeutic medication. This may be d ue to noncompliance (due to side effects or lack of understanding) or increased dosing requ i rements. 6, I ndications for neuroimaging studies: a. New focal-onset seizure or seizure with residual focal neurologic deficit b. Status epilepticus of unknown etiology c. New-onset seizure ( uncerta i n focalityJ without known precipitant d. Any second seizure (except typical a bsence) not preViously i maged . I t is not necessary to re-i mage a patient with a known seizure disorder after a typical seizure (see number 5 above). It is not necessary to i mage a child with typical a bsence seizures. 7. Indications for lumbar puncture: a . Status epilepticus of unknown etiology b. Patients u nder suspicion for suba rachnoid hemorrhage c. Patients u nder suspicion for CNS infection ( mening itis, encephalitis) 8. For seizures secondary to alcohol withdrawal and meta bolic abnormalities, a nticonvulsants are always second-l i ne treatment; first-l ine treatment is d irected at the u nderlying process ( i .e. , treat withdrawa l , correct electrolyte a bnormal i­ ties, correct hypoglycemia , etc . ) 9. Generalized convulsive status epilepticus means contin uous general ized convulsions or repeated generalized convulsions without full recovery of mental status between seizures for a period lasti ng g reater than 30 minutes. Protocol for treatment (Note: Items 1 -4 are generally done nearly simultaneously) 1 . Carefully observe seizure activity. ABCs. Supplemental O2 if necessary. 2 . IV l i n e with norma l sal i ne. Send blood for CBC, electrolytes , BUN , Ca , Mg , glucose, anticonvulsant levels. .Send ABG. Send U/ A, consider tox screen . ECG monitoring. 3 . Accucheck, then 1 00 mg' thiamine , then 50 ml of 50% dextrose solu­ tion if ind icated. Neurology . 26 1

4. Lorazepam 2 mg IV. Do not exceed 2 mg/m i n . May repeat up to 0 . 1 mg/kg . Call neurologist. 5. Phenytoin (Fosphenytoin) 20 mg(pEl/kg IV. When using phenytoin, do not exceed 5 0 mg/m i n . When using Fosphenyto i n , do not exceed 1 50 PE (phenytoi n-equivalents)/m i n . Monitor ECG, respi ra­ tion and blood pressu re. 6. Phenytoin ( Fosphenyto i n ) 5- 1 0 mg(PE)/kg IV. Max i m u m rates per minute as descri bed a bove . Maximum dose 30 mg(PE)/kg . 7. Consider intubation if not already i ntubated . 8 . Phenobarbital 20 mg/kg IV. Do not exceed 1 00 mg/m in. 9. Consider barbiturate coma (in consultation with neurologist) . 1 0. Common drugs having interactions with anticonvulsants include erythromycin, H2 blockers, isoniazid, methylphenidate, phenoth iazines, warfarin, oral contra­ ceptives, and other anticonvulsants. Drug interactions may result in increased or decr.eased a nticonvulsant levels or altered efficacy of the concomitantly adminis­ tered drug . In general, newer anticonvulsants have fewer drug-drug interactions. 1 1 . A rough clinica l gU ide to phenytoin levels: No nystagmus 0- 1 0 Above 1 0: Gaze-evoked nystagmus Ga it ataxia . Above 20: Above 30: limb ataxia Above 40: Stupor/confusion

STR O KE SAV E D B RA I N 5 u bsta n c e a b u se/d r u g s/m e d i ca t i o n s A lte red c oa g u l a t i o n/hype rc oa g u l a b i l ity V a sc u l i t i s E mboli i D i ss e ct i o n : B l ee d/h e m o rr h a g e/AVM R a re c a u ses ( e . g . , m ig ra i n e , i a t ro g e n i c ) A t h e roth rom b o s i s I nfect i o n s N eo p l a s m 262 • Neurology

b

D EA D H EA D S D ru gs/m e d i c a t i o n s E l evated b l ood p res s u re A rt e r i t i s/va s c u l it i s D ecreased p e rf u s i o n ( c a rd i a c a rrest, hypote n s i o n ) H e m o rrha g e o r H ypercoag u l a b i l ity E mbolism A t h e ro sc l e ro s i s D i s s e ct i o n S pa s m ( m i g ra i n e) Note: "DEAD HEADS" emphasizes the vascular causes o f stroke.

C VA S , D O I C T T H E M ? C oca i n e/d rugs V a s c u l i t i s/c o l l a g e n va s c u l a r d is e a s e A t h e roth ro m bos i s S yp h i l i s , t e rt i a ry/m e n i n g ova s c u l a r D is s ecti o n/dys p l a s i a (fi b ro m u s c u l a r) O ra l c o ntraceptives I ntra c ra n i a l b l e e d ( a n e u rys m , AVM ) C a ncer T h ro m b o s i s , s i n u s T ra u m a/h e r n i a t i o n H e ma to l og i c * /hyp e rcoa g u la b l e * * E m b o l i c ( i n c l u d i n g pa ra doxi ca l ) M ig ra i n e

Neurology • 263

•

DO SAVE T H E M B RA I N S D i s s e ct i o n/dys p l a s i a (fi b ro m u s c u l a r) O ra l c o n t ra c e pt ives S i n u s t h ro m b o s i s , ve n o u s A t h e roth r o m b o s i s V a s c u l i t i s/co l l a g e n va s c u l a r d i s e a s e E m b o l i s m ( i n c l u d i n g pa ra d ox i ca l ) T ra u m a/h e r n i a t i o n H e m a to l o g i c * /hypercoa g u l a b l e * * E xog e n o u s toxi n s/d r u g s ( e . g . , coca i n e ) M igraine B l e e d/AVM/a n e u rysm R a diation A ng i og ra p hy I nfect i o n s ( n e u rosyp h i l i s , m e n i n g i t i s ) N eo p l a s t i c ( b l e e d , m e n i n g it i s ) S yst e m i c hypote n s i o n/s h ock *Thrombocytosis, polycythemio, sickle cell anemia * * Protein C deficiency or resistance, protein S deficiency, ontithrombin III deficiency, malig­ nancy, onticordolipin antibody syndrome, factor V deficiency, homocystinuria

N otes Stroke refers to the sudden onset of a focal neurologic deficit that does not re­ solve. The etiology of a stroke is generally vascular, either hemorrhagic or is­ chemic. The vascular event may be precipitated by a d ifferent underlying cause ( infection, tumor, hereditary condition) . Transient ischemic attack (TIA) refers to the sudden onset o f a focal neuro­ logic deficit that resolves in 24 hours or less. Reversible ischemic neurolog ic deficit (RIND) is a neurolog ic deficit that lasts longer than 1 day and less than 3 weeks; essentially, a mild stroke . Hemiparesis refers to a weakness on one side of the body. Hemiplegia refers to paralysis of one side of the body. Astereognosis is the inability to identify obiects by touch only. Agraphesthesio is the inabil ity to identify letters/numbers traced on the skin without visual cues. 264 • Neurology

cd

1 . Types of stroke a . Hemorrhagic- refers to focal bleed i n g , usually i nto bra i n parenchyma .

Associated with acute hypertens ion , coagu lopathy, amyloid angiopathy, occa­ sionally trauma. b . T h romboti c - refers to g radual occl usion of cerebral a rteries by local plaques/thrombi Associated with longstanding hypertension, diabetes, athero­ sclerosis. • Small vessel/ l acu n a r - occ lusion of m icrovessels, typica l ly in deep gray matter and/or brai nstem . • Large vessel throm b osi s m ay not hea r carotid bruit with a low-g rade or a very high-grade stenosis. c. Embolic- refers to a sudden occlusion of cerebral arteries by blood clots that origi nate elsewhere in the vascular system May be a rtery-to-artery (carotid to middle cerebra l , aortic to carotid or vertebrobasilar), cardiogen ic ( heart to bra i n ) , or pa radoxical (venous system through atri a l septa l defect to a rterial system to bra i n ) . Associated with cardiac arrhyth m ias (especially atrial fibril la­ tion) , right to left shunts, valvular heart d isease. 2 . Hemorrhagic strokes can effectively be diag nosed by a noncontrast head CT. Presentation is usually that of a very a brupt onset of neurologic deficit which may not fit wel l i nto the vascular patterns descri bed below. Very la rge hemor­ rhagic strokes in the cerebrum could result in decreased mental status secondary to herniation; posterior fossa hemorrhages may lead to a very rapid decrease in level of consciousness. Etiology is most often hypertension . Treatment consists of gentle control of extreme hypertension, su pportive care, and occasionally (especially in posterior fossa/cerebel lar bleeds) surgical evacuation . Anticoagu lation is contra i ndi­ cated . Prognosis for functional recovery after hemorrhagic strokes is usua l ly better than after ischemic ( i e , th rombotic or embolic) infarcts. 3 . Several stroke syndromes have been descri bed as lacu nar/small vessel thrombosis; that is, i nvolving small i nfa rcts as a result of occlusion of tiny pene­ trating vessels . These presentations i nclude the following clin ical syndromes: a. Pure hemisensory deficit (contralateral to a thalamic infarct) b. Pure hemiparesis (contralateral to an i nternal capsule infarct) c. Clumsy hand-dysarthria (multiple localizations) d. Ataxia/hemiparesis (both contralateral to a pontine infarct) Onset of symptoms may be stuttering, stepwise deterioration or may be one of g radually worsening TIAs . The typical d istri bution of a hem isensory deficit i n­ volves the face, arm.., and leg equally, because the sensory fi bers a re closely compact in the tha lamus, so even a small ischemic lesion will l i kely affect a l l . likewise for pure hemiparesis, which shou ld · be relatively equal i n the face, a rm , and leg, as the corticospinal fi bers a re crowded closely in the i nterna l capsule Etiology is most likely chron ic hypertensive damage to small penetrating ves­ sels. Treatment acutely consi sts of avoiding hypotensio n , using a nti platelet agents, and supportive' care. Long-term treatment i nvolves dimi n ishing risk factors such as smoki ng, hypertension , hyperli pidemia, and diabetes. Anticoagulation -

Neurology • 265

is unproven . Tissue plasmi nogen activator (TPA) may be beneficial within the first 3 hours. 4. Large vessel thrombosis may present with gradua lly worsening (crescendo) TIAs or an a brupt onset of symptoms Usually symptoms occur in a vascular d istri­ bution as descri bed below. Carotid occlusion may presen t with o n ly m iddle cerebral a rtery infarction (due to collateral flow to the i psilateral anterior cere­ bral from the anterior com m u n icating a rtery ) . Etiology is usually an atheroscle­ rotic plaque with loca l t h rom bus formation. Treatment acutely i ncludes TPA, avoiding hypotension , and supportive care . Ca rotid enda rterectomy is i nd i­ cated for symptomatic stenosis of 70% or g reater, often i n the setting of TIAs . E mergent carotid enda rterectomy is u n proven . Anticoagulation is u n p roven . Ca rotid endarterectomy in the setting of com plete carotid occlusion is genera l ly nat ind icated . 5 . Embolism classically presents with an a brupt neurolog ical deficit that is max­ imal at onset. Symptoms occur in a vascu lar d istribution as described below. The hemipa resis of m iddle cerebral artery (MCA) occlusion d iffers from that of lacuna r d isease in that MCA infarction causes hemiparesis that is greater in the face and arm than the leg a n d is usually associated with hemisensory loss in a s i m i lar d istribution . Etiology is by occlusion of an a rtery by a blood clot from either another artery (e . g . , carotid to middle cerebra l ) , the heart (ca rd io­ genic), or the venous system via a right to left shunt ( pa radoxica l ) . Treatment acutely may involve TPA, followed by a nticoagulation , especially in cases of atrial fibri llation and small cerebral infarcts. Acute anticoagulation in the setting of a very large cerebral infarction has an i ncreased risk of precipitating hemor­ rhagic transformation . 6 . Local ization of large vessel disease (thrombotic or embolic) a. Specific signs/symptoms Monocular visual loss Hemi neglect • Anterior ( i . e . , carotid Aphasia Agraphesthesia artery) Visua l-spatial deficits Astereognosis Di plopia Nystagmus • Posterior ( i . e . , vertebral basi lar arteries) Ataxia Bi lateral sig ns/ symptoms Vertigo Face signs/symptoms Vom iting opposite arm/leg signs/symptoms Hemisensory loss . • Either Hemiparesis Dysa rthria Visual field cut ('u sually PCA, but may be present with large MCA i nfarctions) b. Vascular syndromes • Anterior cerebral artery Leg weakness > Contralateral face/ar� I ncontinence 266 • Neurology

..

Middle cerebral artery

Contralateral

Face/ arm weakness > leg Hem isensory deficit Hemia nopsia Contralateral Hemianopsia • Posterior cerebral artery Mild hemiparesis Hemisensory deficit • Vertebral basilar arteries Contralateral Hemi pa resis Ipsi lateral Hemisensory deficit May be bi lateral C ranial nerve palsy Possibly hemiataxia 7. Standard workup for stroke includes a head CT (hemorrhage!, CBC (throm­ bocytosis, polycythemia!, glucose (diabetes!, and lipids (hyperlipidem ia). Other blood tests which may be usefu l include PT/PTI (coagulopathy, inadequate a n­ ticoag u lation ! , ESR (vascul itis), and VDRL/RPR ( neu rosyph ilis). Carotid d uplex should be done in cases of anterior circu lation strokes and TIAs . Tra nscranial Doppler is helpful in eva l uation of posterior circulation (vertebrobasi la r insuffi­ ciency). Echocardiography is performed to rule out valvular lesions and atrial or ventricular thrombi in patients suspected of having an embolic infa rct. Magnetic resonance angiography is a noni nvasive method of visua lizing all of the cranial vasculature (a nterior and poste rior circulation!, and the resolution of MRA has greatly improved over the last few years. 8 . In young patients « 45 years old) or patients with no clear etiology, the work-u p for stroke/cerebral infarction can be m uch more extensive and may in­ clude protein C, protein S, anticard iol i pin a nti body, antithrom bin I I I , factor V, and homocysteine (hypercoagulable states!, angiography (arterial dissection, fi­ bromuscular dysplasia, aneurysm!, MRI (tumor, AVM!, u rine drug screen (coca ine, amphetamines!, LP (i nfection, inflammation/vasculitis!, and transesophageal echo with bubble study (atrial septal defect with paradoxical embolism). 9 . Recently, the use of TPA has been recommended i n acute stroke . Consider it in patients who present to med ical care within 3 hours of onset of neurological sym ptoms, have sign ificant n eu rologic deficits, and have no evidence of in­ tracranial hemorrhage. •

Neu ro logy G lossary

Agraphesthesia is the inability to identify letters/numbers traced on the skin with­ out visual cues

Akathisia descri bes an involuntary restlessness a nd inability to sit still. Altered mental status refers to any acute or subacute change in the level of con­ sciousness, ra n g i ng from m i ld confusion to deep coma . Synonymous with

Neurology • 267 +

1

delirium . Chronic problems such as dementia or menta l retardation a re not considered in th is category. Amaurosis fugax is the subjective com plaint of transient visua l loss in one eye, oMen descri bed as a veil or shade coming over the eye Astereognosis is the inabil ity to identify objects by touch only. Asterixis is a cond ition cha racterized by nonrhythmic, episodic loss of m uscle tone. May be confused with tremor. Ataxia is the subjective complaint or objective find ing of impaired coord ination, usua lly manifested as an i m pa irment of gait or dexterity in the a bsence of sig­ n ificant muscular weakness. Autonomic disorgers constitute a wide range of neurologic derangements which may man ifest prima rily through symptoms of autonomic dysfu nction, including but not l i mited to orthostatic hypotension/syncope, card iac arrhythmias, a l­ tered lacri mation , i m pa i red temperature regulation , dia phoresis/a nhidrosis, sexual dysfunction, and bowel/bladder problems. AVM is the acronym for a rteriovenous ma lformation ; on a bnormal ta ngle of blood vessels that can develop in the central nervous system. Choreoathetosis is an i nvolu ntary movement disorder characterized by ra pid, jerky, dancing-l i ke movements (cho rea ) associated with or superi m posed upon writhing, flowing, continuous movements (athetosis). Clonus is an a brupt, unidirectional series of muscular contractions i n response to a sudden stretch . Also used to describe repetitive, rhyth m i c muscle contrac­ . tions seen i n some types of seizures. Cogwheeling is a form of rigidity cha racterized by rhyth m i c , rachet-l ike resis­ tance throughout the range of motion. CT is the acronym for computed tomography, a diagnostic neuroimaging test. CVA is the acronym for cerebrovascu lar accident; refers to any acute cere­ brovascular pathology, generally ischemia or hemorrhage . Dementia is an acquired condition characterized by chronic deterioration of i n­ tellectual function and associated with i m pairment in at least three of the fol­ lowing a reas : language, memory, visuospatial ski lls, personality, and cogn ition . I t is not associated with on acute confusional state. Diplopia is the subjective symptom of double vision . Dizziness is a symptom with many meani ngs, but particularly used by patients to refer to feelings of fa intness/lig htheadedness, vertigo, a nd/or unsteadi­ ness/d isequili bri u m . Dysconjugate gaze i s the objective exa m i nation finding of eye misalign ment, which may or may not be associated with symptoms of d i plopia . Dysdiadochokinesis is on i m pai rment of the ability to perform rapid alternating movements. Dysesthesia is an uncomforta ble sensation of ting l i n g , prickling, or burn i n g , often elicited by l ight (normally nonpa inful) touch . Dyskinesia is o n a bnorm a l i ty o f movement. T h i s usua l ly refers t o excessive motor activity ( L-dopa- i nd uced dyskinesias, tard ive dysk i nesia ) , but a lso may reflect a severe general ized slowing of move ment ( pa rki nson i a n bradykinesia). 268 • Neurology

".

T

I

..

Dysmetria is impa i rment i n the normal acceleration and deceleration of d irected movements. Usually eva luated by finger-nose-finger and heel-knee-shin tests .

Dystonia is a condition of i m pa i red muscle tone, which usua l ly is i ncreased , persistent, and at an extreme of the range of motion for the affected area .

EMG is the acronym for electromyogra m , a d iagnostic test that exa m i nes the

electrical properties of m uscle tissue (analogous to the electrocard iog ram for the heart) Epilepsy is a term reserved for chronic recurrent seizures. A single seizure does not make a diagnosis of epilepsy. Gegenhalten descri bes an inability to relax muscles subjected to passive move­ ment. On exa m i nation, it feels as if patient is resisting the exam iner's motions. Headache is a genera l term used to describe any pai nful sensation i nvolvi ng the structu res of the cranium-, face, and/or neck. Hemiparesis refers to wea kness/pa rtial paralysis on one side of the body. Hemiplegia refers to com plete paralysis of one side of the body. Hypesthesia is a sensation of n u m bness; d i m i n ished sensation . Synonymous with hypoesthesia I n}ention tremor is an exaggerated oscil lation of a l i m b most pronounced as it is approaching a target, and essentially absent at rest or at the beginning of a movement. I ntention tremor is a man ifestation of dysmetria . . Lead-pipe is a form of rigidity characterized by uniform resistance throughout the range of motion . LP refers to lumba r puncture; also known as a spinal ta p. Monocular visuai loss is either a subjective report of transient visual loss i n one eye (as opposed to one visual field) or an objective find ing of decreased visual acu ity in one eye MRI is the acronym for mag netic resonance i maging, Q diag nostic neuroi mag­ ing test with higher resolution than CT, but which takes longer and is gener­ al ly more expensive Myelopathy is any pathologic process lead ing to spinal cord dysfunction. Myoclonus refers to a sudden, nonrhyth mic contraction or spasm of a m uscle or g roup of muscles . Contractions genera lly a re u n i d i rectional, asynchronous, and asymmetric. Nerve conduction study is a diag nostic test that looks at the electrical function of peripheral nerves and roots . Neuropathy is any d isorder which affects primarily peri phera l nerves a nd is manifested by symptoms of weakness or sensory d isturbance or both . Paresthesia is a sensation of n u mbness or ti ngling. Ptosis is a physical finding of one palpebral fissure being smaller than the other, i e , a drooping eyel id . Reversible ischemic neurolog ic deficit (RIND) is a neurologic deficit that lasts longer than 1 day and less than 3 weeks; essential ly, a m i ld stroke. Rigidity is a continuous or i nterm ittent increase in muscle tone throughout the full -ra nge of passive movement. Seizure is a clinical manifestation of excessive, abnormal , synchronous activity of neurons in the cerebra l cortex . It usually is transient, and manifestations Neurologv • 269

i nclude alterations of consciousness, i nvolu ntary movements, sudden loss of motor tone, and sensory disturbances (especially olfactory or gustatory) . Spasticity is an increase in m uscle tone that is m i ld with slow movement and more pronounced with rapid movement. Classically, rapid passive movement is met with i ncreasing resistance u ntil a point at which the resistance breaks (clasp knife phenomenon). Stroke refers to the sudden onset of a focal neurolog ic deficit that does not re­ solve. The etiology of a stroke generally is vascular, either hemorrhagic or is­ chem ic. The vascular event may be precipitated by a d i fferent underlying cause (e . g . , infection, tumor, hereditary condition). Syncope is defined as a tra nsient loss of consciousness and postural tone due to i m pai red cerebral blood flow. Synonymous with fa inting. Tics a re stereotypic, invol unta ry, repetitive spasmod ic muscular contractions. Typically a ble to be suppressed briefly, o n ly to brea k out with increased severity. Often a ppear purposeful or sem i purposeful . Titubation i s a moderate-frequency head tremor, usua lly antero-posterior. Torticollis is a form of focal dystonia involving persistent contraction of cervical muscles, leading to a head . tilt. Transient ischemic attack (TIA) refers to the sudden onset of a focal neurologic deficit that resolves in 24 hours or less. Tremor is defined as an i nvolunta ry, rhythmic, oscillatory movement. Weakness is the reported symptom or demonstrable sign of decreased strength of m uscular contraction.

270 • Neurology

Em

A p PENDIX Ac ronym Dictiona ry

ABG ALS ANA ARDS ATN AVM AVP BOOP BUN ClDP COPD CPK CVA CXR DDX DKA DVT ECG EEG ESR GERD GVH D ITP IVF LAM LP MCA MCV

Arterial blood gas Amyotrophic lateral sclerosis Anti n uclear antibody Ad ult respi ratory d istress syndrome Acute tubular necrosis Arteriovenous ma lformation Arg i n i ne vasopressi n Bronchiol itis obl itera ns-org a n izing pneumon ia B lood u rea nitrogen C h ronic id iopath ic polyradiculopathy C h ronic obstructive pulmonary d i sease Creati ne phosphoki nase Cerebrovascu lar accident Chest x-ray Differential d iagnosis Diabetic ketoacidosis Deep vei n throm bos is Electroca rd iogram E lectroencepha log ra m E ryth rocyte sed i mentation rate Gastroesophageal reflux d isease Graft versus host d i sease Id iopath ic th rom bocytopen ic purpura I ntervertebral fora men Left atrial myxoma Lumbar puncture Middle cerebral artery Mean cell volume Appendix . 2 7 1

MI MS NCV PCA PIE PT PTI RDW RPR SIADH SLE TIA TPN TSH VDRL VOD

Myocard i a l i n fa rction Multiple sclerosis Nerve cond uction velocity Posterior cerebra l a rtery Postinfectious encepha lomyel itis Prothrombin time Pa rtia l thromboplastin time Red blood cell d i stribution width i ndex Rapid plasma rea g i n Syndrome o f i n a ppropriate secretion o f anti d i u retic hormone System ic lupus erythematosus Tra nsient ischem ic attack Tota l pa renteral n utrition Thyroid-sti m u lati ng hormone Venera l disease research la boratory Veno-occlusive d isease

272 • Appendix

DI FFERENTIAL D IAG NOS I S M N EM O N ICS is a memory aid to help you form comprehensive d ifferential d iagnoses for common i nternal medicine and neu rology problems. Clever, often witty m nemon ics allow you to organize diagnostic possibilities quickly and effectively for a wide va riety of clinical scenarios. The method succeeds because each m nemonic provides you with a framework on which

to construct the

d ifferential . This book assures that you r eva l uations w i l l b e thorough , and d iagnoses will not be m issed! For More Memory Aids . . . The SECRETS SER I ES

®

has been extraordi na ri ly popular,

and the distinctive approach has given birth to a wide range of books i n the major medical specialties and subspecia lties. Questions and short a nswers as wel l as an i nformal tone a re employed to make the text enjoya ble as well as usefu l . The l ist is constantly changi ng and expan d i ng. H ere a re a few of

the more than 50 titles:

CARD I O LOGY SECRETS, 2/e CRITICAL CAR E SECRETS, 2/e EN DOCR I N E SEC R ETS, 2/e GI/LiVER SECRETS HEMATOLOGY/ON CO LOGY SECR ETS , 2/e I N FECTIOUS DISEAS E S EC R ETS N EP H RO LOGY SECR ETS N E U ROLOGY SECRETS N E U ROSCI ENCE SECR ETS P ULMONARY/RES P I RATO RY CAR E S ECRETS R H EU MATOLOGY SECR ETS S U RGICAL SECRETS , 4/e Hanley & Belfus, Inc. , Medical Publishers 2 1 0 South 1 3th Street

Philadelphia , Pennsylvan i a

www.hanleyand belfu$.com