Peripheral Neuropathy - Dra. David, 9-10-12 and 9-12-12

NEURO – PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12

PERIPHERAL NEUROPATHY – – –

TYPES OF FIBERS

LMN lesion  flaccid Reflexes lost early on in disease = peripheral nerve injury Acute spinal cord injury = areflexia

PERIPHERAL NERVOUS SYSTEM All neural structures outside the brain and spinal cord Includes sensory receptors, peripheral nerves, associated ganglia and motor endings Provides links to and from the external environment SPINAL NERVE Inside vertebral foramen Root affected = radiculopathies Disc herniation FUNCTIONAL ANATOMY Dendrites • Receives incoming synaptic signals Soma/cell body • Receives incoming synaptic signals Initial segment/axon hillock • Concentrated Na+ channels • Trigger zone Axon • Conducts action potential Axon terminal • Site of signal transmission

SEGMENTAL DEMYELINATION Focal degeneration of the myelin sheath with sparing of the axon Disappearance of the sheath over segments of variable length, bounded on each end by a preserved segment of myelin WALLERIAN DEGENERATION A reaction of both the axon and myelin distal to the site of disruption of an axon Described as “dying forward”, a process in which the nerve degenerates from th point of axonal damage outward

MICROSCOPIC ANATOMY 3 levels of organization Epineurium • Dense connective tissue • Continuous with dura mater Perineurium • Organizes nerve fascicles • Inner layer continuous with pia/arachnoid Endoneurium • Directly surrounds myelinated and unmyelinated axons MYELIN Produced in PNS by Schwann cell • Average Schwann cel covers ~1mm of axon – internode • ~1um gap of unmyelinated axon occurs between Schwann cels – Node of Ranvier

AXONAL DEGENERATION Dying back phenomenon Axon is affected progressively from the distal most site to the proximal Dissolution of myelin that occurs roughly in parallel with the axonal change “THE TEN P’S” Pattern • Temporal • Anatomical Population of neurons Part of neuron Physiology Pathology Prickling Phenomena Pedigree Plasma Pharmacology (Need picture of the algorithm!) IMMUNE-MEDIATED NEUROPATHIES Guillain-Barre Syndrome Chronic Inflammatory Demyelination Bell’s Palsy GUILLAIN BARRE SYNDROME Acute autoimmune inflammatory polyneuropathy (AIDP) Acute monophasic paralyzing _______

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NEURO – PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12 Provoked by preceding infection

HISTORY 1859 “ascending paralysis” 1916 Motor weakness Areflexia Albuminocytologic dissocation EPIDEMIOLOGY Incidence 1 to 2 per 100,000 per year Mean age: 40 yrs old Slight male preponderance ANTECEDENT EVENTS Infection Viral • Epstein-barr virus • Cytomegalovirus • HIV • Influenza • Herpes simplex • Coxsackie Bacterial • Campylobacter jejuni • Mycoplasma pheumoniae • Escherichia coli Parasitic • Malaria • Toxoplasmosis Systemic Illness Hodgkin’s disease Chornic lymphocytic leukemia Hyperthyroidism Collagen vascular disease Sarcoidosis Renal disease Other Medical Conditions Pregnancy Surgical procedures Bone marrow transplantation Immunization Envenomization Drug ingestion CLINICAL MANIFESTATION Paresthesias Sensory loss Pain Weakness • Ascends from lower extremities • Symmetrical • Bilateral facial • Eye movement • Respiratory muscles Reflexes Autonomic involvement • Labile blood pressure  Tachycardia  Postural hypotension • Cardiac arrhythmias  Tachycardia  Bradycardia, _____ heart block • Urinary incontinence • Constipation COURSE Peak: 2 weeks Nadir: 4 weeks

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Onset of recovery: 28 days Recovery period: 6 months

PATHOGENESIS 1. Complement component are deposited on the outer surface of the myelin fiber 2. Complement induces vesicular myelin degeneration 3. Schwann cells are invaded by macrophages 4. Macrophages penetrate the basal lamina and strip off the myelin VARIANTS Weakness is predominant • Acute inflammatory demyelination (AIDP) • Acute motor axonal neuropathy (AMAN) • Acute motor sensory axonal neuropathy (AMSAN) Weakness is NOT predominant • Fisher syndrome • Acute panautonomic neuropathy? • Pure sensory neuropathy AXONAL VARIANT Commonly preceeded by history of diarrhea, especially related to Campylobacter jejuni Muscle atrophy became apparently relatively early Recovery is prolonged and complete resolution of weakness is uncommon Immune attack is directed at axon plasmalemma AUTOANTIBODIES The one Dra. emphasized from the table is: GBS Subtype *Miller Fisher Syndrome

Autoantibody GQ1b, GT1a

DIAGNOSTIC EVALUATION Cerebrospinal fluid analysis • Elevated protein • Cell count  Normal  Pleocytosis > 10 cells/mm3 Nerve conduction studies • Demyelinating  Conduction block is the hallmark of _____ lesion  Prolonged distal motor and F wave latencies • Axonal  Marked reduction in _____ amplitude Electrophysiologic studies Eletromyographic findings • Demyelinating  Fibrillations and sharp waves (second week) • Axonal  Fibrillation and sharp waves TREATMENT Supportive care • ICU monitoring  Respiratory  Cardiac  Hemodynamic • Prophrylaxis for DVT • Bladder and bowel care • Physical and occupational tx Intubate!

NEURO – PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12

IMMUNOTHERAPY FOR GUILLAIN-BARRE SYNDROME 1. Treatment wth plasma exchange (PE) or immunoglobulin (IVIg) hastens recovery 2. PE and IVIg are equally effective in patients with advanced GBS symptoms 3. PE may carry a greater risk of side effects and more difficult to aminister 4. Combining the two treatments is NOT recommended 5. Steroid treatment is NOT beneficial

Did my best to transcribe this one  Good luck! CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP) Acquired immune-mediated neuropathy with clnical progression for longer than 8-12 weeks Separated from GBS by Austin in 1958 on the basis of • Prolonged and relapsing course • Enlargement of nerves • Responsiveness to corticosteroids Antecedent infection usually NOT identified Peak incidence in the 40-60 year age group CLINICAL FEATURES Slowly progressive or relapsing and symmetric proximal and distal weakness Distal panmodality sensory loss Depressed/absent muscle stretch reflexes Elevated spinal fluid protein w/o pleocytosis… PROGNOSIS Approximately 90% of patients will show initial ______ VARIANTS Multifocal motor neuropathy (MMN) Lewis-Sumner syndrome • Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) • Distal acquired demyelinating sensory neuropathy (DADS) BELL’S PALSY Courses 1 side of the face to be partly or completely paralyzed resulting in: • Eyebrow sagging • Drooping of eye and corner of mouth • One eye will not close completely TREATMENT Mainstay of pharmacologic treatment: early short term oral glucocorticoid Eye care – artificial tears should be applied every our while the patient is awake • In severe cases of Bell’s Palsy, _____ PROGNOSIS Related to the severity of lesion Incomplete lesion _____ HEREDITARY NEUROPATHIES Polyneuropathy that advances slowly over 10 years or more Time of onset usually early in life but often cannot be dated with certain by the patient or family

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Hereditary motor and sensory neuropathies (HMSN) ______

CHARCOT-MARIE TOOTH DISEASE (nice to know!) CMT1 – dominantly inherited myelinopathies CMT2 – dominantly inherited axonopathies CMT3 – contenital myelinopathies (infancy onset) CMT4 – recessive inherited myelinoaxinopathy… CMT1 CLINICAL FEATURES Distal muscle weakness and atrophy (inverted champagne bottle) Clawing of the finger (severe cases) Loss of muscle stretch reflex…. CMT2…. CMT3 -

Dejerine-Sottas Disease Rag doll appearance  lots of head lag Onset at birth or early childhood….. Elevated CSF protein (enlarged spinal roots) Motor NCV slowed usually under 10 m/s in legs and 20 m/s in arms Mutation in PMP22….

PATHOLOGY Onion bulb deformity Repeated cycles of demyelination remyelination result in nerve fibers….

and

TREATMENT Rehab measures Ankle-foot orthoses… HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES (HNPP) Multiple focal thickenings of myelin sheaths, each termed a “fomaculum” HEREDITARY SENSORY NEUROPATHY (HSAN)…..

AND

AUTONOMIC

VASCULITIC NEUROPATHIES VASCULITIS Inflammation and structural damage to blood vessel walls that lead to ischemic hemorrhagic and thrombotic damage to the tissues supplied by those vessels…. CLASSIFICATION Direct infection • Bacterial, fungal, viral (e.g. lyme disease, TB, HSV, CMV, HIV) Immunological mechanism • Systemic necrotizing vasculitis • Hypersensitivity vasculitis • Giant cell artertitis • Localized vasculitis (non-systemic vasculitis) SYSTEMIC NECROTIZING VASCULITIS Classic polyarteritis nodosa (PAN) Antineutrophil cytoplasmic antibody (ANCA) associated with: • Microscopic polyangitis

NEURO – PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12 -

• Churg-Strauss syndrome • Wegener granulomatosis Polyangiitis overlap syndrome Vasculitis with connective tissue disease…

VASCULTIC NEUROPATHY PATHOLOGY Early active lesion… TOXIC NEUROPATHIES PRINCIPLES OF GENERAL NEUROGOXICOLOGY 1. Strong dose-response relationship… 2. Proximity to exposure 3. Coasting 4. Most chemicals that trigger structural damage to the nervous system produce a consistent pattern of disease commensurate with dose and duration of exposure TOXIC NEUROPATHIES Peripheral neuropathy of the distal axonopathy type is the most common form of neurotoxic disease Most instances are caused by pharmaceutical agents (1-6-12) or substance abuse (alcohol) Occupational neuropathies are relatively infrequent NEUROTOXIC DRUGS (drugs that Dra. emphasized are underlined) Amphiphilic cationic drug • Amiodarone, chloroquine Chemotherapeutic agents • Vinca alkaloids, cisplatin, paclitaxel Nucleoside analog • Zalcitabine, didanosine Antibiotics Dapsone, isoniazid, ethambutol, • nitrofurantoin, metronidazole, chloramphenicol anticonvulsants phenytoin • vitamin B6 colchicine METAL TOXICITY ARSENIC CLINICAL FEATURES length dependent sensory-motor (entire length of nerve affected)… Mees lines in fingernails

neuropathy

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Radial innervated….

DIABETIC NEUROPATHIES DIABETES MELLITUS Most common cause of polyneuropathy in general clinical practice Approximately 15% of patients have symptoms of polyneuropathy Both type 1 and 2 diabetic patients are susceptible Most important factor: duration of diabetes DIABETIC NEUROPATHIES Diabetic polyneuropathy Diabetic cranial neuropathies Acute mononeuropathy of limbs/trunk Diabetic amyotrophy (muscles shrink) Autonomic neuropathy PATHOGENESIS Metabolic factors • Accumulation of glycosylation end products • Increase oxidative stress…

advanced

DIABETIC POLYNEUROPATHY Most common type of polyneuropathy Distal and symmetrical, primarly sensory form of polyneuropathy “stocking glove” sensory loss Mild muscle weakness of distal lower limb… DIABETIC CRANIAL NEUROPATHY **third and sixth cranial nerves most often affected** Diabetic third nerve palsy (opthalmoplegia) • Usually in diabetics over age 50 • Retro/supraorbital pain often precedes the opthalmoplegia • Pupillary sparing = hallmark of the condition Patients will recover as long as you treat the diabetes DIABETIC AMYOTROPHY Diabetic lumbosacral radiculoplexus neuropathy Bruns-Garland syndrome… ***mostly thigh muscles affected*** TREATMENT Antidepressants…. LEPROSY Caused by direct invasion of nerves by the acid fast bacilli…. ENTRAPMENT NEUROPATHIES Compression injuries to a specific region/regions of a nerve predisposition by...

LAB FEATURES Normal biopsy LEAD -

Uncommon cause of peripheral neuropathy Neruotoxic effect in both organic and inorganic forms…. Sources of exposure: industrial plants, batteries, welding, paint, gas

CLINICAL FEATURES Predominantly motor neuropathy involving the upper limbs

primarily

MEDIAN NERVE Receives contributions from C6, C7, C8, T1 Distal muscles affected from wrist ANTERIOR INTEROSSEUS NERVE ULNAR NERVE Compressed at wrist/elbow Median nerve = numbness of first 3 fingers and ½ of 4th finger Ulnar nerve = numbness of ½ of 4th and 5th digit

NEURO – PERIPHERAL NEUROPATHY: DRA. DAVID, 9-10-12 and 9-12-12 Median n.

Ulnar n.

MERALGIA PARESTHETICA: LATERAL FEMORAL CUTANEOUS NERVE ENTRAPMENT Most common in obese individuals and people who wear tight pants/underwear PLEXUS DUCHENNE-ERB PARALYSIS …. Waiter’s or bellhop’s tip position… KLUMPKE’S PARALYSIS …. Weakness of medial wrist flexion and of most finger movements including • Finger extension, flexion and abduction RADICULOPATHIES DERMATOME Cutaneous innvervation by a root segment MYOTOME Muscular innvervation by a root segment CAUSES Degeneration and myeloradiculopathy …

structural

compression,