Metabolic Encephalopathy and Metabolic Coma

April 29, 2018 | Author: qlinlyn | Category: Coma, Peripheral Neuropathy, Inflammation, Hypothermia, Electroencephalography
Share Embed Donate


Short Description

Download Metabolic Encephalopathy and Metabolic Coma...

Description

Metabolic encephalopathy and metabolic coma co ma Contributors G Bryan Young MD, MD, author. Dr. Young o f the University of Western Ontario has no relevant financial relationships to disclose. disclose.

Gary R W Hunter MD, MD, author. Dr. Hunter o f the University University of o f Western Ontario has no relevant financial relationships to disclose. Zachary N London MD, MD, editor. Dr. London of the University of Michigan has no relevant financial relationships to disclose. disclose.

Publication dates Originally released July 17, 2007; last updated February 22, 2010; expires February 22, 2013

Historical note and nomenclature The term ³metabolic encephalopathy´ was co ined by Kinnier Wilson in 1912 to describe a clinical state due to various causes in which the brain's integrated activity is impaired in the absence of structural abnormalities. Metabolic encephalopathy is, t hus, not a diagnosis but a syndrome of global cerebral dysfunction induced by systemic stress, and can vary in clinica l presentation from mild executive dysfunction or agitated delirium delirium,, to deep coma with decerebrate posturing. There are also some differences in presentation depending on the metabolic disorder. In this discussion discussion we shall refer to those disorders due to vital organ failure, nutritional deficiencies, electrolyte imbalances, hypoglycemia hypoglycemia,, hyperglycemia, endocrine disorders, and systemic sepsis sepsis;; the following are excluded: cardiac card iac arrest and anoxic-ischemic encephalopathy, direct CNS infections, infections, exogenous toxins (including drugs, alcohol, and poisons), hematological conditions, immune-mediated CNS diseases, diseases, and direct d irect and indirect effects of cancer on the nervous ner vous system. It should be understood that various metabolic disorders causing encephalopathy are combined, rather than occur in isolation, especially in critically ill patients (Kunze 2002). 2002). This reflects the interaction among various organ systems, causing multiple multiple metabolic metabo lic derangements. Clinical manifestations Metabolic encephalopathies may range in degree from a mild confusional state to coma coma,, an unarousable unconscious state. Delirium or acute acut e confusional state is usually the earliest recognized brain malfunction in metabolic encephalopathies. Patients may be either agitated, usually with increased sympathetic nervous system activity, or quiet and withdrawn. The key feature of delirium is impaired concentration and a ttention. Patients cannot keep on track with mental tasks, eg, serial 7s or spelling ³world´ backwards, and are easily distracted. They may

or may not have hallucinations, often visual but sometimes auditory. These are more common in withdrawal (from alcohol or drugs) states. Some clues that the problem is metabolic rather than due to a structural brain lesion include: The setting. Often there is a background of vital o rgan dysfunction or history of some event, eg, toxic exposure that would upset the metabolic milieu of the brain, as opposed to a sudden catastrophic event with instantaneous loss of consciousness, as might o ccur with trauma, seizures, cardiac arrest, etc. There may also be clues from the general examination, eg, jaundice, hyperventilation, signs of chronic pulmonary or cardiac disease, hypothermia or  hyperthermia, etc. Time course. Patients with metabolic encephalopathies are acute or recent in onset and tend to fluctuate in the severity of their impairment o f consciousness, such that they may be coherent and obeying at one point, and a few hours later in a stupor  , rousing only to vigorous stimulation. This is in contrast to structural lesions such as strokes or tumors, which tend to have static or progressive courses. Vital signs. Myxedema coma and Wernicke encephalopathy commonly cause hypothermia, with temperatures below 35°C. Hypothyroidism slows the metabolism and respiratory rate (as reflected in elevations of  PaCO2 on blood gas determination: respiratory acidosis). Wernicke encephalopathy produces metabolic lesions near the ventricular system, including the hypothalamus, which can result in lowering o f body temperature if the posterior  hypothalamus is involved. In some cases, this may be the only clue to the diagnosis in a comatose patient. Hyperthermia is common in thyro id storm, in which metabolism is accelerated. Agitated delirium is typically acco mpanied by increased sympathetic nervous system activity, including hypertension, tachycardia, and perspiration. Hyperventilation producing a respiratory alkalosis is characteristic of  hepatic encephalopathy and early sepsis. Metabolic acidosis from advanced sepsis, renal failure, diabetic ketoacidosis, or lactic acidosis can also produce hyperventilation. Hyperventilation may also accompany lower  PaO2, as with cardiopulmonary disorders. Thus, t he discovery of hyperventilation, along with simple blood gas determination, narrows the diagnostic possibilities. Motor phenomena. Tremor, asterixis, and multifocal myoclonus are strongly suggestive of  a metabolic etiology in encephalopathic or delirious patients. The tremor is of an act ionpostural type and commonly acco mpanies an agitated delirium, as in withdrawal states, uremia, and the early phase of hepatic encephalopathy. Asterixis is a loss of postural tone, best assessed by having the patient hold the arms outstretched, the wrists dorsiflexed, and the fingers extended. The ³flapping tremor´ then appears, often asynchronously. Asterixis may also affect truncal muscles, causing the head or body to drop forward. If they are supported in a frog-leg position, the lower limbs may be affected as well. Although tremor and asterixis are not seen in coma, multifocal myoclonus can be seen from delirium to coma. In the setting of  hepatic coma, multifocal myoclonus is usually an ominous sign and portends a poor  prognosis, although this is not universally true. T he brief twitches occur in various muscles in an asynchronous, non-rhythmic, helter-skelter fashion. They o ften involve the face and limbs and may migrate from one side to the other. Multifocal myoclonus is often confused with seizures but is generally resistant to the usual anticonvulsant drugs and has no epileptiform EEG correlate. Levetiracetam and valproate may be useful in controlling multifocal myoclonus, but it is often refractory to treatment unless the underlying cause is corrected. Neurologic examination. The mental status examination can provide important clues to the metabolic nature of the brain dysfunction in noncomatose patients. Agitation with

hallucinations is common in withdrawal states, but can be found in some metabolic disorders, such as acute intermittent porphyria and the early phase of acute liver failure. The cranial nerve reflexes are spared in most metabolic encephalopathies; these include pupillary, corneal, vestibular-ocular, and pharyngea l reflexes. This is helpful in differentiating metabolic disorders from most structural lesions. However, some structural lesions are multifocal and can mimic metabolic brain diseases. A single structural supratentorial mass lesion may cause a lateral displacement of the brain, causing coma before the pupillary light reflex is affected on the same side. Such patients may show lateralized motor signs. Most coma-producing posterior fossa lesions will alter at least some of the cranial nerve reflexes as the pathways for these run through the rostral reticular formation that is compromised in coma from such lesions. There are also reverse caveat s, in that some metabolic disorders can affect some cranial nerve reflexes. Wernicke encephalopathy, related to thiamine deficiency, commonly causes loss of the vestibular-ocular reflex, even with caloric stimulation. This relates to the site of ³metabolic lesions,´ which includes the vestibular nuclei at the floor of  the 4th ventricle. Other cranial nerve reflexes are spared±a helpful diagnostic clue. Parenteral thiamine usually restores the vestibular-ocular reflex in Wernicke encephalopathy, ano ther  helpful diagnostic and therapeutic point. Hepatic encephalopathy can produce a variety of false localizing signs, including conjugate horizontal or vertical gaze deviations, dysconjugate downgaze, hemiparesis, severe spasticity with sustained clonus, and a variet y of abnormal postures including decortication to painful stimuli. These may be seen in the setting of cerebral edema but can also occur purely due to metabolic dysfunction with normal intracranial pressure. Other well-known metabolic mimics of focal lesions include hypoglycemia and hyperglycemia. Hyperglycemia is also notorious for producing movement disorders, namely hemichorea.

NTRODUCTION Confusion is clinically defined as the inability to maintain a coherent stream of thought or action. Delirium is a confusional state with superimposed hyperactivity of the sympathetic limb of the autonomic nervous system with consequent signs including tremor, tachycardia, diaphoresis, and mydriasis. Acute toxic-metabolic encephalopathy (TME), which enco mpasses delirium and the acute confusional state, is an acute condition of global cerebral dysfunction in the absence of  primary structural brain disease [1]. An overview of TME in hospitalized patients will be discussed here; a diagnostic approach to delirium is presented separately. (See "Diagnosis of  delirium and confusional states".) TME is common among critically ill patients. Furthermore, TME is probably underrecognized and undertreated, especially when it occurs in patients who require mechanical vent ilation [2-4]. TME is usually a consequence o f systemic illness, and the causes of TME are diverse. Most TME is reversible, making prompt recognition and t reatment important. Certain metabolic encephalopathies, including those caused by sustained hypoglycemia and thiamine deficiency (Wernicke's encephalopathy), may result in permanent structural brain damage if untreated. Alcohol withdrawal syndromes must be excluded in patients with suspected TME. (See "Management of moderate and severe alcohol withdrawal syndromes".) PATHOPHYSIOLOGY Normal neuronal activity requires a balanced e nvironment of electrolytes, water, amino acids, excitatory and inhibitory neurotransmitters, and metabolic substrates [5]. In addition, normal blood flow, normal temperature, normal osmolality, and p hysiologic pH are required for optimal central nervous system function [6]. Complex systems, including those mediating arousal and awareness and those involved in higher cognitive functions, are more likely to malfunction when the local milieu is deranged [5-7]. All forms of acute toxic-metabolic encephalopathy (TME) interfere with the function of the ascending reticular activating system and/or its projections to the cerebral co rtex, leading to impairment of arousal and/or awareness [6]. Ultimately, the neurophysiologic mechanisms of  TME include interruption of polysynaptic pathways and altered excitatory-inhibitory amino acid balance [8,9]. The pathophysiology of TME varies according to the underlying etiology: y

y

y y

y

Cerebral edema contributes to acute fulminant hepatic encephalopathy and to hypoosmolar encephalopathies [7]. Drug-induced delirium results from disruption of the normal integration of  neurotransmitters, including dopamine, acetylcholine, glutamate, gamma-aminobutyric acid (GABA), and/or serotonin [7,10]. Electrolyte derangements alter membrane excitability to produce TME [6,8]. Nutritional disorders disturb cellular energy metabolism and may result in neuronal deat h [5,6]. Exogenous toxins, including carbon monoxide and cyanide, cause impaired oxygen delivery and mitochondrial dysfunction [7].

It usually develops acutely or subacutely and is reversible if the systemic disorder is treated. If left untreated, however, metabolic encephalopathy may result in secondary structural damage to the brain. Most encephalopathies are present with neuropsychiatric symptoms, one in particular being depression. However, mood disorders are often co-morbid with cardiovascular, liver, kidney and endocrine disorders, while increasing evidence concurs that depression involves inflammatory and neurodegenerative processes. This would suggest that metabolic disturbances resembling encephalopathy may underscore the basic neuropathology of depression at a far deeper l evel than currently realized. Viewing depression as a form of encephalopathy, and exploiting knowledge gleaned from our understanding of the neurochemistry and treatment of metabolic encephalopathy, may assist in our understanding of the neurobiology of depression, but also in realizing new ideas in the pharmacotherapy of mood disorders. Forty-six patients developed 47 central and three peri pheral neurologic complications. The most common complications were cerebral hemorrhage, metabolic encephalopathy, and CNS infections. All CNS infections occurred with allogeneic BMT Eleven of 16 hemorrhages were subdural hematomas, which were more frequent in autologous than in allogeneic BMT, and in patients with acute myelogenous leukemia than in the remaining leukemia patients. Eight of 11 subdural hematomas occurred in AML patients receiving autologous BMT When we compared patient-, disease-, and transplant-related characteristics of these patients with those without subdural hematoma, only platelet refractoriness correlated with an increased risk of subdural hematoma. The actuarial probability of developing subdural hematoma was 44% in patients with platelet-refractory disease and only 2.5% in the other patients. Ten patients with subdural hematoma did not have surgery and eight had significant clinical improvement associated with reduction or resolution of the hematoma, confirmed by CT scan in six patients. The subdural hematoma was the cause of death in only one patient. The purpose of this study was to determine the pattern of neurologic characteristics, MR imaging abnormalities, and brain neurometabolites i n EMS METHODS: Sixteen patients with EMS and CNS abnormalities and 12 control subjects underwent ev aluation, including medical and neurologic examination, proton MR spectroscopy, and MR imaging. RESULTS: Neurologic findings that were increased in CNS-EMS included mi nor depression, amnesia, and intermittent confusion, although fatigue, motor disorders, recurrent headache, major depression, and dementia also occurred, but at a lesser significance. Self-reported disability was markedly increased in CNS-EMS MR imaging findings included subcortical focal lesions, focal lesions in deep white matter, cortical atrophy, ventricular dilatation, and diffuse and periventricular white matter abnormalities. MR spectroscopic findings established two distinct spectral patterns: 1) increased choline-containing compounds, decreased Nacetylaspartate, and increased lipid-macromolecules, consistent with inflammatory cerebrovascular disease; and 2) increased glutamine, decreased myo-inositol, and decreased choline, consistent with acute CNS injury or metabolic encephalopathy. CONCLUSION: Neurologic abnormalities, self-reported disability, brain lesions, and MR spectroscopic abnormalities are common in CNS-EMS The pattern of  cerebral lesions and neurometabolites is consistent with widespread inflammatory cerebrovascular disease. However, a subgroup of patients with CNS-EMS have neurometabolic changes consistent with a metabolic encephalopathy identical or similar to hepatic encephalopathy. Clinically, it presents as a progressive fatal neurologic syndrome that is not easily distinguished from other feline neurologic conditions. Most cases of FSE have been reported in England, where it was first

detected in 1990, but a few cases have been reported from other European countries. To identify possible cases of FSE in Italy, the Italian Ministry of Health funded a 2-year surveillance project during which the brains from 110 domestic cats with neurologic signs were evaluated histologically for sc

spongiform encephalopathy and immunohistochemically to detect PrP . Although no cases of FSE were found, the study proved useful in monitoring the Italian cat population for other neurologic diseases: neoplasia, toxic-metabolic encephalopathy, granulomatous encephalitis, suppurative encephalitis, trauma, circulatory disorders, degeneration, n onsuppurative encephalitis, and neuromuscular diseases. Logistic regressions were applied on patient samples across and for separate etiologies.For stroke and hemorrhage the ORs with 95% confidence intervals were: 2.05, 4.47, 10.29, for trauma: 1.63, 4.72, 12.89, anoxic: 8.03, 15.50, 5.93, post-operative: 10.66, metabolic encephalopathy: 2.12, 3.60, 7.71, and all etiologies: 2.85, 6.53, and 8.79. Based on six N100 studies, five MMN studies, and six P300 studies, the N 100, MMN, or P300, when present, significantly predicted awakening, P300 and MMN being significantly better predictors than N100.Conclusions: The MMN and P300 appear to be reliable predictors of awakening.Significance: The prognostic assessment of low responsive patients with auditory ERP should take into account both MMN and P300. 2006 International Federation of C linical Neurophysiology. Published by Elsevier Ireland Ltd. Logistic regressions were applied on patient samples across and for separate etiologies.For stroke and hemorrhage the ORs with 95% confidence intervals were: 2.05, 4.47, 10.29, for trauma: 1.63, 4.72, 12.89, anoxic: 8.03, 15.50, 5.93, post-operative: 10.66, metabolic encephalopathy: 2.12, 3.60, 7.71, and all etiologies: 2.85, 6.53, and 8.79. Based on six N100 studies, five MMN studies, and six P300 studies, the N 100, MMN, or P300, when present, significantly predicted awakening, P300 and MMN bei ng significantly better predictors than N100.Conclusions: The MMN and P300 appear to be reliable predictors of awakening.Significance: The prognostic assessment of low responsive patients with auditory ERP should take into account both MMN and P300. 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. Rarely, the drug has been associated with severe hepatotoxicity. We present the case of a 13-year-old girl who developed jaundice and profound liver dysfunction with rapid progression to metabolic encephalopathy while receiving PTU therapy. She died despite extensive therapeutic measures including orthotopic liver transplantation. He lost consciousness after taking acetazolamide for 9 days. There was no finding of  cerebro-vascular disease, electrolyte imbalance and severe liver dysfunction, however the electroencephalograms and brain wave demonstrated metabolic encephalopathy. Serum concentration of acetazolamide was 54 mug/ml suggesting acetazolamide cause consciousness disorder. We utilized an antibody that selectively recognizes the neo epitope generated by caspase-3 mediated cleavage of APP to determine if this proteolytic event occurs in senile plaques in the i nferior frontal gyrus and superior temporal gyrus of autopsied AD and age-matched control brains. Consistent with a role for caspase-3 activation in AD pathology, alphaDELTACcsp-APP immunoreactivity colocalized with a subset of TUNEL-positive pyramidal neurons in A D brains. AlphaDELTACcsp-APP immunoreactivity was found in neurons and glial cells, as well as in small- and medium-size particulate elements, resembling dystrophic terminals and condensed nuclei, respectively, in AD and age-matched control brains. There were a larger number of alphaDELTACcsp-APP immunoreactive elements in the inferior frontal gyrus and superior temporal gyrus of subjects with AD pathology than age-matched controls. AlphaDELTACcsp-APP immunoreactivity in small and medium size particulate elements were the main

component colocalized with 30% of senile plaques in the inferior frontal gyrus and superior temporal gyrus of AD brains. In some control brains, alphaDELTACcsp-APP immunoreactivity appeared to be associated with a clinical history of metabolic encephalopathy. This paper presents clinical and biochemical studies in three patients and unsuccessful prenatal diagnosis in one case with combined D-2- and L-2-hydroxyglutaric aciduria. We sugg est that these patients, who displayed a phenotype of neonatal onset metabolic encephalopathy, present a third variant of 2-hydroxyglutaric aciduria. However, neurologic symptoms with poor prognosis have been regularly reported, mostly in Asian children affected by the severe dengue hemorrhagic fever/dengue shock syndrome, and attributed to a non specific, anoxic or metabolic encephalopathy. Recently, first isolations of dengue viruses from CSF or brain tissue, have renewed this concept. We report 3 dengue fever cases with neurologic manifestations and favorable outcome. Occurrence in adult age, during classic dengue fever, and neurologic sequellae wer e the three outstanding features. We point out the proteiform expression of these neurologic changes and their low incidence rate. HAD is a metabolic encephalopathy caused by productive viral infection of brain mononuclear phagocytes and sustained by paracrine-amplified, inflammatory, neurotoxic responses. MP neurotoxins are, in large measure, homeostatic secretory products that can have a neg ative effect on neuronal cell function when produced in abundance. Proinflammatory cytokines, chemokines, platelet-activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinic acid, progeny virions, and viral structural and regulatory proteins are all included as part of these cel lular and viral toxic elements. In addition, neuronal damage can occur directly by engaging specific receptors or through inducing widespread inflammatory activities in brain tissue that ultimately induce neuronal demise. The mechanisms for immune- and viral-mediated neural injury in HAD are made more striking by the effects of abused drugs on cognitive function. Early symptoms are fatigue, apathy, clumsiness, and concentration deficits. Later a delirious syndrome with generalized seizures and reduced vigilance may progress to coma. The pathophysiological processes that lead to UE are not fully understood. There is a loss of s ynaptic function probably mediated by parathyroid hormone. Imaging studies are unspecific and may be used to exclude other etiologies of  encephalopathy. EEG findings are consistent with a metabolic encephalopathy. Therapy of UE consists of  a normalization of the metabolic derangement, which in most instances leads to a full remission of all neuropsychiatric symptoms. Once UE is effectively treated, if necessary also with repeated dialysis, residual deficits are uncommon. In patients with permanent renal failure, renal transplantation is the therapy of choice. Uremic neuropathy is a predominantly distal, axonal, sensory more than motor neuropathy with burning dysesthesias. Patients with UNP also suffer from entrapment mononeuropathies, most frequently the carpal tunnel syndrome due to a susceptibility for nerve compression. An autonomic neuropathy is seen in up to 50% of the patients. Neurophysiological findings comprise reduction of sensory and motor nerve conduction velocities, distal motor latencies and amplitudes, as well as denervation consistent with an axonal neuropathy. Therapy of UNP consists of  effective dialysis or renal transplantation. Mild UNP can clinically resolve, but severe UNP responds only partially and best to transplantation. Two syndromes associated with dialysis in patients with renal failure are the dialysis disequilibrium syndrome, and dialysis encephalopathy. The former is characterized by agitation, muscle cramps, nausea and mig raineous headaches caused by a rapid decrease of serum osmolarity with brain edema during dialysis. The latter is caused by aluminium

toxicity and manifests itself with speech disturbance, depression, myoclonus and epileptic seizures. In the final stage patients are immobilized and mute. DDS is prevented by slow dialysis techniques. DE is treated with a complete absence of oral aluminium intake and elimination by chelating agents. Because findings from our laboratories have established that HIV-1 infection of astrocytes downregulates high affinity glial glutamate transporters, we further i nvestigated whether secretory products of HIV-1-infected astrocytes could contribute to a met abolic encephalopathy in neurons. We used a xenogeneic system of rodent hippocampal neurons grown in compartmentalized cultures where rodent astrocytes and hippocampal cell bodies from E18 embryos were plated in compartment 1. After 11-14 DIV, hippocampal neurites had migrated through a silicon grease barrier that excluded the passage of  small molecules, into compartment 2, which was devoid of glia. Conditioned media from HIV-1-infected human fetal astrocytes or their sham-infected controls, or VSV HIV-1-infected murine astrocytes, or their sham-infected controls was applied for 18-24 hours to neurites in compartment 2. As an index of  mitochondrial membrane potential, we measured 1 nM TMRE uptake in neurites from compartment 2 and found it to be abolished after treatment with C M from either HIV-1-infected or VSV H IV-1 infected astrocytes, but not their uninfected controls. Dilution of HIV-1 infected C M with culture media restores in part TMRE uptake. The types of RIST were w ith blood stem cells from an HLA-identical or one-locus mismatched related donor, bone marrow from a matched unrelated donor, and unrelated cord blood transplantation. The preparative regimens before RIST were busulfan 8 mg/kg plus fludarabine 150-180 mg/m2 or cladribine 0.77 mg/kg. We added 4 Gy TBI or rabbit antithymocyte globulin in UBMT, and 4 Gy TBI in UCBT, GVHD prophylaxis incorporated cyclosporine or cyclosporine plus short-term methotrexate. Diagnosis of CNS complications was based on clinical, radiological and microbiological findings. When infectious or hemorrhagic etiologies were excluded, CNS complications were classified as metabolic encephalopathy. CNS complications occurred in 19 of the 211 patients, with a me dian onset of 24 days. The symptoms included unconsciousness, seizures and visual disturbances. The type of transplants were BSCT from a related donor, UBMT and UCBT. The CNS complications were classified into 3 categories: infectious, hemorrhagic, and metabolic encephalopathy. The etiology of metabolic encephalopathy were cyclosporin, sepsis, and unknown. Concomitant conditions of metabolic encephalopathy included hyponatremia, hypokalemia, hypomagnesemia and hypertension. Eight patients had fever at the onset of CNS complications, and 2 were on steroid therapy f or acute GVHD The complications promptly improved in 7 patients, while 8 died without improvement within 30 days. The remaining 4 died thereafter without improvement within 100 days. Multivariate analysis using a logistic regression model revealed UCBT as a significant risk factor of early CNS complications. Conclusion: This study demonstrates that early CNS complication is rather common in RIST, particularly when patients received cord blood cells. Early symptoms are fatigue, apathy, clumsiness, and concentration deficits. Later a delirious syndrome with generalized seizures and reduced vigilance may progress to coma. The pathophysiological processes that lead to UE are not fully understood. There is a loss of synaptic function probably mediated by parathyroid hormone. Imaging studies are unspecific and may be used to exclude other etiologies of encephalopathy. EEG findings are consistent with a metabolic encephalopathy. Therapy of  UE consists of a normalization of the metabolic derangement, which in most instances leads to a full

remission of all neuropsychiatric symptoms. Once UE is effectively treated, if necessary also with repeated dialysis, residual deficits are uncommon. In patients with permanent renal failure, renal transplantation is the therapy of choice. Uremic neuropathy is a predominantly distal, axonal, sensory more than motor neuropathy with burning dysesthesias. Patients with UNP also suffer from entrapment mononeuropathies, most frequently the carpal tunnel syndrome due to a susceptibility for nerve compression. An autonomic neuropathy is seen in up to 50% of the patients. Neurophysiological findings comprise reduction of sensory and motor nerve conduction velocities, distal motor latencies and amplitudes, as well as denervation consistent with an axonal neuropathy. Therapy of UNP consists of  effective dialysis or renal transplantation. Mild UNP can clinically resolve, but severe UNP responds only partially and best to transplantation. Two syndromes associated with dialysis in patients with renal failure are the dialysis disequilibrium syndrome, and dialysis encephalopathy. The former is characterized by agitation, muscle cramps, nausea and mig raineous headaches caused by a rapid decrease of serum osmolarity with brain edema during dialysis. The latter is caused by aluminium toxicity and manifests itself with speech disturbance, depression, myoclonus and epileptic seizures. In the final stage patients are immobilized and mute. DDS is prevented by slow dialysis techniques. DE is treated with a complete absence of oral aluminium intake and elimination by chelating agents. Patients with confirmed mold-exposure history completed clinical interviews, a symptom checklist, limited neuropsychological testing, quantitative electroencephalogram with neurometric analysis, and measures of mold exposure. Patients reported high levels of physical, cognitive, and emotional symptoms. Ratings on the SCL-90-R were "moderate" t o "severe," with a factor reflecting situational depression accounting for most of the variance. Most of the patients were found to suffer from acute stress, adjustment disorder, or post-traumatic stress. Differential diagnosis confirmed an etiology of a combination of external stressors, along with organic metabolically based dysregulation of emotions and decreased cognitive functioning as a result of toxic or metabolic encephalopathy. Measures of toxic mold exposure predicted QEEG measures and neuropsychological test performance. QEEG results included narrowed frequency bands and increased power in the alpha and theta bands in the frontal areas of the cortex. These findings indicated a hypoactivation of the frontal cortex , possibly due to brainstem involvement and insufficient excitatory input from the reticular activating system. Neuropsychological testing revealed impairments similar to mild traumatic brain injury. In comparison with premorbid estimates of intelligence, findings of impaired functioning on multiple cognitive tasks predominated. A dose-response relationship between measures of mold exposure and abnormal neuropsychological test results and QEEG measures suggested that toxic mold causes significant problems in exposed individuals. Neurotoxicity is a well-recognized side effect of calcineurin inhibitors. Rapamycin is considered to be significantly less neurotoxic than calcineurin inhibitors. The aim of this study was to retrospectively analyze a group of post-liver transplant patients who had been converted to rapamycin because of CNI-related neurotoxicity.Patients and methods. Orthotopic liver transplantation was performed in 56 consecutive patients between April 1, 2003, an d August 15, 2004. Immunosuppression was administered with tacrolimus, mycophenolic acid, and corticosteroids.Results. Seven patients were converted to rapamycin due to new-onset neurotoxicity or exacerbation of  previous neurological symptoms secondary to CNNone of the patients had toxic levels tacrolimus at the time of symptoms, which persisted despite reduction of CNI dose. The indications for conversion were:

peripheral neuropathy; seizure; metabolic encephalopathy; and central pontine myelinolysis. All patients showed improvement or resolution of their neurological symptoms after conversion to rapamycin. Two patients died, the first due to a hypoxic eve nt and the second due to central pontine myelinolysis with limited improvement and a family decision to withdraw care. There were no complications directly attributed to rapamycin. Specifically, there were no thrombotic events, wound complications, or biliary leaks. Three patients had a rejection episode that was successfully treated with pulse corticosteroids and low-dose tacrolimus.Conclusions. Rapamycin can be safely used in OLT recipients with severe neurological symptoms ascribed to or exacerbated by CNIs. Rapamycin monotherapy may be inadequate to control rejection early after transplantation. Objective: To describe electroencephalographic differences between TWs and GNCSE Methods: We retrospectively compared the electroencephalograms of two groups of patients presenting with decreased level of consciousness; those with TWs associated with metabolic encephalopathy and those with GNCSE We studied the following: demographics, etiology and EEG morphological features. All EEGs were classified blindly by two expert EEGers. Agree ment between experts and concordance with clinical diagnosis were measured. We analysed 87 EEGs with TWs and 27 EEGs with GNCSE Agreement between experts and concordance with clinical diagnosis were excell ent. When compared to TWs, epileptiform discharges associated with GNCSE had a higher frequency, a shorte r duration of phase one, extra-spikes components and less generalized background slowing. Amplitude predominance of phase two was common with TWS. Lag of phase two was absent i n all cases of GNCSE but present in 40.8% of patients with TWs. Noxious or auditory stimulation frequently increased the TWs while it had no effect on the epileptiform pattern. However, critical basic science and clinical research did not progress until the DSM III criteria clearly defined delirium 20 years ago. The term delirium then replaced many nonspecific entities, such as acute confusion state, acute brain syn drome, metabolic encephalopathy, and toxic psychosis. This review discusses the epidemiology, risk factors, interventions, causes, management, and outcomes of delirium. Seventeen of these patients experienced 19 neurological complications during the course of their disease. Fourteen had nervous system metastases or invasion. Nonmetastatic complications, including CNS infections and new onset of seizures secondary to metabolic encephalopathy were seen in 5 cases. By the tim e of the final analysis of the results, 8 of the 17 patients with neurological complications had died. 7 had either been lost to follow-up or were i n the terminal stage of their disease, and 2 were in remission. Both of the patients who were in remission had dumbbell neuroblastoma, and 1 of them, with congenital DNB, also had neurological sequelae, characterized by paraplegia and neurogenic bladder. Neurological complications occurred in 68% of NB and GNB cases. Metastatic complications were more common than nonmetastatic complications and had a poor prognosis. Neurological complications were the primary cause of mortality in this study, mortality being related to neurological complications in 63% of cases, and the final outcome was worse than expected. HAD is a metabolic encephalopathy caused by productive viral infection of brain mononuclear phagocytes and sustained by paracrine-amplified, inflammatory, neurotoxic re sponses. MP neurotoxins are, in large measure, homeostatic secretory products that can have a negative effect on neuronal cell function when produced in abundance. Proinflammatory cytokines, chemokines, platelet-activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinic acid, progeny virions, and viral structural and regulatory proteins are all included as part of these cellular and viral

toxic elements. In addition, neuronal damage can occur directly by engaging specific receptors or through inducing widespread inflammatory activities in brain tissue that ultimately induce neuronal demise. The mechanisms for immune- and viral-mediated neural injury in HAD are made more striking by the effects of abused drugs on cognitive function.

efinition Metabolic encephalopathy describes temporary or permanent damage to the brain that happens when the body¶s metabolic processes are seriously impaired. Most cases occur when the liver  cannot act normally to remove toxins from the bloodstream. The Brain

Copyright © 2005 Nucleus Communications, Inc. All rights reserved. www.nucleusinc.com

Causes Metabolic encephalopathy occurs during significant metabolic derangements, after some types of  poisoning, and during diseases such as cirrhosis or hepatitis that slow or stop liver function. It can also happen during medical conditions that cause blood circulation to bypass the liver. These problems keep the liver from removing toxins like ammonia, which build up in the blood as part of normal metabolism. High levels of these toxins can temporarily or permanently damage the brain, causing metabolic encephalopathy.

Risk Factors A risk factor is something that increases one¶s chance o f getting a disease or condition. y

y

In people who already have liver problems, the risk of metabolic encephalopathy increases by: Low oxygen levels in the blood o Infections o Major surgery o Any serious illness that causes changes in the body¶s chemical make-up or  o metabolism Use of certain medicines, such as sedatives and narcotics o Bleeding within the intestines o Persistent vomiting or  diarrhea that lowers blood potassium levels o Metabolic encephalopathy also happens to people without liver problems who suffer  sudden liver failure due to poisoning, develop severe electrolyte imbalances, or for other  reasons.

Symptoms The symptoms of metabolic encephalopathy include:

y y y y y y y y y y

Confusion or agitation Changes in behavior and personality Forgetfulness Disorientation Insomnia Muscle stiffness or rigidity Tremor (particularly a flapping tremor of the hands) Difficulty speaking Uncontrollable movements, or, rarely, seizures Stupor or  coma

These problems can develop quickly, and may all resolve when the metabolic encephalopathy is reversed. However, prompt treatment is required to save a pat ient that has lapsed into a coma.

Diagnosis Metabolic encephalopathy is a very serious problem that can quickly become a medical emergency. Hospitalization is always required. Doctors will perform a detailed ph ysical examination to assess the patient¶s neurologic condition. Blood tests usually show high blood a mmonia levels and other significant abnormalities related to the failing liver and possible causes for the ensuing encephalopathy. An electroencephalogram (EEG; a reading of electrical activity in the brain) may be useful to determine how seriously the brain is affected.

Treatment During hospitalization, the doctor and hospital staff will work to treat the problems that caused the metabolic encephalopathy in an effort to remove or neutralize toxins that have built up in the bloodstream. Reversing the underlying problem is necessary to treat the encephalopathy, but it does not guarantee that t here will not be residual brain injury if the condition was severe e nough or persisted long enough to cause permanent damage. A low-protein diet is usually prescribed to help lower blood ammonia levels (the body creates ammonia when it metabolizes and uses protein). Special tube feedings may be needed and life support machines may be requ ired, especially in the case of coma. In cases of metabolic encephalopathy due to chronic liver failure (eg, cirrhosis patients), strong consideration is often given for liver transplantation.

Prevention Appropriate early treatment of liver problems may prevent metabolic encephalopathy in some people. If you have longstanding liver problems you should see your healthcare p rovider  immediately if you develop confusion or any type of behavior change.

View more...

Comments

Copyright ©2017 KUPDF Inc.