Toxic-Metabolic Toxic-Metabolic EncephalopathieEncephalopathie

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DefinitionDefinition

Group of neurological disorders Group of neurological disorders whose hallmark is an altered mental whose hallmark is an altered mental statusstatus

Caused by failure of organs other Caused by failure of organs other than nervous system or presence of than nervous system or presence of an endogenous or exogenous toxin or an endogenous or exogenous toxin or drugdrug

BBB isolate brain BBB isolate brain Multifocal cortical disorderMultifocal cortical disorder

DeliriumDelirium

A confusional state with A confusional state with superimposed hyperactivity of the superimposed hyperactivity of the sympathetic limb of the autonomic sympathetic limb of the autonomic nervous system with consequent nervous system with consequent signs including tremor, tachycardia, signs including tremor, tachycardia, diaphoresis, and mydriasisdiaphoresis, and mydriasis

Confusion: inability to maintain a Confusion: inability to maintain a coherent stream of thought or action coherent stream of thought or action

TMETME

Acute toxic-metabolic Acute toxic-metabolic encephalopathy (TME): encompasses encephalopathy (TME): encompasses delirium and the acute confusional delirium and the acute confusional statestate

Acute condition of global cerebral Acute condition of global cerebral dysfunction in the absence of dysfunction in the absence of primary structural brain disease primary structural brain disease

TMETME common among critically ill patients common among critically ill patients probably underrecognized and probably underrecognized and

undertreated undertreated Most TME is reversible, making prompt Most TME is reversible, making prompt

recognition and treatment important recognition and treatment important Certain metabolic encephalopathies, Certain metabolic encephalopathies,

including those caused by sustained including those caused by sustained hypoglycemia and thiamine deficiency hypoglycemia and thiamine deficiency (Wernicke's encephalopathy), may result in (Wernicke's encephalopathy), may result in permanent structural brain damage if permanent structural brain damage if untreated untreated

Clinical manifestations Clinical manifestations

Mental status abnormalities :range from Mental status abnormalities :range from subtle to deep comasubtle to deep coma

Impaired orientation, cognition, Impaired orientation, cognition, memory, affect, perception , judgement memory, affect, perception , judgement

Pupils: sluggish, small, irregularPupils: sluggish, small, irregular Eye movement: disconjugate gazeEye movement: disconjugate gaze Motor: increase in toneMotor: increase in tone Spasticity with extensor plantar Spasticity with extensor plantar

responseresponse

PathophysiologyPathophysiology

Normal neuronal activity requires a Normal neuronal activity requires a balanced environment of electrolytes, balanced environment of electrolytes, water, amino acids, excitatory and water, amino acids, excitatory and inhibitory neurotransmitters, and inhibitory neurotransmitters, and metabolic substrates metabolic substrates

normal blood flow, normal temperature, normal blood flow, normal temperature, normal osmolality, and physiologic pH normal osmolality, and physiologic pH are required for optimal central nervous are required for optimal central nervous system function system function

PathophysiologyPathophysiology All forms of acute toxic-metabolic All forms of acute toxic-metabolic

encephalopathy (TME) interfere with the encephalopathy (TME) interfere with the function of the ascending reticular activating function of the ascending reticular activating system and/or its projections to the cerebral system and/or its projections to the cerebral cortex, leading to impairment of arousal and/or cortex, leading to impairment of arousal and/or awareness awareness

Ultimately, the neurophysiologic mechanisms Ultimately, the neurophysiologic mechanisms of TME include interruption of polysynaptic of TME include interruption of polysynaptic pathways and altered excitatory-inhibitory pathways and altered excitatory-inhibitory amino acid balanceamino acid balance

Increased permeability of the blood-brain Increased permeability of the blood-brain barrier is evidenced by elevated protein in the barrier is evidenced by elevated protein in the CSF, a frequent finding in TME CSF, a frequent finding in TME

PathophysiologyPathophysiologyThe pathophysiology of TME varies according to the underlying The pathophysiology of TME varies according to the underlying

etiology:etiology:

Cerebral edema contributes to acute fulminant hepatic Cerebral edema contributes to acute fulminant hepatic encephalopathy and to hypo-osmolar encephalopathiesencephalopathy and to hypo-osmolar encephalopathies

Drug-induced delirium results from disruption of the normal Drug-induced delirium results from disruption of the normal

integration of neurotransmitters, including dopamine, integration of neurotransmitters, including dopamine, acetylcholine, glutamate, gamma-aminobutyric acid (GABA), acetylcholine, glutamate, gamma-aminobutyric acid (GABA), and/or serotoninand/or serotonin

Electrolyte derangements alter membrane excitability Electrolyte derangements alter membrane excitability

Nutritional disorders disturb cellular energy metabolism and may Nutritional disorders disturb cellular energy metabolism and may result in neuronal death result in neuronal death

Exogenous toxins, including carbon monoxide and cyanide, cause Exogenous toxins, including carbon monoxide and cyanide, cause impaired oxygen delivery and mitochondrial dysfunction impaired oxygen delivery and mitochondrial dysfunction

Clinical findingsClinical findings

Mltifocal myoclonusMltifocal myoclonus CrampsCramps Trousseau’s sign Trousseau’s sign TremorsTremors WeaknessWeakness AsterixisAsterixis Generalized, focal, myoclonic Generalized, focal, myoclonic

seizures seizures

Hepatic encephalopathyHepatic encephalopathy

Liver disease causes encephalopathy Liver disease causes encephalopathy by 2 mechanisms :by 2 mechanisms :

1-Hepatocellular failure1-Hepatocellular failure

2-Diversion of toxins from hepatic 2-Diversion of toxins from hepatic portal vein into the systemic portal vein into the systemic circulation circulation

Precipitating factorsPrecipitating factors

GI bleedGI bleed Drug inducedDrug induced Excess dietary proteinExcess dietary protein HypokalmeiaHypokalmeia ConstipationConstipation infectionsinfections

Toxin hypersensitivity : patients Toxin hypersensitivity : patients becoming more susceptible to effect becoming more susceptible to effect of precipitants of precipitants

Portal systemic encephalopathy: Portal systemic encephalopathy: cirrhosis with shunts cirrhosis with shunts

PathogenesisPathogenesis

The most important factors in the pathogenesis are:The most important factors in the pathogenesis are:

1-severe hepatocellular dysfunction and/or intrahepatic and 1-severe hepatocellular dysfunction and/or intrahepatic and extrahepatic shunting of blood into the systemic extrahepatic shunting of blood into the systemic circulation so that the liver is largely bypassed.circulation so that the liver is largely bypassed.

2- Various toxic substances absorbed by the intestine are not 2- Various toxic substances absorbed by the intestine are not detoxified by the liver and lead to metabolic abnormalities detoxified by the liver and lead to metabolic abnormalities in the CNS.in the CNS.

AmmoniaAmmonia is the substance most often incriminated in is the substance most often incriminated inthe pathogenesis of encephalopathy. Others includethe pathogenesis of encephalopathy. Others includemercaptans, short- chain fatty acids and phenols.mercaptans, short- chain fatty acids and phenols.

Uremic encephalopathyUremic encephalopathy

Coexistence of signs of nervous system Coexistence of signs of nervous system depression (obtundation) and neural excitation depression (obtundation) and neural excitation (twitching, myoclonus, agitation and seizures)(twitching, myoclonus, agitation and seizures)

Dut to:Dut to: Progressive azotemiaProgressive azotemia Effect of treatment :dialysis disequilibrium Effect of treatment :dialysis disequilibrium

syndrome, dementia from aluminum syndrome, dementia from aluminum accumulationaccumulation

Complication of transplantation and Complication of transplantation and immunosupressionimmunosupression

Disorders of glucose Disorders of glucose metabolismmetabolism

Hypoglycemia Hypoglycemia Non-ketotic hyperosmolar comaNon-ketotic hyperosmolar coma DKADKA

B12 deficiencyB12 deficiency

Early : cognitive changesEarly : cognitive changes Late : dementia ,optic atrophyLate : dementia ,optic atrophy Irreversible if not treated earlyIrreversible if not treated early Sub-acute combined degeneration of Sub-acute combined degeneration of

spinal cord spinal cord

Wernicke-Korsakoff Wernicke-Korsakoff encephalopathyencephalopathy

Chronic alcoholismChronic alcoholism Hyperemesis gravidarumHyperemesis gravidarum MalignancyMalignancy GI surgeryGI surgery HDHD Prolonged intravenous feedingProlonged intravenous feeding Anorexia nervosaAnorexia nervosa AIDS AIDS

Wernicke-Korsakoff Wernicke-Korsakoff encephalopathyencephalopathy

Triad of :Triad of : ConfusionConfusion OpthalmoplegiaOpthalmoplegia AtaxiaAtaxia

Pathology : small hemorrhages in Pathology : small hemorrhages in periventricular grey matter around periventricular grey matter around aqueduct,3aqueduct,3rdrd and 4 and 4thth ventricles ventricles

Treatment : Thiamine Treatment : Thiamine glucose glucose

Central pontine Central pontine myelinolysismyelinolysis

Caused by rapid osmotic changeCaused by rapid osmotic change Rapid correction of sodium Rapid correction of sodium Rule : no more than 12 mmol per Rule : no more than 12 mmol per

liter per 24 hrsliter per 24 hrs Clinically : flaccid or spastic Clinically : flaccid or spastic

quadreplegiaquadreplegia Psuedobulbar palsyPsuedobulbar palsy Decrease LOCDecrease LOC

Toxic encephalopathiesToxic encephalopathies

6 groups:6 groups: Alcohol Alcohol BZDBZD Salicylaytes Salicylaytes Acetaminophen Acetaminophen Barbiturates Barbiturates TCA’sTCA’s

Hypoxic-ischemic Hypoxic-ischemic encephalopathyencephalopathy

brain utilizes oxygen to metabolize brain utilizes oxygen to metabolize glucose. It cannot store oxygen and glucose. It cannot store oxygen and survives only for minutes after its survives only for minutes after its oxygen supply is reduced below critical oxygen supply is reduced below critical levels. levels.

Pyramidal cells in Sommer's sector of Pyramidal cells in Sommer's sector of the hippocampus, Purkinje cells of the the hippocampus, Purkinje cells of the cerebellum, and pyramidal cells of the cerebellum, and pyramidal cells of the third and fifth layers of the cerebral third and fifth layers of the cerebral cortex are vulnerable to even moderate cortex are vulnerable to even moderate degrees of anoxia degrees of anoxia

HIEHIE Anoxic anoxiaAnoxic anoxia consists of low arterial oxygen consists of low arterial oxygen

content and tension. This may be secondary to content and tension. This may be secondary to decreased oxygen in the environment or inability for decreased oxygen in the environment or inability for oxygen to enter the circulatory system as in oxygen to enter the circulatory system as in pulmonary diseasepulmonary disease

Anemic anoxiaAnemic anoxia consists of low oxygen content in the consists of low oxygen content in the

blood secondary to decreased hemoglobin content.blood secondary to decreased hemoglobin content.

Ischemic anoxiaIschemic anoxia describes a state of insufficient describes a state of insufficient cerebral blood flow. "Low-flow states" may be cerebral blood flow. "Low-flow states" may be secondary to cardiovascular collapse or conditions of secondary to cardiovascular collapse or conditions of increased vascular resistance as in stroke or increased vascular resistance as in stroke or migrainemigraine

HIEHIE

Result from a number of conditions Result from a number of conditions such as:such as:

Cardiac arrestCardiac arrest CO intoxicationCO intoxication Septic shockSeptic shock

HIEHIE

Spectrum :Spectrum : Syncope : breif global cerebral Syncope : breif global cerebral

ischemic anoxiaischemic anoxia Focal cerebral ischemia : hypotension Focal cerebral ischemia : hypotension

leading to watershed infractionleading to watershed infraction Postanoxic comaPostanoxic coma Persistent vegetative statePersistent vegetative state Cerebral edemaCerebral edema Delayed postanoxic deterioration Delayed postanoxic deterioration

Brain deathBrain death

Irreversible cessation of CNS Irreversible cessation of CNS functionfunction

Diagnosis based on absence of all Diagnosis based on absence of all cerebral and brainstem functions cerebral and brainstem functions persisteng over a peroid of persisteng over a peroid of observation suffeicent to exclude any observation suffeicent to exclude any possibilty of recoverypossibilty of recovery

Prognosis and Prognosis and ComplicationsComplications

post-arrest coma longer than three post-arrest coma longer than three days carried an unfavorable days carried an unfavorable prognosis prognosis

Individuals with the best chance of Individuals with the best chance of recovery had preserved brainstem recovery had preserved brainstem function following the initial insult function following the initial insult

ManagementManagement

Diagnostic difficulty: drugs, sepsisDiagnostic difficulty: drugs, sepsis Continuos monitoringContinuos monitoring Watch for complications: NCSEWatch for complications: NCSE CT brainCT brain LPLP EEGEEG

ManagementManagement

No known specific treatment that No known specific treatment that reverse AIEreverse AIE

Rapid re-establishing circulationRapid re-establishing circulation Normal or somewhat increased BPNormal or somewhat increased BP Normal ABGNormal ABG Control hyperthermia and seizuresControl hyperthermia and seizures AED :if indicatedAED :if indicated