Transcript Toxic-Metabolic Encephalopathies

Toxic-Metabolic
Encephalopathies
Definition
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Group of neurological disorders whose hallmark
is an altered mental status
Caused by failure of organs other than nervous
system or presence of an endogenous or
exogenous toxin or drug
BBB isolate brain
Multifocal cortical disorder
Delirium
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A confusional state with superimposed
hyperactivity of the sympathetic limb of the
autonomic nervous system with consequent
signs including tremor, tachycardia, diaphoresis,
and mydriasis
Confusion: inability to maintain a coherent
stream of thought or action
TME
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Acute toxic-metabolic encephalopathy (TME):
encompasses delirium and the acute confusional
state
Acute condition of global cerebral dysfunction
in the absence of primary structural brain
disease
TME
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common among critically ill patients
probably underrecognized and undertreated
Most TME is reversible, making prompt
recognition and treatment 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
Clinical manifestations
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Mental status abnormalities :range from subtle
to deep coma
Impaired orientation, cognition, memory, affect,
perception , judgement
Pupils: sluggish, small, irregular
Eye movement: disconjugate gaze
Motor: increase in tone
Spasticity with extensor plantar response
Pathophysiology
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Normal neuronal activity requires a balanced
environment of electrolytes, water, amino acids,
excitatory and inhibitory neurotransmitters, and
metabolic substrates
normal blood flow, normal temperature, normal
osmolality, and physiologic pH are required for
optimal central nervous system function
Pathophysiology
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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 cortex, leading to impairment of arousal
and/or awareness
Ultimately, the neurophysiologic mechanisms of TME
include interruption of polysynaptic pathways and
altered excitatory-inhibitory amino acid balance
Increased permeability of the blood-brain barrier is
evidenced by elevated protein in the CSF, a frequent
finding in TME
Pathophysiology
The pathophysiology of TME varies according to the underlying etiology:
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Cerebral edema contributes to acute fulminant hepatic encephalopathy and to hypoosmolar encephalopathies
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Drug-induced delirium results from disruption of the normal integration of
neurotransmitters, including dopamine, acetylcholine, glutamate, gamma-aminobutyric
acid (GABA), and/or serotonin
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Electrolyte derangements alter membrane excitability
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Nutritional disorders disturb cellular energy metabolism and may result in neuronal
death
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Exogenous toxins, including carbon monoxide and cyanide, cause impaired oxygen
delivery and mitochondrial dysfunction
Clinical findings
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Mltifocal myoclonus
Cramps
Trousseau’s sign
Tremors
Weakness
Asterixis
Generalized, focal, myoclonic seizures
Hepatic encephalopathy
Liver disease causes encephalopathy by 2
mechanisms :
1-Hepatocellular failure
2-Diversion of toxins from hepatic portal vein
into the systemic circulation
Precipitating factors
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GI bleed
Drug induced
Excess dietary protein
Hypokalmeia
Constipation
infections
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Toxin hypersensitivity : patients becoming more
susceptible to effect of precipitants
Portal systemic encephalopathy: cirrhosis with
shunts
Pathogenesis
The most important factors in the pathogenesis are:
1-severe hepatocellular dysfunction and/or intrahepatic and extrahepatic
shunting of blood into the systemic circulation so that the liver is largely
bypassed.
2- Various toxic substances absorbed by the intestine are not detoxified by the
liver and lead to metabolic abnormalities in the CNS.
Ammonia is the substance most often incriminated in
the pathogenesis of encephalopathy. Others include
mercaptans, short- chain fatty acids and phenols.
Uremic encephalopathy
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Coexistence of signs of nervous system depression
(obtundation) and neural excitation (twitching,
myoclonus, agitation and seizures)
Dut to:
Progressive azotemia
Effect of treatment :dialysis disequilibrium syndrome,
dementia from aluminum accumulation
Complication of transplantation and
immunosupression
Disorders of glucose metabolism
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Hypoglycemia
Non-ketotic hyperosmolar coma
DKA
B12 deficiency
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Early : cognitive changes
Late : dementia ,optic atrophy
Irreversible if not treated early
Sub-acute combined degeneration of spinal cord
Wernicke-Korsakoff encephalopathy
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Chronic alcoholism
Hyperemesis gravidarum
Malignancy
GI surgery
HD
Prolonged intravenous feeding
Anorexia nervosa
AIDS
Wernicke-Korsakoff encephalopathy
Triad of :
 Confusion
 Opthalmoplegia
 Ataxia
Pathology : small hemorrhages in periventricular grey
matter around aqueduct,3rd and 4th ventricles
Treatment : Thiamine
glucose
Central pontine myelinolysis
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Caused by rapid osmotic change
Rapid correction of sodium
Rule : no more than 12 mmol per liter per 24 hrs
Clinically : flaccid or spastic quadreplegia
Psuedobulbar palsy
Decrease LOC
Toxic encephalopathies
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6 groups:
Alcohol
BZD
Salicylaytes
Acetaminophen
Barbiturates
TCA’s
Hypoxic-ischemic encephalopathy
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brain utilizes oxygen to metabolize glucose. It
cannot store oxygen and survives only for
minutes after its oxygen supply is reduced below
critical levels.
Pyramidal cells in Sommer's sector of the
hippocampus, Purkinje cells of the cerebellum,
and pyramidal cells of the third and fifth layers
of the cerebral cortex are vulnerable to even
moderate degrees of anoxia
HIE
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Anoxic anoxia consists of low arterial oxygen content and
tension. This may be secondary to decreased oxygen in the
environment or inability for oxygen to enter the circulatory
system as in pulmonary disease
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Anemic anoxia consists of low oxygen content in the blood
secondary to decreased hemoglobin content.
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Ischemic anoxia describes a state of insufficient cerebral blood
flow. "Low-flow states" may be secondary to cardiovascular
collapse or conditions of increased vascular resistance as in
stroke or migraine
HIE
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Result from a number of conditions such as:
Cardiac arrest
CO intoxication
Septic shock
HIE
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Spectrum :
Syncope : breif global cerebral ischemic anoxia
Focal cerebral ischemia : hypotension leading to
watershed infraction
Postanoxic coma
Persistent vegetative state
Cerebral edema
Delayed postanoxic deterioration
Brain death
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Irreversible cessation of CNS function
Diagnosis based on absence of all cerebral and
brainstem functions persisteng over a peroid of
observation suffeicent to exclude any possibilty
of recovery
Prognosis and Complications
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post-arrest coma longer than three days carried
an unfavorable prognosis
Individuals with the best chance of recovery had
preserved brainstem function following the
initial insult
Management
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Diagnostic difficulty: drugs, sepsis
Continuos monitoring
Watch for complications: NCSE
CT brain
LP
EEG
Management
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No known specific treatment that reverse AIE
Rapid re-establishing circulation
Normal or somewhat increased BP
Normal ABG
Control hyperthermia and seizures
AED :if indicated