Toxic-Metabolic Encephalopathy

Acute toxic-metabolic encephalopathy (TME) is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease.  There are many canuses of TME, however, it is usually secondary to a systemic illness. Most TME is reversible, making prompt recognition and treatment important because there are specific metabolic encephalopathies, such as thiamine deficiency (Wernicke's encephalopathy), that may result in permanent structural brain damage if untreated. Alcohol withdrawal syndromes must be excluded in patients with suspected TME

 

Pathology - All the etiologies of acute toxic-metabolic encephalopathy (TME) interfere in some way with the function of the ascending reticular activating system and/or its projections to the cerebral cortex which then causes a problem with the patient's consciousness/awareness. The pathophysiology behind the TME differs depending on the underlying etiology such as...

 

- Cerebral edema occurs in the setting of acute fulminant hepatic encephalopathy and hypoossmolar encephalopathies.

 

- Disruption of the balance of neurotransmitters (dopamine, serotonin, GABA and acetylcholine) can cause drug-induced delirium.

 

-Neuronal death can occur from nutritional disorders which can impair normal cellular metabolism

 

-Exogenous toxins such as CO and CN can lead to impairment of mitochrondrial function and decrease delivery of O2 to the brain.

 

-Increased blood-brain barrier permeability may lead to an increase in systemic toxins leading to impariement in neuronal function. Patients who have increased permeability in the BBB may have a larger amount of protein in the CSF fluid.

 

Clinical Manifestations - The manifestations are varied and generalized depending on the etiology. The symptoms can be broken down into categories.

 

-Mental status - impaired attention and fluctuation in attention, disturbed sleep-wake cycle, decreased alertness, hypervigilance, hallucinations, sensory misperceptions, impaired memory,apathy, mania and disorientation

 

-Seizures - usually are generalized clonic-tonic but can also be focal, multifocal or partial complex

 

-Cranial nerve examination - Almost all the causes of TME will leave the patient with intact pupillary function except in the cases of anticholinergic or glutethimide ingestion. Other brainstem reflexes such as gag, oculocephalic or corneal reflex typically remain intact and are only affected in severe TME

 

-Motor examination - a variety of motor abnormalities can be see in TME such as tremor, as

terixis, multifocal myoclonus, primitive reflexes, brinsk deep tendon reflexes and extensor plantar reflexes.

 

-Autonomic instability such as tachycardia, hypertension, fever, diaphoresis is characteristic in delirium

Specific Etiologies

-Septic Encephalopathy - This is THE MOST COMMON CAUSE of acute TME

 

-Hepatic encephalopathy - normal ammonia levels does not exclude the diagnosis

 

-Uremic encephalopathy

 

-Hyponatremia - Hypernatremia

 

-Hypoglycemia

 

-Hyperosmolar hyperglycemia and diabetic ketoacidosis

 

-Wernicke's Encephalopathy - secondary to a thiamine deficiency and may see the classic triad of confusion, ataxia and opthalmoplegia

 

-Hypoxic-ischemic encephalopathy - Hypoxic-ischemic encephalopathy is usually a straightforward diagnosis that follows an obvious precipitating event such as cardiac arrest with prolonged resuscitation efforts

 

-Post-transplantation encephalopathy - Encephalopathy following transplantation may be due to underlying conditions, operative procedures, immunosuppressive medications, cranial radiation, or opportunistic infections

 

Medications - Most immunosuppressant medications used following transplantation are capable of producing encephalopathy: Cyclosporin, steroids, tacrolimus.

 

Diagnsosis - TME is a diagnosiss of exclusion. Tests that would be helpful would be...

 

Laboratory studies - complete blood count, coagulation studies, electrolyte panel, and examination of calcium, magnesium, phosphate, glucose, blood urea nitrogen, creatinine, bilirubin, liver enzymes, ammonia, serum osmolality, and arterial blood gases, toxicologic screening should be performed for suspected intoxications, and blood and CSF cultures obtained if infection appears present. Thyroid function tests, vitamin B12 and serum cortisol concentrations should be assessed if endocrinopathy is in the differential diagonosis.  

 

Neuroimaging - CT or MRI of the head is indicated when focal signs are present on physical examination or when subdural hematoma is suggested by the history.

 

Electroencephalography — The electroencephalogram (EEG) can both confirm global cerebral dysfunction and exclude subclinical seizures with greater sensitivity than clinical examination alone

 

Treatment - the best treatment is to treat the underlying cause of the TME. A thourough check of the medication list would be helpful. Give thiamine for patient's suspicious of wernickes encephalopathy as well as patients on hemodialysis, malnutrition, cancer and hyperemesis gravidarum. Can give haloperidol for agitation but avoid halopaeridol in cases of alcohol withdrawal, anticholinergic toxicity, and benzodiazepine withdrawal, and also in patients with parkinsonism