Metabolic and Toxic Diseases of the CNS

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Metabolic and toxic disorders of the nervous system are common causes of neurological disease.

Several major diseases of the CNS have a metabolic or toxic causation, a reflection of the vulnerability of the nervous system to injury.
The main causes are vitamin deficiency states, liver failure, carbon monoxide poisoning, and alcohol abuse.

Several vitamin deficiency states are associated with damage to the nervous system.
Vitamin B1 (thiamine) deficiency causes Wernicke's encephalopathy.
Vitamin B12 deficiency is commonly associated with pernicious anaemia. In the nervous system this causes degeneration of the lateral and posterior columns of the spinal cord, termed 'sub-acute combined degeneration of the cord, leading to paraesthesiae, ataxia, and sensory abnormalities.

Hepatic encephalopathy is a clinical state that arises in patients with severe liver failure. Patients develop impaired consciousness, which may progress to coma. Disease is thought to be due to the presence of excitatory transmitter substances in the blood, which have not been detoxified by the liver, e.g. GABA.

Carbon monoxide poisoning is commonly encountered, either as an accident (usually involving faulty heating equipment) or as a result of attempted suicide. In patients who survive the acute poisoning and are resuscitated, delayed damage to the brain may occur, signs usually becoming apparent 24-36 hours after exposure to carbon monoxide. There is necrosis of the globus pallidus, demyelination of the hemispheric white matter and, frequently, diffuse cortical laminar necrosis.
The brain and peripheral nerves are frequently damaged in chronic alcoholism

Acute alcohol intoxication causes neuronal depression and may lead to death through cessation of respiration.

Chronic alcoholism is associated with several diseases of both the central and the peripheral nervous system. It has been difficult to determine whether this is due to direct toxicity or whether it is caused by the nutritional and vitamin deficiencies seen commonly in patients dependent on alcohol.

The brains of alcoholic patients show generalized cerebral cortical atrophy, which sometimes causes cognitive decline. Cerebellar ataxia in patients with alcoholism is usually caused by cerebellar degeneration associated with severe atrophy of the cerebellar cortex.

Wernicke's encephalopathy is caused by thiamine deficiency, commonly seen in patients dependent on alcohol. It presents clinically as a triad of confusion, ataxia, and abnormal eye movements with ophthalmoplegia. Pathologically, there are petechial haemorrhages from small vessels in the mammillary bodies, which are associated with necrosis and loss of neurons, leading to eventual shrinkage and gliosis. Acute Wernicke's encephalopathy may prove fatal unless B-complex vitamins (including thiamine) are administered. 
Damage to the limbic system from repeated episodes of Wernicke's encephalopathy causes a permanent impairment of recent memory, termed Korsakoff's psychosis.

Exposure of the fetus to alcohol, when the mother is dependent, leads to growth retardation and cerebral malformations (fetal alcohol syndrome).
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