Nutritional Disorders 

Updated: Aug 15, 2013
  • Author: Abir L Mukherjee, MD; Chief Editor: Adekunle M Adesina, MD, PhD  more...
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Definition

Most nutritional nervous-system disorders involve vitamin deficiency, particularly of the B group. Many of them occur in the context of alcoholism.

Protein-energy malnutrition in children leads to impaired myelin development, [1] but normal neurological development occurs if nutrition is restored.

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Epidemiology

Thiamine

The daily requirement of thiamine is 1-1.5 mg, and body stores can be depleted very quickly. Alcohol increases thiamine utilization, reduces gastrointestinal uptake, and impairs phosphorylation of thiamine. [2]

Cobalamin

The daily requirement of cobalamin is 1-3 µg, and the liver stores 4-5 mg. Cobalamin deficiency usually results from malabsorption of cobalamin due to pernicious anemia and other gastric disorders.

Niacin

Niacin deficiency may result from insufficient dietary intake. The daily requirement of niacin is 13-20 g.

Folate

Folate (vitamin B9) deficiency can occur during pregnancy or treatment with medications that have antifolate activity, such as antiepileptics.

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Etiology

Thiamine

Thiamin is a cofactor for major enzymes involved in brain glucose metabolism. Thiamine deficiency may be nutritional or may result from prolonged intravenous feeding, gastrointestinal procedures and diseases, malignancies, infections, starvation, and hyperemesis gravidarum.

Cobalamin

Cobalamin is a cofactor for enzymes necessary for production of cell membrane and myelin.

Niacin

Pellagra, caused by niacin deficiency, is rare, occurring commonly in persons with alcoholism. It may be seen in vegans and those treated with isoniazid. [3]

Folate

Folate is needed for synthesis of purine nucleotides, methionine, and DNA.

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Location

Thiamine

Thiamine deficiency results in peripheral neuropathy and Wernicke-Korsakoff syndrome involving the mamillary body, medial hypothalamus, thalamus, periaqueductal gray matter, floor of the fourth ventricle, and superior vermis of cerebellum. It is unclear if the cerebellar damage results from thiamin deficiency or effects of alcohol toxicity.

Cobalamin

Cobalamin deficiency results in a demyelinating disorder of spinal cord.

Niacin

Niacin deficiency affects the cerebrum and brainstem.

Folate

Folate deficiency predominantly affects the spinal cord.

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Clinical Features and Imaging

Thiamine

Beriberi, which results from thiamine deficiency, is characterized by a predominant distal motor polyneuropathy.

Wernicke-Korsakoff syndrome also represents a severe manifestation of thiamine deficiency, characterized by ocular abnormalities, cerebellar dysfunction, and altered mental status. MRI shows symmetrical areas of hyperintensity on T2-weighted images in mamillary bodies, medial thalami, and periaqueductal gray matter.

Cobalamin

Cobalamin deficiency results in subacute combined degeneration (SCD), which is characterized by progressive symmetrical sensory disturbance of the lower limb, followed by ataxia, spasticity, and loss of reflexes. MRI shows hyperintensities in the spinal cord on T2-weighted images. [4] These patients also have megaloblastic anemia.

Niacin

Pellagra is characterized by confusion, apathy, depression, abnormal gait, and spastic quadriplegia in severe cases. Apart from central nervous system effects, dermatitis and diarrhea are also common.

Folate

Folate deficiency during pregnancy is associated with neural tube defects, and folic acid supplementation has been shown to reduce the risk of birth defects. [5] Clinical features of folate deficiency resemble those of subacute combined degeneration.

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Gross Findings

Thiamine

The acute phase of Wernicke-Korsakoff syndrome shows petechial hemorrhages in the mamillary body, medial hypothalamus, thalamus, periaqueductal gray matter, and floor of the fourth ventricle. In the chronic state, mamillary bodies shrink and show a brown discoloration.

Cobalamin

Cobalamin deficiency is characterized by atrophy and discoloration of the spinal cord, especially of the posterior and lateral columns.

Niacin

Macroscopically, the brain in pellagra is normal.

Folate

Gross changes are nonspecific.

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Microscopic Findings

Thiamine

Peripheral neuropathy in thiamine deficiency is characterized by demyelination and axonal degeneration. Acute Wernicke-Korsakoff syndrome is characterized by edema, hypertrophy of endothelial cells, and extravasation of erythrocytes. Chronic Wernicke-Korsakoff syndrome is characterized by loss of parenchyma with astrocytosis and hemosiderin-laden macrophages and relative sparing of neurons. Patients with Korsakoff psychosis have neuronal loss in the anterior nucleus of the thalamus. [5]

Cobalamin

Subacute combined degeneration is characterized by demyelination and vacuolation of white matter tracts in the posterior and lateral columns of the spinal cord. In severe cases, destruction of axons and collection of foamy macrophages are observed.

Niacin

Pellagra is characterized by chromatolysis of brainstem nuclei, dentate nuclei, and Betz cells of the cerebral cortex (isoniazid-induced cases).

Folate

Microscopic features are identical to those in subacute combined degeneration.

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Differential Diagnosis

Thiamine and cobalamin

Leigh syndrome is an important differential diagnosis, as it is also associated with symmetrical diencephalic lesions but microscopically shows a relative sparing of neurons and usually does not involve the mamillary bodies.

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