Chapter 32: Systemic & Metabolic Disorders

NUTRITIONAL DEFICIENCIES

Several vitamin B deficiency states are associated with neurologic disease. Severe vitamin B₁ (thiamine) deficiency causes “wet” beriberi, with peripheral edema from cardiomyopathy, as well as peripheral neuropathy and Wernicke-Korsakoff syndrome. In the industrialized world, the neurologic manifestations are seen most often in the setting of alcoholism. They may also occur in cachexia as a result of advanced malignancies, HIV, or hyperemesis gravidarum, or when intravenous glucose, including parenteral nutrition, is administered to a malnourished patient, depleting available thiamine. Milder thiamine deficiency may cause peripheral neuropathy alone, known as “dry” beriberi. Serum thiamine levels do not accurately indicate thiamine status. Whole blood thiamine levels or erythrocyte transketolase activity is typically decreased, although thiamine supplementation (100 mg every 8–12 hours intravenously) can be administered empirically in most acute situations, followed by long-term oral maintenance (50–100 mg/day).

Vitamin B₁₂ (cyanocobalamin) deficiency causes neurologic disease, most commonly myeloneuropathy, and megaloblastic anemia as isolated syndromes or in combination. Dietary deficiency is relatively uncommon but can occur in strict vegans. More common causes include gastric disorders such as pernicious anemia, gastrectomy, bariatric surgery, atrophic gastritis, and achlorhydria; ileal disorders such as bacterial overgrowth, infestation with the fish tapeworm Diphyllobothrium latum, and surgery; and inflammatory bowel disease. Nitrous oxide inactivates cyanocobalamin; hence, myeloneuropathy may complicate nitrous oxide abuse or, in patients with subclinical vitamin B₁₂ deficiency, therapeutic use. Vitamin B₁₂ deficiency is discussed further in Chapter 19.

Vitamin B₆ (pyridoxine) deficiency from severe malabsorption or as a consequence of therapy with isoniazid, cycloserine, hydralazine, or penicillamine can cause peripheral neuropathy. Daily pyridoxine therapy (25 mg/day orally) is standard in patients taking isoniazid. Excess pyridoxine intake can also cause sensory neuronopathy, which manifests clinically as sensory ataxia. Niacin deficiency (pellagra), rare in developed countries, causes dementia and neuropathy in association with dermatitis and diarrhea.

Neurologic disorders may complicate deficiencies of fat-soluble vitamins. Vitamin A deficiency causes night blindness and can lead to permanent blindness from corneal ulceration and scarring. Adults with vitamin D deficiency develop osteomalacia, with bone pain and proximal weakness. In addition to malabsorption, risk factors for vitamin D deficiency include decreased sun exposure (including institutionalization), many antiepileptic drugs, and obesity. Vitamin E deficiency, resulting from chronic fat malabsorption, abetalipoproteinemia, or as a familial disorder, causes neuropathy and cerebellar ataxia. Vitamin K deficiency does not have a recognized neurologic syndrome, although the resulting coagulopathy predisposes to subdural hematoma or intracerebral hemorrhage.

Copper deficiency, due to malabsorption or to excessive zinc consumption, can cause myeloneuropathy resembling that seen in cyanocobalamin deficiency. Muscle weakness and wasting develop in protein-calorie malnutrition states such as kwashiorkor, ...