Wernicke disease, pellagra, scurvy, and polyneuropathy. These authors concluded that the encephalopathy represented an acute form of nicotinic acid deficiency, as most of their patients recovered when treated with a diet of low vitamin B content supplemented by intravenous glucose and saline and large doses of nicotinic acid. Sydenstricker and colleagues (1938) had previously reported the salutary effects of nicotinic acid on the unresponsive state observed in elderly undernourished patients, and Spillane (1947) described a similar syndrome and response to nicotinic acid in the indigent Arab population of the Middle East.
The status of this syndrome and its relation to pellagra are uncertain. The clinical, nutritional, and pathologic features were never delineated precisely. Serdaru and associates reported 22 presumed examples of this syndrome in the alcoholic population of the Salpêtriére clinic in Paris, all diagnosed retrospectively after the finding in postmortem material of pellagra-like changes in nerve cells. The prominent features were confusional states, paratonic rigidity, ataxia, and polymyoclonia, a picture somewhat like that described by Jolliffe and coworkers. Skin lesions were absent. We have not encountered identical cases among the undernourished patients in the alcoholic population.
Pyridoxine deficiency or excess has been associated with a sensory polyneuropathy. The occurrence of neuropathy caused by INH was recognized in the early 1950s, soon after the introduction of this drug for the treatment of tuberculosis. It was characterized by paresthesia and burning pain of the feet and legs, followed by weakness of these parts and loss of ankle reflexes. Rarely, with continued use of the drug, the hands were affected as well. The nature of INH-induced neuropathy was clarified by Biehl and Vilter who found that isoniazid causes a marked excretion of pyridoxine and that the administration of pyridoxine in conjunction with INH prevents the development of neuropathy. Because of this simple preventive measure, very few examples of INH-induced neuropathy are now observed. Hydralazine, closely related in structure to INH, when used in the past caused the formation of pyridoxal-isoniazid complexes (hydrazones), which make pyridoxal (the main form of vitamin B6) unavailable to the tissues. The neuropathy responds favorably to discontinuation of the drug and the administration of pyridoxine.
Pyridoxine deficiency also leads to homocystinemia because the vitamin is a coenzyme for the conversion of homocystine to cystathionine. Vascular thrombosis may result from the excess homocystine.
Severe pyridoxine deficiency in animals and humans also causes seizures. This was first observed in swine by Swank and Adams, and later in infants who were maintained on a milk formula lacking in pyridoxine.
A pyridoxine-responsive seizure disorder (pyridoxine dependency) of the neonatal period is discussed in Chap. 15.
For pyridoxine deficiency caused by malnutrition, the treatment is 50 mg per day orally for several weeks, followed by 2 mg per day and resumption of a normal diet. When the deficiency results from a pyridoxine antagonist such as INH, penicillamine, hydralazine, or cycloserine, the treatment is 50 mg per day, only when the antagonist is in use. Treatment for the inherited form with convulsions is discussed in the section on neonatal seizures in Chap. 15. Lifelong supplementation is required after the seizures are aborted with a large intravenous dose of the vitamin.