Paradoxically, the consumption of large amounts of pyridoxine (mainly by vitamin faddists) may also cause a sensory peripheral neuropathy or ganglionopathy (Schaumburg et al; Albin et al). There is no weakness; the symptoms, including ataxia and areflexia, are purely sensory and can be quite disabling. Symptoms may extend to the trunk, scalp, and face. Improvement is the rule when the drug is withdrawn. This disorder is probably a direct toxic effect of pyridoxine on dorsal root ganglion cells.
Despite the frequency of folic acid deficiency and its hematologic effects, its role in the pathogenesis of nervous system disease has not been established beyond doubt (see reviews by Crellin et al and by Carney). However, folate antagonists such as methotrexate are known to cause a neuropathy that is probably predicated on the vitamin deficiency. The polyneuropathy that occasionally complicates the chronic administration of phenytoin has also been attributed, on uncertain grounds, to folate deficiency. Botez and colleagues have described a group of 10 patients with sensorimotor polyneuropathy (4 also had spinal cord disease) presumably because of intestinal malabsorption; all the patients improved over several months while receiving large doses of folic acid. This experience is unique, however. The possible role of folate deficiency in the pathogenesis of spinal cord disease was mentioned previously in relation to vitamin B12 deficiency, and its putative role in psychiatric disease has been discussed by Carney. In such cases of folate deficiency, if subacute combined degeneration or mental changes occur, they must be rare.
The folate deficiency of pregnancy is a special case that is known to increase the incidence of neural tube defects.
For nutritional folate deficiency, difficult to separate from the lack of other vitamins, replacement is with 1 mg per day. In pregnant women, higher doses are used, separately from a multivitamin preparation in order to avoid vitamin A toxicity. When the folate antagonist methotrexate is the underlying cause, supplemental folinic acid (leukovorin, citrovorum factor) is given orally.
A predominantly sensory neuropathy also has been induced, again in swine, by Swank and Adams, and later in humans by a deficiency of pantothenic acid (a constituent of coenzyme A [CoA]), as reported by Bean and colleagues. In some patients, the administration of pantothenic acid has reportedly reversed the painful dysesthesias of the “burning foot” syndrome.
The spinal cord, brain, optic nerves, and peripheral nerves are all affected by vitamin B12 (cobalamin) deficiency, giving rise to a classic neurologic syndrome in which the spinal cord is usually affected first and often exclusively. The term subacute combined degeneration (SCD) is customarily reserved for the spinal cord lesion of vitamin B12 deficiency and serves to distinguish it from other types of spinal cord diseases that happen to involve the posterior and lateral columns. Whether a peripheral neuropathy is a primary component of the disease or is secondary to damage of the posterior root fibers of entry in the dorsal cord has been debated, but the available pathologic evidence favors the latter, except perhaps for a few advanced cases, in which other nutritional deficiencies could have been responsible.