Achlorhydria is almost invariably present in patients with pernicious anemia; its presence can be inferred by measuring the serum gastrin level. Antibodies to gastric parietal cells are also present in as many as 90 percent of patients with cobalamin deficiency, specifically in those with pernicious anemia as opposed to those with diminished B12 intake, but this test, although diagnostically specific, is positive in only 60 percent of cases. A relationship between helicobacter gastritis and autoimmunity against gastric parietal cells is being explored.
Low cobalamin levels with or without the clinical signs of deficiency may occur in patients with atrophic gastritis or after subtotal gastrectomy as mentioned. The malabsorption in such cases is thought to be because of a failure to extract cobalamin from food rather than a failure of the intrinsic factor mechanism (“food-cobalamin malabsorption”). Because the absorption of free cobalamin is normal, the Schilling test is unimpaired (Carmel, 1990). Infection of the gastric mucosa with Helicobacter pylori has been implicated in some cases. There are also rare inherited defects in the gene for intrinsic factor that render it ineffective.
The results of nerve conduction tests have varied in vitamin B12-deficient patients. Early in the course of SCD, nerve conduction may be normal, but some patients have slowing of distal sensory conduction; others have found reduced amplitudes and minor signs of denervation, suggestive of axonal change. This again raises the controversy regarding the presence of a peripheral nerve disorder in uncomplicated B12 deficiency. Authoritative texts indicate that a neuropathy is present but certainly, such involvement is not integral to the disease as many patients with prominent neurological manifestations, particularly early in the course, have normal nerve conduction studies. In patients with normal peripheral nerve studies, the somatosensory evoked potentials usually show abnormalities attributable to central conduction delays, implicating the posterior columns as the cause of the sensory symptoms (Fine and Hallett). In advanced cases, motor conduction and late responses may be affected to a slight degree. These ambiguities reflect the inconsistent and poorly understood role of the peripheral neuropathic component of this disease.
The MRI lesions in the posterior columns were described earlier; they extend through the cervical and upper thoracic cords and, less often, to the lateral columns. The frequency of these findings, however, is not known, and their absence cannot be considered evidence against the diagnosis.
The diagnosis of pernicious anemia demands the administration of vitamin B12 and the continuation of treatment for the rest of the patient’s life. In cases of pernicious anemia, the patient is given 1,000 µg of cyanocobalamin or hydroxocobalamin intramuscularly each day for several days. The usual approach is to repeat the injection weekly for a month and then monthly for an indefinite period. Although most of the injected cobalamin is excreted, these patients must be given excessive doses of the vitamin because the repletion of cobalamin tissue stores is a function of the dose.
In recent years, the notion that all forms of B12 deficiency must be circumvented by parenteral administration of the vitamin has been questioned and the use of oral cobalamin 500 to 1,000 µg daily has been used as an alternative, particularly for maintenance treatment. Several studies have indicated the effectiveness of this approach in elderly patients with poor B12 absorption and in persons with restricted diets, such as vegans, but we would express reservation regarding the use of oral replacement in the treatment of manifest subacute combined degeneration with neurologic manifestations until further studies have been published.