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Seventy patients with pernicious anemia have been observed for periods of not less than ten years. The clinical course in these cases has been analyzed with particular reference to changes in the neurologic status. Most of the patients, whether treated with oral preparations of stomach or liver, or parenteral crude or refined liver extracts, showed significant improvement of their neurologic manifestations. The period of improvement was limited, essentially, to the first year of therapy. Thirty-six members of the series received treatment regularly and were maintained consistently in complete hematologic remission. Fifteen of the patients did not adhere to an optimal therapeutic regimen, and their blood values were frequently abnormal, although definite relapses did not occur. In the former group there were no instances of development or progression of neural lesions. In the latter such adverse changes as did occur were transient and reversible on resumption of adequate therapy. Nineteen patients in the series suffered clinical and hematologic relapses after their initial response to intensive therapy. The end results in this group were not so favorable, but nevertheless serious progression of spinal cord involvement was rarely observed. The apparent infrequent occurrence of pronounced changes is attributed to the short duration of the relapses and to the relatively mild degree of nervous system involvement present when the diagnosis of pernicious anemia was made. It may be assumed that patients with more extensive neural disease who suffered relapses, progressed to a fatal termination. The observations reported in no way justify the conclusion that irregular or sub-optimal therapy is without serious risk. They are presented in order to indicate what the long-term clinical results may be in the case of patients with pernicious anemia, who frequently fail to adhere to an ideal therapeutic regimen. The early results of treatment with synthetic folic acid, as observed in a series of 15 patients, indicate that both the hematologic and neurologic response to this form of therapy is much less predictable than is the case with stomach or liver preparations. It is suggested that disturbance of folic acid metabolism is not the sole cause of either the hematologic or the neurologic manifestations of pernicious anemia, but that inability to utilize folic acid effectively may play a part in the development of both myeloid and neural abnormalities.

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