Cerebrospinal fluid folate, and vitamin B12 in anticonvulsant-induced megaloblastosis

Eugene P. Frenkel, Mary Sue McCall, Richard G. Sheehan

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Anticonvulsant therapy commonly leads to the development of subnormal serum folate levels, and in some individuals to a true megaloblastic anemia. In addition, the folate depletion has been suggested as a basis for a variety of neurologic and psychiatric defects in such patients. Since neuropsychiatric changes are not seen in most circumstances of folate deprivation by other pathophysiologic mechanisms, a study of cerebrospinal fluid B12 and folate was performed in patients treated with anticonvulsants. Patients on long-term anticonvulsant therapy with no hematologic abnormality were found to have a lower mean cerebrospinal fluid (CSF) B12 level (9.7 pg. per milliliter) than normal subjects (mean: 17.8 pg. per milliliter). Nine patients with anticonvulsant-associated megaloblastosis had the expected low serum and CSF folate levels but in addition had mean CSF B12 levels of 3.7 pg. per milliliter. These CSF B12 levels were similar to those seen in classical pernicious anemia (mean of 1.2 pg. per milliliter). However, the anticonvulsant-associated megaloblastosis patients had a dichotomy between these CSF B12 values and their serum B12 levels, since all had normal or high serum B12 levels. Therapy with vitamin B12 resulted in a reticulocyte response and partial repair of the anemia and improvement in mentation with no increase in seizure rate. These studies suggest that the neuropsychiatric syndromes ascribed to the folate deprivation during anticonvulsant therapy may in fact be secondary to B12 depletion in the central nervous system (CNS) rather than a true folate deficiency.

Original languageEnglish (US)
Pages (from-to)105-115
Number of pages11
JournalThe Journal of laboratory and clinical medicine
Issue number1
StatePublished - Jan 1973

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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