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Abstract
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.
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Article info
Publication history
Accepted:
October 4,
1972
Received:
December 2,
1971
Identification
Copyright
© 1973 Published by Elsevier Inc.