Folate neurological effects

Patients sustain convulsions and neurological deterioration. The urine contains low levels of the metabolites of serotonin, norepinephrine and dopamine. The reductase also plays a role in the maintenance of tetrahydrofolate levels in brain, and some patients have had low folate levels in the serum and CNS. Treatment has been attempted with tryptophan and carbidopa to improve serotonin homeostasis and with folinic acid to replete diminished stores of reduced folic acid. This therapy is sometimes effective. Diagnosis involves assay of DHPR in skin fibroblasts or amniotic cells. Phenylalanine hydroxylase activity is normal. 

Deficiencies of vitamin B12 can result from either low dietary levels or, more commonly, from poor absorption of the vitamin due to the failure of gastric parietal cells to produce intrinsic factor (as in pernicious anemia) or to a loss of activity of the receptor needed for intestinal uptake of the vitamin.5 Nonspecific malabsorption syndromes or gastric resection can also cause vitamin B12 deficiency. The vitamin may be administered orally (for dietary deficiencies), or intramuscularly or deep subcutaneously (for pernicious anemia). [Note Folic acid administration alone reverses the hematologic abnormality and thus masks the B12 deficiency, which can then proceed to severe neurologic dysfunction and disease. Therefore, megaloblastic anemia should not be treated with folic acid alone, but rather with a combination of folate and vitamin B12.] Therapy must be continued for the remainder of the life of a patient suffering from pernicious anemia. There are no known adverse effects of this vitamin. 

Q9 B12 is ineffective when given by mouth if there is deficiency of intrinsic factor, as it would not be absorbed. It must be given as a depot injection, which lasts a few months. Folate supplements can be given by mouth. However, if the patient has neurological symptoms, folic acid supplements alone are not adequate B12 must also be administered. So the two forms of therapy are not equally effective. 

There are two major clinical manifestations of cobalamin (B12) deficiency. One such presentation is hematopoietic (caused by the adverse effects of a B12 deficiency on folate metabolism), and the other is neurologic (caused by hypomethylation in the nervous system). 

Folate deficiency is most likely to occur in patients on long-lasting AED therapy. Furthermore, folate concentrations are inversely related to the number of prescribed AEDs. Patients on combinations of two or more AEDs tend to have lower folate levels than patients on monotherapy. Combinations of AEDs may have synergistic effects on folate absorption and/or metabolism. Moreover, the dietary intake of B vitamins tends to decrease with an increasing number of AEDs. Patients on combination therapy tend to a have more severe epilepsy, often associated with other neurological deficits and may even need to live in institutions. 

Hie toxicity of the vitamin is low and it is safe up to at least 10 X RDA even in pr nant women. There is a risk that taking foUc acid supplements may mask some of the effects of vitamin B12 deficiency without solving the underlying problem, thus resulting in neurological dam-a. Some drugs and xenobiotics reduce folate utilisation including ethanol, aspirin, ibuprofen, trimethoprim, pyrimethamine, phenytoin and phenobarbital. 

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