Clinical and Electrophysiologic Evaluation of Peripheral Nerve Function in Chronic Phenytoin Therapy

Abstract

Analysis of covariance was employed to explore possible correlations among duration of phenytoin therapy, phenytoin and folate serum concentrations, and clinical and electrophysiologic findings in 32 patients receiving single phenytoin therapy. None of our patients volunteered peripheral nervous system complaints. On examination, 9 of 32 (28%) were found to have signs suggestive of neuropathy (absent knee and/or ankle jerks). Neither phenytoin serum concentration nor duration of phenytoin therapy was found to significantly (p greater than 0.05) affect nerve function after an adjustment for age differences. A test for overall effect of folate serum concentration (grouped greater than or equal to 5 or less than 5 ng/ml) also failed to reach statistical significance (p greater than 0.05). Our findings suggest that phenytoin and folate serum concentrations and duration of phenytoin therapy do not have an important role in the development of clinical neuropathy and electrophysiologic abnormalities.

Antiepileptic Drugs and Peripheral Nerve Function: A Multicenter Screening Investigation of 141 Patients with Chronic Treatment

“…In agreement with results of other reports (Encinosa, 1974; Taylor et al, 1985), patient age in our series appeared to influence the risk of polyneuropathy. Even though the adverse effect of AED treatment on the peripheral nerve persisted even after we controlled for age, the greater susceptibility of elderly people to develop peripheral neuropathy when treated with AEDs must be stressed.…”

“…AED dosage and plasma level did not appear to affect the risk of polyneuropathy, as shown by our report and those of other investigators (De Castro et al, 1972;Swift et al, 1981;Taylor et al, 1985). However, our patients were receiving AEDs at standard daily dosages and low to middle plasma concentrations, in contrast to the patients reported by Lovelace and Horwitz (1968), 22% of whom were receiving PHT a500 mg daily, and those of Shorvon and Reynolds (1982), who reported that 66% of their patients with abnormal conduction values had been exposed previously to toxic PHT dosages.…”

“…In the last 25 years, several retrospective clinical investigations of peripheral neuropathy among patients receiving AEDs (Lovelace and Horwitz, 1968; De Castro et al, 1972;Eisen et al, 1974;Encinoza, 1974; Chokroverty and Sayeed, 1975;Zebrowska-Szymusik, 1978;Fujiwara et al, 1979;Swift et al, 1981; Shorvon and Reynolds, 1982;Geraldini et al, 1984;Taylor et al, 1985) documented electrophy siologic abnormalities suggesting polyneuropathy in 689% of patients and provided some evidence of the causative roles of daily doses of PHT and treatment duration. In most studies, however, other AEDs may also have been involved, as most of the patients were receiving polytherapy .…”

Electrophysiologic Effects of γ‐Vinyl GABA and Carbamazepine

“…The data on the effects of AEDs on the peripheral nervous system are controversial, partly owing to methodologic difficulties and to the lack of correlation between AED serum levels and electrophysiologic abnormalities (Geraldini et al, 1984;Taylor et al, 1985). This study emphasizes use of multimodal sensory EPs and quantitative spectral EEG in evaluation of pharmacologic effects within the CNS.…”

Side-effects of drug treatment in epilepsy

“…Peripheral neuropathy, demonstrated clinically and by electrophysiological studies, arise in about 30% of patients treated with PHT alone (45). The patients seldom complain of symptoms.…”