Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs (AEDs) at high cumulative doses or even within the therapeutic drug doses or levels. We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate (TPM) therapy. A 37-year-old woman was presented for the control of active epilepsy (2010). She was resistant to some AEDs as mono- or combined therapies (carbamazepine, sodium valproate, levetiracetam, oxcarbazepine and lamotrigine). She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother, sister and son with active epilepsies. She became seizure free on TPM (2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution. Neurological examination revealed presence of diminished Achilles tendon reflexes, stocking hypesthesia and delayed distal latencies, reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves, indicating demyelinating and axonal peripheral neuropathy of the lower extremities. After exclusion of the possible causes of peripheral neuropathy, chronic TPM therapy is suggested as the most probable cause of patient's neuropathy. This is the first case report of topiramate induced peripheral neuropathy in the literature.

The nutrient-drug interaction between folate and phenytoin is a two-way interaction. Folate deficiency resulting from long-term phenytoin therapy is a common occurrence, but progression of the deficiency to a megaloblastic anemia is rare. However, there are data to suggest nonanemic folate deficiency may be detrimental to the patient. Several mechanisms have been proposed to explain the ability of phenytoin to deplete body folate. The supplementation of folic acid to folate-deficient patients taking phenytoin has been shown to result in lowered serum concentrations of phenytoin, and possibly loss of control of the seizure disorder. Folate appears to be associated with the hepatic metabolism of phenytoin, although the effect of folic acid supplementation on phenytoin elimination kinetics is suggested to be individualized.

Review of the literature shows that long-term phenytoin therapy is associated with peripheral neuropathy and neuromuscular disorder that rarely can be symptomatic. The usual manifestations of the peripheral neuropathy are lower extremity areflexia, sensory deficits, and reduced conduction velocities. The risk for these peripheral nerve abnormalities is greater with increased serum levels or long duration of therapy (usually more than 5 years). The relative risks according to age groups or number and kinds of antiepileptic drugs used are undetermined. It is not known if detected abnormalities are static or slowly progressive. Isolated case reports have claimed the resolution of signs and symptoms after discontinuance of therapy or correction of a state of intoxication. Appropriate measures to prevent the appearance or progression of the complications are discussed in light of the available evidence.

Mean motor conduction velocity of posterior tibial nerves was significantly reduced in epileptic patients treated with diphenylhydantoin formore than 10 years or in patients with serum diphenylhydantoin level above 20 mug/ml. Subnormal serum folate was not responsible for this reduction and clinical peripheral neuropathy was infrequent.