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

Abstract

One hundred forty-one adult patients treated for no less than 6 months with standard daily doses of the commonest antiepileptic drugs (AEDs) were recruited in five Italian centers and submitted to intensive clinical and electrophysiologic investigation to assess the effects of AEDs on peripheral nerves. Eighty percent of the patients were receiving monotherapy. Carbamazepine (CBZ) was the most common AED (51 cases), followed by phenytoin (PHT) (46), phenobarbital (PB) (42), and valproate (VPA) (25). Fifty-three percent of the patients had one or more symptoms of polyneuropathy (paresthesias being the most common complaint). The neurologic examination was abnormal in 32%. Electrophysiologic findings in two or more separate nerves were abnormal in 77 patients (54.6%); of these, 27 (19.1%) had abnormal neurologic findings and 21 (14.9%) also had symptoms of polyneuropathy. Sensory functions were most frequently impaired. Sural nerve biopsy was performed in 4 patients receiving monotherapy with CBZ, PHT, PB, and VPA. Except in patients receiving VPA (in whom no morphologic abnormalities were detected), mild predominantly axonal damage with secondary myelin changes was noted. A correlation was noted between polyneuropathy, age of the patient and, to a lesser extent, receipt of two or more AEDs.

Effects of the antiepileptic drugs on peripheral nerve function

“…While in patients receiving VPA no morphologic abnormalities were detected, mild predominantly axonal damage with secondary myelin changes were noted in the patients on the treatments of the other antiepileptic drugs. A correlation was noted between polyneuropathy and receipt of two or more drugs (5). Bogluin et al.…”

“…Each group contained 15 patients and 20 healthy subjects were examined as the control group. All patients and healthy controls underwent conventional sensory and motor nerve conduction studies of the right limbs with constant monitoring of room temperature, which was maintained at 22–24°C and, when indicated, of skin temperature (5). In each patient, the median, ulnar, sural, tibial, and common peroneal nerves were tested using a Synergy electromyography device (Medelec Ltd, Oxford, UK) with surface recording and stimulating electrodes.…”

“…First, the pathogenic mechanism was thought to be a functional and transient disturbance which was related with the high doses of the drug and which regressed after its interruption (3, 4). Second, there may occur anatomic damage of the peripheral nerve on prolonged therapy, and, occasionally, clinically significant peripheral neuropathy develops (5, 6). Neurophysiological methods provide an objective mean to evaluate the possible effects of AEDs on peripheral nerve function during chronic treatment (7).…”

Topiramate induced peripheral neuropathy: A case report and review of literature

“…It had been reported with short-term treatment (hours to weeks) with PHT in toxic[ 15 - 18 ] or non-toxic doses[ 19 - 21 ] and with long-term (≥ 5 years) PHT therapy[ 22 - 25 ]. Peripheral neuropathy had been also reported with therapy with other AEDs as carbamazepine (CBZ)[ 26 - 28 ], phenobarbital (PB)[ 27 ], sodium valproate (VPA)[ 26 , 27 , 29 , 30 ], gabapentin (GPN)[ 31 ], levetiracetam (LEV)[ 32 ] and lacosamide (LCM)[ 33 ]. There is no previous report for peripheral neuropathy induced by TPM.…”

Unpredictability of Seizures and the Burden of Epilepsy

“…Cognitive side effects of phenobarbitone and pro-apoptotic actions of several drugs may be particularly important in the developing brain [36], the hormonal effects of valproate [37] may have their greatest impact in fertile females, and the induction of ostepenia by enzyme-inducing drugs [38,39] may play a particular role in increasing the risk in the elderly for the development of pathological fractures. Other side effects of chronic intake like the development of cerebellar atrophy and polyneuropathy with phenytoin [40,41], disturbances of hormonal metabolism [42], the induction of mood disorders by several drugs [43] and the development of visual field constrictions with vigabatrin [44] are consequences of long-term intake and pose problems at any age. The task of controlling the development of side effects related to long-term therapy imposes considerable costs on the healthcare system, even if these effects are as rare as certain idiosyncratic reactions, like liver failure or bone marrow aplasia.…”