ORIGINAL RESEARCH Effects of Topiramate on Peripheral Nerve Excitability Ça gdas ¸ Erdo gan,* Mehmet Yücel,† Hakan Akgün,† Tayfun Kas ¸ ıkçı,† Vedat Semai Bek,† and Zeki Gökçil† Purpose: Antiepileptic drugs are generally used to control the cortical hyperexcitable states. But some of them are also effective on the peripheral nervous system, so they may be used in some states like neuropathic pain. Several recent reports suggest the possible effects of antiepileptic drugs on peripheral nerve excitability. Strength duration time properties gives an indirect idea about the persistent, paranodal sodium (Na) channels and may indirectly reflect the peripheral nerve excitability. Topiramate suppresses the cortical hyperexcitability, but previous studies could not prove a significant effect of topiramate on peripheral nerves. The aim of this study is to investigate the probable nerve excitability changes caused by topiramate. Methods: Forty migraine patients and 40 controls were included in the study. Median motor and sensory conduction parameters were recorded. Strength duration properties were also recorded from abductor pollicis longus muscle, with the stimulation of median nerve. The electrophysiological studies were repeated 4 weeks after the initiation of topiramate in the treatment group. Results: Nerve conduction parameters were not significantly affected by 4-week topiramate treatment. But the strength duration time constant decreased significantly, reflecting a reduction in the excitability. This decrement seemed to be more obvious in those in whom topiramate was also clinically useful. Conclusions: The method used demonstrated a probable effect of topiramate on the peripheral nerve excitability. Key Words: Topiramate, Nerve excitability, Migraine, Strength duration time, Rheobase, Nerve conduction. (J Clin Neurophysiol 2012;29: 268–270) A ntiepileptic drugs generally affect ion channels. They are used to control hyperexcitable states like epilepsy and migraine. Some of them are also effective on the peripheral nerve system, so they may be used for the management of neuropathic pain (Johannessen Land- mark, 2008). Especially, gabapentin, pregabalin, and carbamazepine were demonstrated to be effective for the treatment of neuropathic pain. Recent studies revealed that even some of them may effect the peripheral nerve conduction studies (Boylu et al., 2010). Drugs effecting ion channels are commonly used to control the spreading depression wave in migraine (Ye et al., 2011). Top- iramate (TPM) inhibits carbonic anhydrase and plays an important role in the migraine treatment (Mirza et al., 2009). But since now it was not found to be effective in the treatment of neuropathic pain. Also recent studies figured out that it had no effect on the peripheral nerve conduction studies (Boylu et al., 2010). Strength duration time constant (SDTC) gives information about the functions of paranodal sodium (Na) channels and Na/K pumps and should reflect the excitability of a peripheral nerve (Yerdelen et al., 2007b). It was previously studied in diabetic neu- ropathy and successfully demonstrated the nerve excitability prop- erties (Yerdelen et al., 2007a). The aim of this study is to evaluate the probable effects of TPM on peripheral nerve conduction studies and excitability properties. METHODS Design of the Study The study was designed in migraine patients in whom the TPM treatment was recommended. In fact, TPM is primarily used in epilepsy. But there were some difficulties to design this study in epileptic patients. First of all, epilepsy is a heterogeneous state with different pathologies like ion channel deficiencies. So, it was hard to exclude a probable peripheral nerve channelopathy. Moreover, to eliminate the effects of antiepileptic drugs on the peripheral nerve, the patient should be drug-free. It was hard to find such a drug-free group among the epileptic patients. With this purpose, 40 migraine patients and 40 healthy control objects were included in the study with the approval of the Gulhane Military Medicine Faculty Ethical Committee. All individuals were asked for their personal consents. Previous studies have demon- strated that the SDTC values were affected by age and sex (Yerdelen et al., 2006). To avoid such a difference, all the individuals were women at similar ages. Patients who had been admitted to our electromyography laboratory with other diagnoses like carpal tunnel syndrome and who had normal right median nerve conduction studies were included in the control group. All the patients who were diagnosed with migraine without aura were included in the study to avoid group heterogeneity. They were not using any agents or drugs, which may effect the ion channels, for the previous 3 months. The treatment group included patients describing frequent headache attacks and had a history of at least one unsuccessful prophylactic agent treatment for migraine headaches. Patients who had a medical history of renal diseases, diabetes mellitus, thyroid dysfunction, polyneuropathy, and median nerve lesions were excluded from the study. Median motor and sensory conduction studies were applied to all individuals. Patients whose conduction study parameters were not within the normal limits were also excluded from the study. Electrophysiological Evaluation We used a Medelec premier electromyography device for the tests. Bar electrodes were used for motor and sensorial recordings. Initially, median nerve was stimulated from the wrist, and the maximal compound muscle action potential was recorded from abductor pollicis brevis. The distance between the stimulation site and the recording area was 7 cm for all individuals. Forty percent of this maximal amplitude value was calculated as the target amplitude From the *Department of Neurology, Pamukkale University Medical Faculty, Denizli, Turkey; and †Department of Neurology, Gülhane Military Medical Academy, Ankara, Turkey. Address correspondence and reprint requests to Ça gdas ¸ Erdo gan, Department of Neurology, Pamukkale University Hospital, Kinikli, Denizli 20700, Turkey; e-mail: drcagdaserdogan@gmail.com. Copyright Ó 2012 by the American Clinical Neurophysiology Society ISSN: 0736-0258/12/2903-0268 268 Journal of Clinical Neurophysiology  Volume 29, Number 3, June 2012