S54 Motor axon excitability changes during anti-epileptic voltage-gated NA+ channel blocker therapy

Abstract

Objectives Anti-epileptic drugs targeting voltage-gated Na channels (VGSC) are not selective for the brain. The aim of this study was to investigate the excitability of myelinated median nerve motor axons in epileptic patients treated with carbamazepine and other anti-VGSC drugs. Methods Stimulation was carried out at wrist and evoked compound muscle action potential (CMAP) was recorded from the abductor pollicis brevis muscle. Multiple measures of motor excitability using the TRONDNF protocol were carried out using an automatic threshold-tracking setup. In addition, the current required to evoke threshold responses targeting 40–50% of maximal CMAP amplitude was also determined by manual trial-and-error, for cathodic pulses of 0.2, 0.5 and 1 ms duration to measure the strength-duration time constant (SDTC). Results Across the anti-VGSC treated group there was an impairment in motor axon excitability with a 30% reduction in SDTC as compared to age-matched normal controls. A similar reduction in SDTC could be detected by manual threshold tracking in 3 different laboratories, using conventional nerve conduction equipment. The time for manual SDTC measurements was comparable to the full automatic multiple excitability measures protocol. Discussion The excitability impairment by partial VGSC block did not affect conduction of normal motor axons. Conclusions Our data suggest that, at the therapeutic doses of anti-VGSC drugs, there is an impairment in motor axon excitability that can be measured with conventional neurophysiological equipment. Significance Nerve excitability measurements could prove useful for monitoring the functional consequences of the anti-VGSC therapy in epilepsy.