T38. Altered axonal excitability in spinal and bulbar muscular atrophy

Abstract

Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease characterized with prominent fasciculations. Fasciculations suggest motor nerve hyperexcitability and potentially result in a burden to motor neuron. Axonal excitability and nerve conduction studies were performed in 31 patients with SBMA and 140 with amyotrophic lateral sclerosis (ALS). These results were compared with those of 16 healthy males (HM). In SBMA, correlations between neurophysiological studies and clinical profiles were examined. Patient backgrounds in SBMA were as follows; mean age; 58 years, mean disease duration; 152 months, mean ALS functional rating scale (ALSFRS-R); 41, mean CAG repeat expansion; 46, mean compound muscle action potential (CMAP) amplitude on abductor pollicis brevis muscle was 6.0 mV. Compared with HM, SBMA patients had longer strength-duration time constant (SDTC), greater threshold change in depolarizing threshold electrotonus (TEd) and greater supernormality (all p < 0.05). ALS patients had similar findings and smaller late subexcitability (all p < 0.05). In SBMA, TEd (90–100 ms) was related to ALSFRS-R (R = 0.42, p < 0.05), and CAG repeat was related to CMAP amplitude (R = −0.52, p < 0.05) and superexcitability (R = −0.46, p < 0.05). Patients were divided into two groups according to CMAP amplitude (over and under 5 mV). Compared with HM, SBMA patients with over 5 mV had greater TEd (10–20 ms) and greater superexcitability (all p < 0.05). SBMA patients with under 5 mV had longer SDTC, greater TEd and greater superexcitability (all p < 0.05). ALS patients with over 5 mV had greater TEd (90–100 ms) and greater superexcitability (all p < 0.05). ALS patients with under 5 mV had longer SDTC, greater TEd, greater superexcitability and smaller subexcitability (all p < 0.05). A previous study investigated axonal excitabilities in 7 patients with SBMA and revealed increased sodium currents. Our findings suggest that SBMA patients have increased sodium and decreased fast potassium currents. Similar findings and decreased slow potassium currents were found in ALS. This difference may suggest that ALS patients have more hyperexcitable motor nerve. Moreover, our findings suggest that decreased fast potassium currents are related to CAG repeat expansion in SBMA. It is already reported that SBMA patients have disruption of axonal transport. CAG repeat expansion may bring about axonal hyperexcitability and result in a burden to motor neuron.