Abstract
Objectives Strength-duration time constant (SDTC) may now be determined for cortical motor neurones, with activity mediated by transient Na+ conductances. The present study determined whether cortical SDTC is abnormal and linked to the pathogenesis of amyotrophic lateral sclerosis.
Methods Cortical SDTC and rheobase were estimated from 17 ALS patients using a controllable pulse parameter transcranial magnetic stimulation (cTMS) device. Resting motor thresholds (RMTs) were determined at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M-ratio of 0.1, using a figure-of-eight coil applied to the primary motor cortex.
Results SDTC was significantly reduced in ALS patients (150.58±9.98µs; controls 205.94±13.7µs, P<0.01). The reduced SDTC correlated with a rate of disease progression (Rho = -0.440, P<0.05), ALS functional rating score (ALSFRS-R) score (Rho=0.446, P<0.05), and disease duration (R=0.428, P<0.05). The degree of change in SDTC was greater in patients with cognitive abnormalities as manifested by an abnormal total Edinburgh Cognitive ALS Screen score (140.5±28.7µs, P<0.001) and ALS-specific subscore (141.7±33.2µs, P=0.003).
Conclusion Cortical SDTC reduction was associated with a more aggressive ALS phenotype, or with more prominent cognitive impairment. An increase in transient Na+ conductances may account for the reduction in SDTC and be linked to the pathogenesis of ALS.
