%0 Journal Article %T Abnormalities of cortical stimulation strength-duration time constant in amyotrophic lateral sclerosis. %A Pavey NA %A Menon P %A Peterchev AV %A Kiernan MC %A Vucic S %J Clin Neurophysiol %V 164 %N 0 %D 2024 Aug 5 %M 38901111 %F 4.861 %R 10.1016/j.clinph.2024.05.014 %X OBJECTIVE: 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 ± 9.98 µs; controls 205.94 ± 13.7 µs, 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 ± 28.7 µs, P < 0.001) and ALS-specific subscore (141.7 ± 33.2 µs, P = 0.003).
CONCLUSIONS: Cortical SDTC reduction was associated with a more aggressive ALS phenotype, or with more prominent cognitive impairment.
CONCLUSIONS: An increase in transient Na+ conductances may account for the reduction in SDTC, linked to the pathogenesis of ALS.