Abnormalities of cortical stimulation strength-duration time constant in amyotrophic lateral sclerosis

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 ± 9.98 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.

Significance: An increase in transient Na⁺ conductances may account for the reduction in SDTC, linked to the pathogenesis of ALS.