Cortical hyperexcitability and the split-hand plus phenomenon: Pathophysiological insights in ALS

Preferential involvement of thenar muscles compared to flexor pollicis longus (FPL), termed ‘the split-hand plus sign’, appears to be a clinical feature of amyotrophic lateral sclerosis (ALS). In an attempt to understand the pathophysiological mechanisms underlying this clinical phenomenon, threshold tracking transcranial magnetic stimulation techniques were utilized to assess whether cortical mechanisms may be a significant contributing influence. Cortical excitability studies were undertaken on 17 ALS patients, with motor evoked potentials (MEP) recorded from thenar muscles and FPL. Split-hand plus index (SHPI) was derived by dividing motor amplitudes recorded over APB with those recorded over FPL. Results showed the SHPI was significantly reduced in ALS (SHPIALS 0.87 ± 0.12; SHPICONTROLS 1.7 ± 0.2, p < 0.001). Cortical studies disclosed significant increases in MEP amplitudes recorded over thenar muscles (p < 0.05) but not FPL (p = 0.11), and were significantly correlated with the SHPI (R = –0.83, p < 0.01). The cortical silent period duration was reduced from thenar muscles (p < 0.01). Although there was a ubiquitous reduction in short-interval intracortical inhibition (APB, p < 0.01; FPL < 0.05), this reduction was more prominent over the thenar muscles. In conclusion, findings from the present study suggest that cortical dysfunction in the form of hyperexcitability contributes to the pathophysiological basis of the split-hand plus sign in ALS