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

Abstract

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 (SHPI_ALS 0.87 ± 0.12; SHPI_CONTROLS 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.

Key words::

• Abductor pollicis brevis
• amyotrophic lateral sclerosis
• cortical excitability
• flexor pollicis longus
• TMS

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding support provided by the Motor Neuron Disease Research Institute of Australia (MNDRIA) and National Health and Medical Research Council of Australia is gratefully acknowledged.

Notice of correction

Following publication of this article online on 20 February 2014, the affiliation address for Jong Seok Bae changed.