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

Area of Science:

• Neuroscience
• Neurology
• Clinical Electrophysiology

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
• The 'split-hand plus sign,' characterized by preferential thenar muscle involvement over flexor pollicis longus (FPL), is a recognized clinical feature in ALS patients.
• The underlying pathophysiological mechanisms, particularly cortical contributions, require further elucidation.

Purpose of the Study:

• To investigate the role of cortical mechanisms in the split-hand plus sign observed in ALS.
• To assess cortical excitability in thenar muscles and FPL using threshold tracking transcranial magnetic stimulation (TT-TMS).
• To correlate electrophysiological findings with the split-hand plus index (SHPI).

Main Methods:

• Threshold tracking transcranial magnetic stimulation (TT-TMS) was employed on 17 ALS patients and controls.
• Motor evoked potentials (MEPs) were recorded from thenar muscles (APB) and flexor pollicis longus (FPL).
• The split-hand plus index (SHPI) was calculated by dividing the motor amplitude of APB by that of FPL. Cortical silent period (CSP) and short-interval intracortical inhibition (SICI) were also assessed.

Main Results:

• ALS patients exhibited a significantly reduced SHPI compared to controls (0.87 vs. 1.7, p < 0.001).
• Increased MEP amplitudes were observed in thenar muscles (p < 0.05) but not FPL (p = 0.11) in ALS patients, correlating with SHPI (R = -0.83, p < 0.01).
• Reduced CSP duration and a more prominent reduction in SICI were noted in thenar muscles of ALS patients, indicating cortical hyperexcitability.

Conclusions:

• Cortical dysfunction, specifically hyperexcitability, is a significant contributing factor to the split-hand plus sign in ALS.
• These findings highlight the utility of TT-TMS in understanding the neurophysiological basis of specific ALS clinical signs.
• The study suggests that altered cortical excitability in motor pathways innervating thenar muscles plays a key role in the pathophysiology of the split-hand plus sign in ALS.