Cortical inexcitability in ALS: correlating a clinical phenotype

Area of Science:

• Neurology
• Neurophysiology
• Motor Neuron Diseases

Background:

• Cortical inexcitability is an understudied aspect of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS).
• This study investigated the characteristics and impact of cortical inexcitability in a large ALS patient cohort.

Purpose of the Study:

• To identify and characterize cortical inexcitability in ALS patients.
• To compare demographic, clinical, and survival data of inexcitable ALS patients with normal or hyperexcitable cohorts.
• To assess the influence of cortical inexcitability on ALS phenotype and survival.

Main Methods:

• Utilized threshold-tracking transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI).
• Classified 417 ALS patients into three groups: inexcitable, hyperexcitable (SICI≤5.5%), and normal cortical excitability (SICI>5.5%).
• Conducted clinical phenotyping, neurophysiological assessment of lower motor neuron (LMN) function, and survival analysis.

Main Results:

• 26.4% of ALS patients exhibited cortical inexcitability.
• Cortical inexcitability correlated with younger age of onset, advanced disease stage, higher UMN scores, and lower functional/strength scores.
• Survival was comparable across groups, though riluzole use was lower in the inexcitable group.

Conclusions:

• Cortical inexcitability defines an ALS phenotype with pronounced UMN signs, accelerated motor and functional decline, and earlier onset.
• Findings aid in patient management and stratification for clinical trials.
• Further research may explore targeted interventions for this specific ALS subtype.