Cortical hyperexcitability precedes lower motor neuron dysfunction in ALS.

Area of Science:

• Neuroscience
• Neurology
• Motor Neuron Diseases

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons.
• The precise sequence of pathological events in ALS, particularly the relationship between cortical and lower motor neuron dysfunction, remains incompletely understood.

Purpose of the Study:

• To investigate whether cortical hyperexcitability precedes the onset of lower motor neuron (LMN) dysfunction in sporadic ALS.
• To explore the potential primary site of pathology in ALS pathogenesis.

Main Methods:

• Cortical excitability was assessed in 24 ALS patients using motor evoked potentials (MEPs) recorded from the abductor pollicis brevis (APB) muscle.
• Lower motor neuron function was evaluated using electromyography (EMG) and axonal excitability studies of the APB muscle.
• Key measures included short interval intracortical inhibition, resting motor threshold, cortical silent period, CMAP amplitude, and MEP amplitude.

Main Results:

• Despite preserved anatomical and functional integrity of LMNs in the APB muscle (normal CMAP amplitude, absence of fasciculations), significant cortical dysfunction was evident.
• Patients exhibited reduced short interval intracortical inhibition and cortical silent period duration, alongside increased MEP amplitude and intracortical facilitation.
• These findings indicate cortical hyperexcitability in the presence of seemingly intact LMNs.

Conclusions:

• Cortical hyperexcitability appears to occur upstream of apparent lower motor neuronal system dysfunction in ALS.
• Corticomotoneuronal dysfunction may represent a primary event in ALS, suggesting a cortical origin for the disease.
• These results have implications for understanding ALS pathogenesis and potential therapeutic targets.