Physiological Biomarkers of Upper Motor Neuron Dysfunction in ALS

Area of Science:

• Neuroscience
• Neurology
• Biomarkers

Background:

• Upper motor neuron (UMN) dysfunction is a critical diagnostic feature of amyotrophic lateral sclerosis (ALS).
• Identifying UMN signs can be challenging, particularly with severe muscle weakness.
• Transcranial magnetic stimulation (TMS) provides objective physiological biomarkers for UMN dysfunction in ALS.

Purpose of the Study:

• To review physiological biomarkers of UMN dysfunction in ALS.
• To discuss conventional and novel TMS techniques for assessing the corticomotoneuronal system.
• To focus on the pathogenic, diagnostic, and prognostic utility of these biomarkers.

Main Methods:

• Review of conventional and novel Transcranial Magnetic Stimulation (TMS) techniques.
• Discussion of physiological biomarkers such as short interval intracortical inhibition (SICI) and facilitation (SICF).
• Inclusion of emerging techniques like the triple stimulation technique (TST) and resting-state EEG.

Main Results:

• Cortical hyperexcitability, indicated by reduced SICI and increased SICF, correlates with UMN degeneration and disease progression in ALS.
• Reduced SICI shows potential as a diagnostic aid for ALS.
• Novel TMS techniques like TST and resting-state EEG offer enhanced diagnostic utility for UMN dysfunction.

Conclusions:

• Physiological biomarkers derived from TMS techniques are crucial for understanding ALS pathogenesis, diagnosis, and prognosis.
• These biomarkers help interrogate the functional integrity of the corticomotoneuronal system in ALS.
• Continued research into TMS and other neurophysiological techniques will refine diagnostic and prognostic capabilities in ALS.