6th Edition of Neurology World Conference 2026

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of upper (brain cortex) and lower (motoneurons) motor neurons (respectively, UMN & LMN), but its diagnosis mostly relies on LMN affection, common to other diseases. Besides delaying treatment, this also limits clinical trials by postponing patient inclusion, and the gold standard is still LMN evaluation primarily (using EMG), excluding UMN assessment for testing therapy efficacy. Thus, there is a crucial need for UMN biomarkers based on a reliable and easy-use approach. Methods relying on transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) revealed early cortical dysfunction, even at the presymptomatic phase of familial forms, that does not mirror in specific LMN diseases. In both human and mouse ALS models, cortical dysfunction precedes LMN dysfunction and negatively correlates with survival. Cortical dysfunction is not specific to ALS, but its association with LMN signs would help to ensure diagnosis and prognosis. But, TMS and MRI have limited application in the clinical routine of ALS for physiological and technical reasons. Electroencephalogram (EEG) has the potential to fulfill the unmet need for quantitative and reliable biomarkers of cortical dysfunction thanks to recent methodological advances. Our objective was thus to investigate PAC in preclinical models of ALS and in patients to determine whether it could be used as a new biomarker of cortical dysfunctions in ALS. In my talk, I will present the results of the Strasbourg team led by C. Rouaux, who has evidenced the link between PAC and cortical excitability and that PAC is reduced in ALS mice. I will detail the results we obtained in my group in i) control subjects in whom we demonstrated that PAC is modified when the brain cortex is modulated by repetitive TMS and ii) in ALS patients in whom we revealed a specific decrease of PAC in the primary sensorimotor cortex, as observed in preclinical models.