Longitudinal Dynamics of Clinical and Neurophysiological Changes in Parkinson's Disease: A 4.5-Year Cohort Study

Parkinson's disease (PD) is characterized by progressive motor and non-motor symptoms, yet the longitudinal interplay between clinical progression and neurophysiological alterations remains underexplored. In this four-and-a-half-year longitudinal study, we assessed 22 individuals with PD using the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and transcranial magnetic stimulation (TMS) to evaluate cortical excitability. We analyzed changes in resting motor threshold (rMT) and cortical silent period (CSP) across disease stages and examined the impact of the COVID-19 pandemic on disease progression. We observed significant motor function and cortical excitability deterioration over time, with CSP exhibiting potential as a biomarker of disease progression. These alterations were more pronounced in advanced PD and during the post-pandemic period, underscoring the susceptibility of PD patients to environmental stressors. No significant sex-related differences were found in clinical or neurophysiological measures. Our findings highlight the potential of TMS in monitoring PD progression and suggest that integrating neurophysiological assessments into routine clinical practice may enhance patient management. Longitudinal neurophysiological biomarkers could provide insights into disease trajectory and inform therapeutic interventions.