Transcranial magnetic stimulation identifies early cortical abnormalities in radiologically isolated syndrome

Radiologically isolated syndrome (RIS) is a preclinical stage of multiple sclerosis, characterized by demyelinating lesions on MRI. Transcranial magnetic stimulation (TMS) can detect corticospinal dysfunction associated with demyelination and neuronal loss.

This study aimed to investigate motor cortical excitability in RIS using TMS and explore its relationship with cognition, fatigue and MRI lesion characteristics.

Sixteen RIS patients and 16 matched healthy controls underwent TMS to assess resting motor threshold (RMT), motor evoked potential (MEP) latency, central motor conduction time (CMCT), ipsilateral and contralateral cortical silent periods (iCSP, CSP), short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI). Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT), and fatigue using the Fatigue Scale for Motor and Cognitive Functions (FSMC).

Compared to controls, RIS patients showed significantly prolonged CMCT and iCSP, with a trend toward increased MEP latency. No significant differences were observed in RMT, CSP, SICI, or SAI. RIS participants also had lower SDMT scores and higher FSMC scores. TMS parameters did not correlate with MRI lesion count or distribution.

These findings suggest early subclinical corticospinal and interhemispheric dysfunction in RIS. TMS may offer a valuable functional biomarker alongside MRI for identifying individuals at higher risk for MS conversion.