P 166. Absence of delayed facilitation of cortical excitability at early stage of multiple sclerosis: Evidence of altered cortical plasticity?

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal degeneration. By means of Transcranial magnetic stimulation (TMS) MS has been studied. Disabilities correlate with alterations of TMS parameters such as prolonged central motor conduction time, prolonged motor evoked potentials (MEP) latencies and increased motor threshold (MT). TMS has also been used to explore movement-related cortical plasticity. In healthy subjects if exercise is non-exhausting, an early transient facilitation of MEPs can occur immediately after exercise (post-exercise facilitation) and also after 15 min of rest (delayed facilitation). Neural mechanisms underlying post-exercise facilitation seem to reside within motor cortex. The delayed facilitation may be functional evidence of intracortical synaptic reorganization consequent to repetitive motor tasks. We aimed to compare cortical excitability in patients at early stage of MS versus healthy controls. In each subject TMS of non-dominant hemisphere was used to define MEP amplitude and motor threshold (MT). Then subjects performed 3 blocks (30-s, 60-s, and 90-s duration) of a bimanual motor task (exercise condition). Amplitude of MEPs elicited immediately after each block, and then after a 15-min rest period were compared with baseline to evaluate the presence of post-exercise facilitation and delayed facilitation. Patients were not receiving any immunomodulatory or immunosuppressive therapy and their Expanded Disability Status Scale score was between 1 and 2.5 MT resulted significantly lower in patients compared to controls. Compared with baseline, controls had larger MEP amplitudes after 30 and SMP 60 s of exercise (post-exercise facilitation) and also after the rest period (delayed facilitation). In contrast, MEP amplitudes in patients were not significantly different from baseline after any of the exercise conditions or following the rest period. Patients do not show the normal fluctuations of cortical excitability usually found after a bimanual finger motor task. These results suggest a modification in the central circuits and suppose a reduction or alteration in the cortical plasticity. The absence of postexercise facilitation and delayed facilitation in patients suggests a reduction or an alteration in neural plasticity that mediates functions such as learning and memory. We speculate that in SM patients capability to recover from functional impairments caused by demyelination is compromised. In patients at early stage of MS cortical excitability changes can occur before motor performances appear significantly altered. So, when patients present clinical symptoms and the disease becomes evident, cerebral mechanisms of compensation are already totally exploited, and possibility of further increasing performances are already lost. Like in chronic fatigue patients, and maybe in the majority of patients affected by central fatigue, impaired motor cortex plasticity may affect recovery of function in the motor system.