Ricerc@Sapienza

Experimental studies in animals have demonstrated excessive glutamatergic transmission as a key factor contributing to the pathophysiology of L-dopa induced dyskinesias (LIDs) in Parkinson's Disease (PD) (Suppa et al., 2017a). In a recent transcranial magnetic stimulation (TMS) study, we have demonstrated abnormal facilitation of the primary motor cortex (M1), in patients with PD and LIDs (Guerra et al., 2019). More in detail, the enhanced M1 facilitation in patients with LIDs was reflected by abnormally increased short-interval intracortical facilitation (SICF), an indirect measure of glutamatergic activity in M1, in patients with PD and LIDs. We also demonstrated that one month of chronic treatment with safinamide, a currently available drug for PD with dopaminergic (MAO-B inhibitor) and anti-glutamatergic properties, restored SICF and prevented LIDs worsening owing to a "short-term" effect (Guerra et al., 2019). These findings suggest a pathophysiological link between abnormal SICF and overactive glutamatergic transmission in M1, in agreement with the classical model of LIDs pathophysiology.
In this study, we will investigate the "long-term" effects of safinamide in patients with PD and LIDs, by testing several clinical and neurophysiological measures (e.g. SICF), after 12-month of chronic treatment. A total of 20 patients with PD and LID will participate at 3 experimental sessions: 1) baseline (without safinamide); 2) safinamide (14 days) and; 3) safinamide (12 months). We will examine possible changes in clinical motor symptoms, including LIDs and SICF following 12-month of chronic treatment with safinamide. In addition to SICF, the neurophysiological study will also include the examination of possible long-term changes in M1 synaptic plasticity. To this aim, in all sessions, we will also examine long-term changes in motor evoked potential amplitudes induced by the standardized intermittent theta-burst stimulation (iTBS) protocol (Suppa et al., 2016).