Fatigue in fluctuating Parkinson's disease patients: possible impact of safinamide.

Fatigue is a common non-motor symptom in Parkinson's disease (PD). Among other pathophysiological mechanisms, neuroinflammation, a pathological PD hallmark associated with changes in glutamatergic transmission in basal ganglia, has been proposed as a crucial factor closely related to fatigue. To test the hypothesis that safinamide could represent an effective treatment of fatigue in PD patients, given its dual mechanism of action (it selectively and reversibly inhibits MAOB and modulates glutamate release), we administered the validated versions of fatigue severity scale (FSS) and Parkinson fatigue scale-16 (PFS-16) to 39 fluctuating PD patients with fatigue before and after a 24-week treatment period with safinamide as add-on therapy. An assessment of secondary variables such as depression, quality of life (QoL), and motor and non-motor symptoms (NMS) was conducted. After 24 weeks of treatment with safinamide, both FSS (p < 0.001) and PF-S16 (p = 0.02) scores were significantly lower than at baseline. Moreover, 46.2% and 41% of patients scored below the cut-off for the presence of fatigue according to FSS and PFS-16, respectively (responders). At follow-up, a significant difference emerged between responders and non-responders in mood, QoL, and NMS. Fatigue improved in fluctuating PD, and more than 40% of patients were "fatigue-free" after a 6 month treatment with safinamide. Patients without fatigue at follow-up displayed significantly better scores in QoL domains, such as mobility or activities of daily living, although disease severity remained stable, supporting the hypothesis that fatigue could considerably affect QoL. Drugs that interact with multiple neurotransmission systems, such as safinamide, could be useful in reducing this symptom.

The role of cerebellum in timing processing: A contingent negative variation study.

Time management is an important aspect of human behaviour and cognition. Several brain regions are thought to be involved in motor timing and time estimation tasks. However, subcortical regions such as the basal nuclei and cerebellum seem to play a role in timing control. The aim of this study was to investigate the role of the cerebellum in temporal processing. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal transcranial direct current stimulation (tDCS) and studied the effects of this inhibition on contingent negative variation (CNV) parameters elicited during a S1-S2 motor task in healthy subjects. Sixteen healthy subjects underwent a S1-S2 motor task prior to and after cathodal and sham cerebellar tDCS in separate sessions. The CNV task consisted of a duration discrimination task in which subjects had to determine whether the duration of a probe interval trial was shorter (800 ms), longer (1600 ms), or equal to the target interval of 1200 ms. A reduction in total CNV amplitude emerged only after cathodal tDCS for short and target interval trials, while no differences were detected for the long interval trial. Errors were significantly higher after cathodal tDCS than at baseline evaluation of short and target intervals. No reaction time differences were found for any time interval after the cathodal and sham sessions. These results point to a role of the cerebellum in time perception. In particular, the cerebellum seems to regulate temporal interval discrimination for second and sub-second ranges.

Effects of Cerebellar tDCS on Inhibitory Control: Evidence from a Go/NoGo Task.

Response inhibition as an executive function refers to the ability to suppress inappropriate but prepotent responses. Several brain regions have been implicated in the process underlying inhibitory control, including the cerebellum. The aim of the present study was to explore the role of the cerebellum in executive functioning, particularly in response inhibition. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal tDCS and studied the effects of this inhibition on ERP components elicited during a Go/NoGo task in healthy subjects. Sixteen healthy subjects underwent a Go/NoGo task prior to and after cathodal and sham cerebellar tDCS in separate sessions. A reduction in N2-NoGo amplitude and a prolongation in N2-NoGo latency emerged after cathodal tDCS whereas no differences were detected after sham stimulation. Moreover, commission errors in NoGo trials were significantly higher after cathodal tDCS than at the basal evaluation. No differences emerged between performances in Go trials and those after sham stimulation. These data indicate that cerebellar inhibition following cathodal stimulation alters the ability to allocate attentional resources to stimuli containing conflict information and the inhibitory control. The cerebellum may regulate the attentional mechanisms of stimulus orientation and inhibitory control both directly, by making predictions of errors or behaviors related to errors, and indirectly, by controlling the functioning of the cerebral cortical areas involved in the perception of conflict signals and of the basal ganglia involved in the inhibitory control of movement.