In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.

Background and purpose: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide. Methods: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide. Results: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary endpoint: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 AE 2.9 to 8.9 AE 1.8; P = 0.27). Conclusion: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Background The aetiology of Parkinson’s disease (PD) is still very controversial, with a peculiar lack of established risk factors or protective behavior. Methods We carried out a case–control study of 634 idiopathic PD patients admitted from 2011 to 2015 to two hospitals located in central Italy and 532 controls matched by hospital, gender and age (± 5 years). The study questionnaire included questions on host factors, family history, residence, occupation and lifestyle. Odds ratios (ORs) for PD and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for actual and potential confounders. Results A lower OR was observed in females (0.74; 95%CI:0.58–0.96), while older age classes showed a constantly increased risk for PD (p<0.005) starting from the class 65–69 years. Subjects who reported a first degree relative affected by PD showed a borderline increase which was more evident in those enrolled in the urban center of Rome (OR = 1.65; 95%CI: 1.09–2.50). Significant reduction of the risk was associated to current smoking (OR = 0.48; 95%CI: 0.24–0.54), and to vegetables consumption (p<0.03), while borderline increases were associated to meat and cold cut consumption. Occupational activities classified according to ISCO-08 categories did not show increased risk, while higher ORs’ were found for pilots and physicians. Conclusions The results from this study confirmed the higher risk of PD in males and in elderly, and the inverse association with smoking habit. The possible etiological role of familial clustering, dietary habit, and some job tasks is suggested.

Background Laboratory and clinical evidence indicate that continous delivery of levodopa is associated with reduced motor complications compared to standard intermittent levodopa. Objective To assess the pharmacokinetics and efficacy of continuous oral delivery of l‐dopa/carbidopa in PD patients with motor fluctuations. Methods Eighteen PD patients with motor fluctuations were enrolled in an open‐label study comparing pharmacokinetics and efficacy measures between standard intermittent oral l‐dopa/carbidopa and “continuous” oral l‐dopa/carbidopa. Continuous treatment was operationally defined as sips of an l‐dopa dispersion at 5‐ to 10‐minute intervals. On day 1, patients received their usual oral l‐dopa/carbidopa doses. On day 2, patients received l‐dopa/carbidopa dose by “continuous” oral administration. On day 3, patients received a single dose of oral l‐dopa/carbidopa followed by continuous administration of l‐dopa/carbidopa. Each study period was 8 hours, and the total l‐dopa/carbidopa dose administered was the same on each day. Analyses of variability were primarily‐based samples drawn between 4 and 8 hours when subjects were in a relative steady state. Results There was less variability in plasma l‐dopa concentration with continuous versus intermittent oral l‐dopa/carbidopa treatment (fluctuation index was 0.99 ± 0.09 vs. 1.38 ± 0.12 [P < 0.001] and coefficient of variation was 0.35 ± 0.03 vs. 0.49 ± 0.04 [P < 0.001]). Mean OFF time was decreased by 43% (P < 0.001) with continuous oral l‐dopa therapy. No safety or tolerability issues were observed. Conclusions Continuous oral delivery of l‐dopa/carbidopa was associated with less plasma variability and reduced off time in comparison to standard intermittent oral l‐dopa/carbidopa therapy. © 2019 International Parkinson and Movement Disorder Society