Delaying the initiation of levodopa has been proposed to reduce the risk of motor complications in Parkinson’s disease. In a 4-year multicentre study in Ghana, Cilia et al. find that motor fluctuations and dyskinesias are predicted by disease duration and levodopa dose, but not by the duration of levodopa therapy.

The formation of neutralizing antibodies (NAbs) directed specifically against the active neurotoxin part of the botulinum neurotoxin (BoNT) complex is often cited as a major cause of secondary non-responsiveness (SnR) to treatment. This systematic and meta-analytic review evaluates the frequency of NAbs among patients treated with BoNT therapy for any clinical indication. A comprehensive database search strategy was designed to retrieve relevant clinical data from the published literature up to April 2013. All English-language publications that analyzed NAbs prevalence in more than ten patients were included, regardless of BoNT formulation, assay method, and study design. For the meta-analysis, patients were divided into three categories: secondary nonresponse (SnR) patients, clinically responding patients and all patients, independently of BoNT responsiveness. The meta-analysis included 61 studies reporting data for 8525 patients; 4972 dystonic patients, 1170 patients with spasticity, 294 patients with urologic indications, 396 patient with hyperhidrosis, 1659 patients with glabellar line, and 34 patients with hypersalivation. Among the ‘‘all patients’’ group NAbs frequency was 20%for dystonia, 5.9%for spasticity, and 2.7% for urologic patients and 1.1% for other conditions. The prevalence of NAbs was lower (3.5%) among clinically responding patients and higher in 53.5%SnR patients. About a half of patients with SnR do not have NAbs. NAbs was high among patients treated with RIMA but it was not associated with clinical non-responsiveness. Meta-analysis of the frequency of NAbs and SnR are limited by the heterogeneity of study design and reported outcomes. Indeed the analysis of several factors that can influence the development of NAbs, i.e.,MHCof patients, frequency and site of injection, injection technique, cumulative dose, and toxin denaturation, was not specifically evaluated due to the paucity and heterogeneity of data. The identification of all these missing data should be taken into account in order to improve the methodology of future studies.

A BS TRACT: Catechol-O-methyl transferase inhibitors are currently used as first-line add-on therapy to levodopa for the treatment of end-of-dose motor fluctuations in Parkinson's disease patients, as they increase levodopa bioavailability. Several factors hamper the use of current available catechol-O-methyl transferase inhibitors, that is, the moderate efficacy and multiple dosing for entacapone and the risk of liver toxicity with tolcapone. Opicapone, a new long-acting, peripherally selective, once-daily catechol-O-methyl transferase inhibitor, was recently licensed in Europe. Two phase 3 doubleblind clinical trials demonstrated opicapone efficacy in reducing OFF time by an average of about 60 minutes daily compared with placebo, without increasing ON time with troublesome dyskinesias. These effects were also maintained during a subsequent open-label extension consisting of 1-year follow-up. Opicapone showed a good safety profile. From June 2016, Opicapone received the approval for marketing authorization from the European Commission as adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in patients with PD and end-of-dose motor fluctuations. We aimed to review the clinical pharmacological data of opicapone, summarize its clinical efficacy and safety issues, and discuss its potential role in the management of Parkinson's disease.Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. 1 Levodopa (L-dopa) continues to be the most efficacious therapeutic drug for PD treatment. 2 Nevertheless, long-term treatment with L-dopa leads to troublesome motor fluctuations or L-dopa-induced dyskinesia (LID). 3,4 The control of motor fluctuations is a key clinical need for almost all PD patients. 4 Up to 50% of patients can develop mild motor fluctuations within 2 years of initiating L-dopa therapy, 5 and this percentage increases to 70% after 9 years of sustained therapy, 6 with substantial effect on patients' quality of life. 7 End-of-dose motor fluctuations are linked to the short half-life of oral L-dopa (about 60-90 minutes). 8 Catechol-O-methyl transferase (COMT) inhibitors are currently used as add-on therapy to L-dopa for the amelioration of end-of-dose motor fluctuations, as they inhibit peripheral L-dopa metabolism and increase the delivery of L-dopa to the brain. 9 Opicapone (OPC), a new COMT ---

Patients with cervical dystonia reported poor sleep quality and showed impaired sleep architecture. These features however cannot be related to the persistence of muscle activity over the cervical muscles, which disappears in all the sleep stages, reaching significantly decreased values when compared to HC.