Background: Real‐time quaking‐induced conversion (RT‐QuIC) and protein misfolding cyclic amplification (PMCA) have been developed to detect minute amounts of amyloidogenic proteins via amplification techniques and have been used to detect misfolded α‐synuclein (αSyn) aggregates in the cerebrospinal fluid (CSF) and other source materials of patients with Parkinson's Disease and other synucleinopathies.Objectives: The aim of this systematic review and meta‐analysis was to evaluate the diagnostic accuracy of αSyn seed amplification assays (αSyn‐SAAs), including RT‐QuIC and PMCA, using CSF as source material to differentiate synucleinopathies from controls.Methods: The electronic MEDLINE database PubMed was searched for relevant articles published until June 30, 2022. Study quality assessment was performed using the QUADAS‐2 toolbox. A random effects bivariate model was exploited for data synthesis.Results: Our systematic review identified 27 eligible studies according to the predefined inclusion criteria, of which 22 were included in the final analysis. Overall, 1855 patients with synucleinopathies and 1378 non‐synucleinopathies as control subjects were included in the meta‐analysis. The pooled sensitivity and specificity to differentiate synucleinopathies from controls with αSyn‐SAA were 0.88 (95% CI, 0.82–0.93) and 0.95 (95% CI, 0.92–0.97), respectively. Evaluating the diagnostic performance of RT‐QuIC in a subgroup analysis for the detection of patients with multiple system atrophy the pooled sensitivity decreased to 0.30 (95% CI, 0.11–0.59).Conclusions: While our study clearly demonstrated a high diagnostic performance of RT‐QuIC and PMCA for differentiating synucleinopathies with Lewy bodies from controls, results for the diagnosis of multiple system atrophy were less robust.

Objective: The objective of this study was to assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non‐motor symptoms (NMS) in Parkinson's disease (PD).Methods: This was a phase II placebo‐controlled, double‐blind, parallel‐group, enriched enrollment randomized withdrawal trial conducted at the Medical University Innsbruck. A random sample of 47 patients with PD with stable motor disease and disturbing NMS defined by a score of ≥4 points on the Movement Disorder Society ‐ Unified PD Rating Scale‐I (MDS‐UPDRS‐I) underwent open‐label nabilone titration (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was the change of the MDS‐UPDRS‐I between randomization and week 4. Safety was analyzed in all patients who received at least one nabilone dose.Results: Between October 2017 and July 2019, 19 patients received either nabilone (median dose = 0.75 mg) or placebo. At week 4, mean change of the MDS‐UPDRS‐I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI −0.16 to 2.16, p = 0.280, effect size = 0.42) in the nabilone‐group (difference: 1.63, 95% CI 0.09 to 3.18, p = 0.030, effect size = 0.66). Seventy‐seven percent of patients had adverse events (AEs) during open‐label titration, most of them were transient. In the double‐blind phase, similar proportions of patients in each group had AEs (42% in the placebo group and 32% in the nabilone group). There were no serious AEs.Interpretation: Our results highlight the potential efficacy of nabilone for patients with PD with disturbing NMS, which appears to be driven by positive effects on anxious mood and night‐time sleep problems.Trial registry: ClinicalTrials.gov (NCT03769896) and EudraCT (2017‐000192‐86). ANN NEUROL 2020;88:712–722

Objective: To update evidence‐based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).Background: The International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane Risk of Bias tool and a modified version of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).Methods: On January 1, 2023, a literature search was conducted without date limit in the MEDLINE, Embase, and Cochrane databases using the following search terms: Parkinson disease, levodopa and, for the Embase database, randomized controlled trial (RCT). The inclusion criteria for studies were: patients with PD, on oral levodopa therapy, experiencing motor fluctuations, investigating an intervention that was (commercially) available in at least one country, study design RCT, and with a follow‐up duration of at least 3 months.Results: A total of 102 studies were included. Levodopa extended release, pramipexole immediate release and extended release, ropinirole immediate release, rotigotine, opicapone, safinamide, and bilateral subthalamic nucleus deep brain stimulation (DBS) were assessed as efficacious, and continuous intestinal levodopa infusion, continuous subcutaneous levodopa, continuous subcutaneous apomorphine, ropinirole prolonged release, ropinirole patch, entacapone, rasagiline, istradefylline, amantadine extended release, zonisamide, bilateral globus pallidus DBS, and pallidotomy were assessed as likely efficacious for the treatment of motor fluctuations in people with PD who are already being treated with levodopa.Conclusions: There are several treatment options that can improve motor fluctuations in PD. These recommendations will assist physicians and patients in determining which intervention to use. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Although open-label observations report a positive effect of cannabinoids on non-motor symptoms (NMS) in Parkinson’s disease (PD) patients, these effects remain to be investigated in a controlled trial for a broader use in NMS in PD patients. Therefore, we decided to design a proof-of-concept study to assess the synthetic cannabinoid nabilone for the treatment of NMS. We hypothesize that nabilone will improve NMS in patients with PD and have a favorable safety profile. The NMS-Nab Study is as a mono-centric phase II, randomized, placebo-controlled, double-blind, parallel-group, enriched enrollment withdrawal study. The primary efficacy criterion will be the change in Movement Disorders Society-Unified Parkinson’s Disease-Rating Scale Part I score between baseline (i.e. randomization) and week 4. A total of 38 patients will have 80% power to detect a probability of 0.231 that an observation in the treatment group is less than an observation in the placebo group using a Wilcoxon rank-sum test with a 0.050 two-sided significance level assuming a true difference of 2.5 points between nabilone and placebo in the primary outcome measure and a standard deviation of the change of 2.4 points. The reduction of harm through an ineffective treatment, the possibility of individualized dosing, the reduction of sample size, and the possible evaluation of the influence of the placebo effect on efficacy outcomes justify this design for a single-centered placebo-controlled investigator-initiated trial of nabilone. This study should be the basis for further evaluations of long-term efficacy and safety of the use of cannabinoids in PD patients.

Background: The synthetic tetrahydrocannabinol analogue nabilone improved overall non‐motor symptom (NMS) burden in Parkinson's disease (PD) patients in comparison to placebo.Objectives: To characterize the effects of nabilone on different sleep outcomes in PD patients.Methods: We performed a post‐hoc analysis of the controlled, double‐blind, enriched enrollment randomized withdrawal NMS‐Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically‐relevant sleep problems (MDS‐UPDRS‐1.7 ≥ 2 points).Results: After open‐label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS‐UPDRS‐1.7. and the NMS‐Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS‐Scale Domain 2).Conclusions: This post‐hoc analysis of the NMS‐Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.The original trial was registered with ClinicalTrials.gov (NCT03769896, https://clinicaltrials.gov/ct2/show/NCT03769896) and EudraCT (2017–000192‐86).

Background: Anti‐IgLON5 disease is an autoimmune encephalopathy with sleep disturbances as a hallmark in the majority of reported cases. Additional clinical symptoms are heterogenous and include movement disorders, bulbar dysfunction, autonomic disorders, and neurocognitive impairment.Case: Here, we report the case of an 87‐year‐old woman presenting with isolated progressive hemichorea. An extensive diagnostic work‐up revealed antibodies against IgLON5 in the serum. Neither history nor polysomnography (PSG) unveiled signs and features of sleep dysfunction typically reported in anti‐IgLON5 disease.Literature Review: In an extensive literature review we identified twelve other studies reporting about patients with confirmed anti‐IgLON5 disease and chorea as extrapyramidal movement disorder in their clinical phenotype. Subsequently, clinical characteristics of these patients were carefully evaluated.Conclusions: Our results support the diversity of clinical phenotypes in anti‐IgLON5 disease, adding isolated hemichorea to the spectrum of presenting symptoms. As sleep‐related disorders are often not the leading reason for consultation and only revealed by PSG examination, we suggest that screening for antibodies against IgLON5 should be considered in patients presenting with unexplained movement disorders, including isolated hemichorea.