Antipsychotic-associated movement disorders remain common and disabling. Their screening and assessment are challenging due to clinical heterogeneity and different use of nomenclature between psychiatrists and neurologists. An International Parkinson and Movement Disorder Society subcommittee aimed to rate psychometric quality of severity and screening instruments for antipsychotic-associated movement disorders. Following the methodology adopted by previous International Parkinson and Movement Disorders Society subcommittee papers, instruments for antipsychotic-associated movement disorders were reviewed, applying a classification as "recommended," "recommended with caveats," "suggested," or "listed." Our review identified 23 instruments. The highest grade of recommendation reached is "recommended with caveats," assigned to seven severity rating instruments (Extrapyramidal Symptoms Rating Scale, Barnes Akathisia Rating Scale, Abnormal Involuntary Movements Scale, Drug-Induced Extra-Pyramidal Symptoms Scale, Maryland Psychiatric Research Centre involuntary movements scale, Simpson Angus Scale, and Matson Evaluation of Drug Side effects). Only three of these seven (Drug-Induced Extra-Pyramidal Symptoms Scale, Maryland Psychiatric Research Centre, Matson Evaluation of Drug Side effects) were also screening instruments. Their main caveats are insufficient demonstration of psychometric properties (internal consistency, skewing, responsiveness to change) and long duration of administration. Eight "suggested" instruments did not meet requirements for the "recommended" grade also because of insufficient psychometric validation. Other limitations shared by several instruments are lack of comprehensiveness in assessing the spectrum of antipsychotic-associated movement disorders and ambiguous nomenclature. The high number of instruments "recommended with caveats" does not support the need for developing new instruments for antipsychotic-associated movement disorders. However, addressing the caveats with new psychometric studies and revising existing instruments to improve the clarity of their nomenclature are recommended next steps. © 2023 International Parkinson and Movement Disorder Society.

Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD. To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation. Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791). Outpatient. 150 patients with PD and constipation. ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period. The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]). The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P<0.001). Improvement in secondary end points included SBMs (P=0.002), stool consistency (P<0.001), ease of passage (P=0.006), and laxative use (P=0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n=14) versus 2.0 points in the placebo group (n=14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n=5) and from 6.3 to 4.4 in the placebo group (n=6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P<0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P=0.016). Longer treatment periods need to be investigated in future studies. ENT-01 was safe and significantly improved constipation. Enterin, Inc.

Asymmetric chorea unrelated to structural lesions is typically due to systemic etiologies, such as metabolic, autoimmune, or other inflammatory disorders. This is an editorial commenting on a paper by Batot C, Chea M, Zeidan S, et al. Clinical and radiological follow up of Pfizer-BioNTech COVID-19 vaccine-induced hemichorea-hemiballismus. Tremor and Other Hyperkinetic Movements; 2022; 12(1). DOI: https://doi.org/10.5334/tohm.688. A 90-year-old patient is reported who developed hemichorea shortly after his second vaccination against COVID-19. Hypometabolism was noted in the contralateral striatum. This case provides potential insights and raises questions about mechanisms of immune-mediated hemichorea.

Oromandibular dystonia (OMD) is a form of focal dystonia that involves the masticatory, lower facial, labial, and lingual musculature. It is a disabling disorder which had limited treatment options until the recent introduction of botulinum toxin (BoNT) as the recommended first-line therapy by most experts and evidence-based literature. Owing to the complex relationship between the muscles of mastication and surrounding muscles, there is a wide variety of dynamic clinical presentations, making clinical recognition and the corresponding approach to BoNT injection therapy difficult. In this review, the authors provide a framework for practical clinical approaches, beginning with the recognition of clinical subtypes of OMD (jaw-opening, jaw-closing, jaw-deviating, lingual, peri-oral, and/or pharyngeal dystonias), followed by patient selection and clinical evaluation to determine function interferences, with injection techniques illustrated for each subtype. Careful stepwise planning is recommended to identify the muscles that are primarily responsible and employ a conservative approach to dosing titration. Treating physicians should be diligent in checking for adverse events, especially for the first few injection cycles, as muscles involved in OMD are small, delicate, and situated in close proximity. It is recommended that future studies should aim to establish the clinical efficacy of each subtype, incorporating muscle targeting techniques and patient-centred outcome measures that are related to disturbed daily functions.

Although the diagnosis of Parkinson's disease (PD) relies on the clinical effects of dopamine deficiency, this disease is associated with other neurotransmitter deficits that cause various motor and non-motor symptoms. Non-motor features may begin with an earlier pre-motor prodrome. The majority of non-motor features are not related to dopaminergic cell loss. Hyposmia, rapid eye movement sleep behavior disorder (RBD), depression, and constipation can precede the symptoms related to dopamine deficiency.

Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

IntroductionCervical dystonia (CD) is a neurologic movement disorder with potentially disabling effects and significant impact on quality of life of those affected. AbobotulinumtoxinA (aboBoNT-A) was initially approved for a dilution of 500 U/1 mL and subsequently for a dilution of 500 U/2 mL, providing flexibility for clinicians to treat CD. Here, we explore the safety and efficacy of the 500 U/2 mL dilution versus 500 U/1 mL dilution of aboBoNT-A in a retrospective analysis based on published clinical trial data. MethodsThe safety and efficacy of aboBoNT-A in patients with CD was evaluated in three multicenter, double-blind, randomized, placebo-controlled trials and open-label extensions. Trials 1 (NCT00257660) and 2 (NCT00288509) evaluated the 500 U/1 mL dilution in 80 and 116 patients, respectively; Trial 3 (NCT01753310) evaluated the 500 U/2 mL dilution in 125 patients. ResultsComparison of the adjusted mean difference in TWSTRS total scores at Week 4 from baseline for aboBoNT-A in Trial 1 (−6.0; 95% CI, −10.8, −1.3), Trial 2 (−8.8; 95% CI, −12.9, −4.7), and Trial 3 (−8.7; 95% CI, −13.2, −4.2) showed similar, significant improvements. Dysphagia and muscle weakness patterns were comparable across the three trials, indicating that an increased dilution of aboBoNT-A does not result in an increased risk of diffusion-related adverse events. ConclusionThe results of these trials show that aboBoNT-A is similarly efficacious using either dilution, with similar safety and tolerability across trials. Having the 500 U/1 mL and 500 U/2 mL dilution volumes available provides further flexibility in administration, benefiting patient care.