Tardive dyskinesia in Asia— current clinical practice and the role of neurologists in the care pathway

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally

Sustained response in early responders to safinamide in patients with Parkinson's disease and motor fluctuations: A post hoc analysis of the SETTLE study

Safinamide is a selective, reversible, monoamine oxidase B inhibitor for the treatment of patients with Parkinson's disease (PD) and motor fluctuations. This was a post hoc analysis of the SETTLE study, in which patients with PD and motor fluctuations were randomly assigned to 24-week treatment with safinamide (50 mg/day for 2 weeks, increased to 100 mg/day if tolerated) or placebo. In the present analysis, responders were defined according to their treatment responses at Week 2 and Week 24 based on changes in ON-time without troublesome dyskinesia from baseline with cutoffs of 1 hour. It was found that 81% (103/127) of the responders at Week 2 maintained the response through Week 24 in the safinamide group. Other outcomes did not necessarily coincide with the ON-time response; however, “Early” responders who showed a treatment response at both Week 2 and Week 24 had substantial improvements from baseline in OFF-time, UPDRS Part II and III scores, and PDQ-39 summary index scores through Week 24. The safinamide group had a higher proportion of early responders than the placebo group (39% vs 20%, p < 0.0001). At baseline, early responders in the safinamide group had significantly higher UPDRS Part II and III scores, shorter ON-time, and longer OFF-time than the other responder populations. In conclusion, the results of the present post hoc analysis suggest that patients with a short ON-time, severe motor symptoms, and highly compromised activities of daily living can benefit from safinamide early in treatment and over the long term

Early factors for predicting discontinuation to subcutaneous Apomorphine infusion in Parkinson's disease:A prospective analysis of the Thai Apomorphine Registry

INTRODUCTION: Although continuous subcutaneous apomorphine infusion (CSAI) is an effective therapy for Parkinson's disease (PD) with motor fluctuations, data from Asian cohorts is limited. The therapy is often discontinued due to the complexity of its delivery. METHODS: Fifty-one PD patients undergoing CSAI as an add-on therapy were enrolled in the Thai Apomorphine Registry, an electronic database that recorded clinical characteristics and parameters during the 14-consecutive-day titration and long-term follow-up. Factors at the time of titration were documented in order to identify predictors of long-term discontinuation. RESULTS: Following initiation, PD patients were administered a mean CSAI dose of 5.89 mg/h (SD 1.36) over a mean time of 12.28 h (SD 1.90) each day. The mean follow-up period was 626.2 days (SD 619.17). Significant reductions in UPDRS-I, II, III, and IV scores, total NMSQ score, PDQ-8 score, daily off and dyskinesia hours, Timed Up and Go test, walking step test, levodopa-equivalent daily dose, number of times a day the levodopa was taken versus pre-CSAI values were observed (p < 0.05, each). Thirty-five (68.6%) patients discontinued during the follow-up period. Relative risks of variables recorded at the time of titration that determined discontinuation of CSAI therapy were an absence of full-time caregivers, achieving a daily off hours reduction <3.5 h, and NMSQ scores at the time of CSAI titration ≥9.5 points. CONCLUSION: Identifying factors that predict discontinuation of CSAI at the time of its initiation may help physicians to better understand the patient's drug response and how to manage them long-term

Evaluation of Psychometric Properties of Thai Version Telehealth Usability Questionnaire (T-TUQ)

This cross-sectional validation study aimed to translate, cross-culturally adapt, and investigate the psychometric properties of a Thai version of the Telehealth Usability Questionnaire (T-TUQ). Two hundred and ten Thai participants, mean age of 61.2±15.2 years, were recruited from three specialty clinics: 50 (23.8%) hematology, 70 (33.3%) movement disorders, and 90 (42.9%) general neurology. The T-TUQ was translated from the original English version to produce a Thai language version. Back translation and pilot cognitive interviews were completed. All five subscales (usefulness, ease of use, effectiveness, reliability, and satisfaction) showed excellent internal consistency (alpha &gt;0.80), displayed by Cronbach's alpha coefficient of 0.83, 0.94, 0.86, 0.83, and 0.92, respectively. For construct validity, exploratory factor analysis revealed two dimensions from eigenvalues and scree plot, defined as utility and accessibility subscales. In conclusion, the T-TUQ could be a reliable and valid instrument to evaluate the usability of telehealth with a Thai population

Task force consensus on nosology and cut-off values for axial postural abnormalities in parkinsonism

Background: There is no consensus with regard to the nosology and cut-off values for postural abnormalities in parkinsonism. Objective: To reach a consensus regarding the nosology and cut-off values. Methods: Using a modified Delphi panel method, multiple rounds of questionnaires were conducted by movement disorder experts to define nosology and cut-offs of postural abnormalities. Results: After separating axial from appendicular postural deformities, a full agreement was found for the following terms and cut-offs: camptocormia, with thoracic fulcrum (&gt;45°) or lumbar fulcrum (&gt;30°), Pisa syndrome (&gt;10°), and antecollis (&gt;45°). "Anterior trunk flexion," with thoracic (≥25° to ≤45°) or lumbar fulcrum (&gt;15° to ≤30°), "lateral trunk flexion" (≥5° to ≤10°), and "anterior neck flexion" (&gt;35° to ≤45°) were chosen for milder postural abnormalities. Conclusions: For axial postural abnormalities, we recommend the use of proposed cut-offs and six unique terms, namely camptocormia, Pisa syndrome, antecollis, anterior trunk flexion, lateral trunk flexion, anterior neck flexion, to harmonize clinical practice and future research. Keywords: Parkinson's disease; Pisa syndrome; antecollis; atypical parkinsonisms; camptocormia; diagnostic criteria.; postural abnormalities

Six Action Steps to Address Global Disparities in Parkinson Disease: A World Health Organization Priority

Importance: The Global Burden of Disease study conducted between 1990 and 2016, based on a global study of 195 countries and territories, identified Parkinson disease (PD) as the fastest growing neurological disorder when measured using death and disability. Most people affected by PD live in low- and middle-income countries (LMICs) and experience large inequalities in access to neurological care and essential medicines. This Special Communication describes 6 actions steps that are urgently needed to address global disparities in PD. Observations: The adoption by the 73rd World Health Assembly (WHA) of resolution 73.10 to develop an intersectoral global action plan on epilepsy and other neurological disorders in consultation with member states was the stimulus to coordinate efforts and leverage momentum to advance the agenda of neurological conditions, such as PD. In April 2021, the Brain Health Unit at the World Health Organization convened a multidisciplinary, sex-balanced, international consultation workshop, which identified 6 workable avenues for action within the domains of disease burden; advocacy and awareness; prevention and risk reduction; diagnosis, treatment, and care; caregiver support; and research. Conclusions and Relevance: The dramatic increase of PD cases in many world regions and the potential costs of PD-associated treatment will need to be addressed to prevent possible health service strain. Across the board, governments, multilateral agencies, donors, public health organizations, and health care professionals constitute potential stakeholders who are urged to make this a priority

Unmet needs in Parkinson's disease: New horizons in a changing landscape

The success of levodopa and other classes of drugs have meant that most people with Parkinson's disease enjoy a good quality of life for many years. However, despite the availability of several drugs and formulations that can be used as monotherapy and in combination, there are a number of disease features that the current therapies are unable to address. The disease continues to progress despite treatment, patients suffer from a myriad of motor and non-motor symptoms, and a neuroprotective therapy is urgently required. To move forward with medical and surgical management, it is important to consider new insights that recent research offers and in this review we examine how a better understanding of the disease pathology and progression might improve and enrich our daily clinical practice. It is also timely to consider the service provision changes that will increasingly be needed to effectively manage the needs of the aging population

Synucleinopathies from bench to bedside.

Accumulation of alpha-synuclein is a pathological feature in several neurological diseases. Its characterization has allowed for a re-grouping of diseases according to the expected pathology. The clinical syndrome of PD can now be classified into forms with and without alpha-synuclein pathology. DLB and PDD are synucleinopathies, and MSA shows alpha-synuclein pathology with glial inclusions. ADHD symptoms commonly occur in persons that will subsequently develop DLB. A similar phenomenon may be the early personality changes and frontotemporal atrophy in patients with SNCA multiplication. RLS is not known to have alpha-synuclein pathology, but as PD and ADHD, involves a hypodopaminergic state. Furthermore, PD and RLS co-occur in families in a way that suggests common inheritance. A proportion of patients with ET have brainstem Lewy body pathology. Gaucher disease and other lysosomal storage disorders also have alpha-synuclein pathology. Alpha-synuclein is a naturally unfolded protein. Non-fibrillar oligomeres may be the toxic species, and Lewy body formation may in fact be protective. Inhibiting alpha-synuclein toxicity seems to be an attractive novel treatment strategy and several approaches are being developed. When such treatments become available, clinicians will need to be familiar with the clinical features that distinguish the synucleinopathies from their look-alikes