Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading ...to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia - Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism (XDP), dentatorubral-pallidoluysian atrophy (DRPLA), Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy (BAFME), Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 (CAMTA2) gene, and paroxysmal kinesigenic dyskinesia (PKD). We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.
The Monogenic Network of the Global Parkinson's Genetics Program (GP2) aims to create an efficient infrastructure to accelerate the identification of novel genetic causes of Parkinson's disease (PD) ...and to improve our understanding of already identified genetic causes, such as reduced penetrance and variable clinical expressivity of known disease-causing variants. We aim to perform short- and long-read whole-genome sequencing for up to 10,000 patients with parkinsonism. Important features of this project are global involvement and focusing on historically underrepresented populations.
Abstract Background There are limited data on the prevalence of impulsive–compulsive behaviors and subsyndromal impulsive–compulsive behaviors in Asian patients with Parkinson’s disease, who are ...treated with lower dosages of dopaminergic medications. Methods The recently-validated Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s Disease was administered to 200 consecutive patients attending a Malaysian university-based neurology clinic. Informant report was also systematically obtained. Results A high rate of Questionnaire positivity was found (35.0% by combined patient and informant report; 24.6% by patient report alone; 27.4% by informant report alone), despite usage of relatively low dosages of dopaminergic medications (mean/median total l -dopa equivalent units of 528/450 mg/day; mean/median agonist-only l -dopa equivalent units of 74/37 mg/day). Eating, sexual and punding or hobbyism behaviors were relatively common, while gambling and compulsive medication use occurred less frequently. Agreement between patient- and informant-reporting of impulsive–compulsive behaviors was moderate-to-fair (Kappa values ranging from 0.203 to 0.494). Factors associated with Questionnaire positivity on univariate analysis were male gender, younger age at Parkinson’s disease onset, longer disease duration, use of dopamine agonist or amantadine therapy, higher total l -dopa equivalent units and higher dopamine agonist-only l -dopa equivalent units. On multivariate analysis, male gender and longer disease duration independently predicted Questionnaire positivity. No association was found with cognitive or apathy scores. Conclusions Our findings suggest that Asian patients with Parkinson’s disease may be susceptible to dopaminergic medication-related side effects. The data here also contribute to the understanding of the psychometric properties of the Questionnaire for Impulsive–Compulsive Disorders.
Hemichorea-hemiballismus is characterized by unilateral, brief, unpredictable involuntary movements of one side of the body (upper and lower limbs and sometimes also affecting the face). The most ...common causes for this condition are strokes, hyperglycemia-associated hemichorea-hemiballismus, and other focal lesions affecting the basal ganglia KCI Citation Count: 0
The basal ganglia (BG) are susceptible to fluctuations in blood urea levels, sometimes resulting in movement disorders. We described patients with end-stage kidney disease (ESKD) presenting with ...movement disorders associated with bilateral BG lesions on imaging.
We report four patients and systematically reviewed all published cases of ESKD presenting with movement disorders and bilateral BG lesions (EBSCOhost and Ovid).
Of the 72 patients identified, 55 (76.4%) were on regular dialysis. Parkinsonism was the most common movement disorder (n = 39; 54.2%), followed by chorea (n = 24; 33.3%). Diabetes mellitus (n = 51; 70.8%) and hypertension (n = 16; 22.2%) were the most common risk factors. Forty-three (59.7%) were of Asian ethnicity. Complete clinical resolution was reported in 17 (30.9%) patients, while 38 (69.1%) had incomplete clinical resolution with relapse. Complete radiological resolution occurred in 14 (34.1%) patients.
Movement disorders associated with BG lesions should be recognized as a rare and potentially reversible metabolic movement disorder in patients with ESKD.
IMPORTANCE: Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the ...largest population worldwide (ie, Asian). OBJECTIVES: To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts. DESIGN SETTING, AND PARTICIPANTS: Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson’s Disease Society Brain Bank Criteria. MAIN OUTCOMES AND MEASURES: Genotypes of common variants, association with disease status, and polygenic risk scores. RESULTS: Of 31 575 samples identified, 6724 PD cases (mean SD age, 64.3 10 years; age at onset, 58.8 10.6 years; 3472 53.2% men) and 24 851 controls (age, 59.4 11.4 years; 11 030 45.0% men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10−10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10−3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10−12). CONCLUSIONS AND RELEVANCE: This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta–genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.
The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson’s disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this ...locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P=0.019) and 1.2-fold (P=0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies.
Conventional outcome measures (COMs) in Parkinson's disease (PD) refer to rating scales, questionnaires, patient diaries and clinically-based tests that do not require specialized equipment.
It is ...timely at this juncture - as clinicians and researchers begin to grapple with the “invasion” of digital technologies - to review the strengths and weaknesses of these outcome measures.
This paper discusses advances (including an enhanced understanding of PD itself, and the development of clinimetrics as a field) that have led to improvements in the COMs used in PD; their strengths and limitations; and factors to consider when selecting and using a measuring instrument.
It is envisaged that in the future, a combination of COMs and technology-based objective measures will be utilized, with different methods having their own strengths and weaknesses. Judgement is required on the part of the clinician and researcher in terms of which instrument(s) are appropriate to use, depending on the particular clinical or research setting or question.
•Rating scales, questionnaires, patient diaries and clinically-based tests are reviewed.•Their strengths and weaknesses are discussed.•Historical developments are also presented.
Keywords: Parkinson's disease; genetics; genome-wide association; mutation Article Note: Correction added on 6 February 2021, after first online publication: copyright line updated. Relevant ...conflicts of interest/financial disclosures: Dr. Singleton is supported by the Intramural Research Program of the National Institute on Aging and has received grant support from the Michael J. Fox Foundation for Parkinson's Research and the Aligning Science Across Parkinson's Initiative. He has received royalty payments related to a diagnostic for stroke. Dr. Blauwendraat is supported by the Intramural Research Program of the National Institute on Aging and has received grant support from the Michael J. Fox Foundation for Parkinson's Research and the Aligning Science Across Parkinson's Initiative.
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