Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry.

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

Neuropathologic findings of patients with COVID-19: a systematic review.

BACKGROUND: Despite the expanding literature that discusses insights into the clinical picture and mechanisms by which the SARS-CoV-2 virus invades the nervous system, data on the neuropathologic findings of patients who died following SARS-CoV-2 infection is limited. METHODS: A broad literature search was done for published articles that reported on histopathological findings of the brain in patients with COVID-19 in PubMed by MEDLINE, Embase, CENTRAL by the Cochrane Library, and SCOPUS from December 31, 2019 to October 31, 2020. RESULTS: The systematic literature search strategy used resulted in a total of 1608 articles of which 14 were included in the analysis (PROSPERO registration number: CRD42020221022). There were ten case series, two case reports, one retrospective cohort, and one prospective cohort. The age of the patients ranged between 38 and 90 years old, most of them older than 65 years old (n=66, 45.2%) and males (n=79, 54.1%). Most tested negative in SARS-CoV-2 immunohistochemistry (n=70, 47.9%). The striking pathologic changes included diffuse edema (n=25, 17.1%), gliosis with diffuse activation of microglia and astrocytes (n=52, 35.6%), infarctions involving cortical and subcortical areas of the brain (n=4, 2.7%), intracranial bleed (subarachnoid hemorrhage and punctate hemorrhages) (n=18, 12.4%), arteriosclerosis (n=43, 29.5%), hypoxic-ischemic injury (n=41, 28.1%), and signs of inflammation (n=52, 35.6%). The cause of death was attributed to the cardiorespiratory system (n=66, 45.2%). CONCLUSIONS: The neuropathologic changes observed likely represent direct cytopathic effects and indirect effects secondary to host-specific inflammatory response induced by the viral infection. Further studies however are required to better elucidate the pathologic mechanism.

Scientific impact of movement disorders research from Southeast Asia: A bibliometric analysis.

BACKGROUND: The number of scientific publications on movement disorders from Southeast Asia (SEA) is thought to be low. Thus, we looked at the movement disorders research productivity among SEA countries and its associations with country-specific socioeconomic factors. METHODS: We performed a systematic search for publications indexed in PubMed, Scopus, Embase and Cochrane Central Register of Controlled Trials from January 2000 to December 2019 with at least one author from SEA. Bibliometric indices were used to evaluate research impact. The country-specific socioeconomic characteristics were also obtained. RESULTS: Of the 9488 identified articles, 1567 met the eligibility criteria. There was an increasing trend in the total number of publications on movement disorders during the last two decades. Singapore had the highest contribution in all aspects, which highlights the impact of knowledge-based economy type in research productivity. Parkinsonism remained the most studied condition, followed by dystonia, chorea, and tremor. Among the socioeconomic factors, only % gross domestic product (GDP) for research and development showed a positive correlation on the number of publications of a country. On the other hand, GDP per capita, population size and the number of neurologist size did not affect research productivity. CONCLUSIONS: An increasing trend in the movement disorders research output over the last 20 years was seen. Singapore had the highest contribution in all aspects which highlights the impact of economy in research productivity. Among the socioeconomic factors, only % GDP for R&D showed a positive impact on the number of publications of a country.

Thrombolysis Outcomes in Patients with Diabetes and Previous Stroke: A Meta-Analysis.

BACKGROUND: Intravenous tissue-type plasminogen activator (IVtPA) is a proven treatment for acute ischemic stroke; however, diabetes mellitus (DM) and previous cerebral infarction (PCI) were considered relative contraindications for thrombolysis within the 3-4.5 h period. OBJECTIVE: The study aimed to determine the safety and efficacy of IVtPA among diabetic patients with PCI presenting with acute ischemic stroke. METHODS: Studies which evaluated the outcome of IVtPA in terms of symptomatic intracerebral hemorrhage (sICH), functional outcome in modified Rankin scale, and death among diabetic patients with PCI presenting with acute ischemic stroke within the 3-4.5 h period were systematically searched until July 2019. Screening and eligibility criteria were applied. Risk of bias was evaluated using the Newcastle-Ottawa Scale. Odds ratios (ORs) with 95% confidence interval (CI) were used to compare measures of treatment effect. Mantel-Haenszel method and random-effects model were also employed. RESULTS: Four registry-based studies with a total of 44,572 patients were included for quantitative synthesis. Giving IVtPA among DM+/PCI+ patients did not result in significantly increased rate of sICH (OR, 1.09; 95% CI, 0.88, 1.36) compared to No DM+/PCI+ patients. However, there was significantly higher mortality (OR, 1.81; 95% CI, 1.60, 2.06) in the DM+/PCI+ group. Conversely, among those who survived, the DM+/PCI+ patients were more functionally independent at 3 months (OR, 0.76; 95% CI, 0.61, 0.94). CONCLUSION: Limited evidence suggests that thrombolysis in DM+/PCI+ patients does not result in significantly higher incidence of sICH and may improve functional independence. However, the significantly higher mortality in this group warrants an assessment of the individualized risk-benefit ratio in the use of IVtPA.

Efficacy and safety of extended-release amantadine in levodopa-induced dyskinesias: a meta-analysis.

Aim: To determine the effectiveness and safety of extended-release amantadine (ADS-5102) for levodopa-induced dyskinesias (LID) in patients with Parkinson disease (PD) by conducting a meta-analysis of relevant trials. Methods: The electronic databases were searched on or before March 1, 2019 for relevant trials. Only randomized, double-blind, parallel-group, placebo-controlled trials using ADS-5102 for LID in PD were included. Results: The ADS-5102 showed a reduction in the dyskinesia scores (mean difference: -9.56: CI: -10.05 to -9.07; p < 0.00001) and in the on time without troublesome dyskinesia (mean difference 2.50: CI 2.38 to 2.63; p < 0.00001). The adverse events identified in ADS-5102 were visual hallucinations, constipation, dry mouth and fall. Conclusion: ADS-5102 can be used as an adjunct therapy for LID.