Pub Date : 2024-09-13eCollection Date: 2024-01-01DOI: 10.1177/11795735241260563
Erwan Muros-Le Rouzic, Yanic Heer, Sean Yiu, Viola Tozzi, Stefan Braune, Philip van Hövell, Arnfin Bergmann, Corrado Bernasconi, Fabian Model, Licinio Craveiro
Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking.
Objectives: To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data.
Methods: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied.
Results: The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts.
Conclusion: OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS.
Registration: OPERA I (NCT01247324), OPERA II (NCT01412333).
背景:在复发性多发性硬化症(RMS)中,目前尚缺乏比较奥克立珠单抗(OCR)与干扰素(IFN)β-1a以外的其他疾病修饰疗法(DMTs)疗效的临床试验:结合临床试验和实际数据,比较OCR与六种DMTs(IFN β-1a、醋酸格拉替雷、芬戈莫德、富马酸二甲酯、特利氟胺、纳他珠单抗)在临床实践中的治疗效果:方法:利用OPERA试验和开放标签扩展阶段的患者水平数据,以及德国NeuroTransData(NTD)多发性硬化症登记处的数据,建立1:1倾向得分匹配(PSM)队列,控制包括脑成像活动在内的7个基线协变量。疗效结果为首次复发时间和随访5.5年的24周确诊残疾进展时间。无论治疗转换与否,均使用所有结果数据进行意向治疗分析:分析对象包括 611 名 OPERA 患者和 7141 名 NTD 患者。我们建立了 12 个配对队列(每种结果 6 个队列,每种 DMT 2 个队列),以比较 OPERA 中 OCR 与 NTD 中每种 DMT 治疗途径的疗效。配对后,基线协变量和PS达到了很好的平衡(标准化平均差结论):在 5.5 年的时间里,与现实世界的治疗路径相比,OCR 在控制 RMS 复发和残疾进展方面更具优势。这些分析表明,高疗效 DMTs 和高治疗持续性是 RMS 获得最大临床获益的关键:Opera I (NCT01247324)、Opera II (NCT01412333)。
{"title":"Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments.","authors":"Erwan Muros-Le Rouzic, Yanic Heer, Sean Yiu, Viola Tozzi, Stefan Braune, Philip van Hövell, Arnfin Bergmann, Corrado Bernasconi, Fabian Model, Licinio Craveiro","doi":"10.1177/11795735241260563","DOIUrl":"https://doi.org/10.1177/11795735241260563","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking.</p><p><strong>Objectives: </strong>To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data.</p><p><strong>Methods: </strong>Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied.</p><p><strong>Results: </strong>The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts.</p><p><strong>Conclusion: </strong>OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS.</p><p><strong>Registration: </strong>OPERA I (NCT01247324), OPERA II (NCT01412333).</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03eCollection Date: 2024-01-01DOI: 10.1177/11795735241280805
Ying Lou
{"title":"Unlocking the code for stroke treatment and care.","authors":"Ying Lou","doi":"10.1177/11795735241280805","DOIUrl":"10.1177/11795735241280805","url":null,"abstract":"","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.1177/11795735241274186
Aditya Chanpura, Rajesh K Gupta, Shitiz K Sriwastava, Jan Rahmig
Background: Neurosarcoidosis is an inflammatory granulomatous disease. Up to 25% of occult sarcoidosis affecting the nervous system are only detected by autopsy. In addition, in recent years the suspicion arose that the soluble Interleukin-2 Receptor (sIL-2R) might be useful in differentiating between neurosarcoidosis and neurosarcoidosis-like diseases such as neurotuberculosis, multiple sclerosis, or cerebral lymphoma.
Objectives: Therefore, we aimed to systematically review randomized controlled trials (RCT), observational studies, and case-control studies evaluating sIL-2R levels in neurosarcoidosis patients.
Design: For this systematic review, a comprehensive literature search of electronic databases including EMBASE, The Web Of Science, The Cochrane Library, MEDLINE, and Google Scholar was conducted. The search was limited to the English language and publication date up to January 08th, 2024.
Data sources and methods: As part of the search strategy conducted, 6 articles met the inclusion criteria. Two independent reviewers extracted the relevant data from each article. In addition, 2 independent reviewers assessed the quality of each study using the Newcastle-Ottawa Scale (NOS).
Results: We included 6 studies comprising 98 patients suffering from neurosarcoidosis, 525 non-sarcoidosis patients, and 118 healthy controls. Included studies were published between 2010 and 2023. Cerebrospinal fluid (CSF) sIL-2R levels differed significantly between neurosarcoidosis patients and multiple sclerosis, vasculitis, and healthy controls whereas serum sIL-2R levels did not reveal sufficient discriminative power. sIL-2R index was able to discriminate neurosarcoidosis from neurotuberculosis, bacterial/viral meningitis, and healthy controls.
Conclusions: In this systematic review, we found indications that sIL-2R may be a useful biomarker for the diagnosis of neurosarcoidosis. To determine an additional diagnostic value of sIL-2R, large prospective studies are needed that not only examine absolute sIL-2R levels in serum or CSF but also the dynamic changes as well as the implications of renal function on sIL-2R levels.
{"title":"Diagnostic value of soluble Interleukin-2 receptor in patients suffering neurosarcoidosis: A systematic review.","authors":"Aditya Chanpura, Rajesh K Gupta, Shitiz K Sriwastava, Jan Rahmig","doi":"10.1177/11795735241274186","DOIUrl":"10.1177/11795735241274186","url":null,"abstract":"<p><strong>Background: </strong>Neurosarcoidosis is an inflammatory granulomatous disease. Up to 25% of occult sarcoidosis affecting the nervous system are only detected by autopsy. In addition, in recent years the suspicion arose that the soluble Interleukin-2 Receptor (sIL-2R) might be useful in differentiating between neurosarcoidosis and neurosarcoidosis-like diseases such as neurotuberculosis, multiple sclerosis, or cerebral lymphoma.</p><p><strong>Objectives: </strong>Therefore, we aimed to systematically review randomized controlled trials (RCT), observational studies, and case-control studies evaluating sIL-2R levels in neurosarcoidosis patients.</p><p><strong>Design: </strong>For this systematic review, a comprehensive literature search of electronic databases including EMBASE, The Web Of Science, The Cochrane Library, MEDLINE, and Google Scholar was conducted. The search was limited to the English language and publication date up to January 08<sup>th,</sup> 2024.</p><p><strong>Data sources and methods: </strong>As part of the search strategy conducted, 6 articles met the inclusion criteria. Two independent reviewers extracted the relevant data from each article. In addition, 2 independent reviewers assessed the quality of each study using the Newcastle-Ottawa Scale (NOS).</p><p><strong>Results: </strong>We included 6 studies comprising 98 patients suffering from neurosarcoidosis, 525 non-sarcoidosis patients, and 118 healthy controls. Included studies were published between 2010 and 2023. Cerebrospinal fluid (CSF) sIL-2R levels differed significantly between neurosarcoidosis patients and multiple sclerosis, vasculitis, and healthy controls whereas serum sIL-2R levels did not reveal sufficient discriminative power. sIL-2R index was able to discriminate neurosarcoidosis from neurotuberculosis, bacterial/viral meningitis, and healthy controls.</p><p><strong>Conclusions: </strong>In this systematic review, we found indications that sIL-2R may be a useful biomarker for the diagnosis of neurosarcoidosis. To determine an additional diagnostic value of sIL-2R, large prospective studies are needed that not only examine absolute sIL-2R levels in serum or CSF but also the dynamic changes as well as the implications of renal function on sIL-2R levels.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19eCollection Date: 2024-01-01DOI: 10.1177/11795735241271675
Sarojini Bulbule, Carl Gunnar Gottschalk, Molly E Drosen, Daniel Peterson, Leggy A Arnold, Avik Roy
Background: Tetrahydrobiopterin (BH4) and its oxidized derivative dihydrobiopterin (BH2) were found to be strongly elevated in ME/CFS patients with orthostatic intolerance (ME + OI).
Objective: However, the molecular mechanism of biopterin biogenesis is poorly understood in ME + OI subjects. Here, we report that the activation of the non-oxidative pentose phosphate pathway (PPP) plays a critical role in the biogenesis of biopterins (BH4 and BH2) in ME + OI subjects.
Research design and results: Microarray-based gene screening followed by real-time PCR-based validation, ELISA assay, and finally enzyme kinetic studies of glucose-6-phosphate dehydrogenase (G6PDH), transaldolase (TALDO1), and transketolase (TK) enzymes revealed that the augmentation of anaerobic PPP is critical in the regulations of biopterins. To further investigate, we devised a novel cell culture strategy to induce non-oxidative PPP by treating human microglial cells with ribose-5-phosphate (R5P) under a hypoxic condition of 85%N2/10%CO2/5%O2 followed by the analysis of biopterin metabolism via ELISA, immunoblot, and dual immunocytochemical analyses. Moreover, the siRNA knocking down of the taldo1 gene strongly inhibited the bioavailability of phosphoribosyl pyrophosphate (PRPP), reduced the expressions of purine biosynthetic enzymes, attenuated GTP cyclohydrolase 1 (GTPCH1), and suppressed subsequent production of BH4 and its metabolic conversion to BH2 in R5P-treated and hypoxia-induced C20 human microglia cells. These results confirmed that the activation of non-oxidative PPP is indeed required for the upregulation of both BH4 and BH2 via the purine biosynthetic pathway. To test the functional role of ME + OI plasma-derived biopterins, exogenously added plasma samples of ME + OI plasma with high BH4 upregulated inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in human microglial cells indicating that the non-oxidative PPP-induced-biopterins could stimulate inflammatory response in ME + OI patients.
Conclusion: Taken together, our current research highlights that the induction of non-oxidative PPP regulates the biogenesis of biopterins contributing to ME/CFS pathogenesis.
背景:四氢生物蝶呤(BH4)及其氧化衍生物双氢生物蝶呤(BH2)在伴有正性静力性不耐受(ME + OI)的ME/CFS患者中明显升高。在此,我们报告了非氧化磷酸戊糖途径(PPP)的激活在 ME + OI 患者生物蝶呤(BH4 和 BH2)的生物生成过程中起着关键作用:微阵列基因筛选、实时 PCR 验证、ELISA 检测以及葡萄糖-6-磷酸脱氢酶 (G6PDH)、反式脱氢酶 (TALDO1) 和反式酮化酶 (TK) 的酶动力学研究表明,厌氧磷酸戊糖途径 (PPP) 的增强在生物蝶呤的生成过程中起着关键作用。为了进一步研究,我们设计了一种新的细胞培养策略,在85%N2/10%CO2/5%O2的缺氧条件下,用核糖-5-磷酸(R5P)处理人小胶质细胞,诱导非氧化性PPP,然后通过ELISA、免疫印迹和双重免疫细胞化学分析分析生物蝶呤的代谢。此外,在 R5P 处理和缺氧诱导的 C20 人小胶质细胞中,siRNA 敲除 taldo1 基因可强烈抑制磷酸核糖基焦磷酸盐(PRPP)的生物利用率,降低嘌呤生物合成酶的表达,减弱 GTP 环化酶 1(GTPCH1),抑制 BH4 的后续产生及其向 BH2 的代谢转化。这些结果证实,通过嘌呤生物合成途径上调 BH4 和 BH2 确实需要激活非氧化性 PPP。为了测试 ME + OI 血浆衍生生物蝶呤的功能作用,外源添加了高 BH4 的 ME + OI 血浆样本可上调人小胶质细胞中的诱导型一氧化氮合酶(iNOS)和一氧化氮(NO),这表明非氧化性 PPP 诱导的生物蝶呤可刺激 ME + OI 患者的炎症反应:综上所述,我们目前的研究强调,非氧化性 PPP 诱导调节生物蝶呤的生物生成,有助于 ME/CFS 的发病机制。
{"title":"Dysregulation of tetrahydrobiopterin metabolism in myalgic encephalomyelitis/chronic fatigue syndrome by pentose phosphate pathway.","authors":"Sarojini Bulbule, Carl Gunnar Gottschalk, Molly E Drosen, Daniel Peterson, Leggy A Arnold, Avik Roy","doi":"10.1177/11795735241271675","DOIUrl":"10.1177/11795735241271675","url":null,"abstract":"<p><strong>Background: </strong>Tetrahydrobiopterin (BH4) and its oxidized derivative dihydrobiopterin (BH2) were found to be strongly elevated in ME/CFS patients with orthostatic intolerance (ME + OI).</p><p><strong>Objective: </strong>However, the molecular mechanism of biopterin biogenesis is poorly understood in ME + OI subjects. Here, we report that the activation of the non-oxidative pentose phosphate pathway (PPP) plays a critical role in the biogenesis of biopterins (BH4 and BH2) in ME + OI subjects.</p><p><strong>Research design and results: </strong>Microarray-based gene screening followed by real-time PCR-based validation, ELISA assay, and finally enzyme kinetic studies of glucose-6-phosphate dehydrogenase (G6PDH), transaldolase (TALDO1), and transketolase (TK) enzymes revealed that the augmentation of anaerobic PPP is critical in the regulations of biopterins. To further investigate, we devised a novel cell culture strategy to induce non-oxidative PPP by treating human microglial cells with ribose-5-phosphate (R5P) under a hypoxic condition of 85%N<sub>2</sub>/10%CO<sub>2</sub>/5%O<sub>2</sub> followed by the analysis of biopterin metabolism via ELISA, immunoblot, and dual immunocytochemical analyses. Moreover, the siRNA knocking down of the <i>taldo1</i> gene strongly inhibited the bioavailability of phosphoribosyl pyrophosphate (PRPP), reduced the expressions of purine biosynthetic enzymes, attenuated GTP cyclohydrolase 1 (GTPCH1), and suppressed subsequent production of BH4 and its metabolic conversion to BH2 in R5P-treated and hypoxia-induced C20 human microglia cells. These results confirmed that the activation of non-oxidative PPP is indeed required for the upregulation of both BH4 and BH2 via the purine biosynthetic pathway. To test the functional role of ME + OI plasma-derived biopterins, exogenously added plasma samples of ME + OI plasma with high BH4 upregulated inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in human microglial cells indicating that the non-oxidative PPP-induced-biopterins could stimulate inflammatory response in ME + OI patients.</p><p><strong>Conclusion: </strong>Taken together, our current research highlights that the induction of non-oxidative PPP regulates the biogenesis of biopterins contributing to ME/CFS pathogenesis.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16eCollection Date: 2024-01-01DOI: 10.1177/11795735241274203
Nur Shairah Mohamad Faizal, Juen Kiem Tan, Michelle Maryanne Tan, Ching Soong Khoo, Siti Zaleha Sahibulddin, Nursyazwana Zolkafli, Rozita Hod, Hui Jan Tan
Background: Delirium is a prevalent yet underdiagnosed disorder characterized by acute cognitive impairment. Various screening tools are available, including the Confusion Assessment Method (CAM) and 4 A's test (4AT). However, the results of these assessments may vary among raters. Therefore, we investigated the objective use of electroencephalography (EEG) in delirium and its clinical associations and predictive value.
Method: This cross-sectional observational study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan, Malaysia, from April 2021 to April 2023. This study included patients aged ≥18 years with a preliminary diagnosis of delirium. Demographic and clinical data were collected along with EEG recordings evaluated by certified neurologists to classify abnormalities and compare the associated factors between patients with delirium with or without EEG abnormalities.
Results: One hundred and twenty patients were recruited, with 80.0% displaying EEG abnormalities, mostly generalized slowing (moderate to severe) and primarily generalized slowing (mild to severe), and were characterized by theta activity. Age was significantly associated with EEG abnormalities, with patients aged 75 and older demonstrating the highest incidence (88.2%). The CAM scores were strongly correlated with EEG abnormalities (r = 0.639, P < 0.001) and was a predictor of EEG abnormalities (P < 0.012), indicating that EEG can complement clinical assessments for delirium. The Richmond Agitation and Sedation Scale (RASS) scores (r = -0.452, P < 0.001) and Barthel index (BI) (r = -0.582, P < 0.001) were negatively correlated with EEG abnormalities. Additionally, a longer hospitalization duration was associated with EEG abnormalities (r = 0.250, P = 0.006) and emerged as a predictor of such changes (P = 0.030).
Conclusion: EEG abnormalities are prevalent in patients with delirium, particularly in elderly patients. CAM scores and the duration of hospitalization are valuable predictors of EEG abnormalities. EEG can be an objective tool for enhancing delirium diagnosis and prognosis, thereby facilitating timely interventions.
{"title":"Electroencephalography as a tool for assessing delirium in hospitalized patients: A single-center tertiary hospital experience.","authors":"Nur Shairah Mohamad Faizal, Juen Kiem Tan, Michelle Maryanne Tan, Ching Soong Khoo, Siti Zaleha Sahibulddin, Nursyazwana Zolkafli, Rozita Hod, Hui Jan Tan","doi":"10.1177/11795735241274203","DOIUrl":"10.1177/11795735241274203","url":null,"abstract":"<p><strong>Background: </strong>Delirium is a prevalent yet underdiagnosed disorder characterized by acute cognitive impairment. Various screening tools are available, including the Confusion Assessment Method (CAM) and 4 A's test (4AT). However, the results of these assessments may vary among raters. Therefore, we investigated the objective use of electroencephalography (EEG) in delirium and its clinical associations and predictive value.</p><p><strong>Method: </strong>This cross-sectional observational study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan, Malaysia, from April 2021 to April 2023. This study included patients aged ≥18 years with a preliminary diagnosis of delirium. Demographic and clinical data were collected along with EEG recordings evaluated by certified neurologists to classify abnormalities and compare the associated factors between patients with delirium with or without EEG abnormalities.</p><p><strong>Results: </strong>One hundred and twenty patients were recruited, with 80.0% displaying EEG abnormalities, mostly generalized slowing (moderate to severe) and primarily generalized slowing (mild to severe), and were characterized by theta activity. Age was significantly associated with EEG abnormalities, with patients aged 75 and older demonstrating the highest incidence (88.2%). The CAM scores were strongly correlated with EEG abnormalities (r = 0.639, <i>P</i> < 0.001) and was a predictor of EEG abnormalities (<i>P</i> < 0.012), indicating that EEG can complement clinical assessments for delirium. The Richmond Agitation and Sedation Scale (RASS) scores (r = -0.452, <i>P</i> < 0.001) and Barthel index (BI) (r = -0.582, <i>P</i> < 0.001) were negatively correlated with EEG abnormalities. Additionally, a longer hospitalization duration was associated with EEG abnormalities (r = 0.250, <i>P</i> = 0.006) and emerged as a predictor of such changes (<i>P</i> = 0.030).</p><p><strong>Conclusion: </strong>EEG abnormalities are prevalent in patients with delirium, particularly in elderly patients. CAM scores and the duration of hospitalization are valuable predictors of EEG abnormalities. EEG can be an objective tool for enhancing delirium diagnosis and prognosis, thereby facilitating timely interventions.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically.
Objectives: Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown.
Methods: The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms.
Results: Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (P < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (P = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813).
Conclusion: DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.
{"title":"Deep cervical lymph nodes in Parkinson's disease and atypical Parkinson's disease: A potential ultrasound biomarker for differential diagnosis.","authors":"Zhaoying Dong, Xinyi Du, Ling Wang, Xiaoya Zou, Hongzhou Zuo, Yong Yan, Guojun Chen, Oumei Cheng, Yong Zhang","doi":"10.1177/11795735241259429","DOIUrl":"10.1177/11795735241259429","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically.</p><p><strong>Objectives: </strong>Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown.</p><p><strong>Design: </strong>Single-center retrospective cross-sectional study.</p><p><strong>Methods: </strong>The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms.</p><p><strong>Results: </strong>Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (<i>P</i> < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (<i>P</i> = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813).</p><p><strong>Conclusion: </strong>DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined.
Objective: To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow.
Methods: Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH.
Results: A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all P-values <0.05. After adjusting for other covariates, forward mean flow at ipsilateral infarction MCA is still associated with severe WMH independently, OR = 0.537, 95% CI (0.294, 0.981), P = 0.043.
Conclusion: Intracranial artery stenosis patients with coexisting severe WMH suffer from significantly decreased flow, which could explain the poor clinical outcome in this population, and also provide some insight into recanalization therapy in the future.
{"title":"Decreased flow in ischemic stroke with coexisting intracranial artery stenosis and white matter hyperintensities.","authors":"Xiaowei Song, Wenwen Chen, Xihai Zhao, Zhuozhao Zheng, Zhenhua Sang, Rui Li, Jian Wu","doi":"10.1177/11795735241266572","DOIUrl":"10.1177/11795735241266572","url":null,"abstract":"<p><strong>Background: </strong>Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined.</p><p><strong>Objective: </strong>To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow.</p><p><strong>Design: </strong>Single-center cross-sectional cohort study.</p><p><strong>Methods: </strong>Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH.</p><p><strong>Results: </strong>A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all <i>P</i>-values <0.05. After adjusting for other covariates, forward mean flow at ipsilateral infarction MCA is still associated with severe WMH independently, OR = 0.537, 95% CI (0.294, 0.981), <i>P</i> = 0.043.</p><p><strong>Conclusion: </strong>Intracranial artery stenosis patients with coexisting severe WMH suffer from significantly decreased flow, which could explain the poor clinical outcome in this population, and also provide some insight into recanalization therapy in the future.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24eCollection Date: 2024-01-01DOI: 10.1177/11795735241262743
Pavel Potuznik, Jiri Drahota, Dana Horakova, Marek Peterka, Aneta Mazouchova, David Matyas, Zbysek Pavelek, Marta Vachova, Eva Recmanova, Ivana Stetkarova, Jana Libertinova, Jan Mares, Pavel Stourac, Marketa Grunermelova, Alena Martinkova, Jana Adamkova, Pavel Hradilek, Radek Ampapa, Michal Dufek, Eva Kubala Havrdova, Dominika Stastna
Background: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS).
Objectives: Provide experience with cladribine therapy in a real-world setting.
Methods: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence.
Results: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%.
Conclusion: This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.
{"title":"Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry.","authors":"Pavel Potuznik, Jiri Drahota, Dana Horakova, Marek Peterka, Aneta Mazouchova, David Matyas, Zbysek Pavelek, Marta Vachova, Eva Recmanova, Ivana Stetkarova, Jana Libertinova, Jan Mares, Pavel Stourac, Marketa Grunermelova, Alena Martinkova, Jana Adamkova, Pavel Hradilek, Radek Ampapa, Michal Dufek, Eva Kubala Havrdova, Dominika Stastna","doi":"10.1177/11795735241262743","DOIUrl":"10.1177/11795735241262743","url":null,"abstract":"<p><strong>Background: </strong>Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS).</p><p><strong>Objectives: </strong>Provide experience with cladribine therapy in a real-world setting.</p><p><strong>Methods: </strong>This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence.</p><p><strong>Results: </strong>In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%.</p><p><strong>Conclusion: </strong>This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-21eCollection Date: 2024-01-01DOI: 10.1177/11795735241266556
Hanna Lu, Jing Li
Background: Brain age model, including estimated brain age and brain-predicted age difference (brain-PAD), has shown great potentials for serving as imaging markers for monitoring normal ageing, as well as for identifying the individuals in the pre-diagnostic phase of neurodegenerative diseases.
Purpose: This study aimed to investigate the brain age models in normal ageing and mild cognitive impairments (MCI) converters and their values in classifying MCI conversion.
Methods: Pre-trained brain age model was constructed using the structural magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project (N = 609). The tested brain age model was built using the baseline, 1-year and 3-year follow-up MRI data from normal ageing (NA) adults (n = 32) and MCI converters (n = 22) drew from the Open Access Series of Imaging Studies (OASIS-2). The quantitative measures of morphometry included total intracranial volume (TIV), gray matter volume (GMV) and cortical thickness. Brain age models were calculated based on the individual's morphometric features using the support vector machine (SVM) algorithm.
Results: With comparable chronological age, MCI converters showed significant increased TIV-based (Baseline: P = 0.021; 1-year follow-up: P = 0.037; 3-year follow-up: P = 0.001) and left GMV-based brain age than NA adults at all time points. Higher brain-PAD scores were associated with worse global cognition. Acceptable classification performance of TIV-based (AUC = 0.698) and left GMV-based brain age (AUC = 0.703) was found, which could differentiate the MCI converters from NA adults at the baseline.
Conclusions: This is the first demonstration that MRI-informed brain age models exhibit feature-specific patterns. The greater GMV-based brain age observed in MCI converters may provide new evidence for identifying the individuals at the early stage of neurodegeneration. Our findings added value to existing quantitative imaging markers and might help to improve disease monitoring and accelerate personalized treatments in clinical practice.
{"title":"MRI-informed machine learning-driven brain age models for classifying mild cognitive impairment converters.","authors":"Hanna Lu, Jing Li","doi":"10.1177/11795735241266556","DOIUrl":"https://doi.org/10.1177/11795735241266556","url":null,"abstract":"<p><strong>Background: </strong>Brain age model, including estimated brain age and brain-predicted age difference (brain-PAD), has shown great potentials for serving as imaging markers for monitoring normal ageing, as well as for identifying the individuals in the pre-diagnostic phase of neurodegenerative diseases.</p><p><strong>Purpose: </strong>This study aimed to investigate the brain age models in normal ageing and mild cognitive impairments (MCI) converters and their values in classifying MCI conversion.</p><p><strong>Methods: </strong>Pre-trained brain age model was constructed using the structural magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project (N = 609). The tested brain age model was built using the baseline, 1-year and 3-year follow-up MRI data from normal ageing (NA) adults (n = 32) and MCI converters (n = 22) drew from the Open Access Series of Imaging Studies (OASIS-2). The quantitative measures of morphometry included total intracranial volume (TIV), gray matter volume (GMV) and cortical thickness. Brain age models were calculated based on the individual's morphometric features using the support vector machine (SVM) algorithm.</p><p><strong>Results: </strong>With comparable chronological age, MCI converters showed significant increased TIV-based (Baseline: <i>P</i> = 0.021; 1-year follow-up: <i>P</i> = 0.037; 3-year follow-up: <i>P</i> = 0.001) and left GMV-based brain age than NA adults at all time points. Higher brain-PAD scores were associated with worse global cognition. Acceptable classification performance of TIV-based (AUC = 0.698) and left GMV-based brain age (AUC = 0.703) was found, which could differentiate the MCI converters from NA adults at the baseline.</p><p><strong>Conclusions: </strong>This is the first demonstration that MRI-informed brain age models exhibit feature-specific patterns. The greater GMV-based brain age observed in MCI converters may provide new evidence for identifying the individuals at the early stage of neurodegeneration. Our findings added value to existing quantitative imaging markers and might help to improve disease monitoring and accelerate personalized treatments in clinical practice.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19eCollection Date: 2024-01-01DOI: 10.1177/11795735241266601
Sandeep K Subramanian, Riley T Morgan, Carl Rasmusson, Kayla M Shepherd, Carol L Li
Background: Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val66met, met66met; COMT:val158met; met158met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated.
Objective: Examine the influence of genetic polymorphism on post-stroke UL motor improvement.
Design: Systematic Review and Meta-Analysis.
Methods: We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41).
Results: We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val66met and met66met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val158met or met158met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement.
Conclusion: Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement.
{"title":"Genetic polymorphisms and post-stroke upper limb motor improvement - A systematic review and meta-analysis.","authors":"Sandeep K Subramanian, Riley T Morgan, Carl Rasmusson, Kayla M Shepherd, Carol L Li","doi":"10.1177/11795735241266601","DOIUrl":"https://doi.org/10.1177/11795735241266601","url":null,"abstract":"<p><strong>Background: </strong>Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val<sup>66</sup>met, met<sup>66</sup>met; COMT:val<sup>158</sup>met; met<sup>158</sup>met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated.</p><p><strong>Objective: </strong>Examine the influence of genetic polymorphism on post-stroke UL motor improvement.</p><p><strong>Design: </strong>Systematic Review and Meta-Analysis.</p><p><strong>Methods: </strong>We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41).</p><p><strong>Results: </strong>We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val<sup>66</sup>met and met<sup>66</sup>met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val<sup>158</sup>met or met<sup>158</sup>met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement.</p><p><strong>Conclusion: </strong>Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement.</p><p><strong>Registration: </strong>https://osf.io/wk9cf/.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}