Parkinsonism & related disorders最新文献

{"title":"Genetic heterogeneity of early onset Parkinson disease: The dilemma of clinico-genetic correlation.","authors":"Roopa Rajan, Vikram V Holla, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal","doi":"10.1016/j.parkreldis.2024.107146","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2024.107146","url":null,"abstract":"<p><p>With advances in genetic testing increasing proportion of early onset Parkinson disease (EOPD) are being identified to have an underlying genetic aetiology. This is can be in the form of either highly penetrant genes associated with phenotypes with monogenic or mendelian inheritance patterns or those genes known as risk factor genes which confer an increased risk of PD in an individual. Both of them can modify the phenotypic manifestation in a patient with PD. This improved knowledge has helped in deciphering the intricate role of various cellular pathways in the pathophysiology of PD including both early and late and even sporadic PD. However, the phenotypic and genotypic heterogeneity is a major challenge. Different deleterious alterations in a same gene can result in a spectrum of presentation spanning from juvenile to late onset and typical to atypical parkinsonism manifestation. Similarly, a single phenotype can occur due to abnormality in two or more different genes. This conundrum poses a dilemma in the clinical approach and in understanding the clinico-genetic correlation. Understanding the clinico-genetic correlation carries even more importance especially when genetic testing is either not accessible or affordable or in many regions both. In this narrative review, we aim to discuss briefly the approach to various PARK gene related EOPD and describe in detail the clinico-genetic correlation of individual type of PARK gene related genetic EOPD with respect to their classical clinical presentation, pathophysiology, investigation findings and treatment response to medication and surgery.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107146"},"PeriodicalIF":3.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of tremor-modulating effects of primidone and propranolol in essential tremor","authors":"Katarina Vogelnik Žakelj ,&nbsp;Neža Prezelj ,&nbsp;Milica Gregorič Kramberger ,&nbsp;Maja Kojović","doi":"10.1016/j.parkreldis.2024.107151","DOIUrl":"10.1016/j.parkreldis.2024.107151","url":null,"abstract":"<div><h3>Introduction</h3><div>Primidone and propranolol are primary treatments for essential tremor, however the exact mechanisms underlying their efficacy are not fully elucidated. Understanding how these medications alleviate tremor may guide the development of additional pharmacologic treatments. Our prospective observational study employed transcranial magnetic stimulation (TMS) to explore mechanisms of primidone and propranolol effects in essential tremor. Eyeblink classical conditioning (EBCC) was tested as a potential predictor of treatment response.</div></div><div><h3>Methods</h3><div>Patients with essential tremor underwent two evaluations: prior to commencing primidone or propranolol and following a minimum of three months of treatment. Tremor severity was assessed using accelerometry and clinically. TMS was employed to study changes in corticospinal excitability - resting and active motor thresholds, resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short interval intracortical inhibition intensity curve (SICI), long interval intracortical inhibition (LICI), intracortical facilitation (ICF), and short afferent inhibition (SAI). EBCC, a marker of cerebellar function, was studied at baseline.</div></div><div><h3>Results</h3><div>Of the 54 enrolled patients (28 primidone, 26 propranolol), 35 completed both visits. Primidone effect on decreasing hand tremor was associated with decreased corticospinal excitability, prolongation of CSP, increased LICI, increased SAI and decreased SICI. Propranolol effect on hand tremor was associated with decreased corticospinal excitability and increased SAI. Better EBCC at baseline predicted better response to primidone.</div></div><div><h3>Conclusions</h3><div>Primidone exerts its therapeutic effects by blocking voltage-gated sodium channels and by modulating GABA-A and GABA-B intracortical circuits. Propranolol's central effects are likely mediated via noradrenergic modulation of GABA outflow.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107151"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1353802024011635/pdfft?md5=7a924fd04f5bacba5de19fc6195c5673&pid=1-s2.0-S1353802024011635-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of early-onset Parkinson disease (EOPD) worldwide: East versus west.","authors":"Aaron Shengting Mai, Xiao Deng, Eng-King Tan","doi":"10.1016/j.parkreldis.2024.107126","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2024.107126","url":null,"abstract":"<p><p>Parkinson disease (PD) is characterized by the presence of bradykinesia with either rest tremor, muscle rigidity, or postural instability. If the features for PD are present but the age at onset (AAO) is before the usual but later than 21 years of age, it is considered as early-onset PD (EOPD). With Eastern countries projected to account for over 60 % of the world's population, it is paramount to understand the differences in EOPD between Western and Eastern countries. Epidemiology can differ substantially between the East and West, such as China showing a much steeper rise in EOPD prevalence and incidence with age, or Japan and Korea showing a female predominance in EOPD for certain age groups. Symptomatology appears to be similar across Western and Eastern populations, though some Eastern populations may have a higher prevalence of the akinetic-rigid or postural instability/gait difficulty motor phenotypes. Genetic epidemiology, conversely, varies significantly between the East and West, though some genes are frequently implicated in both (such as LRRK2, PINK1, PRKN, and GBA). Next, treatment patterns also exhibit substantial geographical variation, which could be driven by local availability of medications, adequacy of staff training and infrastructure, and local regulatory bodies. Lastly, regardless of region, EOPD exerts a profound psychosocial impact on patients, such as strained relationships, unemployment, and psychological distress. In summary, understanding these differences (and similarities) between the East and West could help generate innovative solutions, while the development of healthy habits and robust social networks should also be actively encouraged in all patients.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107126"},"PeriodicalIF":3.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Causal associations of physical activity and leisure sedentary behaviors with age at onset of Huntington's disease: A Mendelian randomization study.","authors":"Ross Allan Clark","doi":"10.1016/j.parkreldis.2024.107131","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2024.107131","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107131"},"PeriodicalIF":3.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality in elderly Parkinson's disease patients with long-term care needs: A nationwide population-based study in Korea","authors":"Seung Hyun Lee ,&nbsp;Mina Kim ,&nbsp;Woon Chang Heo ,&nbsp;Joong-Goo Kim ,&nbsp;Jung Seok Lee ,&nbsp;Ji Hoon Kang ,&nbsp;Jooyoung Lee","doi":"10.1016/j.parkreldis.2024.107150","DOIUrl":"10.1016/j.parkreldis.2024.107150","url":null,"abstract":"<div><h3>Background</h3><p>The effects of long-term care insurance (LTCI) in reducing medical costs and utilization among older adults have been reported. This study aims to investigate the mortality in patients with Parkinson's disease (PD) requiring LTCI and its relationships with economic status.</p></div><div><h3>Methods</h3><p>This study was conducted using the database of the Korean National Health Insurance Service (NHIS)-Senior Cohort between 2008 and 2019. A total of 5937 patients with PD were included. Hazard ratios (HRs) of mortality associated with LTCI were estimated using a Cox regression model. Potential confounders such as demographics and comorbidities were adjusted.</p></div><div><h3>Results</h3><p>Out of 5937 PD patients, 821 required LTCI, and 5116 did not. Compared to PD patients without LTCI, PD patients with LTCI were older and exhibited a higher comorbidity burden. The overall incidence rate of mortality was 18.63 per 100 person-years in PD patients with LTCI. PD patients requiring LTCI were associated with an increased HR of 3.61 (95 % CI = 3.13–4.16) for mortality compared to PD patients not eligible for LTCI. Low-income status with LTCI was associated with the highest mortality risk (HR = 4.54, 95 % CI = 3.38–6.09), compared to middle-income status (HR = 3.47, 95 % CI = 2.64–4.61) and high-income status (HR = 3.53, 95 % CI = 2.91–4.91).</p></div><div><h3>Conclusions</h3><p>Our study suggests that older PD patients requiring LTCI with low economic status have a higher risk of death. Continuous policy efforts to reduce the mortality risk in this group are needed.</p></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107150"},"PeriodicalIF":3.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis with DNMT3A mutations is associated with multiple system atrophy","authors":"Seungmin Lee ,&nbsp;Han-Joon Kim ,&nbsp;Seoyeon Kim ,&nbsp;Bora Jin ,&nbsp;HoYoung Jeon ,&nbsp;Kyung Ah Woo ,&nbsp;Jung Hwan Shin ,&nbsp;Chansub Lee ,&nbsp;Choonghyun Sun ,&nbsp;Hogune Im ,&nbsp;Hongyul An ,&nbsp;Young Il Koh ,&nbsp;Su-Yeon Choi ,&nbsp;Beomseok Jeon","doi":"10.1016/j.parkreldis.2024.107145","DOIUrl":"10.1016/j.parkreldis.2024.107145","url":null,"abstract":"<div><h3>Background</h3><p>Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular diseases and other disorders, possibly via inflammation. Recent research suggests a connection of CHIP with neurodegenerative disorders.</p></div><div><h3>Objective</h3><p>We aimed to investigate the association between multiple system atrophy (MSA) and CHIP.</p></div><div><h3>Methods</h3><p>We included 100 patients with MSA and 4457 controls. Targeted sequencing of peripheral blood DNA samples was performed, focusing on a panel of 25 genes commonly.</p></div><div><h3>Linked to chip</h3><p>The prevalence of CHIP in patients with MSA was assessed against controls at variant allele frequency (VAF) thresholds of 1.5 % and 2.0 %.</p></div><div><h3>Results</h3><p>DNMT3A mutation rates were significantly higher in patients with MSA, with a VAF of 1.5 %, which remained significant after adjusting for age and sex (adjusted odds ratio, 1.848; 95 % CI, 1.024–3.335; p = 0.0416).</p></div><div><h3>Conclusion</h3><p>Our results suggest an association between DNMT3A mutations and MSA.</p></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107145"},"PeriodicalIF":3.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral thalamic glioblastoma presenting as parkinsonism: A case report","authors":"Daniel Mareček,&nbsp;Viktorie Kopecká,&nbsp;Radoslav Matěj,&nbsp;Ondřej Strýček","doi":"10.1016/j.parkreldis.2024.107147","DOIUrl":"10.1016/j.parkreldis.2024.107147","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107147"},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A useful cognitive motor dual task paradigm in prodromal and manifest Huntington’s disease","authors":"Emma Churchill ,&nbsp;Shelby Hughes ,&nbsp;Andrew Hall ,&nbsp;Braden Culbert ,&nbsp;Daniel J. Goble ,&nbsp;Jody Corey-Bloom ,&nbsp;Paul E. Gilbert","doi":"10.1016/j.parkreldis.2024.107119","DOIUrl":"10.1016/j.parkreldis.2024.107119","url":null,"abstract":"<div><h3>Introduction</h3><div>Individuals with Huntington's disease (HD) experience increased difficulty with balance throughout disease progression. Adding a simultaneous cognitive task to a balance assessment, referred to as a dual task (DT) paradigm, may have a deleterious effect on balance, which can be expressed in terms of a Dual Task Cost (DTC), relative to a single task (ST) condition. The aim of this study is to explore whether a cognitive-motor DT paradigm uncovers balance deficits in prodromal (Pro-HD) and manifest HD, compared to healthy adults (HA).</div></div><div><h3>Methods</h3><div>Balance under ST and DT conditions was examined using the BTracks Balance Plate and Balance software in 30 individuals with HD, 17 individuals with Pro-HD, and 20 HA. During the DT condition, participants were simultaneously administered a version of the Paced Auditory Serial Addition Test (PASAT). DTC is calculated as the relative ratio of ST to DT, controlling for ST performance: DTC= (ST − DT)/ST x100.</div></div><div><h3>Results</h3><div>The HA group performed significantly better than the HD group on both the ST and DT conditions (<em>p</em> &lt; 0.01), while balance scores between the HA and the Pro-HD groups were not significantly different. The DTC scores, however, were significantly better in the HA compared to both the HD (p &lt; 0.001) and Pro-HD (p &lt; 0.05) groups.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that the addition of a cognitive task interferes with participant's balance, reflecting real-life performance, and may have additional value for estimating transition to manifest disease, appraising fall risk, or serving as a valid outcome measure in observational and interventional trials in HD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107119"},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1353802024011313/pdfft?md5=610191a71fe05142942c7245a35df3ab&pid=1-s2.0-S1353802024011313-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative susceptibility mapping analyses of white matter in Parkinson's disease using susceptibility separation technique","authors":"Masahiro Nakashima ,&nbsp;Hirohito Kan ,&nbsp;Tatsuya Kawai ,&nbsp;Kazuhisa Matsumoto ,&nbsp;Takatsune Kawaguchi ,&nbsp;Yuto Uchida ,&nbsp;Noriyuki Matsukawa ,&nbsp;Akio Hiwatashi","doi":"10.1016/j.parkreldis.2024.107135","DOIUrl":"10.1016/j.parkreldis.2024.107135","url":null,"abstract":"<div><h3>Introduction</h3><p>To apply susceptibility separation on quantitative susceptibility mapping (QSM) images of Parkinson's disease (PD) patients to obtain more accurate images and gain pathophysiological insights.</p></div><div><h3>Methods</h3><p>This retrospective study included subjects who underwent head MRI, including QSM between March 2016 and March 2018. Patients with PD were categorized as having mild cognitive impairment (PD-MCI), or normal cognition (PD-CN); healthy controls (HC) were also enrolled. Susceptibility separation generated positive (QSM+) and negative susceptibility (QSM-) labels. Voxel-based whole-brain susceptibility and atlas-based susceptibility were compared among groups on white matter. Correlations between susceptibility and Montreal Cognitive Assessment (MoCA) scores were analyzed.</p></div><div><h3>Results</h3><p>Overall, 65 subjects (mean age 72 years ±6, 35 men) were included. White-matter regions with significant (<em>P</em> &lt; 0.05) group differences were found for QSM+ (HC &gt; PD-MCI, PD-CN &gt; PD-MCI) and QSM- (PD-MCI &gt; HC, PD-MCI &gt; PD-CN). In the atlas-based analyses, PD-MCI exhibited lower QSM + values (vs. HC; <em>P</em> = 0.002, vs. PD-CN; <em>P</em> = 0.001), and higher QSM-values (vs. HC; <em>P</em> = 0.02, vs. PD-CN; <em>P</em> = 0.03) in the genu of corpus callosum (gCC). QSM+ and QSM-showed significant positive and negative correlations with MoCA (<em>P</em> &lt; 0.05). In the gCC, partial correlation analyses revealed a positive correlation between QSM+ and MoCA (R = 0.458, <em>P</em> &lt; 0.001) and a negative correlation between QSM- and MoCA (R = −0.316, <em>P</em> = 0.01).</p></div><div><h3>Conclusion</h3><p>QSM utilizing susceptibility separation is valuable for assessing white matter in PD patients, where nerve fiber loss potentially influences cognitive function.</p></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107135"},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials","authors":"Haotian Zou ,&nbsp;Glenn T. Stebbins ,&nbsp;Tanya Simuni ,&nbsp;Sheng Luo ,&nbsp;Jesse M. Cedarbaum","doi":"10.1016/j.parkreldis.2024.107118","DOIUrl":"10.1016/j.parkreldis.2024.107118","url":null,"abstract":"<div><h3>Introduction</h3><div>Tracking of emergent symptoms (ES) in de novo Parkinson Disease (PD) patients using Parts Ib and II of the MDS-UPDRS rating scale has been proposed as an outcome measure for PD clinical trials, based on observations in the Safety, Tolerability and Efficacy Assessment of Isradipine for PD (STEADY-PD3) clinical trial.</div></div><div><h3>Methods</h3><div>Individual item-level data was extracted from the SURE-PD3 study (coded as “PD-1018” in the C-path pooled dataset). We sought to confirm the observations made in the STEADY-PD3 dataset by analyzing data from a different Phase 3 clinical trial, the Phase 3 Study of Urate Elevation in Parkinson Disease (SURE-PD3), in which MDS-UPDRS was assessed more frequently than the 12-month intervals in STEADY-PD3, using similar methodology.</div></div><div><h3>Results</h3><div>We were able to broadly validate results that demonstrated the frequency of ES, lack of impact of the introduction of symptomatic medications, and in the reduction in sample size required to demonstrate slowing of disease progression at a group level compared with the traditional total MDS-UPDRS summed score scoring methods. Counts of ES generally correlated modestly with summed MDS-UPRDS scores, both for the various sub-parts and for the overall scale as well. However, instability of individual item responses, especially during the first 6 months of observation complicated the assessment of the temporal evolution and stability of ES over time in the course of the SURE-PD3 study.</div></div><div><h3>Conclusion</h3><div>Further validation using data sets with frequent administration of MDS-UPDRS is necessary to assess value of this approach as an outcome measure in PD clinical trials.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107118"},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}