Parkinsonism & related disorders最新文献

{"title":"A new genetic variant, presenting as young onset rapidly progressive dementia and parkinsonism.","authors":"Negin Eissazade, Afagh Alavi, Anthony E Lang, Mohammad Rohani, Maziar Emamikhah, Tara Khoeini","doi":"10.1016/j.parkreldis.2023.105849","DOIUrl":"10.1016/j.parkreldis.2023.105849","url":null,"abstract":"<p><p>There are various neurodegenerative or hereditary causes of Parkinsonism. Therefore, clinicians should consider an increasing range of differential diagnoses when facing a patient with Parkinsonism, especially when associated with additional clinical features. Young-onset Parkinsonism, especially when accompanied by features uncommon in idiopathic Parkinson's disease raises the possibility of genetic etiology. Herein, we present a case of a 40-year-old man with genetic Parkinson's disease, presenting with rapidly progressive dementia. This round will describe our approach to this clinical presentation and the unveiling of a rare genetic condition.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133736","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":"The prospective role of mesenchymal stem cells in Parkinson's disease.","authors":"Pratima Tambe, Vaishali Undale, Avinash Sanap, Ramesh Bhonde, Nishant Mante","doi":"10.1016/j.parkreldis.2024.107087","DOIUrl":"10.1016/j.parkreldis.2024.107087","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a stressful neurodegenerative disorder affecting millions worldwide. PD leads to debilitating motor and cognitive symptoms such as tremors, rigidity, and difficulty walking. Current therapies for PD are symptomatic and don't address the root cause. Therefore, there is an urgent need for better management and intensive research into alternative therapies. Mesenchymal stem cell (MSC) therapy is among the leading contenders among these promising avenues. We examined preclinical and clinical evidence demonstrating the neuroprotective, anti-inflammatory, and regenerative properties of the MSCs. This review focuses on the complex pathophysiological mechanisms of PD, as well as the perspectives of MSCs and their derivatives, such as secretomes and exosomes, in the clinical management of PD. We also analyzed the challenges and limitations of each approach, including delivery methods, timing of administration, and long-term safety considerations.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982973","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":"Correlation between clinical and neuropathological subtypes of PSP: Do clinical symptoms reflect tau distribution?","authors":"Jee Bang, Alexander Pantelyat","doi":"10.1016/j.parkreldis.2024.107108","DOIUrl":"10.1016/j.parkreldis.2024.107108","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140775","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":"Correlation between clinical and neuropathological subtypes of progressive supranuclear palsy.","authors":"Ryuichi Koizumi, Akio Akagi, Yuichi Riku, Hiroaki Miyahara, Jun Sone, Fumiaki Tanaka, Mari Yoshida, Yasushi Iwasaki","doi":"10.1016/j.parkreldis.2024.106076","DOIUrl":"10.1016/j.parkreldis.2024.106076","url":null,"abstract":"<p><strong>Introduction: </strong>Progressive supranuclear palsy (PSP) is characterized by pathology prominently in the basal ganglia, the tegmentum of the brainstem, and the frontal cortex. However, pathology varies according to clinical features. This study aimed to statistically verify the correspondence between the clinical and pathological subtypes of PSP.</p><p><strong>Methods: </strong>We identified patients with a pathological diagnosis of PSP and classified the eight clinical subtypes of the Movement Disorders Society criteria for the clinical diagnosis of PSP (MDS-PSP criteria) into the Richardson, Akinesia, and Cognitive groups. We used anti-phosphorylated tau antibody immunostaining to semi-quantitatively evaluate neurofibrillary tangles (NFTs) and coiled bodies/threads (CB/Ths) in the globus pallidus, subthalamic nucleus, and midbrain tegmentum. In the frontal cortex, tufted astrocytes (TAs) and CB/Ths were assessed on a 3-point scale. We compared the pathology among the three groups, recorded the phenotypes ranked the second and lower in the multiple allocation extinction rule and examined whether the pathology changed depending on applying each phenotype.</p><p><strong>Results: </strong>The Richardson group exhibited severe NFTs and CB/Ths in the midbrain tegmentum. The Akinesia group showed severe NFTs in the globus pallidus. The Cognitive group had severe TAs and CB/Ths in the frontal cortex. TAs and CB/Ths in the frontal cortex correspond to behavioral variant frontotemporal dementia, and supranuclear vertical oculomotor palsy.</p><p><strong>Conclusion: </strong>These clinical symptoms may reflect the distribution of tau pathologies in PSP.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143998","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":"Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: A comparative study with tranylcypromine","authors":"","doi":"10.1016/j.parkreldis.2024.107158","DOIUrl":"10.1016/j.parkreldis.2024.107158","url":null,"abstract":"<div><div>Safinamide (SAF) is currently used to treat Parkinson's disease (PD) symptoms based on its theoretical ability to potentiate the dopamine (DA) signal, blocking monoamine oxidase (MAO) B. The present work aims to highlight the functional relevance of SAF as an enhancer of the DA signal, by evaluating its ability to prolong recovery from DA-mediated firing inhibition of DAergic neurons of the substantia nigra pars compacta (SNpc), compared to another MAO antagonist, tranylcypromine (TCP). Using multielectrode array (MEA) and single electrode extracellular recordings of spontaneous spikes from presumed SNpc DAergic cells <em>in vitro</em>, we show that SAF (30 μM) mildly prolongs the DA-mediated firing inhibition, as opposed to the profound effect of TCP (10 μM). In patch-clamp recordings, we found that SAF (30 μM) significantly reduced the number of spikes evoked by depolarizing currents in SNpc DAergic neurons, in a sulpiride (1 μM) independent manner. According to our results, SAF marginally potentiates the DA signal in SNpc DAergic neurons, while exerting an inhibitory effect on the postsynaptic excitability acting on membrane conductances. Thus, we propose that the therapeutic effects of SAF in PD patients partially depends on MAO inhibition, while other MAO-independent sites of action could be more relevant.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319162","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":"Revisiting sex-gender disparities in MSA: An unfinished narrative.","authors":"Alexandra Pérez-Soriano, Celia Painous, Barbara Segura, Maria José Martí","doi":"10.1016/j.parkreldis.2024.107159","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2024.107159","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351820","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":"Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk","authors":"","doi":"10.1016/j.parkreldis.2024.107153","DOIUrl":"10.1016/j.parkreldis.2024.107153","url":null,"abstract":"<div><h3>Introduction</h3><div>Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study.</div></div><div><h3>Methods</h3><div>We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume.</div></div><div><h3>Results</h3><div>During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81–2.18, P &lt; 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk.</div></div><div><h3>Conclusion</h3><div>In summary, we consider there to be a substantial correlation between anemia and increased PD risk.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311264","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":"Pediatric parkinsonism: In-depth clinical definition and semeiology.","authors":"Vincenzo Leuzzi, Maria Novelli, Ivana Paparella, Serena Galosi","doi":"10.1016/j.parkreldis.2024.107148","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2024.107148","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366199","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":"Movement disorders in Megalencephalic Leukoencephalopathy with subcortical cysts – A case series","authors":"","doi":"10.1016/j.parkreldis.2024.107152","DOIUrl":"10.1016/j.parkreldis.2024.107152","url":null,"abstract":"<div><h3>Background</h3><div>Megalencephalic leukoencephalopathy with subcortical cysts (MLC) has been described in the literature mostly as early-onset leukodystrophy with cerebellar ataxia being the main clinical phenotype. However, other associated movement disorders have also been reported discretely.</div></div><div><h3>Cases</h3><div>Here, we present seven cases of MLC. Cerebellar ataxia was common in them, while dystonia was present in six, parkinsonism in one and stereotypy in two. Six of them, belonging to the Agarwal community, had the common c.135dup variant.</div></div><div><h3>Conclusion</h3><div>Our observation highlights the presence of movement disorders in MLC beyond cerebellar ataxia and phenotypic variability of the c.135dup variant, prevalent in the Agarwal community.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319163","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":"Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes","authors":"","doi":"10.1016/j.parkreldis.2024.107127","DOIUrl":"10.1016/j.parkreldis.2024.107127","url":null,"abstract":"<div><h3>Background</h3><div>Heterozygous variants in the glucocerebrosidase (<em>GBA1</em>) gene are the most common genetic risk factor for Parkinson's Disease (PD). <em>GBA1</em>-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in <em>GBA1</em>-PD, are debated.</div></div><div><h3>Methods</h3><div>This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into <em>GBA1</em>-PD and non-<em>GBA1</em>-PD groups, with non-<em>GBA1</em>-PD further divided into cognitive <em>fast-progressors</em> and <em>slow-progressors</em>.</div></div><div><h3>Results</h3><div><em>GBA1</em> variants were present in 13.5 % of patients. <em>GBA1</em>-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-<em>GBA1</em>-PD. Non-<em>GBA1</em>-PD <em>fast-progressors</em> exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but <em>slow-progressors</em> showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD).</div></div><div><h3>Conclusions</h3><div><em>GBA1</em>-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-<em>GBA1</em>-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, <em>GBA1</em>-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359651","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}