European Journal of Neurology最新文献

{"title":"Complement activation by IgM autoantibodies linked to immune-mediated neuropathies depends on C2.","authors":"Kevin Budding, Kim Dijkxhoorn, Elisabeth de Zeeuw, Lauri M Bloemenkamp, W Ludo van der Pol, Nicolette C Notermans, Monique C Minnema, Jeanette H W Leusen, C Erik Hack, Inge Van de Walle","doi":"10.1111/ene.16541","DOIUrl":"https://doi.org/10.1111/ene.16541","url":null,"abstract":"<p><strong>Background and purpose: </strong>Complement factor C2 is a potential therapeutic target in immune-mediated neuropathies. However, literature suggests that classical complement pathway activation may proceed to C3 in the absence of C2, a so-called \"C2 bypass.\" Here, we evaluated a C2 bypass mechanism during complement activation by pathogenic human IgM from patients with immune-mediated neuropathies.</p><p><strong>Methods: </strong>IgM autoantibodies from 51 patients with multifocal motor neuropathy (MMN) or anti-myelin-associated glycoprotein (MAG) neuropathy (AMN) were used to activate complement in ex vivo disease models. C2 bypass was evaluated using C2-depleted (C2D) serum and a therapeutic anti-C2 antibody.</p><p><strong>Results: </strong>In two different disease models of MMN, IgM anti-GM1 and IgM anti-GM2 autoantibodies from MMN patients were bound to induced pluripotent stem cell-derived motor neurons and Schwann cells, respectively, and fixed C3 upon incubation with fresh serum. C3 fixation was inhibited by anti-C2 and did not occur with C2D serum. Similarly, in an AMN model, IgM anti-MAG antibodies were incubated with fresh serum fixed C3, which in all cases was abrogated in the absence of C2 or in the presence of anti-C2.</p><p><strong>Conclusions: </strong>In ex vivo disease models of MMN and AMN, complement activation by IgM autoantibodies from 51 patients was in all cases dependent on C2 and was inhibited by an antihuman C2 antibody. No evidence of a C2 bypass mechanism was found.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16541"},"PeriodicalIF":4.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of affective disturbances and cognitive impairment following small spontaneous supratentorial intracerebral hemorrhage.","authors":"Qiuyi Jiang, Chunyang Liu, Hongli Zhang, Rui Liu, Jian Zhang, Jinyi Guo, Enzhou Lu, Shouyue Wu, Jianda Sun, Yan Gao, Qiunan Yang, Guangyao Shi, Chao Yuan, Yanchao Liang, Huan Xiang, Lu Wang, Guang Yang","doi":"10.1111/ene.16544","DOIUrl":"https://doi.org/10.1111/ene.16544","url":null,"abstract":"<p><strong>Background and purpose: </strong>Affective disturbances and cognitive impairment are common sequelae of intracerebral hemorrhage (ICH), yet predictive models for these outcomes remain limited, especially for spontaneous supratentorial ICH with small hematomas (<30 mL). The aim of this study was to investigate predictors of affective disturbances and cognitive impairment following small spontaneous supratentorial intracerebral hemorrhage.</p><p><strong>Methods: </strong>We retrospectively analyzed 1692 patients with spontaneous supratentorial ICH between January 2018 and December 2020 at the First Affiliated Hospital of Harbin Medical University. Of these, 1563 patients completed a median follow-up of 3.5 years. Cognitive function was evaluated using the modified Telephone Interview for Cognitive Status, and affective disturbances using the Hamilton Depression Scale and the Hamilton Anxiety Scale. Restricted cubic spline analyses were employed to examine the relationships between predictors and outcomes.</p><p><strong>Results: </strong>In this cohort, 58.5% had cognitive impairment, 52.8% reported depressive symptoms, and 39.4% exhibited anxiety symptoms. Logistic regression models using Boruta's algorithm demonstrated strong predictive capacity, with areas under the curve of 0.82 for cognitive impairment, 0.78 for depressive symptoms, and 0.73 for anxiety symptoms. Hematoma volume was significantly linked to depressive symptoms (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.38-1.76) and inversely to cognitive impairment (OR 0.67, 95% CI 0.59-0.77). Uric acid levels displayed a nonlinear relationship with cognitive impairment (OR 0.70, 95% CI 0.61-0.81). Hospitalization days significantly raised the risk of both depressive (OR 1.16, 95% CI 1.03-1.30) and anxiety symptoms (OR 1.17, 95% CI 1.04-1.31).</p><p><strong>Conclusions: </strong>The logistic regression model, enhanced by Boruta's algorithm, provides a valuable tool for predicting affective disturbances and cognitive impairment after ICH. It facilitates early identification and improves risk assessment for these neuropsychiatric outcomes in patients with small hematomas.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16544"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of different surgical strategies for cervical dystonia: Evidence from Bayesian network analysis.","authors":"Youjia Qiu, Tao Xue, Yutong Bai, Chunlei Han, Minjia Xie, Haiyin Teng, Ziqian Yin, Zhouqing Chen, Jianguo Zhang, Zhong Wang","doi":"10.1111/ene.16527","DOIUrl":"https://doi.org/10.1111/ene.16527","url":null,"abstract":"<p><strong>Background and purpose: </strong>Several surgical techniques have been used to treat cervical dystonia (CD), however, to date, the optimal surgical technique for CD remains controversial. We therefore conducted the first network meta-analysis to compare different surgical strategies for CD to inform clinical practice.</p><p><strong>Methods: </strong>Electronic databases were searched for surgical strategies for treating CD. The primary outcome was improvement in total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score. Subgroup analysis was performed to compare short-term (< 1 year) and long-term (≥ 1 year) outcomes. Safety outcomes included surgery-related adverse events (AEs).</p><p><strong>Results: </strong>A total of 55 trials with 2032 patients employing five surgical strategies were identified, including globus pallidus internus (GPi)/subthalamic nucleus (STN)-deep brain stimulation (DBS), selective peripheral denervation (SPD), microvascular decompression (MVD) and pallidotomy. All strategies led to significant improvement in total TWSTRS score (mean improvement range 18.65-28.22). GPi-DBS showed significantly greater enhancement than SPD for the whole dataset (mean difference [MD] 7.03, 95% credible interval [Crl] 1.53-12.56), while both GPi-DBS (MD 8.05, 95% Crl 2.35-13.80) and STN-DBS (MD 10.71, 95% Crl 2.22-19.20) exhibited more long-term improvement than SPD. Regarding safety outcomes, GPi/STN-DBS and MVD were associated with fewer surgery-related AEs than SPD (ln odds ratio range -1.68 to -1.41).</p><p><strong>Conclusion: </strong>We conclude that DBS should be the preferred surgical option for CD, and the STN is a promising alternative target choice due to its comparable efficacy with the GPi. However, more direct evidence is still required.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16527"},"PeriodicalIF":4.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Operationalisation of post-COVID condition case definition in a comprehensive research protocol.","authors":"Federico Masserini, Alessia Nicotra, Arianna Forgione, Francesca Calcaterra, Elena Perdixi, Clara Di Vito, Anna Carletti, Chiara Gallo, Pietro Emiliano Doneddu, Fabrizia Terenghi, Simone Pomati, Eduardo Nobile-Orazio, Agostino Riva, Domenico Mavilio, Leonardo Pantoni","doi":"10.1111/ene.16543","DOIUrl":"https://doi.org/10.1111/ene.16543","url":null,"abstract":"<p><strong>Background and purpose: </strong>Post-COVID-19 condition (PCC) is a prevalent and high-burden sequela of SARS-CoV-2 infection. Because of the complexity of its manifestations, PCC case definition currently lacks standardisation and reproducibility. We aimed to devise a simple screening tool to boost reproducibility and comparability of PCC case definition across PCC studies, and to provide a framework in which to reliably identify suspected PCC cases. We also developed a comprehensive assessment protocol based on the most frequently reported PCC characteristics.</p><p><strong>Methods: </strong>Within a European multi-centre study and based on the conclusions of a previous systematic review, we devised a checklist to assess the presence of PCC-associated symptoms and their temporal relationship with COVID-19.</p><p><strong>Results: </strong>The checklist was developed to include three symptom cores (cognitive, psychiatric, and general). For each symptom, onset is assessed within 3 months after COVID-19 resolution and persistence for at least 2 months. Any symptom fulfilling this criterion is sufficient to prompt suspicion of PCC. At least one symptom is required in the cognitive or psychiatric domains to suspect PCC with neuropsychiatric involvement. Our protocol features an extensive neuropsychological evaluation and self-administered scales for mood, anxiety, stress-related symptoms, sleep disorders, quality of life, disability, mental health, and personality traits; scales for quantitative assessment of fatigue and headache are also included.</p><p><strong>Conclusions: </strong>Consistent identification of PCC cases is crucial to correctly include patients in research and clinical studies. We propose a simple, reproducible, and flexible screening tool and a proposal for a comprehensive assessment that could be employed to enhance standardisation and comparability.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16543"},"PeriodicalIF":4.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paramagnetic rim lesions are associated with inner retinal layer thinning and progression independent of relapse activity in multiple sclerosis.","authors":"Nik Krajnc, Leo Hofer, Fabian Föttinger, Assunta Dal-Bianco, Fritz Leutmezer, Barbara Kornek, Paulus Rommer, Gregor Kasprian, Thomas Berger, Berthold Pemp, Lukas Haider, Gabriel Bsteh","doi":"10.1111/ene.16529","DOIUrl":"https://doi.org/10.1111/ene.16529","url":null,"abstract":"<p><strong>Background and purpose: </strong>Paramagnetic rim lesions (PRLs) are chronic active lesions associated with a severe disease course in multiple sclerosis (MS). This study was undertaken to investigate an association between retinal layer thinning (annualized loss of peripapillary retinal nerve fiber layer [aLpRNFL] and ganglion cell-inner plexiform layer [aLGCIPL]) and PRLs in patients with MS (pwMS).</p><p><strong>Methods: </strong>In this study, pwMS with brain magnetic resonance imaging and ≥2 optical coherence tomography scans were included. Cox proportional hazard regression models were performed using progression independent of relapse activity (PIRA) as the dependent variable, and aLpRNFL, aLGCIPL, or the number of PRLs as independent variables, adjusted for covariates.</p><p><strong>Results: </strong>We analyzed data from 97 pwMS (mean age = 35.2 years [SD = 9.9], 71.1% female, median disease duration = 2.3 years [interquartile range = 0.9-9.0]). The number of PRLs was associated with aLpRNFL and aLGCIPL. PIRA was observed in 18 (18.6%) pwMS, with aLpRNFL (hazard ratio [HR] = 1.44 per %/year), aLGCIPL (HR = 1.61 per %/year), and the number of PRLs (HR = 1.24 per PRL) being associated with increased risk of PIRA.</p><p><strong>Conclusions: </strong>The number of PRLs is associated with inner retinal layer thinning and increased risk of PIRA. A combination of PRLs and retinal layer thinning could serve as a surrogate for pwMS at highest risk of disability progression.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16529"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small fiber neuropathy associated with COVID-19 infection and vaccination: A prospective case-control study.","authors":"Vincenzo Donadio, Alex Incensi, ALessandro Furia, Sara Parisini, Francesco Colaci, Maria Pia Giannoccaro, Luana Morelli, Fortuna Ricciardiello, Vitoantonio Di Stasi, Andrea De Maria, Giovanni Rizzo, Rocco Liguori","doi":"10.1111/ene.16538","DOIUrl":"https://doi.org/10.1111/ene.16538","url":null,"abstract":"<p><strong>Background: </strong>Small fiber neuropathy (SFN) after both COVID-19 infection or vaccination has been reported in sporadic cases, but a detailed description and comparison are missing. We aimed to screen a large cohort of patients complaining of pain and autonomic symptoms after COVID-19 natural infection or vaccination to ascertain the presence of SFN and its correlation with autoimmune diseases.</p><p><strong>Methods: </strong>We prospectively recruited for this case-control study 66 patients: 33 developing sensory and autonomic symptoms after a natural COVID-19 infection (P-COVID) and 33 after a mRNA vaccination against COVID-19 (P-VAC). We also used 33 matched healthy controls (HC) collected before 2019 when the COVID-19 virus appeared. Patients underwent neurological examination and clinical scales, an extensive serum screening, and skin biopsy to detect small nerve fiber involvement.</p><p><strong>Results: </strong>Clinical scales showed higher scores for autonomic symptoms in P-COVID patients than in P-VAC patients, but the other scales did not differ. P-COVID and P-VAC patients showed a significant decrease in somatic small nerve fibers compared with HC, whereas autonomic innervation did not differ. SFN was more frequent in P-COVID patients (94%) than in P-VAC patients (79%). Epidermal innervation was correlated with clinical scales for pain and autonomic dysfunctions. Autoimmune abnormalities were frequent in both groups but importantly they were not correlated with SFN.</p><p><strong>Conclusions: </strong>Somatic SFN was frequently found in both P-COVID and P-VAC patients, with a higher incidence in the former group. Spared skin autonomic innervation was spared in both groups although a subtle autonomic involvement in P-COVID patients was suggested by a high COMPASS-31 scale score. SFN was not correlated with autoimmune dysfunctions, although autoimmune diseases were frequent in both groups.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16538"},"PeriodicalIF":4.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain neurovascular coupling in amyotrophic lateral sclerosis: Correlations with disease progression and cognitive impairment.","authors":"Francesca Trojsi, Antonietta Canna, Minoo Sharbafshaaer, Federica di Nardo, Fabrizio Canale, Carla Passaniti, Maria Agnese Pirozzi, Marcello Silvestro, Ilaria Orologio, Antonio Russo, Mario Cirillo, Alessandro Tessitore, Mattia Siciliano, Fabrizio Esposito","doi":"10.1111/ene.16540","DOIUrl":"https://doi.org/10.1111/ene.16540","url":null,"abstract":"<p><strong>Background and purpose: </strong>'Neurovascular coupling' (NVC) alterations, assessing the interplay between local cerebral perfusion and neural activity within a given brain region or network, may reflect neurovascular unit impairment in amyotrophic lateral sclerosis (ALS). The aim was to explore NVC as a correlation between the functional connectivity and cerebral blood flow within the large-scale resting-state functional magnetic resonance imaging brain networks in a sample of ALS patients compared to healthy controls (HCs).</p><p><strong>Methods: </strong>Forty-eight ALS patients (30 males; mean age 60.64 ± 9.62 years) and 32 HC subjects (14 males; mean age 55.06 ± 16 years) were enrolled and underwent 3 T magnetic resonance imaging. ALS patients were screened by clinical and neuropsychological scales and were retrospectively classified as very fast progressors (VFPs), fast progressors and slow progressors (SPs).</p><p><strong>Results: </strong>Neurovascular coupling reduction within the default mode network (DMN) (p = 0.005) was revealed in ALS patients compared to HCs, observing, for this network, significant NVC differences between VFP and SP groups. Receiver operating characteristic curve analysis showed that impaired NVC in the DMN at baseline best discriminated VFPs and SPs (area under the curve 75%). Significant correlations were found between NVC and the executive (r = 0.40, p = 0.01), memory (r = 0.32, p = 0.04), visuospatial ability (r = 0.40, p = 0.01) and non-ALS-specific (r = 0.40, p = 0.01) subscores of the Edinburgh Cognitive and Behavioural ALS Screen.</p><p><strong>Conclusions: </strong>The reduction of brain NVC in the DMN may reflect largely distributed abnormalities of the neurovascular unit. NVC alterations in the DMN could play a role in anticipating a faster clinical progression in ALS patients, aiding patient selection and monitoring during clinical trials.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16540"},"PeriodicalIF":4.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged use of chlormadinone acetate and risk of intracranial meningioma: A population-based cohort study.","authors":"Noémie Roland, Pierre Nguyen, Anke Neumann, Léa Hoisnard, Thibault Passeri, Lise Duranteau, Joël Coste, Sébastien Froelich, Mahmoud Zureik, Alain Weill","doi":"10.1111/ene.16505","DOIUrl":"10.1111/ene.16505","url":null,"abstract":"<p><strong>Background and purpose: </strong>Chlormadinone acetate (CMA) is a synthetic progestin for which cases of intracranial meningioma have been reported following prolonged exposure.</p><p><strong>Method: </strong>An observational cohort study was conducted based on the French national health data system. Women aged 10-70 years and who started CMA between 2007 and 2017 were included. Participants were considered to be exposed if they had received a cumulative dose >360 mg of CMA during the first 6 months and very slightly exposed (control group) when they had received a cumulative dose ≤360 mg. The outcome was surgery or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma.</p><p><strong>Results: </strong>In total, 828,499 women were included: 469,976 in the exposed group (mean age 39.1 years, SD 10.1) and 358,523 in the control group (38.3 years, SD 11.0). Surgery or radiotherapy for intracranial meningioma between 2007 and 2017 was recorded for 164 and 104 women in the exposed and control groups, respectively. The incidence of meningioma was 18.5 and 6.8 per 100,000 person-years for the exposed and control groups respectively (crude RR = 2.7, 95% confidence interval [CI] 2.1-3.5; age-adjusted RR = 3.1, 95% CI 2.4-4.0). Meningioma incidence reached almost 47 cases/100,000 person-years in the most exposed group (>8.64 g), giving an age-adjusted RR of 6.9, 95% CI 5.1-9.2, relative to the control group.</p><p><strong>Conclusions: </strong>A strong dose-effect relationship was observed between prolonged use of CMA and risk of meningiomas. As with other progestogens, meningiomas associated with CMA are more likely to be found at the base of the skull.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16505"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mobile stroke units services in Germany: A cost-effectiveness modeling perspective on catchment zones, operating modes, and staffing.","authors":"Johann S Rink, Kristina Szabo, Carolin Hoyer, Jeffrey L Saver, May Nour, Heinrich J Audebert, Wolfgang G Kunz, Matthias F Froelich, Armin Heinzl, Andrej Tschalzev, Jens Hoffmann, Stefan O Schoenberg, Fabian Tollens","doi":"10.1111/ene.16514","DOIUrl":"10.1111/ene.16514","url":null,"abstract":"<p><strong>Background and purpose: </strong>Investigating the cost-effectiveness of future mobile stroke unit (MSU) services with respect to local idiosyncrasies is essential for enabling large-scale implementation of MSU services. The aim of this study was to assess the cost-effectiveness for varying urban German settings and modes of operation.</p><p><strong>Methods: </strong>Costs of different operating times together with different personnel configurations were simulated. Different possible catchment zones, ischemic stroke incidence, circadian distribution, rates of alternative diagnoses, as well as missed cases were incorporated to model case coverage and patient numbers. Based on internationally reported clinical outcomes of MSUs, a 5-year Markov model was applied to analyze the cost-effectiveness for the different program setups.</p><p><strong>Results: </strong>Compared with standard stroke care, MSUs achieved an additional 0.06 quality-adjusted life years (QALYs) over a 5-year time horizon. Assuming a catchment zone of 750,000 inhabitants and 8 h/7 day operation resulted in an incremental cost-effectiveness ratio (ICER) of €37,182 per QALY from a societal perspective and €45,104 per QALY from a healthcare perspective. Lower ICERs were possible when coverage was expanded to 16 h service on 7 days per week and larger populations. Sensitivity analyses revealed that missing ischemic strokes significantly deteriorated economic performance of MSU.</p><p><strong>Conclusions: </strong>Major determinants of cost-effectiveness should be addressed when setting up novel MSU programs. Catchment zones of more than 500,000-700,000 inhabitants and operating times of at least 12-16 h per day, 7 days per week could enable the most cost-effective MSU services in the German healthcare system.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16514"},"PeriodicalIF":4.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Parkinson disease in Spain: Genetic and clinical insights.","authors":"Pilar Gómez-Garre, Miguel Martín-Bórnez, Laura Muñoz-Delgado, Rafael Díaz-Belloso, María Teresa Periñán, Marta Bonilla-Toribio, Dolores Buiza-Rueda, Daniel Macías-García, Silvia Jesús, Astrid Adarmes-Gómez, Elena Ojeda, Antonio Luque-Ambrosiani, Sergio García-Díaz, Rocío Pineda Sánchez, Fátima Carrillo, Pablo Mir","doi":"10.1111/ene.16499","DOIUrl":"https://doi.org/10.1111/ene.16499","url":null,"abstract":"<p><strong>Background and purpose: </strong>Parkinson disease (PD) is a complex and heterogeneous neurodegenerative disorder with a broad spectrum of clinical manifestations, determined by a complex interplay of environmental and genetic factors. This study aimed to investigate genetic variants associated with PD and assess their impact on the disease phenotype through genotype-phenotype correlations.</p><p><strong>Methods: </strong>We employed a targeted resequencing panel to analyze 27 genes linked to PD in a cohort of 1185 PD patients from southern Spain. Variants were categorized based on the American College of Medical Genetics and Genomics pathogenicity criteria. Demographic and clinical data were also collected.</p><p><strong>Results: </strong>Among the patients analyzed, 13.5% carried potential disease-causing pathogenic or likely pathogenic variants in 12 different genes, indicating significant genetic heterogeneity. The most frequently affected genes were LRRK2, PRKN, and GBA1 (accounting for 72.1% of positive cases). Sex-specific differences were observed, with a higher proportion of female patients carrying LRRK2 variants. Differences in age at onset and clinical features were also observed among the different mutated genes. Notably, variants in genes associated with atypical parkinsonism presented distinct clinical presentations, highlighting the importance of genetic factors in the differential diagnosis.</p><p><strong>Conclusions: </strong>Our study provides valuable information on the genetic landscape of PD and its clinical manifestations. The observed genotype-phenotype correlations, along with sex-specific differences, emphasize the complexity of PD pathogenesis, underlining the importance of personalized approaches to PD diagnosis and treatment. Further investigations into genetic interactions and population-specific effects are warranted to enhance our understanding of PD etiology and improve patient care.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":" ","pages":"e16499"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}