Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Mechanistic biology linking traumatic brain injury to multiple sclerosis susceptibility.","authors":"David Baker, Lars Alfredsson, Anna Karin Hedström, Klaus Schmierer","doi":"10.1136/jnnp-2024-335304","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335304","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a major, immune-mediated, demyelinating disease and the major cause of non-traumatic disability in young adults. Susceptibility to disease is controlled by a variety of interacting features that include genetic and notably environmental factors. One of these risk factors appears to be the occurrence of traumatic brain injury. In a follow-on to previous analysis of head injury-induced risk factors for MS, analysis of Swedish Registry data of MS and matched controls demonstrates enhanced susceptibility to MS, notably when stratified for the presence of HLA-DRB1*15.01, absence of HLA-A*02.01 and occurrence of smoking, which are known risk factors, the risk of MS increases to OR 65.4 (95% CI 8.35 to 512). This can be mechanistically supported by a number of routes whereby brain injury can lead to expression of autoantigenic targets, or damage-related release of neuroantigens that could generate a novel autoantigenic response in draining lymph nodes following glymphatic/meningeal lymphatic drainage. These may be different from other mechanisms that are relevant to susceptibility due to human leucocyte antigen expression and smoking.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum level changes of the synaptic marker beta-synuclein in Alzheimer's disease continuum and other dementias.","authors":"Lorenzo Barba, Giovanni Bellomo, Daniel Alcolea, Anna L Wojdala, Lorenzo Gaetani, Juan Fortea, Samir Abu-Rumeileh, Alberto Lleó, Lucilla Parnetti, Olivia Belbin, Markus Otto, Patrick Oeckl","doi":"10.1136/jnnp-2025-336189","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336189","url":null,"abstract":"<p><strong>Background: </strong>Beta-synuclein is an emerging blood biomarker for detecting synaptic damage in Alzheimer's disease (AD) but its role in early AD as well as in other dementias is unclear.</p><p><strong>Methods: </strong>We measured with immunoprecipitation mass-spectrometry serum beta-synuclein levels in an exploratory cohort of 80 patients recruited at the University of Perugia (Perugia, Italy) (n=56 AD; n=24 controls) and in a validation cohort of 269 patients recruited at the University of Barcelona (Barcelona, Spain) (n=108 AD; n=53 frontotemporal lobar degeneration (FTLD); n=73 dementia with Lewy bodies and mild cognitive impairment (MCI) with Lewy bodies, together Lewy body disease (LBD); n=27 controls). We tested associations with diagnostic groups, cognitive decline and other cerebrospinal fluid (CSF) and blood markers (phosphorylated tau protein in position 181 (pTau181), neurofilament light chain protein (NfL), glial fibrillar acidic protein (GFAP)).</p><p><strong>Results: </strong>Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all). The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96). High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=-0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006). Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001).</p><p><strong>Conclusion: </strong>High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using prodromal non-motor symptoms to predict Parkinson's disease onset and motor phenotype.","authors":"Joshua Pearson, James B Badenoch, Daniel Van Wamelen","doi":"10.1136/jnnp-2024-335429","DOIUrl":"10.1136/jnnp-2024-335429","url":null,"abstract":"<p><strong>Background: </strong>Non-motor symptoms are highly prevalent in prodromal Parkinson's disease (PD); however, their impact on PD trajectory remains largely unexplored. We aimed to assess whether prevalent prodromal non-motor symptoms could predict future motor phenotype and time-to-PD diagnosis.</p><p><strong>Methods: </strong>We studied the prodromal cohort of the ongoing Parkinson's Progression Markers Initiative (n=958), which prospectively assesses individuals with prodromal PD features (genetic: n=361, hyposmia: n=298, rapid eye movement behaviour disorder: n=136, combination: n=163) with up to 10 years of follow-up. The presence of prevalent prodromal symptoms was defined by evidence-based cut-off scores. In unmedicated or OFF-state PD converters (total n=52), binary logistic regression models established whether these predicted non-tremor-dominant (n=35) and tremor-dominant (n=17) motor phenotypes at diagnosis. Cox proportional hazards models determined whether identified prodromal symptoms predicted a shorter time-to-phenoconversion across all PD converters (n=59) and non-converters (n=343). Both models adjusted for age and sex.</p><p><strong>Results: </strong>Prodromal anxiety and hyposmia were each associated with an increased risk of subsequent non-tremor-dominant PD, compared with other motor phenotypes (adjusted OR=4.45, 95% CI 1.34 to 15.27 and adjusted OR=3.90, 95% CI 1.01 to 15.16, respectively). Concurrent prodromal anxiety and hyposmia predicted an increased risk of PD phenoconversion over time (HR=4.93, 95% CI 2.71 to 8.98).</p><p><strong>Conclusion: </strong>In this exploratory analysis, individuals with prodromal hyposmia and anxiety phenoconverted to PD sooner and more often had a non-tremor-dominant phenotype, potentially reflecting more widespread pathology or specific pathophysiology underlying these symptoms. This may improve phenotyping prodromal PD and stratifying poorer prognostic trajectories for earlier and more personalised management.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF levels of the somatodendritic protein MAP2 are increased in ALS and predict shorter survival.","authors":"Federico Verde, Jakub Vávra, J Dorst, Zeynep Elmas, Maximilian Wiesenfarth, Anna De Gobbi, Antonia Ratti, Barbara Poletti, Hayrettin Tumani, Jochen Weishaupt, Vincenzo Silani, Nicola Ticozzi, Markus Otto, Albert C Ludolph, Patrick Oeckl","doi":"10.1136/jnnp-2025-336208","DOIUrl":"10.1136/jnnp-2025-336208","url":null,"abstract":"<p><strong>Background: </strong>Previous proteomic work has identified the somatodendritic protein MAP2 as a new candidate cerebrospinal fluid (CSF) biomarker for amyotrophic lateral sclerosis (ALS).</p><p><strong>Methods: </strong>We measured CSF levels of MAP2 and neurofilament light chain (NFL) in a retrospective cohort of 251 patients with ALS and 108 neurological controls (NCs).</p><p><strong>Results: </strong>Patients with ALS had a higher median CSF MAP2 level compared with NCs, leading to an area under the curve (AUC) of 0.7080 (p<0.0001). They also had a higher median CSF NFL level (p<0.0001), resulting in an excellent diagnostic performance (AUC=0.9641; p<0.0001). Among patients with ALS, CSF MAP2 correlated with disease progression rate (DPR) (r=0.3099; p<0.0001) and was negatively associated with survival (HR=3.174). CSF NFL also correlated with DPR (r=0.4936; p<0.0001) and was negatively associated with survival (HR=2.759). The association of MAP2 with DPR was independent from NFL (p=0.0037). Stratifying patients based on median levels of both biomarkers resulted in significant differences in median survival times (low NFL/low MAP2, 66 months; high NFL/low MAP2 and vice versa, 35 months; high NFL/high MAP2, 26 months; p<0.0001). MAP2 was also associated with genetic status in patients with ALS, as patients with no mutations in <i>C9ORF72</i> or in <i>SOD1</i>, as well as <i>C9ORF72</i>-positive ones, had higher median levels compared with NCs (p<0.0001), while patients with <i>SOD1</i> mutations did not significantly differ from NCs (p>0.9999).</p><p><strong>Conclusions: </strong>Our study shows that the somatodendritic protein MAP2 is a promising candidate CSF biomarker for ALS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSM predicts haemorrhage risk in brainstem cavernous malformations: a multicentre prospective study.","authors":"Si-Hui Wang, Hong-Wei Li, Jian-Cong Weng, Yan-Bing Yu, Gui-Jun Zhang, Bo-Han Yao, Pan-Pan Liu, Lu Kong, Hui Zhou, Hao-Yu Zhang, Xiao-Jun Zeng, Ze-Yu Wu, Cong Ren, Wei Wang, Hong-Jun Zhang, Jun-Peng Ma, Xiao-Ying Xu, Lai-Rong Song, Jun-Ting Zhang, Zhen Wu, Liang Wang, Sheng-Jun Sun, Da Li","doi":"10.1136/jnnp-2025-336149","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336149","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the predictive value of baseline quantitative susceptibility mapping (QSM) metrics for assessing the risk of future symptomatic haemorrhages in patients with brainstem cavernous malformations (CMs).</p><p><strong>Methods: </strong>From July 2020 to September 2023, a prospective multicentre cohort of 155 patients with brainstem CMs was enrolled from 12 institutions. We analysed baseline QSM metrics, including lesional mean, median, IQR and maximum susceptibility. Propensity score matching was adjusted for baseline confounders, and Cox regression models assessed haemorrhage risk. Risk stratification was performed based on thresholds determined from planned receiver operating characteristic (ROC) analyses.</p><p><strong>Results: </strong>Postmatching cohorts (56 haemorrhage-free vs 30 haemorrhage cases) showed balanced baseline characteristics. Over a mean follow-up of 22.6 months, the baseline QSM metrics, particularly the median susceptibility (QSMmedian) (HR 58.896, 95% CI 8.544 to 405.989, p<0.001; Bonferroni-adjusted p=0.0001, k=4) and IQR of susceptibility (QSMIQR) (HR 29.754, 95% CI 6.101 to 145.119, p<0.001; Bonferroni-adjusted p=0.0001, k=4) were associated with prospective haemorrhage after adjusting for age, gender, lesion volume and prior haemorrhage. QSMmedian (area under curve (AUC)=0.759) and QSMIQR (AUC=0.740) demonstrated modest predictive performance. Risk stratification based on QSMmedian and QSMIQR demonstrated 2-year haemorrhage-free survival rates of 83.3%, 62.8% and 35.7% for the low-risk, intermediate-risk and high-risk groups, respectively. High-risk patients showed a 7.7-fold greater risk of haemorrhage compared with the low-risk group.</p><p><strong>Conclusions: </strong>This study explored the predictive value of QSM metrics for future symptomatic haemorrhage, suggesting that QSM may serve as a complementary imaging biomarker to existing prognostic models. Further validation in larger, independent cohorts is warranted.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Object naming after epilepsy surgery in the dominant left temporal lobe: risk factors, time course and long-term outcome.","authors":"Katrin Walther, Caroline Reindl, Michael Schwarz, Stephanie Gollwitzer, Burkhard S Kasper, Johannes Dominik Lang, Jenny Stritzelberger, Sebastian Brandner, Karl Rössler, Yining Zhao, Arnd Dörfler, Hajo M Hamer","doi":"10.1136/jnnp-2024-334491","DOIUrl":"10.1136/jnnp-2024-334491","url":null,"abstract":"<p><strong>Background: </strong>Deterioration in naming function is a common sequelae after epilepsy surgery in the language-dominant temporal lobe but information on recovery and long-term outcome is scarce. We, therefore, assessed short-term and long-term outcome of object naming in patients undergoing surgery in the temporal lobe and determined factors affecting deterioration and recovery of naming function.</p><p><strong>Method: </strong>Object naming (Boston naming test) before surgery, at early follow-up (FU, 6-12 months) and late FU (≥2 years) was assessed in people with epilepsy (PWE) undergoing resections in the language-dominant left and non-dominant right temporal lobe.</p><p><strong>Results: </strong>Sixty-six patients with left temporal lobe epilepsy (LTLE) and 87 control patients with right temporal lobe epilepsy (RLTE) were included. At early FU, 28 patients with LTLE (42%) and three patients with RTLE (3%) showed a significant naming decline. In patients with LTLE, risk for deterioration increased with lower verbal memory before surgery, older age at seizure onset and was particularly high with posterior temporal resections (≥40 mm from the temporal pole) and seizure onset >16 years. Of the patients with LTLE with early naming decline, 11 patients (39%) recovered fully in their naming abilities at late FU, averaging almost 10 years. Recovery was associated with the degree of postoperative naming decline at early FU. PWE with a decline of less than 10 items (<20%) had a good prognosis of recovery at late FU. Postoperative seizure control had no significant effect on recovery.</p><p><strong>Conclusions: </strong>In our cohort, less than 50% of PWE showed significantly deteriorated naming function after resection of the dominant temporal lobe. If a decline occurred, it appeared to recover to a certain degree and remained as a permanent deficit in 26% of the patients. Long-term outcome of visual object naming can be predicted by the degree of early postoperative decline.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"630-638"},"PeriodicalIF":7.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxic complications of chimeric antigen receptor (CAR) T-cell therapy.","authors":"Frederick W Vonberg, Imran Malik, Maeve O'Reilly, Harpreet Hyare, Aisling S Carr, Claire Roddie","doi":"10.1136/jnnp-2024-333924","DOIUrl":"10.1136/jnnp-2024-333924","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy has revolutionised the treatment of haematological malignancies and has demonstrated efficacy in early trials for solid tumours, neurological and rheumatological autoimmune diseases. However, CAR-T is complicated in some patients by neurotoxicity syndromes including immune-effector cell-associated neurotoxicity syndrome, and the more recently described movement and neurocognitive treatment-emergent adverse events, and tumour inflammation-associated neurotoxicity. These neurotoxic syndromes remain poorly understood and are associated with significant morbidity and mortality. A multidisciplinary approach, including neurologists, haematologists and oncologists, is critical for the diagnosis and management of CAR-T neurotoxicity. This approach will be of increasing importance as the use of CAR-T expands, its applications increase and as novel neurotoxic syndromes emerge.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"665-678"},"PeriodicalIF":8.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apheresis therapies in MOGAD: a retrospective study of 117 therapeutic interventions in 571 attacks.","authors":"Carolin Schwake, Theodoros Ladopoulos, Vivien Häußler, Ingo Kleiter, Marius Ringelstein, Orhan Aktas, Tania Kümpfel, Daniel Engels, Joachim Havla, Martin W Hümmert, Julian Reza Kretschmer, Daria Tkachenko, Corinna Trebst, Ana Beatriz Ayroza Galvão Ribeiro Gomes, Anne-Katrin Pröbstel, Mirjam Korporal-Kuhnke, Brigitte Wildemann, Sven Jarius, Refik Pul, Mosche Pompsch, Markus Krämer, Florian Then Bergh, Clemens Gödel, Patricia Schwarz, Markus C Kowarik, Paulus Stefan Rommer, Ioannis Vardakas, Makbule Senel, Alexander Winkelmann, Nele Retzlaff, Martin S Weber, Leila Husseini, Annette Walter, Patrick Schindler, Judith Bellmann-Strobl, Friedemann Paul, Ralf Gold, Ilya Ayzenberg","doi":"10.1136/jnnp-2024-334863","DOIUrl":"10.1136/jnnp-2024-334863","url":null,"abstract":"<p><strong>Background: </strong>Incomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data on apheresis outcomes in MOGAD attacks remain limited.</p><p><strong>Methods: </strong>We retrospectively evaluated all apheresis treated attacks occurring in patients with MOGAD between 2008 and 2023 at 18 Neuromyelitis Optica Study Group centres. Treatment response was categorised as complete, partial or no remission. Preattack and follow-up Expanded Disability Status Scale (EDSS) and visual Functional System Scores (FSS) were used to calculate absolute outcomes (ΔEDSS/Δvisual FSS). Predictors of complete remission were analysed using a generalised linear mixed model.</p><p><strong>Results: </strong>Apheresis was used for 117/571 (20.5%) attacks in 85/209 (40.7%) patients. Attacks with simultaneous optic neuritis and myelitis were treated more often with apheresis (42.4%, n=14) than isolated myelitis (25.2%, n=35), cerebral manifestation (21.0%, n=17) or isolated optic neuritis (17.6%, n=51). Apheresis was initiated as first-line therapy in 12% (4.5 (IQR 0-11) days after attack onset), second-line therapy in 62% (15 (IQR 6.75-31) days) and third-line therapy in 26% (30 (IQR 19-42) days). Complete remission was achieved in 21%, partial remission in 70% and no remission in 9% of patients. First-line apheresis (OR 2.5, p=0.040) and concomitant disease-modifying therapy (OR 1.5, p=0.011) were associated with complete remission. Both parameters were also associated with a favourable ΔEDSS. No differences in outcomes were observed between the apheresis types.</p><p><strong>Conclusion: </strong>Apheresis is frequently used in MOGAD attacks. An early start as first-line therapy and concomitant disease-modifying therapy predict full attack recovery.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"639-646"},"PeriodicalIF":7.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of seizure control during pregnancy with adverse offspring outcomes in women with epilepsy.","authors":"Yutong Fu, Fanfan Shi, Leihao Sha, Weihong Lin, Ying Ma, Hua Yan, Pei Wang, Jiajia Fang, Qun Huang, Fang Chen, Xiaoyi Li, Yun Li, Changqing Liu, Qingxia Kong, Hua Huang, Qi Zhang, Rong Mei, Yuan Wu, Shixu He, Yanbing Han, Hua Zhang, Bo Xiao, Kuiyun Wang, Zhanghui Peng, Xi Zhu, Jian Wang, Xunyi Wu, Yanmei Zhu, Ting Wu, Xuelian He, Haizhi Guo, Ming Yu, Min Zhong, Qing Zhang, Xiangshu Hu, Yan Su, Mei Zou, Jian Zhou, Yaqing Liu, Bozhong Pu, Chonglun Guo, Qin Feng, Jing Gao, Wanhui Lin, Torbjörn Tomson, Lei Chen","doi":"10.1136/jnnp-2024-335751","DOIUrl":"10.1136/jnnp-2024-335751","url":null,"abstract":"<p><strong>Background: </strong>Information on fetal risks with maternal seizures during pregnancy is scarce. This study investigates seizure control during pregnancy and fetal risks associated with maternal seizures in different stages of pregnancy among pregnant women with epilepsy (PWWE).</p><p><strong>Methods: </strong>The nested case-control study enrolled PWWE between 2009 and 2023 in China. Information was obtained on maternal seizures, antiseizure medication (ASM), folic acid supplementation and pregnancy outcomes. The primary outcome was composite including major congenital malformations (MCMs), neurodevelopmental delay, low birth weight (LBW) and fetal death. Univariate and multivariate logistic regression analyses were conducted to adjust for ASM effects and other confounders.</p><p><strong>Results: </strong>Among 1110 pregnancies from 934 PWWE included, 56.6% experienced seizures. Seizure deterioration during pregnancy compared with prepregnancy was observed in 25.9% of pregnancies, while 20.9% experienced worsening seizures from the first to second or third trimesters. Seizures (adjusted OR (aOR) 1.472, 95% CI 1.024 to 2.137), particularly status epilepticus (aOR 2.906, 95% CI 1.364 to 5.93), generalised tonic-clonic seizures (aOR 1.581, 95% CI 1.066 to 2.354) and seizure deterioration (aOR 1.829, 95% CI 1.233 to 2.69) were associated with composite adverse outcomes. Specifically, seizures occurring (aOR 2.324, 95% CI 1.320 to 4.084) or deteriorating (aOR 2.396, 95% CI 1.471 to 3.866) during second and third trimesters were associated with the risk of LBW. No significant association was found between seizures and MCMs.</p><p><strong>Conclusions: </strong>While nearly half of PWWE remain seizure-free during pregnancy, those who do experience seizures face increased risks of adverse offspring outcomes. For PWWE, every effort should be made to optimise seizure control in order to minimise risks to both mother and child.</p><p><strong>Trial registration number: </strong>ChiCTR2100046318.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"621-629"},"PeriodicalIF":8.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals.","authors":"Nontapat Sukhonpanich, Fatemeh Koohi, Amy A Jolly, Hugh S Markus","doi":"10.1136/jnnp-2024-334823","DOIUrl":"10.1136/jnnp-2024-334823","url":null,"abstract":"<p><strong>Background: </strong>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype is becoming milder with better risk factor treatments and other care improvements is unknown. In a large longitudinal CADASIL cohort, we determined whether the prognosis has changed over 23 years.</p><p><strong>Methods: </strong>Patients were identified from the Cambridge CADASIL register and the UK Familial stroke study. Change in age at stroke over the time of recruitment was determined using linear mixed-effects model, and the impact of genetic and vascular risk factors on stroke and dementia risk was further evaluated using Cox proportional hazard regression.</p><p><strong>Results: </strong>A total of 555 patients with CADASIL were recruited between 2001 and 2023. The age of stroke onset significantly increased over time (p<0.001), with the mean age of stroke onset for patients recruited before 2016 (n=265) at 46.7±9.2 years and 51.6±9.5 years for those recruited since 2016 (n=290). Patients recruited since 2016 had lower risks of both stroke (HR 0.36, 95% CI 0.26 to 0.50, p<0.001) and dementia (HR 0.43, 95% CI 0.19 to 0.99, p=0.046) after adjusting for sex, hypertension history, smoking status, epidermal growth factor-like repeat position and calendar effect.</p><p><strong>Conclusions: </strong>The clinical phenotype of CADASIL is improving. While this may be partly explained by reduced vascular risk factors such as smoking and the identification of milder cases, differences persisted after controlling for risk factors and mutation sites. These updated risk estimates should be used when counselling patients with CADASIL on prognosis.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"690-696"},"PeriodicalIF":7.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}