Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Subthalamic deep brain stimulation in isolated generalised or segmental dystonia (RELAX Study): a multicentre, randomised, double-blind, controlled trial.","authors":"Lin Wang, Huifang Shang, Lingjing Jin, Nian Xiong, Xingyue Hu, Wei Wang, Yiming Liu, Jun Yan, Lingling Gao, Yaning Wang, Yanying Wang, Peng Fu, Huaying Cai, Wenbin Zhang, Shujun Xu, Fei Teng, Ruwei Ou, Lei Qiao, Yingmai Yang, Mengyu Zhang, Yi Guo, Xinhua Wan","doi":"10.1136/jnnp-2025-335829","DOIUrl":"10.1136/jnnp-2025-335829","url":null,"abstract":"<p><strong>Background: </strong>The safety and effectiveness of deep brain stimulation of the subthalamic nucleus (STN-DBS) for the treatment of dystonia lack high-level evidence-based medical support. This study aimed to clarify the efficacy and safety of STN-DBS and perform a post hoc analysis comparing it with DBS of the internal globus pallidus (GPi-DBS).</p><p><strong>Methods: </strong>This multicentre, randomised, double-blind, controlled trial included 67 patients aged 6-60 years old diagnosed with genetic or idiopathic isolated generalised or segmental dystonia. They were enrolled from seven hospitals in China and randomly assigned to undergo GPi-DBS or STN-DBS. After surgery, they were randomised to receive either neurostimulation or sham stimulation for 3 months. At the 3-month follow-up, neurostimulation was also initiated in the sham stimulation group, and all patients were followed up for more than 3 years after treatment. The primary outcome was the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) score.</p><p><strong>Results: </strong>In the STN group, the neurostimulation subgroup exhibited significant improvement (p<0.001), which is also superior to the sham stimulation subgroup (p=0.028) at 3-month follow-up. At the 6-month and >3-year follow-ups, all patients receiving STN-DBS showed a significant improvement in BFMDRS-M scores (p<0.001). Further post hoc analysis revealed that both STN-DBS and GPi-DBS could produce similar therapeutic effects on motor symptoms (P_{6 months}=0.865, P_{>3 years}=0.905). There were no ongoing serious adverse events throughout the study.</p><p><strong>Conclusions: </strong>For isolated generalised and segmental dystonia patients, the STN is a selectable DBS target with ensured safety and efficacy. STN-DBS and GPi-DBS may achieve comparable therapeutic effects on motor symptoms.</p><p><strong>Trial registration number: </strong>NCT03017586.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1077-1088"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248333","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 neuronal pentraxin 2 levels are associated with shorter survival in amyotrophic lateral sclerosis.","authors":"Soha Alali, Jonas Dubin, Frederik Hobin, Shreyasee Das, Charlotte Lambrechts, Erik Stoops, Eugen Vanmechelen, Philip van Damme, Koen Poesen","doi":"10.1136/jnnp-2025-336198","DOIUrl":"10.1136/jnnp-2025-336198","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1126-1128"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302311","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":"Clinical specificities and outcome of LGI1-antibody encephalitis according to age, sex and HLA.","authors":"Lucia Campetella, Macarena Villagrán-García, Antonio Farina, Marine Villard, Marie Benaiteau, Alberto Vogrig, Raffaele Iorio, Nicolás Lundahl Ciano-Petersen, Dimitri Psimaras, Vincent Navarro, Vicente Peris Sempere, David Gonçalves, Géraldine Picard, Véronique Rogemond, Bastien Joubert, Emmanuel Mignot, Jérôme Honnorat, Sergio Muñiz-Castrillo","doi":"10.1136/jnnp-2025-335960","DOIUrl":"https://doi.org/10.1136/jnnp-2025-335960","url":null,"abstract":"<p><strong>Background: </strong>Patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) encephalitis are typically elderly men that often carry human leucocyte antigen (HLA)-<i>DRB1*07:01</i> (≈90%). Herein, we aimed to investigate whether patients with atypical demographic profiles or not carrying <i>DRB1*07:01</i> have distinct clinical manifestations and outcome.</p><p><strong>Methods: </strong>Retrospective chart review of LGI1-Ab patients diagnosed at the French Reference Centre and three other European centres.</p><p><strong>Results: </strong>Among 238 patients included, median age at onset was 66 years (IQR: 60-73), 65% were male, 89% carried <i>DRB1*07:01</i> and 10% <i>DRB1*04:02</i>, another known secondary HLA association. We identified three age groups (young, typical, old) based on percentiles of age distribution. Young (≤51 years) patients were less commonly male (35%, p=0.004), while faciobrachial dystonic seizures (FBDS; 65%, p=0.047) and hyponatraemia (64%, p=0.046) were more frequent in old (≥79 years) patients. Old patients experienced poor outcome (modified Rankin Scale [mRS] >2 at last follow-up) more frequently (64%, p<0.001). There were no significant differences between males and females. <i>DRB1*07:01</i> non-carriers were younger (p=0.005) and less frequently male (47%, p=0.044), while non-carriers of both <i>DRB1*07:01</i> and <i>DRB1*04:02</i> experienced poor outcome more commonly (64%, p=0.005). Older age (adjusted OR: 1.08, 95% CI [1.02 to 1.14], p=0.008), higher mRS at nadir (4.22 [2.46-7.24], p<0.001) and <i>DRB1*07:01</i> non-carrier status (8.39 [1.88-37.44], p=0.005) were independently associated with poor outcome. Moreover, older age (1.08 [1.04-1.11], p<0.001), FBDS (2.20 [1.17-4.13], p=0.014) and hyponatraemia (2.30 [1.22-4.34], p=0.010) were associated with severe encephalitis (mRS >3 at nadir).</p><p><strong>Conclusions: </strong>Age appears to be the main driver of clinical presentation, severity and outcome in LGI1-Ab encephalitis. Remarkably, <i>DRB1*07:01</i> non-carriers are younger, more commonly female and experience poorer prognosis, reflecting a distinct pathophysiology.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301532","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":"Quantification of muscle glycogen distribution in Pompe disease using 7 Tesla ¹³C NMR spectroscopy.","authors":"Gry H Beha, Mads Godtfeldt Stemmerik, Vincent O Boer, Ans T van der Ploeg, Nadine Ame van der Beek, Henning Andersen, Anouk Marsman, Laura N Jacobsen, Maudy T M Theunissen, Esben T Petersen, John Vissing","doi":"10.1136/jnnp-2025-336628","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336628","url":null,"abstract":"<p><strong>Background: </strong>Late-onset Pompe disease has a characteristic pattern of fat replacement and wasting of especially axial and hamstring muscles. This characteristic pattern of muscle degeneration is still to be explained but could relate to differences in how glycogen is deposited in the different muscles. This cross-sectional observational study investigates the glycogen levels of different muscle groups in young late-onset Pompe subjects and matched controls.</p><p><strong>Methods: </strong>¹³C-MR Spectroscopy at 7 Tesla field strength was used to quantify glycogen concentration in four muscle groups: the calf, hamstring, anterior thigh and lumbar muscles of patients with late-onset Pompe disease and healthy controls. An unpaired t-test with correction for multiple comparisons was used to test the difference between Pompe subjects and healthy controls for each muscle area.</p><p><strong>Results: </strong>11 late-onset Pompe patients (6 female, mean age 31, range 20-44) and 16 healthy volunteers (10 female, mean age 27, range 19-35) were included. We found that Pompe subjects had 1.8 (95% CI 1.56 to 2.16) times more glycogen in hamstring muscles (p≤0.001) and 2.2 (95% CI 1.24 to 2.48) times more in lumbar muscles (p≤0.004), 1.4 (95% CI 1.07 to 1.73) times more in the anterior thigh muscles (p=0.045) while levels were similar to healthy persons in the calf (95% CI 0.83 to 1.12, p=0.7).</p><p><strong>Conclusions: </strong>The first muscles to degenerate in Pompe disease are hamstring and paraspinals. Our findings, therefore, suggest that high glycogen levels precede fatty degeneration of muscles, and that monitoring glycogen levels could be an important biomarker to assess treatment effect in Pompe disease.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301507","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":"Neurological immune-related adverse events with immune checkpoint inhibitors: collaboration is key.","authors":"Anadil Javaid, Tobias Peres, James Larkin","doi":"10.1136/jnnp-2025-336813","DOIUrl":"10.1136/jnnp-2025-336813","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1023"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753618","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":"Stereotactic radiosurgery versus observation for intracranial low-grade dural arteriovenous fistulas.","authors":"Andrea Becerril-Gaitan, Pedram Peesh, Collin Liu, Cheng-Chia Lee, Huai-Che Yang, Ajay Niranjan, Lawrence Dade Lunsford, Zhishuo Wei, Andrew Hoang, Jason Sheehan, Samantha Dayawansa, Selçuk Peker, Yavuz Samanci, Robert M Starke, Ahmed Abdelsalam, Douglas Kondziolka, Kenneth Bernstein, Ying Ming, Go Ikeda, Hideyuki Kano, Manjul Tripathi, Roman Liscak, Jaromir May, Qian Wang, Wen Li, Babu Welch, Jennifer O'Con, Sepideh Amin-Hanjani, Quang Nguyen, Guiseppe Lanzino, Waleed Brinjikji, Minako Hayakawa, Edgar Samaniego, Rose Du, Rosalind Lai, Colin Derdeyn, Adib Abla, Bradley Gross, Felipe Albuquerque, Michael Lawton, Louis Kim, Michael Levitt, Ali Alaraj, Ethan Winkler, Nohra Chalouhi, Brian Hoh, Diederik Bulters, Andrew Durnford, Junichiro Satomi, Yoshiteru Tada, J Marc C van Dijk, Adriaan R E Potgieser, Dimitri Laurent, Josh Osbun, Brigette Bahmani, Gregory Zipfel, Ching-Jen Chen","doi":"10.1136/jnnp-2024-335675","DOIUrl":"10.1136/jnnp-2024-335675","url":null,"abstract":"<p><strong>Background: </strong>Given the low haemorrhagic risk of intracranial low-grade dural arteriovenous fistulas (dAVFs), the benefits of routine intervention remain controversial. This study compares patient outcomes treated with stereotactic radiosurgery (SRS) versus conservative management.</p><p><strong>Method: </strong>Multicentre retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research and the International Radiosurgery Research Foundation data. Inclusion criteria were (1) intracranial low-grade dAVF diagnosed by catheter-based angiography, (2) no prior dAVF-related haemorrhage and (3) management with upfront SRS (intervention group) or conservative management (observation group). The primary outcome was symptomatic improvement. Secondary outcomes included dAVF obliteration, up-conversion, haemorrhage, improvement and favourable modified Rankin Scale (mRS) at follow-up.</p><p><strong>Results: </strong>304 patients with a mean age of 56 years (SD 13.5) and a follow-up of 46.7 months (SD 45.5) were included. 135 (44.4%) were managed conservatively and 169 (55.6%) had upfront SRS. Compared with the observation group, symptomatic and mRS Score improvement (≥1-point decrease in baseline score) was more likely in the intervention group (95.1% vs 58.5%; OR=13.75 (5.61-33.69) and 37.0% vs 24.0%; OR=1.85 (1.09-3.15), respectively). These findings remained significant after multiple imputation and propensity score matching. Remaining outcomes were similar between groups. The all-cause mortality rate was 5.4% (n=16), unrelated to the dAVF or treatment. Five (3.0%) SRS-related complications were reported and resolved during the follow-up period.</p><p><strong>Conclusions: </strong>SRS was associated with increased symptomatic and mRS Score improvement for low-grade dAVFs compared with conservative management. SRS had a low complication risk and did not appear to alter dAVF obliteration or haemorrhage. Future prospective trials on SRS as a first-line intervention for symptomatic low-grade dAVFs should be considered.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1117-1125"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248332","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":"Neurological immune-related adverse events with checkpoint inhibitor therapy: challenges for the neurologist.","authors":"Mark D Willis, Ben Schroeder, Laura Marandino, Samra Turajlic, Aisling S Carr","doi":"10.1136/jnnp-2025-335998","DOIUrl":"10.1136/jnnp-2025-335998","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI) have had a dramatic effect on cancer outcomes with their use increasing as indications expand. Despite impressive efficacy across a range of tumour types, their role in activating the immune system results in frequent immune-related adverse events (irAE). While gastrointestinal, endocrine, respiratory and cutaneous toxicities are common, neurological irAEs (N-irAEs) occur more rarely. N-irAEs have been well reported in the literature, can affect any part of the nervous system and are associated with significant morbidity and mortality. Treating oncologists have a high index of suspicion for irAEs and a low threshold for initiating treatment. The role of the neurologist is to consider the differential diagnosis, direct investigation according to the clinical syndrome and guide management, efficacy monitoring and rehabilitation. Once alternative aetiologies have been excluded, the ICI should be either paused or discontinued depending on clinical severity, and immunosuppressive treatment commenced. There is no high-level evidence for toxicity management in this emerging field, so there is much variation in clinical practice and the medical literature. While describing the range of neurological toxicities related to ICIs and current experience of management and outcome, this review focuses on the potential utility of predictive biomarkers, the risk of re-ignition of pre-existing neurological autoimmune disease and the question of rechallenge after a N-irAE. Given the paucity of data specifically relating to N-irAE, we also discuss cancer outcomes in the context of irAEs and associated immunosuppression and consider some outstanding questions pertinent to ICI-related neurotoxicity and potential future directions for research.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1024-1037"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659450","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":"Cluster analysis showed long-term cognition can be predicted by looking at regional grey matter atrophy in the first two years of multiple sclerosis course.","authors":"Stefano Ziccardi, Maddalena Guandalini, Francesco Crescenzo, Luigi Martinelli, Agnese Tamanti, Gian Marco Schiavi, Albulena Bajrami, Valentina Camera, Damiano Marastoni, Massimiliano Calabrese","doi":"10.1136/jnnp-2025-335925","DOIUrl":"10.1136/jnnp-2025-335925","url":null,"abstract":"<p><strong>Background: </strong>Grey matter (GM) atrophy is associated with cognitive impairment (CI) in multiple sclerosis (MS). We aimed to investigate the predictive role of early regional GM damage for long-term CI.</p><p><strong>Methods: </strong>A post-hoc cluster analysis was conducted on 175 patients with MS followed for 20 years from onset. Participants underwent a 1.5T-MRI scanning at diagnosis and after 2 years, and a comprehensive neuropsychological assessment after 20 years.</p><p><strong>Results: </strong>Three clusters have been identified: cluster 1 (primarily patients with long-term normal cognition), cluster 2 (primarily patients with long-term mild CI) and cluster 3 (primarily patients with long-term severe CI). Five brain regions have been identified showing a significant difference in early atrophy from cluster 1 and both clusters 2 and 3: precuneus (1 vs 2: p<0.001, relative risk ratio (RRR)=4.9, 95% confidence intervals (95% CIs) =2.4-10.1; 1 vs 3: p<0.001, RRR=5.5, 95% CIs=3.1-9.7), insula (1 vs 2: p<0.001, RRR=4.1, 95% CIs=1.9-8.6; 1 vs 3: p<0.001, RRR=4.3, 95% CIs=2.5-7.5), parahippocampal gyrus (1 vs 2: p<0.001, RRR=3.2, 95% CIs=1.8-5.7; 1 vs 3: p<0.001, RRR=3.1, 95% CIs=2.1-4.6), cingulate gyrus (1 vs 2: p<0.001, RRR=3.0, 95% CIs=1.7-5.3; 1 vs 3: p<0.001, RRR=2.2, 95% CIs=1.6-5.3) and cerebellum (1 vs 2: p=0.027, RRR=2.6, 95% CIs=1.5-4.6; 1 vs 3: p<0.001, RRR=2.1, 95% CIs=1.5-2.9). Four additional brain regions showed a significant difference in terms of early atrophy between cluster 1 and cluster 3: precentral gyrus (p<0.001, RRR=7.3, 95% CIs=3.1-17.3), postcentral gyrus (p<0.001, RRR=4.6, 95% CIs=2.2-9.8), superior frontal gyrus (p<0.001, RRR=4.0, 95% CIs=2.0-8.0) and hippocampus (p<0.001, RRR=2.4, 95% CIs=1.6-3.6).</p><p><strong>Conclusions: </strong>Cluster analysis identified the most specific brain regions whose early atrophy best distinguished future patients with CI. Long-term CI accumulation in MS can be predicted by early GM volume loss of specific cortical/deep GM regions.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1089-1092"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012036","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":"Evolution of autonomic nervous system abnormalities in multiple sclerosis: a 6-year follow-up.","authors":"Berislav Ruška, Ivan Adamec, Luka Crnosija, Tereza Gabelić, Barbara Barun, Anamari Junakovic, Magdalena Krbot Skoric, Mario Habek","doi":"10.1136/jnnp-2024-335376","DOIUrl":"10.1136/jnnp-2024-335376","url":null,"abstract":"<p><strong>Background: </strong>Due to the lack of long-term studies, this research aimed to explore the changes and predictors of autonomic dysfunction (AD) in people with multiple sclerosis (pwMS) over a 6-year period from disease onset.</p><p><strong>Methods: </strong>Among the 121 pwMS cohort, 75 underwent autonomic function tests at baseline and year 6. Autonomic symptoms were assessed using the Composite Autonomic System Score-31 (COMPASS-31), while the results of autonomic tests were recorded using the Composite Autonomic Scoring Scale (CASS) at baseline and biennially over 6 years. Symptomatic dysautonomia was identified by a COMPASS-31 score greater than 7.913 and a CASS score greater than 0.</p><p><strong>Results: </strong>No significant changes were noted in the COMPASS-31 and CASS scores from baseline to year 6. However, there was a significant decline in the cardiovagal index (p=0.001) and the sudomotor index (p=0.036 and p=0.001, respectively) at years 4 and 6, compared with baseline. The number of participants with symptomatic dysautonomia increased significantly from year 0 to 6 (14 (20.9%) vs 29 (39.2%), respectively; p=0.049). Multivariable logistic regression analysis revealed that experiencing a relapse during the 6 years increased the likelihood of symptomatic dysautonomia (Exp(B) 3.886, 95% CI 1.019 to 14.825, p=0.047). Conversely, transitioning to high-efficacy disease-modifying therapy (HET) reduced the probability of having a CASS score greater than 0 at year 6 (Exp(B) 0.221, 95% CI 0.067 to 0.734, p=0.014).</p><p><strong>Conclusions: </strong>Dysfunction of the cardiovagal and sudomotor systems progresses alongside disease duration in pwMS. The early initiation of HET may help mitigate the risk of developing AD.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1093-1098"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986489","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":"Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis.","authors":"Venla Ahola, Maija Saraste, Marjo Nylund, Markus Matilainen, Amelie Luoma, Anna Vuorimaa, Jussi Lehto, Sini Laaksonen, Eeva-Christine Brockmann, Jens Kuhle, David Leppert, Tero Soukka, Urpo Lamminmäki, Laura Airas","doi":"10.1136/jnnp-2025-336063","DOIUrl":"10.1136/jnnp-2025-336063","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) progression independent of relapses is driven by brain innate immune cell activation. The aim of this study was to evaluate the association between chitinase-3-like protein 1 (CHI3L1), expressed in brain by astrocytes and microglia, measured from blood and smouldering inflammation measured using 18 kDa translocator protein (TSPO) positron emission tomography (PET) in patients with MS.</p><p><strong>Methods: </strong>The study cohort included 55 patients with MS (25 progressive MS (PMS) and 30 relapsing remitting MS (RRMS)) and 17 healthy controls (HC). CHI3L1 was measured with commercial ELISA from plasma samples. A subcohort (44 MS and 9 HC) underwent TSPO-PET to assess [¹¹C]PK11195 distribution volume ratio (DVR) and MRI concurrent to blood sampling. These imaging outcomes were used in respective correlation and linear regression analyses.</p><p><strong>Results: </strong>CHI3L1 concentration in plasma was higher in PMS (23.5 ng/mL) compared with HC (16.8 ng/mL, p=0.0055) and RRMS (19.3 ng/mL, p=0.049). CHI3L1 associated with brain [¹¹C]PK11195 DVR in all MS (standardised estimate 0.89, 95% CI 0.23 to 1.55, p=0.010) and in PMS (Spearman correlation ρ=0.58, 95% CI 0.058 to 0.86, p=0.032). Additionally, CHI3L1 was associated with smaller brain volume in both MS (-0.75, -1.38 to -0.11, p=0.023) and PMS (ρ=-0.56, -0.83 to -0.095, p=0.021). Furthermore, CHI3L1 was associated with Expanded Disability Status Scale (0.70, 0.12 to 1.28, p=0.019) and age (0.93, 0.37 to 1.48, p=0.002) among all patients with MS.</p><p><strong>Conclusions: </strong>Association of CHI3L1 with glial activation and brain volume loss identifies plasma CHI3L1 as a promising biomarker for smouldering inflammation and MS progression-related pathology.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1053-1060"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086257","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}