Brain最新文献

{"title":"Thalamic stereoEEG in epilepsy: from cortical dogma to network-based hypotheses.","authors":"Fabrice Bartolomei, Francesca Pizzo","doi":"10.1093/brain/awag389","DOIUrl":"https://doi.org/10.1093/brain/awag389","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149357104","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":"Network disruption in post-stroke depressive symptoms: a Bayesian multicohort study.","authors":"Julian Klingbeil, Max Wawrzyniak, Thomas Tourdias, Igor Sibon, Nick A Weaver, Geert Jan Biessels, Jae-Sung Lim, Hee-Joon Bae, Nicholas T Trapp, Aaron D Boes, Daniel Tranel, Jordan Grafman, Anika Stockert, Dorothee Saur, Christoph Sperber","doi":"10.1093/brain/awag387","DOIUrl":"https://doi.org/10.1093/brain/awag387","url":null,"abstract":"<p><p>Post-stroke depressive symptoms are common, but studies on the contributions of lesion locations to depression symptoms remain inconsistent. Bayesian statistics offer the possibility to clarify these inconsistencies by providing evidence in favor and against observed associations. We reanalyzed four previously published observational cohorts with 1,864 patients with stroke characterized for depressive symptoms from France, Korea, Germany and the USA. We performed voxel-wise Bayes factor mapping using general linear models. Lesion maps were used to test for associations of post-stroke depressive symptoms with lesion location. Network level associations were tested based on structural disconnection and functional lesion network maps estimated by reference to normative connectome data. Due to a sample size with broad lesion coverage, Bayesian inference was informative in large parts of the brain. Lesion associations were found in clusters in the right hemisphere including cortical (frontal, insular, parietal) and subcortical regions (striatum, amygdala, hippocampus) and adjacent white matter. Evidence of no contribution to post-stroke depressive symptoms was observed in large parts of the left hemisphere. Structural disconnection was linked to depressive symptoms in the bilateral frontal white matter prominently involving the corpus callosum and anterior thalamic radiation. Lesion network mapping revealed evidence of an association of post-stroke depressive symptoms with network connectivity in the left posterior cingulate cortex and precuneus, and less consistently, the bilateral anterior insula, along with widespread absence of associations in other regions. Depressive symptoms were most strongly associated with right frontal lesions and right-dominant structural disconnection in frontal cortico-subcortical circuits.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340711","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":"Dysregulated CSF T-cell responses and their evolution after intravenous immunoglobulin in Guillain-Barré syndrome.","authors":"Alexander H Morrison, Tony Yao, Michael C Isfort, Jonathan Morena, Tom Liu, Jonathan Roell, Billur Akkaya, Stephen J Kolb, Erica H Bell, Naresha Saligrama, Benjamin M Segal","doi":"10.1093/brain/awag379","DOIUrl":"https://doi.org/10.1093/brain/awag379","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) is an acute immune-mediated neuropathy that frequently results in long-term disability. The cellular mechanisms underlying GBS and the immunomodulatory effects of intravenous immunoglobulin (IVIg) remain incompletely understood. In this prospective observational cohort study, we performed single-cell RNA sequencing with paired T cell receptor (TCR) sequencing on peripheral blood and cerebrospinal fluid (CSF) collected before and after IVIg treatment from treatment-naïve patients with GBS. Pre-treatment blood and CSF were obtained from nine and eight patients, respectively; post-treatment samples were available from six patients for blood and three patients for CSF. Previously published healthy control (HC) blood and CSF single-cell datasets were analyzed for comparison. We characterized immune cell composition, transcriptional states, TCR clonality, and clonal dynamics across peripheral and CSF compartments as well as following treatment. Individuals with GBS exhibited enrichment of T helper 1 (Th1)-polarized CD4+ T cells, activated and resident-memory CD8+ T cells, and macrophages in CSF relative to paired peripheral blood. This CSF-to-blood enrichment was greater than in healthy controls (HCs) for Th1 cells, activated effector-memory CD8+ T cells, and inflammatory macrophages, although the overall degree of T-cell clonal expansion was similar between groups. In both GBS and HCs, expanded CSF CD4+ clonotypes were predominantly Th1-polarized and largely absent from blood, whereas expanded CD8+ clonotypes showed greater overlap between compartments. Among clonotypes detected in both blood and CSF, CD4+ and CD8+ T cells exhibited more activated transcriptional states in the CSF, a shift that was particularly pronounced in GBS. Following IVIg treatment, peripheral blood showed minimal changes, whereas CSF T-cell populations exhibited more substantial alterations, including reductions in Th1-associated and activated effector-memory states, increases in T helper 2 (Th2) and regulatory T cell populations, and changes in the clonal repertoire. Expanded T cell clonotypes with sequence-based predicted specificity for pathogens associated with GBS were identified in six patients, and convergent clonotype groups were detected both within and across patients. Demyelinating GBS is characterized by compartmentalized enrichment and activation of pro-inflammatory T-cell populations within the CSF rather than an overall increase in T-cell clonal expansion. Exploratory longitudinal findings further suggest that CSF T-cell populations are altered following IVIg treatment. Integrated single-cell transcriptomic and TCR analyses provide insight into the early immune response in GBS and identify candidate cellular pathways for biomarker development and therapeutic investigation.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149332411","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":"Salovum® reduces mortality in isolated severe traumatic brain injury: a randomized phase II trial.","authors":"David Cederberg, Bradley M Harrington, Iain Walker, Ruan Grobler, Nitesh Naranbhai, Ryan K Jacobs, Edward Visse, Niklas Marklund, Adriaan Johannes Vlok, Peter Siesjö","doi":"10.1093/brain/awag241","DOIUrl":"10.1093/brain/awag241","url":null,"abstract":"<p><p>Isolated severe traumatic brain injury (TBI) is associated with high mortality and long-term morbidity, especially in low- and middle-income countries (LMICs). Despite promising results using pharmacological and non-pharmacological therapies in the experimental setting, no clinical trials have demonstrated robust efficacy. We aimed to investigate the effect of antisecretory factor (Salovum®) on 30-day mortality in adult patients with severe TBI. This was a prospective, double-blind, placebo-controlled phase 2 trial, conducted from September 2017 to February 2022 in a tertiary trauma centre (university hospital) in Cape Town, South Africa (www.clinicaltrials.gov: NCT03339505). The participants were adults with isolated severe TBI (Glasgow Coma Score 6-8), receiving intracranial pressure (ICP) monitoring and neurointensive care. Participants were administered either Salovum® (freeze-dried egg yolk powder enriched with the active compound antisecretory factor) or placebo (freeze dried egg yolk powder) via the nasogastric tubing, dosed according to weight (10-17 g/4 h) and initiated at 32.9 h ± 10.7 h (mean ± standard deviation) post-injury. Study drug or placebo were administered until the ICP monitor was removed or for a maximum of 5 days. The primary outcome of this trial was 30-day mortality and secondary outcome measures were therapy intensity level (TIL) and ICP. One hundred participants aged 18-61 were included, with 49 and 51 patients in the treatment and control groups, respectively. Most patients were male (96%) and the mean age was 33 years. The 30-day mortality rate was 20% in the treatment group and 39% in the control group, yielding a relative risk ratio of 0.52 (confidence interval: 0.271-0.997) and a P-value of 0.040 (chi-square test). TIL and ICP were similar in both groups. No significant adverse events were noted. Antisecretory factor significantly reduced 30-day mortality in severe TBI in an LMIC environment. Further studies investigating the mechanisms by which antisecretory factor act are warranted. The safety, easy administration and marked efficacy of antisecretory factor support exploration in multicentre randomized controlled trials.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3780-3788"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905020","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":"Reply: The disconnectome as a target in Alzheimer disease: a promising framework or a premature end point?","authors":"Lorenzo Pini, Bruno P Imbimbo, Maurizio Corbetta","doi":"10.1093/brain/awag263","DOIUrl":"10.1093/brain/awag263","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e101-e102"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677104","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":"Low-dose IL-2 fails to expand Tregs after alemtuzumab: insight into impaired immune tolerance in multiple sclerosis.","authors":"Zoya G Georgieva, Sarah K Howlett, Daniel B Rainbow, Valerie Coppard, Lou Ellis, Lorna B Jarvis, Evangelia Williams, Jennie H M Yang, Bo Sun, Timothy Tree, Alasdair J Coles, Linda S Wicker, Joanne L Jones","doi":"10.1093/brain/awag171","DOIUrl":"10.1093/brain/awag171","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) are essential to preventing autoimmunity. They depend upon interleukin-2 (IL-2) for optimal function and, due to high expression of the CD25 subunit of the IL-2 receptor, are 10-fold more sensitive to IL-2 than effector T cells (Teffs). Consequently, low-dose IL-2 can be used to expand Tregs preferentially, a therapeutic strategy that has shown promise in a number of autoimmune and inflammatory conditions-including graft-versus-host disease and lupus-where IL-2 driven expansion correlates with improvements in some clinical markers of disease activity. Autoimmunity is a frequent delayed complication of treatment with the lymphocyte-depleting drug alemtuzumab in relapsing-remitting multiple sclerosis (RRMS). Here, using in vitro assays, a pre-clinical mouse model and an experimental medicine study, we investigated whether low-dose IL-2 could selectively expand Tregs in alemtuzumab-treated RRMS patients. Six months after alemtuzumab treatment, the frequency of patient-derived naïve CD4+ Teffs expressing high-affinity IL-2 receptors increased from 30.11% ± 5.09% to 72.88% ± 5.57%, and the density of receptors per cell increased, rendering them six times more sensitive to IL-2 in vitro, at concentrations that typically favour Tregs. Using a human CD52-expressing transgenic mouse model of alemtuzumab treatment, we found that IL-2 could still preferentially expand Tregs, but only when administered at a later time point, corresponding to more than 6 months post-treatment in patients. Guided by these findings, we evaluated low-dose IL-2 for Treg expansion in a prospective open-label mechanistic study of RRMS patients who had received alemtuzumab more than 6 months previously. IL-2, at a dose and frequency similar to that previously shown to expand Tregs in autoimmune diabetes (0.3 × 106 IU/m2 twice a week), was well tolerated and safe, but unexpectedly failed to expand Tregs. We discuss the potential reasons underlying this lack of response, ruling out sIL2RA-related neutralization and instead considering ceiling effects on Treg proliferation, Treg exhaustion and intrinsic Treg dysfunction in MS as possible contributors. Together, our findings demonstrate that low-dose IL-2 alone is not an effective strategy for promoting Treg expansion post-alemtuzumab and is therefore not a viable approach on its own for preventing post-treatment autoimmune complications.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"4035-4051"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926174","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":"Diagnosing multiple sclerosis: implementation and unintended effects of the 2024 McDonald criteria.","authors":"Michael A Foster, Charles Wade, Helen L Ford, Klaus Schmierer","doi":"10.1093/brain/awag293","DOIUrl":"10.1093/brain/awag293","url":null,"abstract":"<p><p>Diagnostic criteria for multiple sclerosis have evolved substantially since the Schumacher criteria were published in 1965. The most recent iteration, the 2024 McDonald diagnostic criteria, was recently released. Each revision has broadened the range of evidence that can support diagnosis while attempting to preserve specificity. The central question raised by the 2024 revision is therefore not simply whether the criteria are valid in principle, but whether they can be applied safely outside expert centres, where imaging quality, laboratory infrastructure and subspecialist interpretation vary substantially. In this review, we evaluate the 2024 criteria not only as a consensus document but as an intervention in clinical behaviour, with particular attention to misdiagnosis risk, operational feasibility and equity of implementation. In particular, we consider the role of the optic nerve and of the central vein sign and paramagnetic rim lesions in diagnosis, and how the criteria bring more diverse populations and presentations into consideration. We also review how the greater options available to achieve a diagnosis may introduce heterogeneity into diagnostic approaches, and what safeguards can be taken to minimize the risk of inappropriate application of the criteria and subsequent misdiagnosis (and inappropriate treatment). The review finishes by proposing how the changes introduced in this iteration might be refined, with more robust definitions on acquiring and interpreting the novel biomarkers.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3747-3758"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838889","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":"Paediatric functional seizures: when care models meet clinical reality.","authors":"Apurva Parikh, Dara V F Albert, Ilana Yel, Brian Bronson","doi":"10.1093/brain/awag168","DOIUrl":"10.1093/brain/awag168","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3699-3702"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833329","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":"Divergent tau pathology profiles induced by distinct alpha-synuclein aggregates in non-human primates.","authors":"Morgane Darricau, Camille Neu-Faber, Mathieu Bourdenx, Sandra Dovero, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Nuria Garcia-Carrillo, Maria Trinidad Herrero, Miquel Vila, Jose A Obeso, Vincent Planche, Erwan Bezard, Benjamin Dehay","doi":"10.1093/brain/awag284","DOIUrl":"10.1093/brain/awag284","url":null,"abstract":"<p><p>Proteinopathies are frequently accompanied by co-pathologies, which complicate understanding the pathophysiological mechanisms of neurodegenerative diseases. In this study, we employed a well-characterized baboon cohort to investigate the occurrence of tau pathology following intrastriatal injections of two distinct α-synuclein extracts [small aggregates (SA) and large aggregates (LA)] derived from the brains of patients with Parkinson's disease (PD). Biochemical and histopathological analyses (6, 12 or 24 months after injections) revealed significantly higher phosphorylated tau expression and greater frequency of neuropil threads in both LA- (n = 18) and SA-injected baboons (n = 12) compared with control animals. We also observed distinct patterns of tau pathology depending on the assembly of α-synuclein aggregates. Baboons injected with SA exhibited tangle-like phosphorylated tau lesions and neuropil threads, with no significant differences across post-injection time points. Moreover, a uniform distribution of tau pathology was detected along the rostro-caudal axis of the medial temporal lobe, affecting neuronal, oligodendroglial and astrocytic cell types. On the other hand, baboons injected with LA exhibited neuropil threads and few glial lesions but lacked phosphorylated tau intraneuronal aggregates. The occurrence of phosphorylated tau lesions was associated with phosphorylated synuclein pathology. These observations suggest a link between nigrostriatal synucleinopathy and limbic tau co-pathology, providing pathophysiological insights into PD dementia.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3771-3779"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787829","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":"Mapping brain imaging heterogeneity in multiple sclerosis.","authors":"Tomas Uher, Guy Nagels","doi":"10.1093/brain/awag349","DOIUrl":"10.1093/brain/awag349","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3687-3689"},"PeriodicalIF":12.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134640","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}