Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"MOG Antibody in Pregnancy and Breast Milk: An Analysis of 2 Case Reports.","authors":"Anastasia Vishnevetsky, Philippe A Bilodeau, Nicole Elena Resnick, Michael Levy","doi":"10.1212/NXI.0000000000200673","DOIUrl":"10.1212/NXI.0000000000200673","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200673"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148919","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":"Reduced Paramagnetic Rim Visibility Signals Lesion Aging and Tissue Degeneration in Progressive Multiple Sclerosis: Impact on Clinical Trials.","authors":"Simone Sacco, Haojun Zhao, Shuiting Cheng, Amit Vijay Akula, Elaina Luskin, Jiuyi Zhang, Olga Manouvakhova, Tiffany P Cooper, William Stern, Valerie J Block, Akash Virupakshaiah, Refujia Gomez, Adam Santaniello, Pascal Sati, Nico Papinutto, Riley Bove, Jeffrey M Gelfand, Douglas S Goodin, Ari J Green, Jorge Oksenberg, Emmanuelle Waubant, Michael R Wilson, Scott S Zamvil, Bruce A C Cree, Stephen L Hauser, Roland G Henry","doi":"10.1212/NXI.0000000000200655","DOIUrl":"10.1212/NXI.0000000000200655","url":null,"abstract":"<p><strong>Background and objectives: </strong>Paramagnetic rim lesions (PRLs) in multiple sclerosis (MS) indicate chronic, innate immune-mediated inflammation contributing to disease progression. Rim disappearance or attenuation is interpreted as a treatment response; however, it remains uncertain whether reduced susceptibility signal-likely reflecting decreased iron within the rim compartment-represents true resolution of chronic inflammation, natural lesion aging, and/or advanced tissue degeneration. Cross-sectionally, PRLs show variable rim conspicuity, enabling classification as Definite or Probable. We used quantitative MRI (qMRI) to assess underlying tissue destruction in Definite vs Probable PRLs in people with progressive MS (PwPMS).</p><p><strong>Methods: </strong>One hundred six PwPMS (34 primary progressive [PP], 72 secondary progressive; age 56 ± 10 years; median Expanded Disability Status Scale [EDSS] 5.5; 44% on disease-modifying therapy) underwent 3D-EPI and multishell diffusion MRI. PRLs (N = 155) were classified as Definite (N = 114) or Probable (N = 41). Prior clinical MRI scans estimated lesion age using an accelerated failure time model accounting for censoring. Whole-lesion, rim, and core regions were segmented; lesion size, quantitative susceptibility mapping, diffusion tensor imaging, Neurite Orientation Dispersions Density Imaging metrics, and T1 signal intensity were compared after multiple comparison correction.</p><p><strong>Results: </strong>In total, 52% of PwPMS had ≥1 PRL; only 33% had Definite PRLs. Probable PRLs were more frequent in secondary vs PP MS (24% vs 9%, <i>p</i> = 0.05). Higher PRL counts were associated with younger age (<i>p</i> < 0.001), and PRLs were more often Definite in younger PwPMS (<i>p</i> < 0.0004). Participants with only Definite PRLs had shorter disease duration than those with ≥1 Probable PRL or no PRLs, and Probable PRLs were significantly older. Definite PRLs showed higher rim susceptibility (22 vs 8 ppb, <i>p</i> < 0.001); Probable PRLs demonstrated greater tissue disruption at qMRI-higher mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and FISO and lower neurite density index (NDI), and larger lesion size (all <i>p</i> < 0.001).</p><p><strong>Discussion: </strong>In progressive MS, PRLs with lower rim susceptibility are more likely classified as Probable but may represent older lesions with greater tissue damage. Because chronic active lesions do not require iron pathologically and rims can fade over time, rim disappearance at MRI cannot be interpreted unequivocally as resolving inflammation and may reflect natural lesion evolution. Rim persistence may be a more informative marker of ongoing compartmentalized inflammation than rim disappearance is of its resolution.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200655"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017719","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":"Tenofovir in Progressive Multifocal Leukoencephalopathy: Virus Suppression Without Clinical Benefit in 2 Cases.","authors":"Julia Lier, Achmed Mrestani, Max Braune, Mario Hönemann, Johann Otto Pelz, Jost-Julian Rumpf, Florian Then Bergh","doi":"10.1212/NXI.0000000000200647","DOIUrl":"10.1212/NXI.0000000000200647","url":null,"abstract":"<p><strong>Objectives: </strong>Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the CNS caused by reactivation of the JC polyomavirus (JCV), typically in immunocompromised individuals. As no specific therapy against JCV exists, current management focuses on immune reconstitution. Recently, a potential therapeutic effect of tenofovir was reported.</p><p><strong>Methods: </strong>We report 2 patients with PML who received tenofovir under a compassionate use protocol. Treatment was accompanied by MRI, clinical, and virologic monitoring.</p><p><strong>Results: </strong>In both patients (serum and CSF), viral load was markedly reduced. In 1 patient, this was accompanied by temporary clinical stabilization and reduction in MRI lesion burden. The other patient further declined clinically, accompanied by progression of MRI lesion size and contrast enhancement. Dense lymphocytic infiltration on biopsy suggested predominant effects of alleviated immunosuppression rather than the direct antiviral drug effect. Both patients ultimately died of the disease.</p><p><strong>Discussion: </strong>Despite virus reduction in both cases, sustained clinical improvement was not achieved. This suggests that viral load reduction alone is insufficient, and pathogenesis may be largely driven by the immune response to the infection. A combination of tenofovir with low-dose anti-inflammatory drugs may be a useful addition to PML therapy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200647"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920377","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":"Antibody-Dependent Cellular Phagocytosis and Cytotoxicity in Patients With LGI1 and CASPR2 Encephalitis.","authors":"Pietro Businaro, Stefano Masciocchi, Silvia Scaranzin, Chiara Morandi, Federica Zuliani, Antonio Malvaso, Denise Cerne, Paolo Barone, Antonella Toriello, Carla Arbasino, Silvia Cenciarelli, Irene Volonghi, Silvia Casagrande, Stefano Nassani, Marco Currò-Dossi, Sara Micheli, Francesco Fattapposta, Alvino Bisecco, Carmela Leone, Enrico Marchioni, Diego Franciotta, Marianna Spatola, Elisabetta Zardini, Luana Benedetti, Matteo Gastaldi","doi":"10.1212/NXI.0000000000200646","DOIUrl":"10.1212/NXI.0000000000200646","url":null,"abstract":"<p><strong>Background and objectives: </strong>Antibodies against LGI1 and CASPR2 (LGI1/CASPR2-IgG) associate with forms of autoimmune encephalitis (AE) that improve with immunotherapy but often show long-term residual disability. We aimed to investigate whether autoantibody effector functions contribute to pathogenic mechanisms and might act as prognostic biomarkers in patients with LGI1/CASPR2-AE.</p><p><strong>Methods: </strong>We included patients with LGI1/CASPR2-AE, sufficient clinical information, and 1 serum sample available. We assessed the functional profile of LGI1/CASPR2-IgG using in vitro cell-based assays for complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC). Outcome was measured using the modified Rankin Scale (mRS) and the Clinical Assessment Scale in AE.</p><p><strong>Results: </strong>We enrolled 55 patients (LGI1 = 31 and CASPR2 = 24). Coexistent ADCC and ADCP (ADCC+/ADCP+) were found in 28/55 patients (10/31 with LGI1 and 18/24 with CASPR2), while an isolated ADCP (ADCC-/ADCP+) was detected in 15 patients (12 with LGI1-IgG and 3 with CASPR2-IgG), and an isolated ADCC (ADCC+/ADCP-) was detected in 2 LGI1-IgG-positive patients. Because most patients (84%) showed a combination of IgG1/IgG3 and IgG4 subclass, no specific functional profiles could be identified according to the predominant subclass. Quantitative ADCP levels showed only a moderate correlation with CASPR2/LGI1-IgG titers (rho = 0.35, <i>p</i> = 0.02), while ADCC showed a moderate/strong correlation (rho = 0.54, <i>p</i> = 0.002). None of the patients showed CDC activation. In a multivariate logistic regression model (including functional profile, rituximab treatment, relapsing course, and cognitive impairment at onset), the ADCC+/ADCP + profile was the only predictor of poor outcome (mRS > 1, OR: 10.97 [95% CI 1.96-106.9]; <i>p</i> = 0.014).</p><p><strong>Discussion: </strong>ADCC and ADCP, but not CDC, are common effector functions of LGI1/CASPR2-IgG, and their presence correlates with long-term poor outcome, suggesting that they might represent a useful prognostic biomarker and suggest additional pathogenic mechanisms. We provide the proof- of principle for a framework that could be applied to other autoantibody-mediated disorders.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200646"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030994","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":"Serum Glial-Related Biomarkers Show Distinct Contributions to Radiologic and Clinical Outcomes in Early Multiple Sclerosis.","authors":"Manuel Comabella, Luca Bollo, Nicolas Fissolo, Pascal Benkert, Ingrid Klass, Carmen Tur, Estibaliz Saez de Gordoa, Lucia Gutierrez, Cristina Auger, Jordi Rio, Jaume Sastre-Garriga, Mar Tintore, Jens Kuhle, Àlex Rovira, Xavier Montalban","doi":"10.1212/NXI.0000000000200663","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200663","url":null,"abstract":"<p><strong>Background and objectives: </strong>To investigate the association between serum levels of glial-related biomarkers, including glycoprotein nonmetastatic melanoma B (GPNMB), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), galectin-3, serpin peptidase inhibitor clade A member 3 (SERPINA3), chitotriosidase-1 (CHIT1), and chitinase 3-like 1 (CHI3L1) and 2 (CHI3L2), and the presence of paramagnetic rim lesions (PRLs) and the risk of progression independent of relapse activity (PIRA) in patients with a first demyelinating event.</p><p><strong>Methods: </strong>PRLs were identified using 3T susceptibility-based imaging. Univariable and multivariable linear regression models assessed the association between biomarker levels and the presence of PRLs at baseline. Univariable and multivariable Cox proportional hazards models investigated the association between biomarker levels and risk of PIRA during follow-up. sTREM2 and CHI3L1 levels were measured using single molecule array assays, whereas levels of the remaining biomarkers were determined using ELISA.</p><p><strong>Results: </strong>We included 135 patients (median age, 34.4 [interquartile range (IQR) 29.2-41.7] years; 98 [72.6%] women; median follow-up, 5.4 [IQR 2.7-9.4] years). PRLs were detected in 59 (43.7%) patients. The presence of ≥1 PRLs at baseline was associated with increased levels of CHI3L1 in univariable (multiplicative effect [ME] = 1.32; 95% CI 1.10-1.58; <i>p</i> = 0.003) and multivariable analyses (ME = 1.31; 95% CI 1.05-1.63; <i>p</i> = 0.01). Thirty (22.2%) patients developed PIRA during follow-up. Doubling of serum galectin-3 levels was associated with an increased risk of PIRA in univariable (hazard ratio [HR] = 1.76; 95% CI 1.06-2.94; <i>p</i> = 0.02) and multivariable analyses (HR = 2.15; 95% CI 1.22-3.80; <i>p</i> = 0.008). Similarly, doubling of serum CHI3L2 levels was associated with an increased risk of PIRA in both univariable (HR = 1.36; 95% CI 1.05-1.76; <i>p</i> = 0.02) and multivariable analyses (HR = 1.36; 95% CI 1.02-1.82; <i>p</i> = 0.03). The combined elevation of galectin-3 and CHI3L2 was associated with an increased risk of PIRA in multivariable analysis (HR = 8.44; 95% CI 3.01-23.70; <i>p</i> < 0.0001).</p><p><strong>Discussion: </strong>These findings suggest distinct contributions of glial-related biomarkers to radiologic and clinical outcomes in early multiple sclerosis. Validation in independent cohorts will be required before their value as blood prognostic biomarkers can be established.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200663"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195596","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":"Functional and Structural Imaging Features of Cognitive Profiles in Multiple Sclerosis.","authors":"Kshiteeja Jain, Paola Valsasina, Damiano Mistri, Alessandro Meani, Paolo Preziosa, Massimo Filippi, Maria A Rocca","doi":"10.1212/NXI.0000000000200669","DOIUrl":"10.1212/NXI.0000000000200669","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cognitive impairment affects 40%-70% of patients with multiple sclerosis (MS). Although recent hypothesis-driven and data-driven efforts have identified cognitive phenotypes, functional substrates underlying impairment in such phenotypes are still not clear. Our objective was to identify distinct cognitive phenotypes using clustering in a large cohort of patients with MS and characterize their associated clinical, structural MRI, and resting-state (RS) functional connectivity (FC) features.</p><p><strong>Methods: </strong>We conducted an observational, cross-sectional study with right-handed patients with MS and age-matched and sex-matched healthy controls (HCs) who underwent neurologic and neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological tests). Latent profile analysis on cognitive test Z-scores identified MS cognitive phenotypes. 3.0T MRI was used to derive atrophy measures and RS FC within default mode network (DMN I/II), executive control network (ECN), left/right fronto-parietal, language, and salience networks. Linear regression models compared structural MRI and RS FC across cognitive phenotypes and HCs, while polynomial contrasts assessed RS FC patterns across groups.</p><p><strong>Results: </strong>Three hundred and sixty-nine patients with MS and 168 HCs were enrolled. Four cognitive phenotypes were detected: preserved cognition ([PC], n = 67[18.2%]), mild single-domain verbal fluency involvement (MSD-VF, n = 37[10.0%]), mild single-domain attention involvement (MSD-A, n = 197[53.4%]), and severe multidomain (SMD) involvement (SMD, n = 68[18.4%]). At corrected threshold, PC patients showed decreased deep gray matter (GM) volumes (<i>p</i> < 0.001-0.001) and similar RS FC vs HCs, whereas MSD-VF exhibited no significant atrophy and no differences in RS FC vs HCs. MSD-A displayed lower cortical/deep GM volumes vs HCs (<i>p</i> < 0.001-0.005), whereas SMD had worse clinical and atrophy features (<i>p</i> < 0.001-0.04), as well as decreased DMN II RS FC (<i>p</i> = 0.01-0.04) vs other groups. Polynomial contrast analyses revealed significant quadratic patterns with increased RS FC in MSD-VF vs HC/PC groups, followed by decrease in MSD-A and SMD, within DMN II (<i>p</i> = 0.005), ECN (<i>p</i> = 0.005), and language network (<i>p</i> < 0.001).</p><p><strong>Discussion: </strong>PC exhibited intact RS FC, whereas SMD presented widespread structural and DMN RS FC damage. These findings advance our understanding of cognitive heterogeneity in MS by revealing distinct structural and functional neuroimaging profiles across cognitive phenotypes, encouraging future longitudinal and multimodal investigations to improve disease characterization and prognostic stratification.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200669"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195506","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":"The Weiner Prize in Neuroimmunology.","authors":"Vijay K Kuchroo, Oleg Butovsky, Francisco J Quintana","doi":"10.1212/NXI.0000000000200624","DOIUrl":"10.1212/NXI.0000000000200624","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200624"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813744","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":"Parkinsonism as a Potential Neurologic Immune-Mediated Adverse Event of Immune Checkpoint Inhibitors.","authors":"Cristina Birzu, Kevin Bihan, Mathias Wehrung, Aurelie Kas, Frederic Valette, Hélène Pouclet-Courtemanche, Loic Diop Jaffrelot, Delphine Leclercq, Pascale Palassin, Louise Gaboriau, Judith Raimbourg, Lila Autier, Antonio Farina, Bastien Joubert, Jerome Honnorat","doi":"10.1212/NXI.0000000000200644","DOIUrl":"10.1212/NXI.0000000000200644","url":null,"abstract":"<p><strong>Objectives: </strong>Immune checkpoint inhibitor (ICI)-related parkinsonism is an exceedingly rare neurologic immune-related adverse event (irAE).</p><p><strong>Methods: </strong>We reviewed retrospectively the French Pharmacovigilance Agency and French National Center for Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes Lyon databases (2015-2025) following identification of index case.</p><p><strong>Results: </strong>We identified 4 male and one female patient, with a median age of 67 years (range 34-75), who developed acute-to-subacute parkinsonism after a median of 4 ICI cycles (range 1-12). The predominant phenotype was bilateral akinetic-rigid syndrome (rigidity n = 5, bradykinesia n = 4, tremor n = 3); the median modified Rankin Scale score at onset was 3. CSF analysis showed pleocytosis in 2/4 tested patients and elevated protein in 4/4 tested patients. Dopamine transporter imaging demonstrated bilateral dopaminergic denervation in both patients tested (n = 2), with documented reversibility in one. ICI discontinuation alone (n = 1/2) or combined with immunomodulatory therapy (n = 3) yielded clinical improvement over a median follow-up of 15 months (range 3-30). Levodopa/carbidopa supplementation was required in 2 patients.</p><p><strong>Discussion: </strong>Post-ICI-related parkinsonism is a rare but potentially reversible irAE. Early recognition and prompt ICI discontinuation may favor significant clinical recovery. Immunosuppressive therapy should be considered for severe cases or those not improving after ICI discontinuation alone.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200644"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707257","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":"Data-Driven Fatigue Trajectories in Multiple Sclerosis and Their Predictors.","authors":"Alessandro Cruciani, Emanuele Olivieri, Ronja Christensen, Sarmad Al-Araji, Samih Fourali, Weaam Hamed, Anna He, Baris Kanber, Davide Maccarrone, Suraya Mohamud, Riccardo Nistri, Anestis Passalis, Valeria Pozzilli, Ferran Prados, Charmaine Yam, Marios C Yiannakas, Alan J Thompson, Frederik Barkhof, Ahmed T Toosy, Olga Ciccarelli","doi":"10.1212/NXI.0000000000200643","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200643","url":null,"abstract":"<p><strong>Background and objectives: </strong>Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), yet its longitudinal trajectories and determinants remain poorly characterized. We aimed to identify trajectories of cognitive and physical fatigue in relapsing-remitting MS (RRMS) and to determine baseline clinical and MRI predictors of worsening fatigue.</p><p><strong>Methods: </strong>We conducted a prospective, single-center cohort study embedded in the Predicting Optimal INdividualised Treatment response in MS (POINT-MS) program at the Queen Square MS Centre (London, United Kingdom). Adults with RRMS initiating a new disease-modifying therapy within 3 months of baseline were enrolled and underwent clinical and MRI assessments at baseline, 6 months, and 18 months. Key inclusion criteria were a diagnosis of RRMS, availability of baseline brain and cervical spinal cord MRI, and completion of at least 3 Modified Fatigue Impact Scale (MFIS) assessments. The primary outcome was the longitudinal change in MFIS cognitive and physical subscale scores. Fatigue trajectories were identified using growth mixture modeling. Baseline predictors included demographic factors, disability, cognitive performance, depression diagnosis, proportion of disease duration on disease-modifying treatments (DMTs), and MRI-derived measures of cervical spinal cord cross-sectional area (C-CSA) and regional brain volumes standardized to healthy-control norms. Predictor importance was assessed with conditional random forests, followed by multivariable modeling.</p><p><strong>Results: </strong>We enrolled 225 participants. Three distinct fatigue trajectories emerged for both cognitive and physical MFIS subscales, including improving, stable/mild-worsening, and worsening classes. Worsening trajectories showed annualized increases of +3.32 points/year (cognitive) and +3.37 points/year (physical). Smaller baseline C-CSA was the strongest MRI predictor of worsening trajectories. Clinically, the proportion of disease duration spent on DMTs was the most influential predictor.</p><p><strong>Discussion: </strong>Fatigue in RRMS follows heterogeneous trajectories over short-term follow-up. Smaller cervical spinal cord area was the strongest MRI predictor of worsening fatigue. Damage to ascending somatosensory axons within the cervical cord may reduce afferent input to the thalamus and diminish thalamocortical drive, contributing to both the motor and the cognitive-arousal dimensions of fatigue. These findings support incorporating cervical cord MRI into prognostic models and future fatigue research.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200643"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796003","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":"Long-Term Outcomes in Autoimmune Encephalitis: A Nationwide, Clinical Study in Denmark.","authors":"Thomas Agerbo Gaist, Lisbeth Rosenlund Lodahl, Henrik Akre Thorup, Mette Scheller Nissen, Klaus Hansen, Thomas Harbo, Sophia Rekers, Carsten Finke, Morten Blaabjerg","doi":"10.1212/NXI.0000000000200641","DOIUrl":"10.1212/NXI.0000000000200641","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autoimmune encephalitis is a rare disease associated with considerable morbidity in the acute phase of the disease. Nationwide cohort studies investigating long-term cognitive outcomes are rare. Furthermore, although bedside cognitive assessments are frequently used in clinical practice to evaluate patients with AE, there is currently no consensus on the optimal test for this purpose. Using the unique Danish centralized antibody testing setup, we identified an unselected, nationwide AE cohort. We then performed a comprehensive evaluation of long-term cognitive outcomes.</p><p><strong>Methods: </strong>All adult patients with seropositive AE diagnosed in Denmark from 2009 to 2022 were identified and invited to participate in the study. Participants underwent neuropsychological testing and bedside cognitive testing (Montreal Cognitive Assessment [MoCA], Mini-Mental State Examination [MMSE], Addenbrooke's Cognitive Examination [ACE], and Frontal Assessment Battery [FAB]). Fatigue, depression, anxiety, life satisfaction, and quality of life were assessed using questionnaires.</p><p><strong>Results: </strong>We included 86 of 108 eligible patients. The median time from symptom onset to participation was 77 months (interquartile range 35/125). All patients with anti-<i>N</i>-methyl-D-Aspartate receptor (NMDAR) encephalitis (NMDARE) (n = 33) and 86% of patients with limbic encephalitis (n = 37) obtained modified Rankin Scale (mRS) 0-2 at the time of testing, while 45% of patients with NMDARE and 43% of limbic encephalitis had multidomain cognitive deficits on formal neuropsychological testing. Memory, visuoconstruction, and executive function were the most affected cognitive domains. Postencephalitic dementia was present in 15% of the cohort, affecting primarily patients with limbic encephalitis, and was associated with higher mRS at peak disease, older age at disease onset, and relapsing disease. The MoCA had the strongest correlation with mean neuropsychological <i>z</i>-score and had the highest sensitivity and specificity for detecting cognitive impairment among patients with NMDARE and limbic encephalitis, when compared with the other bedside cognitive screening tools. There was a high prevalence of fatigue (38% NMDARE and 29% limbic encephalitis), and overall life satisfaction correlated strongly with both fatigue and depression scores in both groups.</p><p><strong>Discussion: </strong>Long-term cognitive impairment and fatigue were prevalent in AE, despite good functional outcomes as measured by the mRS. The MoCA correlated well with neuropsychological performance and could be the bedside test of choice if a neuropsychologist is not readily available.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200641"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813677","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}