Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"FCRL5, a B-Cell Marker With Novel Diagnostic and Prognostic Value for Multiple Sclerosis.","authors":"Matthieu Deltombe, Anna Stölting, Pietro Maggi, Vincent van Pesch","doi":"10.1212/NXI.0000000000200485","DOIUrl":"10.1212/NXI.0000000000200485","url":null,"abstract":"<p><strong>Background and objectives: </strong>Fc receptor-like 5 (FCRL5) is an IgG-binding receptor frequently reported to be highly expressed on double-negative and atypical memory B cells, both of which are frequently expanded in inflammatory conditions. However, its expression profile in multiple sclerosis (MS) remains unclear. This study aims to characterize FCRL5 expression in CSF, serum, and peripheral blood mononuclear cells (PBMC) of patients with MS and to define the phenotypic and transcriptional features of FCRL5⁺ B cells in MS.</p><p><strong>Methods: </strong>A proximity extension assay-based proteomic analysis was conducted on the CSF of patients with relapsing-remitting MS (RRMS, n = 59) and controls (n = 29). The observed FCRL5 upregulation was validated using single-molecule array analysis in a cohort comprising patients with RRMS (n = 40), controls (n = 30), and individuals with other inflammatory neurologic diseases (OIND, n = 20). Serum FCRL5 levels were also assessed in a cohort of patients with MS characterized by 3T MRI (n = 58). In addition, flow cytometry-based techniques and RNA sequencing were performed on PBMC from patients with RRMS and controls to investigate the phenotype and transcriptional profiles of FCRL5⁺ B cells. Finally, the effect of Bruton tyrosine kinase inhibitors (BTKi) on FCRL5 regulation was also evaluated in vitro.</p><p><strong>Results: </strong>FCRL5 was significantly upregulated in the CSF of patients with RRMS compared with that in controls and OIND. Elevated CSF FCRL5 levels were associated with an increased risk of new brain lesions within 24 months. Serum FCRL5 levels were not correlated with CSF measurements but were inversely correlated with the cortical and juxtacortical lesion burdens. Moreover, flow cytometry analysis revealed that peripheral CD19⁺FCRL5⁺ B cells of patients with RRMS differed from those of controls by their strong CD11c expression. The transcriptional profiles of CD19⁺CD11c⁺FCRL5⁺ cells also differed significantly between the 2 groups, characterized by reduced expression of humoral response genes and enhanced inflammatory signaling. In addition, FCRL5 regulation was found to be BTK-dependent.</p><p><strong>Discussion: </strong>The soluble form of FCRL5 can be measured in the CSF and could serve as a promising biomarker for MS diagnosis and disease activity prediction. In addition, this study highlights that CD19⁺CD11c⁺FCRL5⁺ B cells in MS display a distinct transcriptional profile compared with controls.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200485"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177136","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":"Outcomes in Patients With Immune Checkpoint Inhibitor-Related Myopathy and Prolonged Follow-Up.","authors":"Yahel Segal, Georgios Mangioris, Michel Toledano, Lisa Kottschade, Eoin P Flanagan, Andrew McKeon, Ronen Stoff, Elie Naddaf, Sean J Pittock, Divyanshu Dubey, Anastasia Zekeridou","doi":"10.1212/NXI.0000000000200484","DOIUrl":"10.1212/NXI.0000000000200484","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myopathy is one of the most common neurologic immune-related adverse events (irAEs) reported after treatment with immune checkpoint inhibitor (ICI) cancer immunotherapies. Current knowledge on disease course relates to short-term outcomes, and long-term outcome data are lacking. The aim of this study was to evaluate the long-term outcomes of patients with ICI-related myopathy.</p><p><strong>Methods: </strong>We reviewed Mayo Clinic patients diagnosed with ICI-related myopathy between 2013 and 2024 with at least 6 months of follow-up; we compared them with patients who died because of myopathy within 2 months from disease onset.</p><p><strong>Results: </strong>Twenty-three patients were identified; the median follow-up duration was 13 months (range 6-76). The median age at presentation was 73 years (range 34-87), and 57% were male. The most common presentations were ocular involvement (78%, including oculomotor and ptosis), followed by proximal limb (74%), axial (61%), and bulbar (48%) weakness. Myocarditis was present in 35%. At disease nadir, 43% had an irAE grade >2. All patients were treated with corticosteroids; 61% received additional immunosuppressive/immunomodulatory treatment in the acute setting. The median treatment duration was 5 months (range 1-17). At the last follow-up, 87% of patients had a favorable outcome (irAE grade ≤2), yet residual symptoms/signs were common (48%). Gradual improvement was observed in most patients, even after immunosuppressive/immunomodulatory treatment was discontinued. The only patient with a truly refractory course had biopsy findings of nemaline rods. Compared with patients with long-term follow-up, patients who died within 2 months (N = 9) were more commonly men (57% vs 100%, <i>p</i> = 0.03) and more likely to have bulbar or axial involvement (<i>p</i> = 0.01 and <i>p</i> = 0.04, respectively).</p><p><strong>Discussion: </strong>Approximately half of the patients with ICI-related myopathy and long-term follow-up had some residual symptoms/signs, despite good functional outcomes. Symptoms continue to improve over 12 months regardless of immunosuppressive/immunomodulatory treatment duration. Male sex and axial and bulbar symptoms/signs were all associated with a terminal disease course. A prolonged refractory disease course might suggest an atypical pathology.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200484"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239248","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":"Paraneoplastic Brachial Amyotrophic Diplegia With Favorable Outcome and Anti-Ank3 Antibodies: A Case Report.","authors":"Florent Cluse, Le Duy Do, Emilien Bernard, Véronique Rogemond, Sterenn Closs, Elva Rumnici, Isabelle Quadrio, Marie Benaiteau, Jerome Honnorat","doi":"10.1212/NXI.0000000000200488","DOIUrl":"10.1212/NXI.0000000000200488","url":null,"abstract":"<p><strong>Objectives: </strong>To report a case of paraneoplastic motor neuron disease (MND) with a favorable outcome after cancer treatment.</p><p><strong>Methods: </strong>Clinical, electrophysiologic, radiologic, and serum/CSF study of a patient with brachial amyotrophic diplegia/flail-arm syndrome (BAS/FAS).</p><p><strong>Results: </strong>A 68-year-old man presented with a subacute-onset upper limb weakness and atrophy evocative of BAD/FAS. Electrodiagnostic study (EDX) confirmed MND; CSF examination found oligoclonal bands and elevated neurofilament light chains (NfL). A prostate adenocarcinoma was concomitantly diagnosed in a context of dysuria and elevated prostate-specific antigen level. One month after onset of cancer treatment (double hormonotherapy), the patient's impairment started to improve. Subsequently, the muscle denervation signs on EDX disappeared and CSF NfL levels decreased. At last follow-up visit, 2 years after onset, he was asymptomatic and unimpaired. Anti-ankyrin-3 (Ank3) autoantibodies were detected in the CSF by tissue-based immunofluorescence and confirmed by cell-based assay.</p><p><strong>Discussion: </strong>We herein describe an original case of subacute-onset BAD/FAS with evidence of CSF inflammatory changes, autoantibodies of unknown significance, and simultaneous diagnosis of prostate cancer suggesting a possible paraneoplastic neurological syndrome (PNS). The outcome was remarkably favorable after hormonotherapy. Even in the absence of usual onconeural antibodies, MND may be encountered among PNS, and their prognosis is not always poor.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200488"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239280","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":"Anti-CD19 CAR T-Cell Therapy in Advanced Stiff-Person Syndrome and Concomitant Myasthenia Gravis.","authors":"Ilya Ayzenberg, Athina-Maria Aloizou, Clarissa Lohmann, Simon Faissner, Christiane Schneider-Gold, Dominic Borie, Thomas Mika, Roland Schroers, Jeremias Motte, Ralf Gold","doi":"10.1212/NXI.0000000000200479","DOIUrl":"10.1212/NXI.0000000000200479","url":null,"abstract":"<p><strong>Background: </strong>Autologous chimeric antigen receptor (CAR) T-cell therapy has recently gained interest in the treatment of rheumatic and neuroimmunologic diseases.</p><p><strong>Methods: </strong>We report a 62-year-old female patient with a 14-year history of treatment-refractory anti-GAD-positive stiff-person syndrome (SPS) and concomitant anti-AChR-positive myasthenia gravis. Despite a relatively stable disease course in the first 8 years, SPS dramatically progressed afterward. In 2023, she was able to walk less than 10-15 m and suffered from severe persistent stiffness in the left arm superimposed with painful muscle spasm attacks (MSAs). Numerous immunotherapies, including intravenous immunoglobulins, plasma exchange, steroids, azathioprine, and rituximab, were ineffective. Consequently, she was escalated to compassionate use of autologous anti-CD19 CAR T-cell therapy (KYV-101).</p><p><strong>Results: </strong>From the third month post-CAR-T, we observed a substantial improvement in walking distance, pain, anxiety, and MSAs in the arm. By the sixth month, she was able to walk 500 m. The anti-GAD titers declined from 1:320 to 1:32. Side effects included grade 2 cytokine release syndrome and moderate leukopenia, without serious infections.</p><p><strong>Discussion: </strong>CAR T-cell therapy was effective at mitigating SPS symptoms, despite the long history and severe refractory disease course in our patient. Controlled trials are needed to evaluate its potential in SPS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200479"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239197","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":"Epstein-Barr Virus in Multiple Sclerosis: Past, Present, and Future.","authors":"Farah Wahbeh, Joseph J Sabatino","doi":"10.1212/NXI.0000000000200460","DOIUrl":"10.1212/NXI.0000000000200460","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a very common herpesvirus that infects more than 90% of the general population. Epidemiologic data indicate that EBV is a requisite risk factor for the development of multiple sclerosis (MS); however, the mechanisms by which EBV contributes to MS pathogenesis are unclear. In this review, we discuss how EBV alters the functions of B cells, its primary cellular reservoir, and the associated dysregulation of anti-EBV immunity in patients with MS. We comprehensively explore the evidence for different potential mechanisms by which EBV may lead to the development of MS, including the so-called driver and hit-and-run models. Finally, we discuss key outstanding scientific questions that must be addressed to advance not only our understanding of the role of EBV in MS pathology but also the development of novel disease therapies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200460"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069896","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":"CSF Beta-Synuclein, SNAP-25, and Neurogranin in Infectious and Autoimmune Inflammatory Neurologic Diseases.","authors":"Samir Abu-Rumeileh, Deborah K Erhart, Lorenzo Barba, Franz Felix Konen, Caroline Stapf, Makbule Senel, Dominica Hudasch, Petra Steinacker, Patrick Oeckl, Christopher M Weise, Nicola Ticozzi, Steffen Halbgebauer, Federico Verde, Kurt-Wolfram Sühs, Hayrettin Tumani, Markus Otto","doi":"10.1212/NXI.0000000000200491","DOIUrl":"10.1212/NXI.0000000000200491","url":null,"abstract":"<p><strong>Background and objectives: </strong>Beta-synuclein (beta-syn), synaptosomal-associated protein 25 (SNAP-25), and neurogranin are CSF biomarkers of synaptic damage, which have been poorly investigated in non-neurodegenerative neurologic diseases. In this study, we examined the diagnostic and prognostic role of these markers compared with the neuroaxonal damage marker neurofilament light chain protein (NfL) in infectious and autoimmune inflammatory neurologic diseases (IINDs and AINDs).</p><p><strong>Methods: </strong>This cohort study included CSF samples from patients with different etiologies of IIND (varicella-zoster virus, herpes simplex virus, tick-borne meningoencephalitis, bacterial meningitis/(meningo)encephalitis, neuroborreliosis, or other/unknown etiology) or AIND (autoimmune encephalitis or other etiology) as well as controls.</p><p><strong>Results: </strong>A total of 123 patients with IINDs (mean age 55.23 ± 18.04 years, 43.2% female), 22 with AINDs (age 60.41 ± 16.03 years, 81.8% female), and 95 controls (age 52.39 ± 17.94 years, 56.9% female) were enrolled. Compared with the control group, participants with IINDs and AINDs showed higher concentrations of beta-syn (<i>p</i> < 0.001 and <i>p</i> = 0.038, respectively), neurogranin (<i>p</i> = 0.039 and <i>p</i> = 0.002, respectively), and NfL (<i>p</i> < 0.001 and <i>p</i> = 0.001, respectively), with no differences between the 2 latter groups. Overall, synaptic markers and NfL demonstrated poor-to-moderate diagnostic accuracy in discriminating between diagnostic groups (area under the curve 0.366-0.809). All synaptic biomarkers were elevated in participants with IINDs presenting with altered mental status (beta-syn, <i>p</i> < 0.001; SNAP-25, <i>p</i> = 0.002; and neurogranin, <i>p</i> = 0.008), seizures (beta-syn, <i>p</i> = 0.013; SNAP-25, <i>p</i> = 0.005; and neurogranin, <i>p</i> = 0.004), and inflammatory changes on neuroimaging (beta-syn, <i>p</i> = 0.016; SNAP-25, <i>p</i> = 0.029; and neurogranin, <i>p</i> = 0.007). Participants with AINDs requiring intensive care showed higher levels of beta-syn (<i>p</i> = 0.033) and NfL (<i>p</i> = 0.002). Participants with IINDs with a poor functional status (modified Rankin Scale [mRS] scores of 3-6) exhibited higher concentrations of beta-syn (<i>p</i> < 0.001), SNAP-25 (<i>p</i> = 0.022), neurogranin (<i>p</i> = 0.004), and NfL (<i>p</i> < 0.001) compared with those with mRS scores of 0-2. Accordingly, higher levels of synaptic markers were associated with poorer short-term outcomes in patients with IINDs, but not in those with AINDs.</p><p><strong>Discussion: </strong>Elevated CSF levels of beta-syn, neurogranin, and NfL may suggest a common pattern of synaptic and neuroaxonal damage in both IINDs and AINDs. Although these biomarkers have limited value in distinguishing between different diseases, they are associated with clinical severity and with short-term outcome, particularly in patients with IINDs.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200491"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252143","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":"Pregnancy and Infant Outcomes in Multiple Sclerosis: Findings From the Global MAPLE-MS Pharmacovigilance Program.","authors":"Kerstin Hellwig, Hugh H Tilson, Sandra Thiel, Kathryn Ball, Joerg Seebeck, Muriel Danten, Nancy Dubois, Meritxell Sabidó","doi":"10.1212/NXI.0000000000200486","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200486","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200486"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963429","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":"Relation of Visual Function, Retinal Thickness by Optical Coherence Tomography, and MRI Brain Volume in Pediatric-Onset Multiple Sclerosis.","authors":"Anna Sosa, Kimberly A O'Neill, Ruben Jauregui, Ugo Nwigwe, Thibo Billiet, Rachel Kenney, Lauren B Krupp, Steven L Galetta, Laura J Balcer, Scott N Grossman","doi":"10.1212/NXI.0000000000200480","DOIUrl":"10.1212/NXI.0000000000200480","url":null,"abstract":"<p><strong>Background and objectives: </strong>While reductions in optical coherence tomography (OCT) pRNFL and ganglion cell-inner plexiform layer thicknesses have been shown to be associated with brain atrophy in adult-onset MS (AOMS) cohorts, the relationship between OCT and brain MRI measures is less established in pediatric-onset MS (POMS). Our aim was to examine the associations of OCT measures with volumetric MRI in a cohort of patients with POMS to determine whether OCT measures reflect CNS neurodegeneration in this patient population, as is seen in AOMS cohorts.</p><p><strong>Methods: </strong>This was a cross-sectional study with retrospective ascertainment of patients with POMS evaluated at a single center with expertise in POMS and neuro-ophthalmology. As part of routine clinical care, patients with POMS are evaluated by a POMS expert and undergo volumetric brain MRI, including whole-brain (WB), subregional, and gray matter (GM) volume analyses. Patients with POMS are routinely referred to neuro-ophthalmology for evaluation that includes high-contrast visual acuity, color vision testing, and OCT. Generalized estimating equation (GEE) models, accounting for within-patient, intereye correlations (both eyes of each patient were included), MS disease duration, and disease-modifying therapy efficacy, were used to determine the relationship between visual pathway structure and function and volumetric MRI measures.</p><p><strong>Results: </strong>Among 61 patients (122 eyes) with POMS, the mean age at the time of the volumetric MRI scan was 19.2 (SD = 3.7, range 10-27) years, with a median disease duration of 2.8 (range 0-14) years. Lower (worse) pRNFL thicknesses (mean 87.4 [17.2] µm) were associated with reduced volume percentiles of WB (<i>p</i> < 0.001, GEE models), total GM (<i>p</i> = 0.025), and thalamus (<i>p</i> = 0.038). pRNFL thinning was also associated with greater lesion (<i>p</i> = 0.006) and black hole (<i>p</i> = 0.028) volumes. Reduced color vision and decreased high-contrast visual acuity were associated with lower hippocampal volumes (<i>p</i> = 0.012 and <i>p</i> = 0.015, respectively).</p><p><strong>Discussion: </strong>Our results demonstrate that changes in visual pathway structures are associated with reductions in overall brain volume and GM volumes, as well as greater lesion and black hole burden. Collectively, our results emphasize the importance of visual assessment in POMS and suggest that OCT reflects overall CNS neurodegeneration in this cohort.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200480"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030396","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":"Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor Antibodies: Clinical Features and Outcomes.","authors":"Mar Guasp, Albert Saiz, Marina Ruiz-Vives, Miriam Almendrote, Jordi Bruna, Jordi González-Menacho, Juntaro Kaneko, Lorena Martín-Aguilar, Francisco Antonio Martínez-García, Kazuyuki Noda, Angel Ruiz Molina, Sara Sequeiros, Mateus Mistieri Simabukuro, Megumi Takenaka, Martín Zurdo, Josep O Dalmau, Takahiro Iizuka, Francesc Graus","doi":"10.1212/NXI.0000000000200473","DOIUrl":"10.1212/NXI.0000000000200473","url":null,"abstract":"<p><strong>Background and objectives: </strong>The aim of this study was to describe the clinical features and long-term outcome of patients with glycine receptor (GlyR) antibody-mediated progressive encephalomyelitis with rigidity and myoclonus (PERM), a disease commonly included under the term of stiff-person spectrum disorders (SPSDs).</p><p><strong>Methods: </strong>We conducted a retrospective analysis of patients with PERM and GlyR antibodies diagnosed in our laboratory and a systematic literature review (following Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] 2020 reporting guideline) of previously reported patients with sufficient clinical information and ≥12 months of follow-up. Neurologic disability was measured with the modified Rankin Scale (mRS). Relapses were defined as any event occurring >6 months after the first episode that required immunotherapy.</p><p><strong>Results: </strong>Forty-one patients were identified, 22 from our database and 19 from the literature. The median age was 58 years (IQR: 43-66 years), and 36 (88%) were male and 5 female. The median time from symptom onset to admission was 2 weeks (IQR: 1-4 weeks). Predominant presentations included brainstem symptoms, mainly dysphagia and trismus, in 23 patients (56%); muscle stiffness and myoclonus in 9 (22%); dysesthesias or pruritus in 7 (17%); and cacosmia with dysgeusia in 2 (5%). Five patients (12%) never developed muscle stiffness. The median (range) mRS score at nadir was 5 (3-5). All patients received immunotherapy. Eleven patients died, 8 from complications of PERM. There were 12 relapses in 10 (28%) of 36 patients who lived >6 months. All relapses responded to immunotherapy. The functional status at the last visit, median time 24 months (IQR: 18-72 months), was good (mRS score <3) in 23 (70%) of the 33 patients who did not die from PERM. Age (HR: 1.06; 95% CI 1.01-1.11; <i>p</i> = 0.019) and admission to the intensive care unit (HR: 5.26; 95% CI 1.41-19.57, <i>p</i> = 0.013) were independent predictors of bad outcome (mRS score ≥3).</p><p><strong>Discussion: </strong>GlyR antibody-mediated PERM is a rapidly progressive and severe disease that predominantly affects men and frequently presents with brainstem involvement. Its distinct demographic and clinical features suggest that it should be considered separately from SPSDs, which typically follows a chronic course and is more commonly associated with glutamic acid decarboxylase antibodies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200473"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069933","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":"Genomic and Serologic Characterization of Enterovirus A71 Brainstem Encephalitis.","authors":"Kristoffer E Leon, Ryan D Schubert, Didac Casas-Alba, Isobel A Hawes, Prashanth S Ramachandran, Akshaya Ramesh, Carly K Cheung, Emily D Crawford, Lillian M Khan, Cristian Launes, Hannah A Sample, Kelsey C Zorn, Maria Cabrerizo, Ana Valero-Rello, Charles Langelier, Carmen Muñoz-Almagro, Joseph L DeRisi, Michael R Wilson","doi":"10.1212/NXI.0000000000200505","DOIUrl":"10.1212/NXI.0000000000200505","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 6","pages":"e200505"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239187","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}