Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis: A 3-Year Longitudinal Study.","authors":"Omar Al-Louzi,&nbsp;Vijay Letchuman,&nbsp;Sargis Manukyan,&nbsp;Erin S Beck,&nbsp;Snehashis Roy,&nbsp;Joan Ohayon,&nbsp;Dzung L Pham,&nbsp;Irene Cortese,&nbsp;Pascal Sati,&nbsp;Daniel S Reich","doi":"10.1212/NXI.0000000000001120","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001120","url":null,"abstract":"<p><strong>Background and objectives: </strong>The central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CVS profiles of new white matter lesions in patients with MS followed over time and investigate demographic and clinical risk factors associated with new CVS+ or CVS- lesion development.</p><p><strong>Methods: </strong>In this retrospective longitudinal cohort study, adults from the NIH MS Natural History Study were considered for inclusion. Participants with new T2 or enhancing lesions were identified through review of the radiology report and/or longitudinal subtraction imaging. Each new lesion was evaluated for the CVS. Clinical characteristics were identified through chart review.</p><p><strong>Results: </strong>A total of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) were included. Of this cohort, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1-Q3: 0.7-6.3) of follow-up; lesions eligible for CVS evaluation were found in 62 (65%). Of 233 new CVS-eligible lesions, 159 (68%) were CVS+, with 30 (48%) individuals having only CVS+, 12 (19%) only CVS-, and 20 (32%) both CVS+ and CVS- lesions. In gadolinium-enhancing (Gd+) lesions, the CVS+ percentage increased from 102/152 (67%) at the first time point where the lesion was observed, to 92/114 (82%) after a median follow-up of 2.8 years. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3-0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1-1.9) were associated with increased likelihood of new CVS+ lesion development.</p><p><strong>Discussion: </strong>In a cohort of adults with MS followed over a median duration of 3 years, most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (48%) developed new CVS+ lesions only. Importantly, the effects of edema and T2 signal changes can obscure small veins in Gd+ lesions; therefore, caution and follow-up is necessary when determining their CVS status.</p><p><strong>Trial registration information: </strong>Clinical trial registration number NCT00001248.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that younger age and higher CVS+ percentage at baseline are associated with new CVS+ lesion development.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/6d/NEURIMMINFL2021039347.PMC8759076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39818759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune Encephalomyelitis.","authors":"Jana Remlinger,&nbsp;Adrian Madarasz,&nbsp;Kirsten Guse,&nbsp;Robert Hoepner,&nbsp;Maud Bagnoud,&nbsp;Ivo Meli,&nbsp;Moritz Feil,&nbsp;Mathias Abegg,&nbsp;Christopher Linington,&nbsp;Anthony Shock,&nbsp;Babak Boroojerdi,&nbsp;Peter Kiessling,&nbsp;Bryan Smith,&nbsp;Volker Enzmann,&nbsp;Andrew Chan,&nbsp;Anke Salmen","doi":"10.1212/NXI.0000000000001134","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001134","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS disorder, distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. Characterized by pathogenic immunoglobulin G (IgG) antibodies against MOG, a potential treatment strategy for MOGAD is to reduce circulating IgG levels, e.g., by interference with the IgG recycling pathway mediated by the neonatal Fc receptor (FcRn). Although the optic nerve is often detrimentally involved in MOGAD, the effect of FcRn blockade on the visual pathway has not been assessed. Our objective was to investigate effects of a monoclonal anti-FcRn antibody in murine MOG-IgG-associated experimental autoimmune encephalomyelitis (EAE).</p><p><strong>Methods: </strong>We induced active MOG_35-55 EAE in C57Bl/6 mice followed by the application of a monoclonal MOG-IgG (8-18C5) 10 days postimmunization (dpi). Animals were treated with either a specific monoclonal antibody against FcRn (α-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic disability was scored daily on a 10-point scale. Visual acuity was assessed by optomotor reflex. Histopathologic hallmarks of disease were assessed in the spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by immunohistochemistry, demyelination by Luxol fast blue staining and complement deposition and number of retinal ganglion cells by immunofluorescence.</p><p><strong>Results: </strong>In MOG-IgG-augmented MOG_35-55 EAE, anti-FcRn treatment significantly attenuated neurologic disability over the course of disease (mean area under the curve and 95% confidence intervals (CIs): α-FcRn [n = 27], 46.02 [37.89-54.15]; isotype IgG [n = 24], 66.75 [59.54-73.96], 3 independent experiments), correlating with reduced amounts of demyelination and macrophage infiltration into the spinal cord. T- and B-cell infiltration and complement deposition remained unchanged. Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity over the course of disease (median cycles/degree and interquartile range: α-FcRn [n = 16], 0.50 [0.48-0.55] to 0.50 [0.48-0.58]; isotype IgG [n = 17], 0.50 [0.49-0.54] to 0.45 [0.39-0.51]).</p><p><strong>Discussion: </strong>We show preserved optomotor response and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG-IgG to mimic MOGAD. Selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/90/NEURIMMINFL2021039382.PMC8759074.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39819156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Visual Outcome Measures to Advance Therapy Development in Neuroimmunologic Disorders.","authors":"Jennifer S Graves,&nbsp;Frederike Cosima Oertel,&nbsp;Anneke Van der Walt,&nbsp;Sara Collorone,&nbsp;Elias S Sotirchos,&nbsp;Gorm Pihl-Jensen,&nbsp;Philipp Albrecht,&nbsp;E Ann Yeh,&nbsp;Shiv Saidha,&nbsp;Jette Frederiksen,&nbsp;Scott Douglas Newsome,&nbsp;Friedemann Paul","doi":"10.1212/NXI.0000000000001126","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001126","url":null,"abstract":"<p><p>The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible. Quantification of visual acuity, visual fields, visual quality of life, and electrophysiologic parameters allows assessment of function, whereas optical coherence tomography (OCT) provides reliable measures of the structural integrity of the anterior afferent visual pathway. The technology of oculomotor biometrics continues to advance, and discrete measures of fixation, smooth pursuit, and saccadic eye movement abnormalities are ready for inclusion in future trials of MS progression. Visual outcomes allow tracking of neuroaxonal injury and aid in distinguishing MS from diseases such as neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). OCT has also provided unique insights into pathophysiology, including the identification of foveal pitting in NMOSD, possibly from damage to Müller cells, which carry an abundance of aquaporin-4 channels. For some study designs, the cost-benefit ratio favors visual outcomes over more expensive MRI outcomes. With the next frontier of therapeutics focused on remyelination and neuroprotection, visual outcomes are likely to take center stage. As an international community of collaborative, committed, vision scientists, this review by the International MS Visual System Consortium (IMSVISUAL) outlines the quality standards, informatics, and framework needed to routinely incorporate vision outcomes into MS and NMOSD trials.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/ad/NEURIMMINFL2021038746.PMC8711076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39763740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease: A Cross-sectional Study.","authors":"Rui Li,&nbsp;Thomas Francis Tropea,&nbsp;Laura Rosa Baratta,&nbsp;Leah Zuroff,&nbsp;Maria E Diaz-Ortiz,&nbsp;Bo Zhang,&nbsp;Koji Shinoda,&nbsp;Ayman Rezk,&nbsp;Roy N Alcalay,&nbsp;Alice Chen-Plotkin,&nbsp;Amit Bar-Or","doi":"10.1212/NXI.0000000000001125","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001125","url":null,"abstract":"<p><strong>Background and objectives: </strong>There has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.</p><p><strong>Methods: </strong>Peripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.</p><p><strong>Results: </strong>The discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.</p><p><strong>Discussion: </strong>Our findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/d9/NEURIMMINFL2021039126.PMC8711073.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39763308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-NMDAR Encephalitis in the Netherlands, Focusing on Late-Onset Patients and Antibody Test Accuracy.","authors":"Anna E M Bastiaansen,&nbsp;Marienke A A M de Bruijn,&nbsp;Sabine L Schuller,&nbsp;Eugenia Martinez-Hernandez,&nbsp;Juliëtte Brenner,&nbsp;Manuela Paunovic,&nbsp;Yvette S Crijnen,&nbsp;Maxim J H L Mulder,&nbsp;Marco W J Schreurs,&nbsp;Esther de Graaff,&nbsp;Peter A E Smitt,&nbsp;Rinze F Neuteboom,&nbsp;Juna M de Vries,&nbsp;Maarten J Titulaer","doi":"10.1212/NXI.0000000000001127","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001127","url":null,"abstract":"<p><strong>Background and objectives: </strong>To describe the clinical features of anti-NMDAR encephalitis, emphasizing on late-onset patients and antibody test characteristics in serum and CSF.</p><p><strong>Methods: </strong>Nationwide observational Dutch cohort study, in patients diagnosed with anti-NMDAR encephalitis between 2007 and 2019.</p><p><strong>Results: </strong>One hundred twenty-six patients with anti-NMDAR encephalitis were included with a median age of 24 years (range 1-86 years). The mean annual incidence was 1.00/million (95% CI 0.62-1.59). Patients ≥45 years of age at onset (19%) had fewer seizures (46% vs 71%, <i>p</i> = 0.021), fewer symptoms during disease course (3 vs 6 symptoms, <i>p</i> = 0.020), and more often undetectable serum antibodies compared with younger patients (<i>p</i> = 0.031). In the late-onset group, outcome was worse, and all tumors were carcinomas (both <i>p</i> < 0.0001). CSF was more accurate than serum to detect anti-NMDAR encephalitis (sensitivity 99% vs 68%, <i>p</i> < 0.0001). Using cell-based assay (CBA), CSF provided an unconfirmed positive test result in 11/2,600 patients (0.4%); 6/11 had a neuroinflammatory disease (other than anti-NMDAR encephalitis). Patients with anti-NMDAR encephalitis, who tested positive in CSF only, had lower CSF antibody titers (<i>p</i> = 0.003), but appeared to have an equally severe disease course.</p><p><strong>Discussion: </strong>Anti-NMDAR encephalitis occurs at all ages and is less rare in the elderly patients than initially anticipated. In older patients, the clinical phenotype is less outspoken, has different tumor association, and a less favorable recovery. Detection of antibodies in CSF is the gold standard, and although the CBA has very good validity, it is not perfect. The clinical phenotype should be leading, and confirmation in a research laboratory is recommended, when in doubt.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/0b/NEURIMMINFL2021039367.PMC8696553.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39749576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Optical Coherence Tomography in Neuromyelitis Optica.","authors":"","doi":"10.1212/NXI.0000000000001132","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001132","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8723887/pdf/NXI-D-21-00010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39749579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated Memory Loss in Anti-NMDAR Encephalitis.","authors":"Raffaele Iorio,&nbsp;Eleonora Sabatelli,&nbsp;Lucia Campetella,&nbsp;Claudia Papi","doi":"10.1212/NXI.0000000000001128","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001128","url":null,"abstract":"<p><strong>Background and objectives: </strong>To report a case of anti-NMDAR encephalitis presenting with isolated memory dysfunction.</p><p><strong>Methods: </strong>A 29-year-old woman was admitted to the Neurology Department referring memory impairment with a subacute onset. The initial assessment included EEG, neuropsychological tests, and brain MRI. Serum and CSF samples were collected for immunologic studies. The diagnostic evaluation was completed with a total body PET scan.</p><p><strong>Results: </strong>Patient's neurologic examination was unremarkable apart from an episodic memory deficit, confirmed by neuropsychological examination. The EEG revealed epileptiform discharges in the temporal lobes, whereas brain MRI showed bilateral temporal lobes hyperintense lesions on fluid-attenuated inversion recovery images and T2-weighted images. NMDAR-IgG was detected in the patient's serum and CSF by cell-based assay confirming the diagnosis of definite anti-NMDAR encephalitis. The total body PET showed only a slight hypometabolism in the right temporal cortex and in the cerebellar hemispheres. After a course of IV immunoglobulin and corticosteroid therapy, a marked improvement of the memory deficit was observed.</p><p><strong>Discussion: </strong>This case shows that anti-NMDAR encephalitis can present with isolated memory loss. Neural antibody testing in these patients could play a pivotal role in early diagnosis and prompt treatment.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/9c/NEURIMMINFL2021039484.PMC8696551.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39749578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population-Based Epidemiology Study of Paraneoplastic Neurologic Syndromes.","authors":"Shailee Shah,&nbsp;Eoin P Flanagan,&nbsp;Pritikanta Paul,&nbsp;Carin Y Smith,&nbsp;Sandra C Bryant,&nbsp;Michelle F Devine,&nbsp;Vanda A Lennon,&nbsp;Andrew McKeon,&nbsp;Sean J Pittock,&nbsp;Divyanshu Dubey","doi":"10.1212/NXI.0000000000001124","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001124","url":null,"abstract":"<p><strong>Objectives: </strong>Population-based epidemiologic data for paraneoplastic neurologic syndromes (PNSs) in the United States are lacking. Our objective was to evaluate the incidence, prevalence, and associated morbidity of PNS.</p><p><strong>Methods: </strong>We performed a population-based epidemiology study in Olmsted County, Minnesota, with patients identified between January 1, 1987, and December 31, 2018, using the medical records linkage system of the Rochester Epidemiology Project (REP) who met the definite/probable 2021 PNS criteria and 2004 PNS criteria. Patients with dermatomyositis and myasthenia gravis with underlying tumors were included. Age- and sex-specific population counts were obtained from REP resources for January 1, 2014 (prevalence denominator) and annually for 1987-2018 (incidence denominator). Morbidity was estimated using disability-adjusted life years (DALYs; years lived with disability [YLD] plus years of life lost [YLL]).</p><p><strong>Results: </strong>There were 28 patients with PNS identified (50% female) residing in Olmsted County, Minnesota, with median age at diagnosis of 54.5 (IQR 46.5-69.0) years. All patients had a cancer diagnosis, and 18 (64%) patients were neural autoantibody positive including antineuronal nuclear autoantibody type 1 (ANNA-1/anti-Hu; n = 1), ANNA-2/anti-Ri (n = 1), muscle-type acetylcholine receptor (AChR; n = 6), Purkinje cell cytoplasmic antibody type 1 (PCA-1/anti-Yo; n = 1), kelch-like protein 11 (KLH11; n = 3), collapsin response mediator protein 5 (CRMP-5/anti-CV2; n = 2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (n = 1), neurofilament light chain (n = 1), leucine zipper 4 (LUZP4; n = 1), and unclassified neural antibodies (n = 1). PNS incidence was 0.6/100,000 person-years and increased over time from 0.4/100,000 person-years (1987-2002) to 0.8/100,000 person-years (2003-2018) (<i>p</i> = 0.06). Prevalence was 5.4/100,000 people. The median follow-up period after PNS diagnosis was 3.1 years (IQR, 1.1-9.9 years). Total disability-adjusted life years (DALYs) for 28 patients with PNS were 472.7 years, based on total years of life lost (YLL) for patients dying between 1987 and 2018 (n = 15) of 445.3 years plus years lived with disability (YLD) 27.4 years.</p><p><strong>Discussion: </strong>PNSs are rare neurologic disorders but are associated with severe morbidity and mortality. The estimated number of prevalent PNS cases in the United States is 17,099, and predicted DALY for all US PNS cases is 292,393 years. Their apparent increasing rate of detection is attributable to increasing physician awareness and availability of serologic testing.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/cd/NEURIMMINFL2021039376.PMC8696552.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39749574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy.","authors":"","doi":"10.1212/NXI.0000000000001129","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001129","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689446/pdf/NXI-D-21-00009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39620414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siponimod Inhibits the Formation of Meningeal Ectopic Lymphoid Tissue in Experimental Autoimmune Encephalomyelitis.","authors":"Rosa Margareta Brand,&nbsp;Jolien Diddens,&nbsp;Verena Friedrich,&nbsp;Monika Pfaller,&nbsp;Helena Radbruch,&nbsp;Bernhard Hemmer,&nbsp;Katja Steiger,&nbsp;Klaus Lehmann-Horn","doi":"10.1212/NXI.0000000000001117","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001117","url":null,"abstract":"<p><strong>Background and objectives: </strong>To investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by the sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model of multiple sclerosis (MS).</p><p><strong>Methods: </strong>A murine spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, featuring meningeal inflammatory infiltrates resembling those in MS, was used. To prevent or treat EAE, siponimod was administered daily starting either before EAE onset or at peak of disease. The extent and cellular composition of mELT, the spinal cord parenchyma, and the spleen was assessed by histology and immunohistochemistry.</p><p><strong>Results: </strong>Siponimod, when applied before disease onset, ameliorated EAE. This effect was also present, although less prominent, when treatment started at peak of disease. Treatment with siponimod resulted in a strong reduction of the extent of mELT in both treatment paradigms. Both B and T cells were diminished in the meningeal compartment.</p><p><strong>Discussion: </strong>Beneficial effects on the disease course correlated with a reduction in mELT, suggesting that inhibition of mELT may be an additional mechanism of action of siponimod in the treatment of EAE. Further studies are needed to establish causality and confirm this observation in MS.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/26/NEURIMMINFL2021039301.PMC8674936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39605560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}