Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Younger Age at Onset Is Associated With Worse Long-term Behavioral Outcomes in Anti-NMDA Receptor Encephalitis.","authors":"Anusha Yeshokumar,&nbsp;Eliza Gordon-Lipkin,&nbsp;Ana Arenivas,&nbsp;Mark Rosenfeld,&nbsp;Kristina Patterson,&nbsp;Raia Blum,&nbsp;Brenda Banwell,&nbsp;Arun Venkatesan,&nbsp;Eric Lancaster,&nbsp;Jessica Panzer,&nbsp;John Probasco","doi":"10.1212/NXI.0000000000200013","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200013","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-NMDA receptor encephalitis (anti-NMDARE) is one of the most common causes of encephalitis. It typically presents in adolescence and young adulthood, but little is known about its potential long-term consequences across the lifespan. Adaptive behavior describes an individual's ability to respond and adapt to environmental demands and unanticipated changes in daily routines. In this study, we evaluate the relationship between features from clinical presentation, including age, and long-term adaptive behavior in participants with anti-NMDARE.</p><p><strong>Methods: </strong>Cross-sectional informant-reported data were collected between 2017 and 2019 from 41 individuals/caregivers of individuals with anti-NMDARE treated at 3 major academic hospitals. Neurologic disability was assessed by record review using the modified Rankin Scale (mRS). Functional outcomes were assessed using the validated Adaptive Behavior Assessment System, Third Edition (ABAS-3).</p><p><strong>Results: </strong>The mean age at the time of study enrollment was 23.4 years (SD 17.0 years), and the mean time from symptom onset to study enrollment was 4.0 years. Seventeen participants were aged <12 years at symptom onset, 19 participants were aged 12-30 years, and 5 participants were aged >30 years. Mean ABAS-3 scores at study enrollment for all participants were in the average range (mean general adaptive composite standard score 92.5, SD 18.7). Individuals aged <12 years at symptom onset had lower mean ABAS-3 scores and were in the below average range compared with those aged 12-30 years at symptom onset, whose mean scores were in the average range (87 vs 99, <i>p</i> < 0.05). Similar differences were seen in 3 of the individual subscales (functional academics, health and safety, and self-care). There were no significant differences in mRS scores between age groups (<i>p</i> > 0.05).</p><p><strong>Discussion: </strong>Although anti-NMDARE is associated with an overall favorable outcome, younger age at onset associates with worse long-term adaptive behavior despite no differences in neurologic disability. These findings suggest that the disease may have distinct consequences on the early developing brain. Future studies should evaluate behavioral recovery and quality of life after anti-NMDARE and identify additional factors associated with differential recovery.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258981/pdf/NXI-2022-200019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40486365","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":"The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis.","authors":"Ingrid Anne Lie,&nbsp;Kristin Wesnes,&nbsp;Silje S Kvistad,&nbsp;Iman Brouwer,&nbsp;Stig Wergeland,&nbsp;Trygve Holmøy,&nbsp;Rune Midgard,&nbsp;Alla Bru,&nbsp;Astrid Edland,&nbsp;Randi Eikeland,&nbsp;Sonia Gosal,&nbsp;Hanne F Harbo,&nbsp;Grethe Kleveland,&nbsp;Yvonne S Sørenes,&nbsp;Nina Øksendal,&nbsp;Frederik Barkhof,&nbsp;Hugo Vrenken,&nbsp;Kjell-Morten Myhr,&nbsp;Lars Bø,&nbsp;Øivind Torkildsen","doi":"10.1212/NXI.0000000000200008","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200008","url":null,"abstract":"<p><strong>Background and objectives: </strong>The relationship between smoking, long-term brain atrophy, and clinical disability in patients with multiple sclerosis (MS) is unclear. Here, we assessed long-term effects of smoking by evaluating MRI and clinical outcome measures after 10 years in smoking and nonsmoking patients with relapsing-remitting MS (RRMS).</p><p><strong>Methods: </strong>We included 85 treatment-naive patients with RRMS with recent inflammatory disease activity who participated in a 10-year follow-up visit after a multicenter clinical trial of 24 months. Smoking status was decided for each patient by 2 separate definitions: by serum cotinine levels measured regularly for the first 2 years of the follow-up (during the clinical trial) and by retrospective patient self-reporting. At the 10-year follow-up visit, clinical tests were repeated, and brain atrophy measures were obtained from MRI using FreeSurfer. Differences in clinical and MRI measurements at the 10-year follow-up between smokers and nonsmokers were investigated by 2-sample <i>t</i> tests or Mann-Whitney tests and linear mixed-effect regression models. All analyses were conducted separately for each definition of smoking status.</p><p><strong>Results: </strong>After 10 years, smoking (defined by serum cotinine levels) was associated with lower total white matter volume (β = -21.74, <i>p</i> = 0.039) and higher logT2 lesion volume (β = 0.22, <i>p</i> = 0.011). When defining smoking status by patient self-reporting, the repeated analyses found an additional association with lower deep gray matter volume (β = -2.35, <i>p</i> = 0.049), and smoking was also associated with a higher score (higher walking impairment) on the log timed 25-foot walk test (β = 0.050, <i>p</i> = 0.039) after 10 years and a larger decrease in paced auditory serial addition test (attention) scores (β = -3.58, <i>p</i> = 0.029).</p><p><strong>Discussion: </strong>Smoking was associated with brain atrophy and disability progression 10 years later in patients with RRMS. The findings imply that patients should be advised and offered aid in smoking cessation shortly after diagnosis, to prevent long-term disability progression.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/f5/NXI-2022-200009.PMC9223432.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40334242","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":"Refractory Anti-NMDA Receptor Encephalitis in Early Pregnancy: A Case Report of Treatment Course and Pregnancy Outcomes.","authors":"Sarah Fredrich,&nbsp;Cynthia Wang,&nbsp;Ram Narayan,&nbsp;Lauren Tardo,&nbsp;Kyle M Blackburn,&nbsp;Steven Vernino","doi":"10.1212/NXI.0000000000200007","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200007","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis classically affects women of childbearing age, producing a disproportionate number of pregnant women with anti-NMDAR encephalitis. The typical presentation includes progressive neuropsychiatric symptoms, seizures, and alterations in consciousness, all of which present potential risks to the fetus. First-line and second-line treatments similarly pose teratogenic potential; therefore, randomized studies with supportive data on pregnancy and fetal outcomes are lacking.</p><p><strong>Methods: </strong>We present a case of refractory anti-NMDAR encephalitis during the first and second trimesters of pregnancy with the successful use of rituximab and cyclophosphamide and resultant healthy pregnancy.</p><p><strong>Results: </strong>The patient was treated with an escalating immunotherapy regimen from 11 to 15 weeks of gestation, including steroids, plasma exchange, IV immunoglobulins, and rituximab, with no clinical response. At 16 weeks of gestation, she received cyclophosphamide with clinical improvement after 4 weeks. She subsequently gave birth to a healthy, term baby boy, who continued to do well at the follow-up.</p><p><strong>Discussion: </strong>This case illustrates the effective use of cyclophosphamide in the second trimester of pregnancy for anti-NMDAR encephalitis. The use of second-line therapies remains an individualized decision because the relative risk-to-benefit ratio in pregnant women is incompletely understood.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/3d/NXI-2022-200007.PMC9219494.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40150634","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":"Comment: Humoral and T-cell Immunities to SARS-CoV-2 Vaccines: Safety, Efficacy, and Challenges in Autoimmune Neurology.","authors":"Marinos C Dalakas,&nbsp;Josep Dalmau","doi":"10.1212/NXI.0000000000200010","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200010","url":null,"abstract":"With the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccinations, we have been witnessing a new era in vaccinology because these vaccines do not contain viral proteins but mRNA or viral vectors that instruct the cells to make viralspecific protective antibodies. To effectively fight SARS-CoV-2 infection, however, these vaccines need to induce both humoral and cell-mediated immune responses, with antibodies that block viral replication and viral-specific T cells that kill viral-infected cells and generate antibodyproducing plasma cells and long-lived memory cells. The need for such vaccine-induced coordinated immunities has generated concerns in autoimmune neurology questioning whether (1) the existing autoimmune disease affects the vaccines’ efficacy, (2) the underlying autoimmunity predisposes patients to SARS-CoV-2mRNA–triggered disease exacerbations, and (3) the immunomodulating or immunosuppressive therapies they receive prevent the generation of sufficient antibodies or T-cell responses to ensure vaccine effectiveness. These issues have been especially concerning to patients with multiple sclerosis (MS) treated with immunomodulating drugs; B-cell–depleting agents such as rituximab, ocrelizumab, and ofatumumab; or with molecules altering cell trafficking and lymphocyte DNA synthesis, such as fingolimod and cladribine. Similar concerns are also raised in patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy, and autoimmune myopathies who commonly receive steroids and immunosuppressants, such as mycophenolate, azathioprine, cyclosporine, or tacrolimus. These issues have now been addressed in 2 important new studies, one in MS and the other in MG evaluating the generation of anti–region-binding domain (RBD) neutralizing antibodies and spike (S)-specific T-cell responses after 2 SARS-CoV-2 vaccinations.","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219497/pdf/NXI-2022-200016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40150253","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":"Immune Response and Safety of SARS-CoV-2 mRNA-1273 Vaccine in Patients With Myasthenia Gravis.","authors":"David Reyes-Leiva,&nbsp;Joaquín López-Contreras,&nbsp;Esther Moga,&nbsp;Francesc Pla-Juncà,&nbsp;Elionor Lynton-Pons,&nbsp;Ricardo Rojas-Garcia,&nbsp;Janina Turon-Sans,&nbsp;Luis Querol,&nbsp;Montse Olive,&nbsp;Rodrigo Álvarez-Velasco,&nbsp;Marta Caballero-Ávila,&nbsp;Álvaro Carbayo,&nbsp;Ana Vesperinas-Castro,&nbsp;Pere Domingo,&nbsp;Isabel Illa,&nbsp;Eduard Gallardo,&nbsp;Elena Cortés-Vicente","doi":"10.1212/NXI.0000000000200002","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200002","url":null,"abstract":"<p><strong>Background and objectives: </strong>Evidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG.</p><p><strong>Methods: </strong>We performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates.</p><p><strong>Results: </strong>Ninety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46-24.09, <i>p</i> = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13-7.13, <i>p</i> = 0.024).</p><p><strong>Discussion: </strong>Our findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/5e/NXI-2022-200002.PMC9219516.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40150254","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":"MRI Characteristics of Autoimmune Encephalitis With Autoantibodies to GABAA Receptor: A Case Series.","authors":"Bo Deng,&nbsp;Mengfei Cai,&nbsp;Yue Qiu,&nbsp;Xiaoni Liu,&nbsp;Hai Yu,&nbsp;Xiang Zhang,&nbsp;Huifen Huang,&nbsp;Xiuhe Zhao,&nbsp;Wenbo Yang,&nbsp;Siqi Dong,&nbsp;Lei Jin,&nbsp;Shuguang Chu,&nbsp;Xiangjun Chen","doi":"10.1212/NXI.0000000000001158","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001158","url":null,"abstract":"<p><strong>Background and objectives: </strong>To characterize the clinical and neuroimaging phenotypes of patients with autoantibodies to γ-aminobutyric acid type A receptor (GABA_AR).</p><p><strong>Methods: </strong>Ten patients with autoantibodies against GABA_AR from Huashan Hospital Autoimmune Encephalitis cohort were identified. We used MRI assessments and clinical examinations to summarize major clinical profile and visualize and quantify lesion distribution features. The relationship between clinical features, neuroimaging phenotypes, and topology of GABA_AR expression were further investigated.</p><p><strong>Results: </strong>The median age at onset of 10 patients (8 male patients and 2 female patients) with anti-GABA_AR encephalitis was 41.5 years (range: 17-73 years). All patients had prominent seizures and multifocal spotted or confluent lesions involved in limbic, frontal, and temporal lobes on brain MRI. Bilateral but asymmetric lesions in cingulate gyri were observed in all patients. These involved lesions could change dynamically with immunotherapies and relapse. Distribution of patients' brain MRI lesions was positively correlated with gene expression level of β3 subunit-containing GABA_AR (Spearman ρ = 0.864, <i>p</i> = 0.001), the main target of autoantibodies. According to topology of lesions, patients with anti-GABA_AR encephalitis could be classified into 2 clinical-radiological types: confluent type with bilateral confluent lesions involved in almost all limbic, frontal, and temporal lobes and spotted type with multiple scattered small-to-medium patchy lesions. Patients with confluent type exhibited worse clinical presentations and outcomes when compared with those with spotted type (maximum modified Rankin scale [mRS]: 5 [5-5] vs 3.5 [3-4], respectively, <i>p</i> = 0.008; follow-up mRS: 4 [2-6] vs 0.5 [0-1], respectively, <i>p</i> = 0.016).</p><p><strong>Discussion: </strong>Anti-GABA_AR encephalitis has distinctive neuroimaging phenotype. Cingulate gyri were frequently involved in this disorder. The topology of lesions might be associated with the distribution of β3 subunit-containing GABA_AR and reflected patients' disease severity and outcomes.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/5c/NEURIMMINFL2021039442.PMC8958939.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40330407","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":"Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies.","authors":"Luise Appeltshauser,&nbsp;Julia Messinger,&nbsp;Katharina Starz,&nbsp;David Heinrich,&nbsp;Anna-Michelle Brunder,&nbsp;Helena Stengel,&nbsp;Bianca Fiebig,&nbsp;Ilya Ayzenberg,&nbsp;Frank Birklein,&nbsp;Christian Dresel,&nbsp;Johannes Dorst,&nbsp;Florian Dvorak,&nbsp;Alexander Grimm,&nbsp;Alexander Joerk,&nbsp;Frank Leypoldt,&nbsp;Mathias Mäurer,&nbsp;Patrick Merl,&nbsp;Sebastian Michels,&nbsp;Kalliopi Pitarokoili,&nbsp;Mathias Rosenfeldt,&nbsp;Anne-Dorte Sperfeld,&nbsp;Marc Weihrauch,&nbsp;Gabriel Simon Welte,&nbsp;Claudia Sommer,&nbsp;Kathrin Doppler","doi":"10.1212/NXI.0000000000001163","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001163","url":null,"abstract":"<p><strong>Background and objectives: </strong>Nodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM).</p><p><strong>Methods: </strong>We retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1-associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections.</p><p><strong>Results: </strong>The frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31-6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti-contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected.</p><p><strong>Discussion: </strong>We report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/f4/NEURIMMINFL2021039610.PMC8936686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310043","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":"Combined Central and Peripheral Demyelination With IgM Anti-Neurofascin 155 Antibodies: Case Report.","authors":"Antoine Pegat,&nbsp;Emilien Delmont,&nbsp;Juliette Svahn,&nbsp;Emilien Bernard,&nbsp;Lola Lessard,&nbsp;Romain Marignier,&nbsp;Francoise Bouhour","doi":"10.1212/NXI.0000000000001160","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001160","url":null,"abstract":"Immunoglobulin (Ig) G anti – neurofascin 155 antibodies (anti-NF155 Abs) have been described in rare forms of chronic in fl ammatory demyelinating polyradiculoneuropathy (CIDP) and in combined central and peripheral demyelination (CCPD). 1 We report herein a case of a patient presenting CCPD and IgM anti-NF155 Ab. quadridistal hypesthesia, gait, tendon re fl exes. Overall Neuropathy Limitations (ONLS) was 1/12. Electroneuromyography (ENMG) revealed a di ff use homogeneous demyelinating neuropathy. Nerve ultrasonography and of the cervical plexus 1, D and a di ff use enlargement of peripheral structures. CSF analysis showed elevated protein level (0.7 g/L, normal <0.4) and 14 white blood cells/mm 3 (normal <2) with oligoclonal IgG bands. Cerebral MRI revealed multiple hyperintensities in the periventricular and juxtacortical white matter (diagnosis of radiologically isolated syn-drome). All the 97 genes of a panel of genes involved in hereditary neuropathies, especially demyelinating Charcot-Marie-Tooth (CMT), were negative. Peripheral","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/e4/NEURIMMINFL2021039570.PMC8936685.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310042","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":"Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder.","authors":"Hisashi Murata,&nbsp;Makoto Kinoshita,&nbsp;Yoshiaki Yasumizu,&nbsp;Daisuke Motooka,&nbsp;Shohei Beppu,&nbsp;Naoyuki Shiraishi,&nbsp;Yasuko Sugiyama,&nbsp;Keigo Kihara,&nbsp;Satoru Tada,&nbsp;Toru Koda,&nbsp;Hachiro Konaka,&nbsp;Hyota Takamatsu,&nbsp;Atsushi Kumanogoh,&nbsp;Tatsusada Okuno,&nbsp;Hideki Mochizuki","doi":"10.1212/NXI.0000000000001149","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001149","url":null,"abstract":"<p><strong>Background and objectives: </strong>Recently accumulating evidence suggests the pivotal role of type 1 interferon (IFN-1) signature in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). However, the mechanism of the initial trigger that augments IFN-1 pathway in the peripheral immune system of NMOSD has yet to be elucidated.</p><p><strong>Methods: </strong>Clinical samples were obtained from 32 patients with aquaporin-4 antibody-positive NMOSD and 23 healthy subjects. IFN-1 induction in peripheral blood mononuclear cells (PBMCs) by serum-derived cell-free DNA (cfDNA) was assessed in combination with blockades of DNA sensors in vitro. CfDNA fraction was analyzed for DNA methylation profiles by bisulfite sequencing, elucidating the cellular origin of cfDNA. The induction of neutrophil extracellular trap related cell death (NETosis) was further analyzed in NMOSD and control groups, and the efficacy of pharmacologic intervention of NETosis was assessed.</p><p><strong>Results: </strong>Enhanced IFN-1 induction by cfDNA derived from NMOSD was observed in PBMCs with cofactor of LL37 antimicrobial peptide. DNase treatment, cGAS inhibitor, and Toll-like receptor 9 antagonist efficiently inhibited IFN-1 production. DNA methylation pattern of cfDNA in patients with NMOSD demonstrated that the predominant cellular source of cfDNA was neutrophils. Whole blood transcriptome analysis also revealed neutrophil activation in NMOSD. In addition, enhanced NETosis induction was observed with NMOSD-derived sera, and efficient pharmacologic inhibition of NETosis with dipyridamole was observed.</p><p><strong>Discussion: </strong>Our study highlights the previously unrevealed role of cfDNA predominantly released by neutrophil in the induction of IFN-1 signature in NMOSD and further indicate a novel pharmacologic target in NMOSD.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/6a/NEURIMMINFL2021039592.PMC8874356.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39819606","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":"Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis.","authors":"Ana Zabalza,&nbsp;Georgina Arrambide,&nbsp;Paula Tagliani,&nbsp;Simón Cárdenas-Robledo,&nbsp;Susana Otero-Romero,&nbsp;Juliana Esperalba,&nbsp;Candela Fernandez-Naval,&nbsp;Jesus Trocoli Campuzano,&nbsp;Mónica Martínez Gallo,&nbsp;Mireia Castillo,&nbsp;Mercè Bonastre,&nbsp;Mireia Resina Sallés,&nbsp;Jordina Beltran,&nbsp;Pere Carbonell-Mirabent,&nbsp;Marta Rodríguez-Barranco,&nbsp;Samuel López-Maza,&nbsp;Pedro José Melgarejo Otálora,&nbsp;Mariano Ruiz-Ortiz,&nbsp;Agustin Pappolla,&nbsp;Breogán Rodríguez Acevedo,&nbsp;Luciana Midaglia,&nbsp;Angela Vidal-Jordana,&nbsp;Alvaro Cobo-Calvo,&nbsp;Carmen Tur,&nbsp;Ingrid Galán,&nbsp;Joaquín Castilló,&nbsp;Jordi Río,&nbsp;Carmen Espejo,&nbsp;Manuel Comabella,&nbsp;Carlos Nos,&nbsp;Jaume Sastre-Garriga,&nbsp;Mar Tintore,&nbsp;Xavier Montalban","doi":"10.1212/NXI.0000000000001143","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001143","url":null,"abstract":"<p><strong>Background and objectives: </strong>Information about humoral and cellular responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antibody persistence in convalescent (COVID-19) patients with multiple sclerosis (PwMS) is scarce. The objectives of this study were to investigate factors influencing humoral and cellular responses to SARS-CoV-2 and its persistence in convalescent COVID-19 PwMS.</p><p><strong>Methods: </strong>This is a retrospective study of confirmed COVID-19 convalescent PwMS identified between February 2020 and May 2021 by SARS-CoV-2 antibody testing. We examined relationships between demographics, MS characteristics, disease-modifying therapy (DMT), and humoral (immunoglobulin G against spike and nucleocapsid proteins) and cellular (interferon-gamma [IFN-γ]) responses to SARS-CoV-2.</p><p><strong>Results: </strong>A total of 121 (83.45%) of 145 PwMS were seropositive, and 25/42 (59.5%) presented a cellular response up to 13.1 months after COVID-19. Anti-CD20-treated patients had lower antibody titers than those under other DMTs (<i>p</i> < 0.001), but severe COVID-19 and a longer time from last infusion increased the likelihood of producing a humoral response. IFN-γ levels did not differ among DMT. Five of 7 (71.4%) anti--CD20-treated seronegative patients had a cellular response. The humoral response persisted for more than 6 months in 41/56(81.13%) PwMS. In multivariate analysis, seropositivity decreased due to anti-CD20 therapy (OR 0.08 [95% CI 0.01-0.55]) and increased in males (OR 3.59 [1.02-12.68]), whereas the cellular response decreased in those with progressive disease (OR 0.04 [0.001-0.88]). No factors were associated with antibody persistence.</p><p><strong>Discussion: </strong>Humoral and cellular responses to SARS-CoV-2 are present in COVID-19 convalescent PwMS up to 13.10 months after COVID-19. The humoral response decreases under anti-CD20 treatment, although the cellular response can be detected in anti-CD20-treated patients, even in the absence of antibodies.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5a/25/NEURIMMINFL2021039285.PMC8808353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39878634","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}