Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Long-term Follow-up and Muscle Imaging Findings in Brachio-Cervical Inflammatory Myopathy.","authors":"Matteo Lucchini,&nbsp;Sara Bortolani,&nbsp;Mauro Monforte,&nbsp;Manuela Papacci,&nbsp;Enzo Ricci,&nbsp;Massimiliano Mirabella,&nbsp;Giorgio Tasca","doi":"10.1212/NXI.0000000000001016","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001016","url":null,"abstract":"<p><strong>Objective: </strong>To report on a cohort of patients diagnosed with brachio-cervical inflammatory myopathy (BCIM), with specific focus on muscle MRI and follow-up data.</p><p><strong>Methods: </strong>Clinical, histopathologic, serologic, and pre- and post-treatment MRI findings of patients diagnosed with BCIM were retrospectively evaluated.</p><p><strong>Results: </strong>Six patients, all females with a mean age at onset of 53 years (range 37-62 years), were identified. Mean diagnostic delay was 17 months, and mean follow-up was 35 months. Most common clinical features encompassed predominant involvement of neck and proximal upper limb muscles, followed by distal upper limb, facial, and bulbar muscle weakness with different severity. Lower limb involvement was rare, although present in severe cases. Muscle biopsies showed a heterogeneous degree of perivascular and endomysial inflammatory changes. Myositis-specific antibodies were absent in all patients, whereas all resulted positive for antinuclear antibodies; half of the patients had anti-acetylcholine receptor antibodies without evidence of muscle fatigability. MRI showed disproportionate involvement of upper girdle and neck muscles compared with lower limbs, with frequent hyperintensities on short-tau inversion recovery sequences. Partial clinical and radiologic improvement with steroid and immunosuppressant therapy was obtained in most patients, especially in proximal upper limb muscles, whereas neck weakness persisted.</p><p><strong>Conclusion: </strong>BCIM is an inflammatory myopathy with a peculiar clinical and radiologic presentation and a relatively broad spectrum of severity. Long-term follow-up data suggest that appropriate and early treatment can prevent chronic muscle function impairment. MRI characterization can be helpful in reducing diagnostic and treatment delay with positive consequence on clinical outcome.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/6e/NEURIMMINFL2020038091.PMC8192058.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38998189","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":"Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.","authors":"Francesc Graus, Alberto Vogrig, Sergio Muñiz-Castrillo, Jean-Christophe G Antoine, Virginie Desestret, Divyanshu Dubey, Bruno Giometto, Sarosh R Irani, Bastien Joubert, Frank Leypoldt, Andrew McKeon, Harald Prüss, Dimitri Psimaras, Laure Thomas, Maarten J Titulaer, Christian A Vedeler, Jan J Verschuuren, Josep Dalmau, Jerome Honnorat","doi":"10.1212/NXI.0000000000001014","DOIUrl":"10.1212/NXI.0000000000001014","url":null,"abstract":"<p><strong>Objective: </strong>The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS.</p><p><strong>Methods: </strong>A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project.</p><p><strong>Results: </strong>The panel proposed to substitute \"classical syndromes\" with the term \"high-risk phenotypes\" for cancer and introduce the concept of \"intermediate-risk phenotypes.\" The term \"onconeural antibody\" was replaced by \"high risk\" (>70% associated with cancer) and \"intermediate risk\" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided.</p><p><strong>Conclusions: </strong>The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38995711","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":"Exosomes From Subjects With Multiple Sclerosis Express EBV-Derived Proteins and Activate Monocyte-Derived Macrophages.","authors":"May F Mrad,&nbsp;Esber S Saba,&nbsp;Layane Nakib,&nbsp;Samia J Khoury","doi":"10.1212/NXI.0000000000001004","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001004","url":null,"abstract":"<p><strong>Objective: </strong>To investigate in a cross-sectional study the effect of serum-derived exosomes on primary human blood monocyte-derived macrophages (MDMs) comparing exosomes from healthy donors vs patients with relapsing-remitting multiple sclerosis in remission and in relapse and to assess whether the response correlates with exosomal Epstein-Barr virus (EBV) protein expression.</p><p><strong>Methods: </strong>A total of 45 serum-derived exosome preparations were isolated from patients and healthy controls and verified for the expression of exosomal and EBV markers. MDMs were differentiated from monocytes for 7 days and incubated for 24 hours with exosomes, and then, cell supernatants were collected for cytokine measurement by cytometric bead array. Cells were immunophenotyped before and after differentiation.</p><p><strong>Results: </strong>Serum-derived exosomes of patients with multiple sclerosis (MS) expressed higher levels of EBV proteins than healthy controls. Of interest, expression of EBV nuclear antigen EBNA1 and latent membrane proteins LMP1 and 2A was higher on exosomes derived from patients with active RRMS compared with healthy controls and stable patients. After data normalization, we observed that incubation with EBV(+) exosomes induced CXCL10 and CCL2 secretion by MDMs. MDMs differentiated from patients with active disease were better secretors of CXCL10 and other interferon-γ-inducible chemokines, including CCL2 and CXCL9, than MDMs from healthy and stable MS groups. MDMs from active patients had a higher frequency of a CD14(++) subset that correlated with the secreted CXCL10.</p><p><strong>Conclusion: </strong>Exosomes expressing EBV proteins correlate with disease activity and induce an inflammatory response in MDMs that is compounded by the origin of the responder cells.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/0a/NEURIMMINFL2020037150.PMC8130999.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38995710","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":"Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy.","authors":"Franziska Hopfner,&nbsp;Nora Möhn,&nbsp;Britta Eiz-Vesper,&nbsp;Britta Maecker-Kolhoff,&nbsp;Jens Gottlieb,&nbsp;Rainer Blasczyk,&nbsp;Nima Mahmoudi,&nbsp;Kaweh Pars,&nbsp;Ortwin Adams,&nbsp;Martin Stangel,&nbsp;Mike P Wattjes,&nbsp;Günter Höglinger,&nbsp;Thomas Skripuletz","doi":"10.1212/NXI.0000000000001020","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001020","url":null,"abstract":"<p><strong>Objective: </strong>Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating opportunistic infection of the brain caused by the ubiquitously distributed JC polyomavirus. There are no established treatment options to stop or slow down disease progression. In 2018, a case series of 3 patients suggested the efficacy of allogeneic BK virus-specific T-cell (BKV-CTL) transplantation.</p><p><strong>Methods: </strong>Two patients, a bilaterally lung transplanted patient on continuous immunosuppressive medication since 17 years and a patient with dermatomyositis treated with glucocorticosteroids, developed definite PML according to AAN diagnostic criteria. We transplanted both patients with allogeneic BKV-CTL from partially human leukocyte antigen (HLA) compatible donors. Donor T cells had directly been produced from leukapheresis by the CliniMACS IFN-γ cytokine capture system. In contrast to the previous series, we identified suitable donors by HLA typing in a preexamined registry and administered 1 log level less cells.</p><p><strong>Results: </strong>Both patients' symptoms improved significantly within weeks. During the follow-up, a decrease in viral load in the CSF and a regression of the brain MRI changes occurred. The transfer seemed to induce endogenous BK and JC virus-specific T cells in the host.</p><p><strong>Conclusions: </strong>We demonstrate that this optimized allogeneic BKV-CTL treatment paradigm represents a promising, innovative therapeutic option for PML and should be investigated in larger, controlled clinical trials.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that for patients with PML, allogeneic transplant of BKV-CTL improved symptoms, reduced MRI changes, and decreased viral load.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/c8/NEURIMMINFL2021038606.PMC8130010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38910640","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":"Delayed Benefit From Aggressive Immunotherapy in Waxing and Waning Anti-IgLON5 Disease.","authors":"Pauline Shambrook,&nbsp;Adèle Hesters,&nbsp;Clémence Marois,&nbsp;Daniel Zemba,&nbsp;Jérôme Servan,&nbsp;Bertrand Gaymard,&nbsp;Fernando Pico,&nbsp;Cécile Delorme,&nbsp;Catherine Lubetzki,&nbsp;Isabelle Arnulf,&nbsp;Dimitri Psimaras,&nbsp;Jérôme Honnorat,&nbsp;Ana Gales,&nbsp;Aurélie Méneret","doi":"10.1212/NXI.0000000000001009","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001009","url":null,"abstract":"Anti-IgLON5 disease is a rare disorder characterized by the variable association of movement disorders, sleep disturbances, cognitive impairment, bulbar symptoms, and respiratory dysfunction. Pathophysiology likely involves both autoimmune and neurodegenerative processes, and prognosis is considered to be poor. Here, we report a case with a waxing and waning course, who eventually responded well to aggressive and sustained immunotherapy.","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/34/NEURIMMINFL2020037135.PMC8192057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38980449","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":"Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis.","authors":"Delphine Sterlin,&nbsp;Martin Larsen,&nbsp;Jehane Fadlallah,&nbsp;Christophe Parizot,&nbsp;Marina Vignes,&nbsp;Gaëlle Autaa,&nbsp;Karim Dorgham,&nbsp;Catherine Juste,&nbsp;Patricia Lepage,&nbsp;Jennifer Aboab,&nbsp;Savine Vicart,&nbsp;Elisabeth Maillart,&nbsp;Olivier Gout,&nbsp;Catherine Lubetzki,&nbsp;Romain Deschamps,&nbsp;Caroline Papeix,&nbsp;Guy Gorochov","doi":"10.1212/NXI.0000000000000997","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000997","url":null,"abstract":"<p><strong>Objective: </strong>Based on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.</p><p><strong>Methods: </strong>We investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.</p><p><strong>Results: </strong>We show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (<i>r</i> = -0.647, <i>p</i> < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>Gut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/27/NEURIMMINFL2020033407.PMC8114833.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38889880","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-Adenylate Kinase 5 Encephalitis With Histologic Evidence of CNS Vasculitis.","authors":"Alex Vicino,&nbsp;Valentin Loser,&nbsp;Paolo Salvioni Chiabotti,&nbsp;Jean Philippe Brouland,&nbsp;Renaud Du Pasquier","doi":"10.1212/NXI.0000000000001010","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001010","url":null,"abstract":"Basic laboratory tests were normal. A brain MRI at admission (1 month after symptoms onset) showed bilateral, right predominant, mesiotemporal T2—fluid-attenuated inversion recovery (FLAIR) hyperintensity with gadolinium enhancement (figure). CSF analysis showed lymphocytic pleocytosis (120 cells/mm, 98% lymphocytes), hyperproteinorachia (1,032 mg/L), intrathecal IgG synthesis, and normal glucose and lactate levels. PCR for encephalitis, including HSV-1, was negative. Tuberculosis and Whipple disease were ruled out. Immunologic studies, CSF cytology, and flow cytometry were unremarkable.","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/02/9b/NEURIMMINFL2020038569.PMC8114832.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38889881","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":"Tissue Transglutaminase Expression Associates With Progression of Multiple Sclerosis.","authors":"Claudia Sestito,&nbsp;Cyra E Leurs,&nbsp;Martijn D Steenwijk,&nbsp;John J P Brevé,&nbsp;Jos W R Twisk,&nbsp;Micha M M Wilhelmus,&nbsp;Benjamin Drukarch,&nbsp;Charlotte E Teunissen,&nbsp;Anne-Marie van Dam,&nbsp;Joep Killestein","doi":"10.1212/NXI.0000000000000998","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000998","url":null,"abstract":"<p><strong>Objective: </strong>The clinical course of multiple sclerosis (MS) is variable and largely unpredictable pointing to an urgent need for markers to monitor disease activity and progression. Recent evidence revealed that tissue transglutaminase (TG2) is altered in patient-derived monocytes. We hypothesize that blood cell-derived TG2 messenger RNA (mRNA) can potentially be used as biomarker in patients with MS.</p><p><strong>Methods: </strong>In peripheral blood mononuclear cells (PBMCs) from 151 healthy controls and 161 patients with MS, TG2 mRNA was measured and correlated with clinical and MRI parameters of disease activity (annualized relapse rate, gadolinium-enhanced lesions, and T2 lesion volume) and disease progression (Expanded Disability Status Scale [EDSS], normalized brain volume, and hypointense T1 lesion volume).</p><p><strong>Results: </strong>PBMC-derived TG2 mRNA levels were significantly associated with disease progression, i.e., worsening of the EDSS over 2 years of follow-up, normalized brain volume, and normalized gray and white matter volume in the total MS patient group at baseline. Of these, in patients with relapsing-remitting MS, TG2 expression was significantly associated with worsening of the EDSS scores over 2 years of follow-up. In the patients with primary progressive (PP) MS, TG2 mRNA levels were significantly associated with EDSS, normalized brain volume, and normalized gray and white matter volume at baseline. In addition, TG2 mRNA associated with T1 hypointense lesion volume in the patients with PP MS at baseline.</p><p><strong>Conclusion: </strong>PBMC-derived TG2 mRNA levels hold promise as biomarker for disease progression in patients with MS.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that in patients with MS, PBMC-derived TG2 mRNA levels are associated with disease progression.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/8b/NEURIMMINFL2020034967.PMC8105890.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38914818","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":"Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab.","authors":"Nicolás Fissolo,&nbsp;Beatrice Pignolet,&nbsp;Jordi Rio,&nbsp;Patrick Vermersch,&nbsp;Aurélie Ruet,&nbsp;Jerome deSèze,&nbsp;Pierre Labauge,&nbsp;Sandra Vukusic,&nbsp;Caroline Papeix,&nbsp;Laurent Martinez-Almoyna,&nbsp;Ayman Tourbah,&nbsp;Pierre Clavelou,&nbsp;Thibault Moreau,&nbsp;Jean Pelletier,&nbsp;Christine Lebrun-Frenay,&nbsp;Bertrand Bourre,&nbsp;Gilles Defer,&nbsp;Xavier Montalban,&nbsp;David Brassat,&nbsp;Manuel Comabella","doi":"10.1212/NXI.0000000000001003","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001003","url":null,"abstract":"<p><strong>Objectives: </strong>The study aimed to assess the potential for serum neurofilament light chain (NFL) levels to predict the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab (NTZ)-treated patients with multiple sclerosis (MS) and to discriminate PML from MS relapses.</p><p><strong>Methods: </strong>NFL levels were measured with single molecule array (Simoa) in 4 cohorts: (1) a prospective cohort of patients with MS who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr); (2) a cohort of patients whose blood was collected during PML; (3) an independent cohort of non-PML NTZ-treated patients with serum NFL determinations at 2 years (replication cohort); and (4) a cohort of patients whose blood was collected during exacerbations.</p><p><strong>Results: </strong>Serum NFL levels were significantly increased after 2 years of NTZ treatment in pre-PML patients compared with NTZ-ctr. The prognostic performance of serum NFL levels to predict PML development at 2 years was similar in the NTZ-ctr group and replication cohort. Serum NFL levels also distinguished PML from MS relapses and were 8-fold higher during PML compared with relapses.</p><p><strong>Conclusions: </strong>These results support the use of serum NFL levels in clinical practice to identify patients with relapsing-remitting MS at higher PML risk and to differentiate PML from clinical relapses in NTZ-treated patients.</p><p><strong>Classification of evidence: </strong>This study provides Class I evidence that serum NFL levels can identify NTZ-treated patients with MS who will develop PML with a sensitivity of 67% and specificity of 80%.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/49/NEURIMMINFL2020037796.PMC8105883.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38910507","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":"Discontinuation of Immunosuppressive Therapy in Patients With Neuromyelitis Optica Spectrum Disorder With Aquaporin-4 Antibodies.","authors":"","doi":"10.1212/NXI.0000000000001013","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001013","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192055/pdf/NXI-D-21-00005.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38896694","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}