Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Baicalin Promotes CNS Remyelination via PPARγ Signal Pathway.","authors":"Ruo-Song Ai, Kun Xing, Xin Deng, Juan-Juan Han, Dong-Xia Hao, Wen-Hui Qi, Bing Han, Ya-Na Yang, Xing Li, Yuan Zhang","doi":"10.1212/NXI.0000000000001142","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001142","url":null,"abstract":"Background and Objectives Demyelinating diseases in the CNS are characterized by myelin sheath destruction or formation disorder that leads to severe neurologic dysfunction. Remission of such diseases is largely dependent on the differentiation of oligodendrocytes precursor cells (OPCs) into mature myelin-forming OLGs at the demyelinated lesions, which is defined as remyelination. We discover that baicalin (BA), a natural flavonoid, in addition to its well-known antiinflammatory effects, directly stimulates OLG maturation and CNS myelin repair. Methods To investigate the function of BA on CNS remyelination, we develop the complementary in vivo and in vitro models, including physiologic neonatal mouse CNS myelinogenesis model, pathologic cuprizone-induced (CPZ-induced) toxic demyelination model, and postnatal OLG maturation assay. Furthermore, molecular docking, pharmacologic regulation, and transgenic heterozygous mice were used to clarify the target and action of the mechanism of BA on myelin repair promotion. Results Administration of BA was not only merely effectively enhanced CNS myelinogenesis during postnatal development but also promoted remyelination and reversed the coordination movement disorder in the CPZ-induced toxic demyelination model. Of note, myelin-promoting effects of BA on myelination or regeneration is peroxisome proliferator-activated receptor γ (PPARγ) signaling-dependent. Discussion Our work demonstrated that BA promotes myelin production and regeneration by activating the PPARγ signal pathway and also confirmed that BA is an effective natural product for the treatment of demyelinating diseases.","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/cf/8d/NEURIMMINFL2021039378.PMC8808354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39580140","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":"Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression.","authors":"Paolo Preziosa,&nbsp;Elisabetta Pagani,&nbsp;Alessandro Meani,&nbsp;Lucia Moiola,&nbsp;Mariaemma Rodegher,&nbsp;Massimo Filippi,&nbsp;Maria A Rocca","doi":"10.1212/NXI.0000000000001139","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001139","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic active lesions contribute to multiple sclerosis (MS) severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T₁- and T₂-weighted scans (i.e., slowly expanding lesions [SELs]) have been proposed as a marker of chronic inflammation. In this study, we assessed whether SEL burden and microstructural abnormalities were associated with Expanded Disability Status Scale (EDSS) score worsening and secondary progressive (SP) conversion at 9.1-year follow-up in patients with relapsing-remitting (RR) MS.</p><p><strong>Methods: </strong>In 52 patients with RRMS, SELs were identified among WM lesions by linearly fitting the Jacobian of the nonlinear deformation field between time points obtained combining 3T brain T₁- and T₂-weighted scans acquired at baseline and months 6, 12, and 24. Logistic regression analysis was applied to investigate the associations of SEL number, volume, magnetization transfer ratio (MTR), and T₁-weighted signal intensity with disability worsening (i.e., EDSS score increase) and SP conversion after a median follow-up of 9.1 years.</p><p><strong>Results: </strong>At follow-up, 20/52 (38%) patients with MS showed EDSS score worsening; 13/52 (25%) showed SP conversion. A higher baseline EDSS score (for each point higher: OR = 3.15 [95% CI = 1.61; 8.38], <i>p</i> = 0.003), a higher proportion of SELs among baseline lesions (for each % increase: OR = 1.22 [1.04; 1.58], <i>p</i> = 0.04), and lower baseline MTR values of SELs (for each % higher: OR = 0.66 [0.41; 0.92], <i>p</i> = 0.033) were significant independent predictors of EDSS score worsening at follow-up (C-index = 0.892). A higher baseline EDSS score (for each point higher: OR = 6.37 [1.98; 20.53], <i>p</i> = 0.002) and lower baseline MTR values of SELs (for each % higher: OR = 0.48 [0.25; 0.89], <i>p</i> = 0.02) independently predicted SPMS conversion (C-index = 0.947).</p><p><strong>Discussion: </strong>The proportion of SELs is associated with MS progression after 9 years. More severe SEL microstructural abnormalities independently predict EDSS score worsening and SPMS conversion. The quantification of SEL burden and damage using T₁-, T₂-weighted, and MTR sequences may identify patients with RRMS at a higher risk of long-term disability progression and SPMS conversion.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that in patients with RRMS starting treatment with natalizumab or fingolimod, the proportion of SELs on brain MRI was associated with EDSS score worsening and SPMS conversion at 9-year follow-up.</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/53/de/NEURIMMINFL2021039374.PMC8808355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39580139","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":"Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis.","authors":"Eero Rissanen,&nbsp;Kelsey Carter,&nbsp;Steven Cicero,&nbsp;John Ficke,&nbsp;Marie Kijewski,&nbsp;Mi-Ae Park,&nbsp;Joseph Kijewski,&nbsp;Emily Stern,&nbsp;Tanuja Chitnis,&nbsp;David Silbersweig,&nbsp;Howard L Weiner,&nbsp;Chun K Kim,&nbsp;Jennifer Lyons,&nbsp;Joshua P Klein,&nbsp;Shamik Bhattacharyya,&nbsp;Tarun Singhal","doi":"10.1212/NXI.0000000000001136","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001136","url":null,"abstract":"<p><strong>Background and objectives: </strong>This [¹⁸F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich, glioma-inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined.</p><p><strong>Methods: </strong>FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non-LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses.</p><p><strong>Results: </strong>P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non-LGI1-AE group, AD group, and NCs (all <i>p</i> < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84-0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non-LGI1-AE groups when compared with NCs (both <i>p</i> < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all <i>p</i> < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up.</p><p><strong>Discussion: </strong>Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/eb/c3/NEURIMMINFL2021039229.PMC8802686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39745454","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":"Optic Nerve Lesion Length at the Acute Phase of Optic Neuritis Is Predictive of Retinal Neuronal Loss.","authors":"Mickael Denis,&nbsp;Jean-Philippe Woillez,&nbsp;Vasily M Smirnov,&nbsp;Elodie Drumez,&nbsp;Julien Lannoy,&nbsp;Julie Boucher,&nbsp;Mickael Zedet,&nbsp;Jean-Pierre Pruvo,&nbsp;Julien Labreuche,&nbsp;Helene Zephir,&nbsp;Xavier Leclerc,&nbsp;Olivier Outteryck","doi":"10.1212/NXI.0000000000001135","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001135","url":null,"abstract":"<p><strong>Background and objectives: </strong>Acute optic neuritis (ON) is a classical presenting symptom of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and anti-MOG-associated disorders. The resulting visual impairment is variable and can be severe. Clinicians are in need of predictive biomarkers to optimize the management of acute ON. In this longitudinal study (IRMANO, NCT03651662), we evaluated the ability of optic nerve lesion length measured on MRI at the acute phase of ON to predict retinal neuro-axonal loss and visual impairment at a chronic stage.</p><p><strong>Methods: </strong>We conducted a longitudinal study (IRMANO, NCT03651662) of patients who presented a clinical episode of ON (≤8 weeks). All patients underwent a retinal optical coherence tomography (OCT) and a brain/optic nerve MRI, including 3D double-inversion recovery (DIR) sequence at the acute phase of ON and 12 months later. Primary outcomes were optic nerve DIR hypersignal lesion length, macular ganglion cell-inner plexiform layer (GCIPL) volume measured on OCT, and low-contrast monocular visual acuity (LCMVA).</p><p><strong>Results: </strong>The study group included 51 patients (33 women, mean age of 32.4 years ± 7.9). We recruited patients with a clinically isolated syndrome (n = 20), a relapsing-remitting MS (n = 23), an isolated ON (n = 6), and a first clinical episode of NMOSD (n = 2). Optic nerve DIR hypersignal was observed in all but 1 symptomatic optic nerves. At inclusion, the mean optic nerve lesion length (in mm) was 12.35 ± 5.98. The mean GCIPL volume (in mm³) significantly decreased between inclusion (1.90 ± 0.18) and M₁₂ (1.67 ± 0.21; <i>p</i> < 0.0001). Optic nerve lesion length at inclusion was significantly associated with GCIPL thinning (estimate ± SD; -0.012 ± 0.004; <i>p</i> = 0.0016) and LCMVA at M₁₂ (0.016 ± 0.003; <i>p</i> < 0.001). Optic nerve lesion length significantly increased at M₁₂ (15.76 ± 8.70; <i>p</i> = 0.0007). The increase in optic nerve lesion length was significantly associated with the GCIPL thinning between inclusion and M₁₂ (-0.012 ± 0.003; <i>p</i> = 0.0011).</p><p><strong>Discussion: </strong>At the acute phase of ON, optic nerve lesion length is an imaging biomarker predictive of retinal neuro-axonal loss and chronic visual impairment, which can help to stratify future therapeutic strategies in acute ON.</p><p><strong>Classification of evidence: </strong>This study provides Class I evidence that optic nerve lesion length measured on MRI during the acute phase of a first episode of ON is associated with long-term retinal neuro-axonal loss and visual impairment.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/d0/NEURIMMINFL2021039451.PMC8802684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39745453","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":"Progranulin Suppressed Autoimmune Uveitis and Autoimmune Neuroinflammation by Inhibiting Th1/Th17 Cells and Promoting Treg Cells and M2 Macrophages.","authors":"Chaokui Wang,&nbsp;Wenjun Zhou,&nbsp;Guannan Su,&nbsp;Jianping Hu,&nbsp;Peizeng Yang","doi":"10.1212/NXI.0000000000001133","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001133","url":null,"abstract":"<p><strong>Background and objectives: </strong>Progranulin (PGRN) is an important immune regulatory molecule in several immune-mediated diseases. The objective of this study is to investigate the role of PGRN in uveitis and its counterpart, experimental autoimmune uveitis (EAU), and experimental autoimmune encephalomyelitis (EAE).</p><p><strong>Methods: </strong>Serum PGRN levels in patients with Behcet disease (BD) or Vogt-Koyanagi-Harada (VKH) disease and normal controls were measured by ELISA. EAE and EAU were induced in B10RIII, wild-type, and PGRN^-/- mice to evaluate the effect of PGRN on the development of these 2 immune-mediated disease models. The local and systemic immunologic alterations were detected by ELISA, flow cytometry, and real-time PCR. RNA sequencing was performed to identify the hub genes and key signaling pathway.</p><p><strong>Results: </strong>A significantly decreased PGRN expression was observed in patients with active BD and active VKH. Recombinant PGRN significantly reduced EAU severity in association with a decreased frequency of Th17 and Th1 cells. PGRN^-/- mice developed an exacerbated EAU and EAE in association with strikingly increased frequency of Th1 and Th17 cells and reduced frequency of regulatory T (Treg) cells. In vitro studies revealed that rPGRN could inhibit IRBP_161-180-specific Th1 and Th17 cell response and promote Treg cell expansion. It promoted non-antigen-specific Treg cell polarization from naive CD4⁺ T cells in association with increased STAT5 phosphorylation. Using RAN sequencing, we identified 5 shared hub genes including <i>Tnf, Il6, Il1b, Cxcl2,</i> and <i>Ccl2</i> and the most significantly enriched MAPK and tumor necrosis factor signaling pathway in PGRN^-/- EAU mice. The aggravated EAE activity in PGRN^-/- mice was associated with a skew from M2 to M1 macrophages.</p><p><strong>Discussion: </strong>Our results collectively reveal an important protective role of PGRN in EAU and EAE. These studies suggest that PGRN could serve as an immunoregulatory target in the study of prevention and treatment for the Th1/Th17-mediated diseases.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/10/NEURIMMINFL2021039127.PMC8791655.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39951659","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":"Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions.","authors":"Nicole Zinger,&nbsp;Gerald Ponath,&nbsp;Elizabeth Sweeney,&nbsp;Thanh D Nguyen,&nbsp;Chih Hung Lo,&nbsp;Ivan Diaz,&nbsp;Alexey Dimov,&nbsp;Leilei Teng,&nbsp;Lily Zexter,&nbsp;Joseph Comunale,&nbsp;Yi Wang,&nbsp;David Pitt,&nbsp;Susan A Gauthier","doi":"10.1212/NXI.0000000000001138","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001138","url":null,"abstract":"<p><strong>Background and objectives: </strong>To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro.</p><p><strong>Methods: </strong>This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell-derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared.</p><p><strong>Results: </strong>Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI -5.87 to -0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro.</p><p><strong>Discussion: </strong>Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity.</p><p><strong>Classification of evidence: </strong>This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/26/NEURIMMINFL2021039481.PMC8771666.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39834315","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":"Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study.","authors":"Pietro Iaffaldano,&nbsp;Giuseppe Lucisano,&nbsp;Alessia Manni,&nbsp;Damiano Paolicelli,&nbsp;Francesco Patti,&nbsp;Marco Capobianco,&nbsp;Vincenzo Brescia Morra,&nbsp;Patrizia Sola,&nbsp;Ilaria Pesci,&nbsp;Giacomo Lus,&nbsp;Giovanna De Luca,&nbsp;Alessandra Lugaresi,&nbsp;Paola Cavalla,&nbsp;Sara Montepietra,&nbsp;Giorgia Teresa Maniscalco,&nbsp;Franco Granella,&nbsp;Paolo Ragonese,&nbsp;Marika Vianello,&nbsp;Laura Brambilla,&nbsp;Rocco Totaro,&nbsp;Simona Toscano,&nbsp;Simona Malucchi,&nbsp;Maria Petracca,&nbsp;Lucia Moiola,&nbsp;Diana Ferraro,&nbsp;Vito Lepore,&nbsp;Paola Mosconi,&nbsp;Michela Ponzio,&nbsp;Gioacchino Tedeschi,&nbsp;Giancarlo Comi,&nbsp;Mario Alberto Battaglia,&nbsp;Massimo Filippi,&nbsp;Maria Pia Amato,&nbsp;Maria Trojano","doi":"10.1212/NXI.0000000000001141","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001141","url":null,"abstract":"<p><strong>Background and objectives: </strong>Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR).</p><p><strong>Methods: </strong>A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered.</p><p><strong>Results: </strong>A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (<i>p</i> < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], <i>p</i> < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], <i>p</i> = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], <i>p</i> < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home.</p><p><strong>Discussion: </strong>This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/55/NEURIMMINFL2021039360.PMC8771668.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39834317","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":"Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial.","authors":"Thomas E Williams,&nbsp;Katherine P Holdsworth,&nbsp;Jennifer M Nicholas,&nbsp;Arman Eshaghi,&nbsp;Theodora Katsanouli,&nbsp;Henrietta Wellington,&nbsp;Amanda Heslegrave,&nbsp;Henrik Zetterberg,&nbsp;Chris Frost,&nbsp;Jeremy Chataway","doi":"10.1212/NXI.0000000000001130","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001130","url":null,"abstract":"<p><strong>Background and objectives: </strong>Improved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS.</p><p><strong>Methods: </strong>The MS-STAT trial randomized patients to 80 mg simvastatin or placebo. Serum was analyzed for NfL and NfH using Simoa technology. We used linear mixed models to investigate the treatment effects of simvastatin compared with placebo on NfL and NfH. Additional models examined the relationships between neurofilaments and MRI and clinical measures of disease severity.</p><p><strong>Results: </strong>A total of 140 patients with SPMS were included. There was no evidence for a simvastatin treatment effect on NfL or NfH: compared with placebo, NfL was 1.2% lower (95% CI 10.6% lower to 9.2% higher; <i>p</i> = 0.820) and NfH was 0.4% lower (95% CI 18.4% lower to 21.6% higher; <i>p</i> = 0.969) in the simvastatin treatment group. Secondary analyses suggested that higher NfL was associated with greater subsequent whole brain atrophy, higher T2 lesion volume, and more new/enlarging T2 lesions in the previous 12 months, as well as greater physical disability. There were no significant associations between NfH and MRI or clinical variables.</p><p><strong>Discussion: </strong>We found no evidence of a simvastatin treatment effect on serum neurofilaments. While confirmation of the neuroprotective benefits of simvastatin is awaited from the ongoing phase 3 study (NCT03387670), our results suggest that treatments capable of slowing the rate of whole brain atrophy in SPMS, such as simvastatin, may act via mechanisms largely independent of neuroaxonal injury, as quantified by NfL. This has important implications for the design of future phase 2 clinical trials in PMS.</p><p><strong>Trial registration information: </strong>MS-STAT: NCT00647348.</p><p><strong>Classification of evidence: </strong>This study provides class I evidence that simvastatin treatment does not have a large impact on either serum NfL or NfH, as quantified in this study, in SPMS.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/a2/NEURIMMINFL2021039196.PMC8759719.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39822760","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":"Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease: A Case Series.","authors":"Christine Strippel,&nbsp;Anna Heidbreder,&nbsp;Andreas Schulte-Mecklenbeck,&nbsp;Lisanne Korn,&nbsp;Tobias Warnecke,&nbsp;Nico Melzer,&nbsp;Heinz Wiendl,&nbsp;Matthias Pawlowski,&nbsp;Catharina C Gross,&nbsp;Stjepana Kovac","doi":"10.1212/NXI.0000000000001137","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001137","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite detection of autoantibodies, anti-IgLON5 disease was historically considered a tau-associated neurodegenerative disease, with limited treatment options and detrimental consequences for the patients. Observations in increasing case numbers hint toward underlying inflammatory mechanisms that, early detection provided, open a valuable window of opportunity for therapeutic intervention. We aimed to further substantiate this view by studying the CSF of patients with anti-IgLON5.</p><p><strong>Methods: </strong>We identified 11 patients with anti-IgLON5 from our database and compared clinical, MRI, and CSF findings with a cohort of 20 patients with progressive supranuclear palsy (PSP) (as a noninflammatory tauopathy) and 22 patients with functional neurologic disorder.</p><p><strong>Results: </strong>Patients with anti-IgLON5 show inflammatory changes in routine CSF analysis, an increase in B-lymphocyte frequency, and the presence of plasma cells in comparison to the PSP-control group and functional neurologic disease controls. Patients with intrathecal plasma cells showed a clinical response to rituximab.</p><p><strong>Discussion: </strong>Our findings indicate the importance of inflammatory mechanisms, in particular in early and acute anti-IgLON5 cases, which may support the use of immune-suppressive treatments in these cases. The main limitation of the study is the small number of cases due to the rarity of the disease.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/53/NEURIMMINFL2021039397.PMC8759718.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39821879","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":"SEZ6L2 Antibody-Associated Cerebellar Ataxia Responsive to Sequential Immunotherapy.","authors":"Ayla Mehdiyeva,&nbsp;Aki Hietaharju,&nbsp;Jussi Sipilä","doi":"10.1212/NXI.0000000000001131","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001131","url":null,"abstract":"<p><strong>Objectives: </strong>Seizure-related 6 homolog like 2 (SEZ6L2) antibody-associated ataxia is an extremely rare disease. Six patients have been reported and none of them improved significantly with immunotherapy. Herein, we present the case of a patient with cerebellar ataxia and SEZ6L2 antibodies who benefited from immunotherapy, which dramatically altered the course of her disease.</p><p><strong>Methods: </strong>We present a case report of a 73-year-old woman with progressive balance problems. Her condition had rapidly deteriorated in the 2 weeks before the admission to our hospital leading to repeated falls and eventually left her bed-ridden.</p><p><strong>Results: </strong>She presented with severe trunk ataxia, bidirectional nystagmus, dysarthric speech, and persistent nausea. With the exception of cerebellar atrophy, extensive imaging studies revealed no pathology. SEZ6L2 antibodies were found in both CSF and serum. Over a period of 9 months, our patient received immunotherapy consisting of steroid pulse therapy, IV immunoglobulin infusions, rituximab, and cyclophosphamide. Consequently, her condition improved markedly, and she was discharged home from the neurologic rehabilitation unit.</p><p><strong>Discussion: </strong>Our case report shows that intense sequential immunotherapy may considerably improve level of functioning in some patients with SEZ6L2 antibody-associated cerebellar ataxia.</p><p><strong>Classification of evidence: </strong>This provides Class IV evidence. It is a single observational study without controls.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/bc/NEURIMMINFL2021039448.PMC8759717.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39822761","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}