Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis
Discussion Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 23, 2022 Category: Neurology Authors: Vasileiou, E. S., Hu, C., Bernstein, C. N., Lublin, F., Wolinsky, J. S., Cutter, G. R., Sotirchos, E. S., Kowalec, K., Salter, A., Saidha, S., Mowry, E. M., Calabresi, P. A., Marrie, R. A., Fitzgerald, K. C. Tags: Research Article Source Type: research

Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies
Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological...
Source: Neurology Neuroimmunology and Neuroinflammation - November 22, 2022 Category: Neurology Authors: Ziemssen, T., Bhan, V., Chataway, J., Chitnis, T., Campbell Cree, B. A., Havrdova, E. K., Kappos, L., Labauge, P., Miller, A., Nakahara, J., Oreja-Guevara, C., Palace, J., Singer, B., Trojano, M., Patil, A., Rauser, B., Hach, T. Tags: Review Source Type: research

More Efficient Complement Activation by Anti-Aquaporin-4 Compared With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies
The objective was to study complement-mediated cytotoxicity induced by immunoglobulin G (IgG) anti–aquaporin-4 antibodies (AQP4-IgG) and anti–myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) in human serum samples from patients suffering from the rare demyelinating diseases of the CNS neuromyelitis optica spectrum disorder (NMOSD) and MOG-IgG–associated disease (MOGAD). Methods A cell-based assay with HEK293A cells expressing different MOG isoforms (MOGα1-3β1-3) or AQP4-M23 was used. Cells were incubated with human MOG-IgG or AQP4-IgG–positive serum samples together with active o...
Source: Neurology Neuroimmunology and Neuroinflammation - November 22, 2022 Category: Neurology Authors: Lerch, M., Schanda, K., Lafon, E., Würzner, R., Mariotto, S., Dinoto, A., Wendel, E. M., Lechner, C., Hegen, H., Rostasy, K., Berger, T., Wilflingseder, D., Höftberger, R., Reindl, M. Tags: Research Article Source Type: research

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination
We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. Methods The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including ...
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2022 Category: Neurology Authors: Francis, A. G., Elhadd, K., Camera, V., Ferreira dos Santos, M., Rocchi, C., Adib-Samii, P., Athwal, B., Attfield, K., Barritt, A., Craner, M., Fisniku, L., Iversen, A. K. N., Leach, O., Matthews, L., Redmond, I., O'Riordan, J., Scalfari, A., Tanasescu, R Tags: Research Article Source Type: research

Sustained Low Relapse Rate With Highly Variable B-Cell Repopulation Dynamics With Extended Rituximab Dosing Intervals in Multiple Sclerosis
The objective of this study was to determine clinical and neuroradiologic disease activity, as well as B-cell repopulation dynamics, after implementation of extended rituximab dosing in RRMS. Methods We conducted a prospective observational study in a specialized-care, single-center setting, including patients with RRMS participating in the COMBAT-MS and MultipleMS observational drug trials, who had received at least 2 courses of rituximab (median follow-up 4.2 years, range 0.1–8.9 years). Using Cox regression, hazard ratios (HRs) of clinical relapse and/or contrast-enhancing lesions on MRI were calculated in relati...
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2022 Category: Neurology Authors: Starvaggi Cucuzza, C., Longinetti, E., Ruffin, N., Evertsson, B., Kockum, I., Jagodic, M., Al Nimer, F., Frisell, T., Piehl, F. Tags: Research Article Source Type: research

Serum Neurofilament Identifies Patients With Multiple Sclerosis With Severe Focal Axonal Damage in a 6-Year Longitudinal Cohort
Discussion sNfL levels associate with severe focal axonal damage as reflected by development of persistent T1 lesions. Baseline sNfL values predicted NEDA-3T1 status at 6-year follow-up. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2022 Category: Neurology Authors: Steffen, F., Uphaus, T., Ripfel, N., Fleischer, V., Schraad, M., Gonzalez-Escamilla, G., Engel, S., Groppa, S., Zipp, F., Bittner, S. Tags: Research Article Source Type: research

Serum Levels of CXCL13 Are Associated With Teriflunomide Response in Patients With Multiple Sclerosis
Discussion Altogether, these results point to CXCL13 as a treatment response biomarker to teriflunomide in relapsing-remitting patients with MS, and the change in CXCL13 levels during the first year of treatment can be used in clinical practice to identify optimal responders to teriflunomide. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2022 Category: Neurology Authors: Fissolo, N., Pappolla, A., Rio, J., Villar, L. M., Perez-Hoyos, S., Sanchez, A., Gutierrez, L., Montalban, X., Comabella, M. Tags: Research Article Source Type: research

Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy
Discussion Cladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence. Trial Registration Information ClinicalTrials.gov Identifier: NCT03364036. Date re...
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2022 Category: Neurology Authors: Wiendl, H., Schmierer, K., Hodgkinson, S., Derfuss, T., Chan, A., Sellebjerg, F., Achiron, A., Montalban, X., Prat, A., De Stefano, N., Barkhof, F., Leocani, L., Vermersch, P., Chudecka, A., Mwape, C., Holmberg, K. H., Boschert, U., Roy, S., on behalf of Tags: Research Article Source Type: research

Guillain-Barre Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies
In this study, 52 patients with ZIKV-GBS were compared with 134 ZIKV-infected patients without GBS and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens were validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. Results Overall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated cocultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared with all controls. IgM antibody immunoreactivity to dorsal ...
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2022 Category: Neurology Authors: Davies, A. J., Lleixa, C., Siles, A. M., Gourlay, D. S., Berridge, G., Dejnirattisai, W., Ramirez-Santana, C., Anaya, J.-M., Falconar, A. K., Romero-Vivas, C. M., Osorio, L., Parra, B., Screaton, G. R., Mongkolsapaya, J., Fischer, R., Pardo, C. A., Halste Tags: Research Article Source Type: research

CLIPPERS Responsive to Cladribine as a Durable Steroid-Sparing Agent
This study provides Class IV evidence that cladribine is a steroid-sparing treatment consideration in CLIPPERS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 17, 2022 Category: Neurology Authors: Thebault, S., Bergman, H., Atkins, H. L., Freedman, M. S., Brooks, J. Tags: Clinical/Scientific Note Source Type: research

CD59 Expression in Skeletal Muscles and Its Role in Myasthenia Gravis
Discussion CD59, which acts as a complement regulator, may protect the NMJ from complement attack. Our findings could provide a basis for further research that investigates the underlying pathogenesis in MG and the immunomodulating interactions of the muscle cells. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 17, 2022 Category: Neurology Authors: Iwasa, K., Furukawa, Y., Yoshikawa, H., Yamada, M., Ono, K. Tags: Research Article Source Type: research

Longitudinal Postvaccine SARS-CoV-2 Immunoglobulin G Titers, Memory B-Cell Responses, and Risk of COVID-19 in Multiple Sclerosis Over 1 Year
Discussion Postvaccine anti-S IgG titers decrease over time regardless of MS treatment and are associated with breakthrough COVID-19. Both humoral and specific memory B-cell responses are diminished on S1P modulators. Within anti-CD20–treated patients, B-cell count at first vaccine determines anti-S IgG production, whereas postvaccine anti-CD20 infusions negatively affect spike-specific memory B cells. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 17, 2022 Category: Neurology Authors: Disanto, G., Galante, A., Cantu', M., Sacco, R., Mele, F., Eisler, J. J., Keller, F., Bernasconi, E., Sallusto, F., Zecca, C., Gobbi, C. Tags: Research Article Source Type: research

Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis
Discussion Higher levels of sGFAP correlated with subsequent progression, particularly in nonactive patients, whereas sNfL reflected acute disease activity in patients with MS at high risk of underlying progressive pathology. Thus, sGFAP and sNfL levels may be used to stratify patients with progressive MS for clinical research studies and clinical trials and may inform clinical care. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 14, 2022 Category: Neurology Authors: Barro, C., Healy, B. C., Liu, Y., Saxena, S., Paul, A., Polgar-Turcsanyi, M., Guttmann, C. R. G., Bakshi, R., Kropshofer, H., Weiner, H. L., Chitnis, T. Tags: Research Article Source Type: research

Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study
This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 14, 2022 Category: Neurology Authors: Levraut, M., Laurent-Chabalier, S., Ayrignac, X., Bigaut, K., Rival, M., Squalli, S., Zephir, H., Alberto, T., Pekar, J.-D., Ciron, J., Biotti, D., Puissant-Lubrano, B., Camdessanche, J.-P., Tholance, Y., Casez, O., Toussaint, B., Marion, J., Moreau, T., Tags: Research Article Source Type: research

Recurrent Optic Neuritis and Perineuritis Followed by an Unexpected Discovery: From the National Multiple Sclerosis Society Case Conference Proceedings
We describe a woman with a history of relapsing acute optic neuritis and perineuritis. Testing failed to confirm a specific diagnosis; hence, she was diagnosed with seronegative neuromyelitis optica spectrum disorder and treated with the immunotherapy rituximab, later in conjunction with mycophenolate mofetil. She achieved a durable remission for 9 years until she presented with paresthesia affecting her left fifth digit, right proximal thigh, and left foot, while also reporting a 25-pound weight loss over the prior 3 months. New imaging demonstrated a longitudinally extensive and enhancing optic nerve, in conjunction with...
Source: Neurology Neuroimmunology and Neuroinflammation - November 10, 2022 Category: Neurology Authors: Pimentel Maldonado, D. A., Lisak, R., Galetta, S., Balcer, L., Varkey, T., Goodman, A., Graves, J., Racke, M., Zamvil, S. S., Newsome, S., Frohman, E. M., Frohman, T. C. Tags: Diagnostic [amp ] Treatment Challenges Source Type: research