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The article presents a study which explores the use of gradient echo magnetic resonance imaging (MRI) for quantifying the severity of multiple sclerosis (MS) white matter lesions. gradient echo MRI was specifically used to correlate the disability, differentiate clinical MS subtypes, and determine prevalence of veins co-localized with lesions. An overview of the methods of the study is given, along with a discussion of its results and conclusions.

Objective: To contrast differences in pain and treatment outcomes between neuromyelitis optica (NMO) and multiple sclerosis (MS). Design: Retrospective, cross-sectional cohort study. Setting: Academic MS center. Patients: Complete ascertainment of an academic MS center cohort of NMO and an MS comparison sample cohort. Main Outcome Measures: Current pain was quantified by a 10-point scale and the McGill Pain Questionnaire. Expanded Disability Status Scale score and number of involved spinal cord levels were collected in addition to testing for cognition, fatigue, depression, and quality of life. Number and types of pain medications were tabulated. Results: Current pain was more common in subjects with NMO (n=29) vs MS (n=66) (86.2% vs 40.9%; P<.001) and more severe on a 10-point scale (5.38 vs 1.85; P<.001). Pain remained more common after controlling for disability and number of spinal cord segments (P=.03). Prescription pain medication was used more frequently in subjects with NMO compared with subjects with MS(75.9% vs 37.8%; P<.001), often requiring more than 1 medication (65.5% vs 15.2%; P<.001). No subject with NMO taking pain medication (22 of 29) rated their current pain as 0 of 10, whereas almost half of those taking pain medication with MS were currently free of pain (0% vs 48%; P=.006). Conclusions: Neuromyelitis optica is frequently associated with severe pain that appears insufficiently controlled by pharmacologic interventions. Future studies should evaluate the efficacy of a multidisciplinary and multimodal approach to pain management. [ABSTRACT FROM AUTHOR]

Background: Employment is often affected in persons with multiple sclerosis (MS), and changes in employment status are associated with reduced quality of life. However, there is limited research on the maintenance of employment and work productivity in persons with MS using a disease-modifying therapy. Objectives: To evaluate working status and work productivity in persons with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) for up to 5 years. Methods: In this analysis, we included RRMS North American Research Committee on Multiple Sclerosis (NARCOMS) Registry participants from the United States who reported DMF initiation in any semiannual update survey between Fall 2013 and Spring 2018; participants also had to have ≥1 year of follow-up data. The index survey was considered the survey when DMF was initiated. Work productivity was assessed by reported reduction in hours worked (yes/no) and number of work days missed. Time to change in working status (employed full-time to part-time, employed full- or part-time to not working) was evaluated using the Kaplan-Meier method. Participants were censored at last follow-up or DMF discontinuation, whichever came first. Results: A total of 608 participants with RRMS initiated DMF within the study period and had follow-up at 1 year. There were 294 (48.4%) participants employed at initiation of DMF (full-time, 73.8%). Most employed participants were female (86.1%) and Caucasian (82.6%) and had a bachelor's degree or higher education level (65.1%), and the mean (SD) age was 47.7 (9.5) years. The mean (SD) age at diagnosis was 36.0 (8.3) years. The median (interquartile range) PDDS level at initiation was 1 (0, 7) and follow-up was 2 (1, 3.5) years. Overall, 49 (16.7%) participants decreased employment; 13 (4%) changed from full-time to part-time status, and 36 (12%) changed from employed (full- or part-time) to not working. During follow-up, 31 (10.5%) salreported reducing their hours worked and there was a median of 3 (1, 6) missed work days per year. Of the 314 participants not employed, 23 (7.3%) participants went from not employed to employed. Conclusions: Among NARCOMS Registry participants who were treated with DMF for up to 5 years, most maintained their baseline level of working status and maintained stable levels of work productivity as assessed by missed work days and the proportion reducing work hours. The NARCOMS Registry provides an opportunity to longitudinally assess outcomes in DMF-treated persons with MS. [ABSTRACT FROM AUTHOR]

Importance: Multiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists., Objective: To evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS., Design, Setting, and Participants: A 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024., Exposure: Comorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders., Main Outcomes and Measures: The main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging., Results: A total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14)., Conclusions and Relevance: In this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.

Background and Objectives: Despite their high health care use, it is unclear whether the health care needs of people with MS are being met and what their priorities are. We assessed priorities for access to, and affordability of care, by people living with MS in the United States. We also tested the association between perceived inadequate access to care and health-related quality of life (HRQoL)., Methods: In Fall 2022, we conducted a cross-sectional survey of participants in the North American Research Committee on Multiple Sclerosis Registry about access to care and HRQoL (Health Utilities Index Mark III). We used multivariable polytomous logistic regression to test sociodemographic and clinical factors associated with access to care. We used multivariable linear regression analysis to test the association between access to care and HRQoL., Results: We included 4,914 respondents in the analysis, of whom 3,974 (80.9%) were women, with a mean (SD) age 64.4 (9.9) years. The providers who were most reported as needed but inaccessible were complementary providers (35.5%), followed by allied health providers (24.2%), occupational therapists (22.7%), and mental health providers (20.7%). Over 80% of participants reported that it was important or very important to be able to get an appointment with their primary MS health care provider when needed, to have sufficient time in their appointments to explain their concerns, to see their neurologist if their status changed, and that their health care providers communicated to coordinate their care. Participants who reported needing to see the provider but not having access or seeing the provider but would like to see them more often had lower HRQOL (ranging from -0.059 to -0.176) than participants who saw the provider as much as needed., Discussion: Gaps in access to care persist for people with MS in the United States and substantially affect HRQoL. Improving access to care for people with MS should be a health system priority., Competing Interests: R.A. Marrie receives research funding from CIHR, Research Manitoba, MS Canada, Multiple Sclerosis Scientific Foundation, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense, and is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis and serves on the editorial board of Neurology. S. Lancia has nothing to disclose. G.R. Cutter serves on Data and Safety Monitoring Boards for Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc., Consulting or Advisory Boards for Alexion, Antisense Therapeutics, Biogen, Clinical Trial Solutions LLC, Entelexo Biotherapeutics, Inc., Genzyme, Genentech, GW Pharmaceuticals, Immunic, Immunosis Pty Ltd, Klein-Buendel Incorporated, Merck/Serono, Novartis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Roche, SAB Biotherapeutics. He is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc., a private consulting company located in Birmingham AL. R.J. Fox receives personal consulting fees from AB Science, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, INmune Bio, Janssen, Lily, Novartis, Sanofi, Siemens, and TG Therapeutics; clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi. A. Salter receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, CMSC and the Department of Defense Congressionally Directed Medical Research Program, and is a member of editorial board for Neurology. She serves as a consultant for Gryphon Bio, LLC. She is a member of the Data and Safety Monitoring Board for Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2), Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), and Ocrelizumab for Preventing Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease (CELLO). She holds the Kenney Marie Dixon‐Pickens Distinguished Professorship in Multiple Sclerosis Research. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Background: Calorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures. This trial studied the effects of 12-week iCR on metabolic, immunological, and clinical outcomes in pwMS., Method: Relapsing-remitting MS participants were randomised to iCR or a control group. Study visits were conducted at baseline, 6 and 12 weeks. The primary outcome was reduction in serum leptin levels at 12 weeks. Feasibility and safety were assessed by diet adherence and adverse events (AEs). Secondary outcomes included changes in anthropometric and body composition measures, metabolic and immunologic profiling, and clinical measures. Mixed effects linear regression models were used to evaluate outcome differences between and within groups over time., Results: Forty-two pwMS were randomised, 34 completed the study (17/group). Leptin serum levels at 12 weeks were significantly lower in the iCR versus the control group (mean decrease -6.98 µg/dL, 95% CI: -28.02 to 14.06; p=0.03). Adherence to iCR was 99.5% and 97.2% at 6 and 12 weeks, respectively, and no serious AEs were reported. An increase in blood CD45RO + regulatory T-cell numbers was seen after 6 weeks of iCR. Exploratory cognitive testing demonstrated a significant improvement in the Symbol Digit Modality Test Score in the iCR group at 12 weeks., Conclusions: iCR has the potential to benefit metabolic and immunologic profiles and is safe and feasible in pwMS., Trial Registration Number: NCT03539094 ., Competing Interests: Competing interests: LP has received research funding from the National MS Society, the NIH, the Department of Defense and Fondazione Italiana Sclerosi Multipla; she has been funded by Alector and Biogen for a project not related to the one included in this manuscript. She is one of the Editor-in-Chief of Journal of Neuroimmunology. AHC received compensation for consulting for Biogen, EMD Serono, Bristol Myers Squibb, TG Therapeutics, Octave, Genentech, Roche, Novartis, Horizon and Janssen (J&J). AHC was supported by the Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology during this study. CAR received compensation for consulting for CoreTechs.ai, Eli Lilly, Voxelwise, Neurevolution. GFW received compensation for consulting for EMD Serono, Genzyme, Novartis, Sangamo, Roche, Alumis and the US Department of Justice. He has received research grant funding from the NIH, National MS Society, Doris Duke Foundation, US Department of Veterans Affairs, Biogen, EMD Serono and Genentech. He serves on the editorial boards of Neurology: Neuroimmunology & Neuroinflammation and the Journal of Neuroimmunology. He serves on advisory boards for Progentec and Genentech. RTN has consulted for Alexion Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, EMD Serono, Horizon Therapeutics, Novartis, TG Therapeutics. AS receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, CMSC and the Department of Defense Congressionally Directed Medical Research Program and is a member of the editorial board for Neurology. She serves as a consultant for Gryphon Bio and Abata Therapeutics. She is a member of the Data and Safety Monitoring Board for Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2), Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), Ocrelizumab for Preventing Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease (CELLO) and Methotrexate treatment of Arthritis caused by Chikungunya virus (MARCH). She holds the Kenney Marie Dixon-Pickens Distinguished Professorship in Multiple Sclerosis Research., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Conventional magnetic resonance imaging (MRI) methods do not quantify the severity of multiple sclerosis (MS) white matter lesions or measure pathology within normal-appearing white matter (NAWM)., Objective: Gradient Echo Plural Contrast Imaging (GEPCI), a fast MRI technique producing inherently co-registered images for qualitative and quantitative assessment of MS, was used to 1) correlate with disability; 2) distinguish clinical MS subtypes; 3) determine prevalence of veins co-localized within lesions in WM., Methods: Thirty subjects representing relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) subtypes were scanned with clinical and GEPCI protocols. Standard measures of physical disability and cognition were correlated with magnetic resonance metrics. Lesions with central veins were counted for RRMS subjects., Results: Tissue damage load (TDL-GEPCI) and lesion load (LL-GEPCI) derived with GEPCI correlated better with MS functional composite (MSFC) measures and most other neurologic measures than lesion load derived with FLAIR (LL-FLAIR). GEPCI correctly classified clinical subtypes in 70% subjects. A central vein could be identified in 76% of WM lesions in RRMS subjects on GEPCI T2*-SWI images., Conclusion: GEPCI lesion metrics correlated better with neurologic disability than lesion load derived using FLAIR imaging, and showed promise in classifying clinical subtypes of MS. These improvements are likely attributable to the ability of GEPCI to quantify tissue damage.

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology., Objective: Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions., Methods: Subjects greater than or equal to 12 months from a clinical episode of transverse myelitis underwent a novel transaxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS and 10 healthy controls were included., Results: Within T2 affected white matter regions, radial diffusivity was increased in both NMO and MS compared with healthy controls (p<0.001, respectively), and to a greater extent in NMO than MS (p<0.001). Axial diffusivity was decreased in T2 lesions in both NMO and MS compared with controls (p<0.001, p=0.001), but did not differ between the two diseases. Radial diffusivity and fractional anisotropy within white matter regions upstream and downstream of T2 lesions were different from controls in each disease., Conclusions: Higher radial diffusivity within spinal cord white matter tracts derived from diffusion tensor imaging were appreciated in NMO compared with MS, consistent with the known greater tissue destruction seen in NMO. DTI also detected tissue alterations outside T2 lesions and may be a surrogate of anterograde and retrograde degeneration.