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Background: The relation of sarcopenia and disability in MS is unknown., Objective: To investigate the relation of temporal muscle thickness (TMT) and disability., Methods: A cohort of 132 people who presented with a clinically isolated syndrome (CIS) suggestive of MS at a mean age of 30.0 years, were prospectively followed clinically and with MRI over 30-years. TMT and expanded disability status scale (EDSS) were assessed at baseline, one- five- ten- fourteen- twenty- and thirty-year follow-up., Results: At 30-years, 27 participants remained classified as having had a CIS, 34 converted to relapsing remitting MS, 26 to secondary progressive MS, and 16 had died due to MS. Using linear mixed effect models with subject nested in time, greater annualized TMT-thinning was seen in individuals who developed MS (-0.04 mm/a, 95%CI: -0.07 to -0.01, p = 0.023). In those who converted to MS, a thinner TMT was reached at 14- (p = 0.008), 20- (p = 0.002) and 30-years (p< 0.001). TMT was negatively correlated with EDSS at 20-years (R=-0.18, p = 0.032) and 30-years (R-0.244, p = 0.005). Longitudinally, TMT at earlier timepoints was not predictive for 30-year clinical outcomes., Conclusion: TMT thinning is accelerated in MS and correlated with disability in later disease stages, but is not predictive of future disability., Competing Interests: Declaration of Competing Interest LH has no conflicts of interest relevant to this study. KC has received honoraria for speaking at meetings, advisory work or support to attend meetings from Merck, Biogen Idec, Sanofi Genzyme and Roche. SM has no conflicts of interest relevant to this study. JF has no conflicts of interest relevant to this study. OC has served as a consultant for Novartis and has received a speaker honorarium from Merck. She has obtained funding from NIHR, UCLH NIHR BRC, National and UK MS Society, PMSA, and MRC. DC is a consultant Hoffmann-La Roche. In the last three years he has been a consultant for Biogen, has received research funding from Hoffmann-La Roche, the International Progressive MS Alliance, the MS Society, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, and a speaker's honorarium from Novartis. He co-supervises a clinical fellowship at the National Hospital for Neurology and Neurosurgery, London, which is supported by Merck. FB is a consultant for Biogen, Bayer, Merck, Roche, Novartis, IXICO and Combinostics; has received funding from European Commission Horizon (2020), UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre and GE healthcare; and serves on the editorial boards of Radiology, Brain, Neuroradiology, Multiple Sclerosis Journal, and Neurology., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Declaration of Competing Interest J.S, SY.X, DC.T, YY.D, XL.X, S.L, GM.C, FD.S, ZZ.Z, XH.Z and Y.L declared there is no conflict of interest. D.C. is a consultant for Biogen and Hoffmann-La Roche. In the last three years he has received research funding from Hoffmann-La Roche, the International Progressive MS Alliance, the MS Society, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research center, and a speaker's honorarium from Novartis. He co-supervises a clinical fellowship at the National Hospital for Neurology and Neurosurgery, London, which is supported by Merck. F.B acts as a consultant for Bayer-Schering, Biogen-Idec, GeNeuro, Ixico, Merck-Serono, Novartis and Roche. He has received grants, or grants are pending, from the Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) initiative, the Biomedical Research center at University College London Hospitals, the Dutch MS Society, ECTRIMS–MAGNIMS, EU-H2020, the Dutch Research Council (NWO), the UK MS Society, and the National Institute for Health Research, University College London. He has received payments for the development of educational presentations from Ixico and his institution from Biogen-Idec and Merck. He is on the editorial board of Radiology, Neuroradiology, Multiple Sclerosis Journal and Neurology.

Background: Patients with multiple sclerosis (MS) who are treated with monoclonal antibodies frequently report an increase of MS-related symptoms prior to the next dose known as the wearing-off phenomenon. The objective of this study was to assess the prevalence and predicting factors of the wearing-off phenomenon in patients with MS using ocrelizumab., Methods: This was a prospective cohort study in patients with MS receiving ocrelizumab ≥1 year. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses., Results: Seventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1-4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks., Conclusions: The wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Spasticity is a common problematic symptom in Multiple Sclerosis with over one third of patients failing first line therapies. Intrathecal baclofen is a safe and efficacious option for treatment resistant spasticity. Anecdotally patients report improved concentration/cognitive performance when switching to intrathecal baclofen (ITB) from systemic medications., Aim: To explore whether subjects who proceed with ITB pump implantation for spasticity management and reduce oral anti-spasticity agents will have improved cognitive function., Methods: Subjects were admitted for trial of ITB via lumbar puncture and subsequent pump implantation. Spasticity and cognitive measures before ITB trial and 3 months post implant were recorded. Paired t-test or Wilcoxon Signed Ranks test was used for within subject change and effect sizes (Cohen's d z ) were calculated. Subgroup analysis of those on ≥2, or ≤ 1 spasticity medications at baseline was performed., Results: 27 subjects with MS completed per protocol. Mean age 46 years [26 - 56], disease duration 15 years [6 - 26], RRMS = 3, SPMS = 17 and PPMS=7. The majority were on multiple spasticity medications. Spasticity scores significantly improved post pump implant. Mean ITB dose at 3 months was 143 mcg / day and 19 discontinued all other treatments for spasticity. There was no deterioration on any cognitive or mood measure. An improvement of moderate effect size was found in Backwards Digit Span (d=0.41, p=0.059) and HADS - anxiety (d=0.37, p=0.097). Fatigue Severity Scale score decreased substantially (d=0.81, p=0.005). Small improvements in Symbol Digit Modalities Test score (d=0.24) and Sustained Attention to Response Task response time (d=0.23) were non-significant. Performance on other measures did not change. Effect sizes were larger in subgroup on ≥2 oral spasticity medications at baseline, compared to the group on ≤1 medication (SDMT, d=0.42 vs d=0.07; Backwards digit span 0.45 vs 0.28; HADS-anxiety 0.39 vs 0.32; HADS-depression d=0.32 vs 0.05 and FSS, d= 1.14 vs 0.42)., Conclusions: In a pilot study exploring the impact of ITB on cognition, spasticity scores improved universally and beneficial effects on some measures of fatigue, anxiety, auditory attention and verbal working memory were found. Improvement of speed of processing in those withdrawing higher doses of oral medication was also demonstrated suggesting that switching to ITB has added cognitive and psychological benefits for people with MS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Paroxysmal tonic spasms [PTS] are common in patients with neuromyelitis optica spectrum disorder (NMOSD).1 2 In patients with demyelinating disease, PTS can significantly reduce the quality of life, limit activities of daily living and the rehabilitative process following an acute relapse 3. As in patients with multiple sclerosis (MS), paroxysmal tonic spasms in NMOSD usually respond well to treatment with carbamazepine.2 However, the optimal treatment in patients where carbamazepine is contraindicated or poorly tolerated is unclear. We describe a patient with NMOSD with severe paroxysmal tonic spasms who did not tolerate carbamazepine but was successfully treated with lacosamide (Vimpat)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology., Aim: To assess HLA-DRB(*)1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology., Methods: Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB(*)1501 haplotype was determined by genotyping (rs3135388)., Results: No significant differences were observed in MRI measures between the HLA-DRB(*)1501 subgroups., Conclusions: The HLA-DRB(*)1501 haplotype is not strongly associated with MRI-visible grey matter pathology., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: In multiple sclerosis (MS), recent work suggests that cervical cord atrophy is more consistently correlated with physical disability than brain white matter lesion load and atrophy. Although spinal cord imaging has not been routinely obtained in many clinical trial and research studies, brain volumetric imaging usually has and includes the upper cervical cord., Objectives: Using volumetric T1-weighted brain images, we investigated cross-sectional area measures in the uppermost cervical cord and compared them with areas at the standard C2/3 level., Methods: Using T1-weighted brain scans from 13 controls and 37 people with MS, and an active surface technique, cross-sectional area was measured over 5mm and 1mm cord segments at C2/3, below the level of odontoid peg, and 2cm and 2.5cm below the pons. Brain volume was also measured., Results: Cord area measurements were most reliable in a 5mm segment 2.5cm below the pons (inter-rater coefficient of variation 1.5%, intraclass correlation coefficient 0.99). Cord area at this level correlated more with that at C2/3 area than with brain volume (r=0.811 with C2/3, r=0.502 with brain volume)., Conclusion: Whereas the standard C2/3 level is often not within the field of view on brain images, the level 2.5cm below the pons usually is, and measurement at this level may be a good way to investigate upper cervical cord atrophy when only brain images are available., (Copyright © 2014 Elsevier B.V. All rights reserved.)