Multiple Sclerosis Journal - Experimental, Translational and Clinical最新文献

Background and purpose: Multiple sclerosis (MS) has a high incidence of debilitating spasticity. Central Nervous System (CNS) intrafusal settings have an impact on spasticity level. Mechanoreceptors of the Peripheral Nervous System (PNS) communicate monosynaptically with the central nervous system (CNS). This case series assesses feasibility of multimodal treatment of individuals with MS using a direct current electrical stimulation (DC) to influence mechanoreceptors.

Case description and intervention: Seven MS diagnosed participants with Expanded Disability Status Scale (EDSS) = 6.0-8.0 completed 18 visits over 6 weeks of using DC combined with neuromuscular reeducation. Design included pre-, post- outcome measures of EDSS, 12-item MS Walking Scale (MSWS-12), Range of Motion (ROM), Manual Muscle Testing (MMT), Modified Ashworth Test (MAT), Timed 25-Foot walk (T25WT), Timed Up and Go (TUG) and the Multiple Sclerosis Impact Scale-29 (MSIS-29).

Outcome: 125 out of a possible 126 visits were completed, demonstrating a high level of tolerance. Individual results included trends towards improvement in spasticity and agonists.

Discussion: This case series design of seven heterogenous subjects with MS is a low sample size for statistical analysis and should be considered a pilot. The study demonstrates a high level of feasibility and possible correlations to consider. Further research is warranted.

Background: Functional connectome fingerprinting can identify individuals based on their functional connectome. Previous studies relied mostly on short intervals between fMRI acquisitions.

Objective: This cohort study aimed to determine the stability of connectome-based identification and their underlying signatures in patients with multiple sclerosis and healthy individuals with long follow-up intervals.

Methods: We acquired resting-state fMRI in 70 patients with multiple sclerosis and 273 healthy individuals with long follow-up times (up to 4 and 9 years, respectively). Using functional connectome fingerprinting, we examined the stability of the connectome and additionally investigated which regions, connections and networks supported individual identification. Finally, we predicted cognitive and behavioural outcome based on functional connectivity.

Results: Multiple sclerosis patients showed connectome stability and identification accuracies similar to healthy individuals, with longer time delays between imaging sessions being associated with accuracies dropping from 89% to 76%. Lesion load, brain atrophy or cognitive impairment did not affect identification accuracies within the range of disease severity studied. Connections from the fronto-parietal and default mode network were consistently most distinctive, i.e., informative of identity. The functional connectivity also allowed the prediction of individual cognitive performances.

Conclusion: Our results demonstrate that discriminatory signatures in the functional connectome are stable over extended periods of time in multiple sclerosis, resulting in similar identification accuracies and distinctive long-lasting functional connectome fingerprinting signatures in patients and healthy individuals.

Background: Despite tremendous development in the treatment of neuromyelitis optica spectrum disorder (NMOSD), less is known about the characteristics of hospitalized patients and inpatient care utilization.

Objective: To investigate the development of inpatient NMOSD case numbers and implemented immunotherapies in the last decade in Germany.

Methods: We conducted a nationwide retrospective study using an administrative database of all hospitalized NMOSD patients between 2010 and 2021. We evaluated yearly data on case numbers, demographics, treatment regimens, and seasonal variations of apheresis therapy as a surrogate marker of severe relapse incidence.

Results: During the observational period case number of inpatients substantially increased (2010:n = 463, 2021:n = 992). The mean age was 48.1 ± 2.5 years (74% females). The pooled yearly rate of plasmapheresis/immunoadsorption was 14% (95% CI [13-15%]), without seasonal variations. Its application peaked in 2013 (18%, 95% CI [15-21%]) with decreasing trend since. Predominant immunotherapy was rituximab (40%, 95% CI [34-45%]), followed by tocilizumab (4%, 95% CI [3-5%]) since 2013 and eculizumab (4%, 95% CI [3-5%]) since 2020. Inpatient mortality ranged between 0% and 1% per year.

Conclusions: Inpatient case numbers of NMOSD substantially increased during the past decade, probably reflecting improving disease awareness. In parallel with the administration of highly effective therapies rate of apheresis therapies decreased. A stable apheresis rate over the year makes seasonal variations of the steroid-refractive relapses unlikely.

People with multiple sclerosis (pwMS) have an increased risk of infection. As disease-modifying therapies (DMTs) and other treatments may interact with the immune system, there may be concerns about vaccine efficacy and safety. Therefore, it is important to evaluate possible interactions between DMTs and vaccines. The fumarates, dimethyl fumarate, diroximel fumarate, and monomethyl fumarate, are approved for the treatment of relapsing multiple sclerosis. This review assesses the evidence on vaccine response in pwMS treated with fumarates, with a particular focus on COVID-19 vaccines. Treatment with fumarates does not appear to result in blunting of humoral responses to vaccination; for COVID-19 vaccines, particularly RNA-based vaccines, evidence indicates antibody responses similar to those of healthy recipients. While data on the effect of fumarates on T-cell responses are limited, they do not indicate any significant blunting. COVID-19 vaccines impart a similar degree of protection against severe COVID-19 infection for pwMS on fumarates as in the general population. Adverse reactions following vaccination are generally consistent with those observed in the wider population; no additional safety signals have emerged in those on fumarates. Additionally, no increase in relapse has been observed in pwMS following vaccination. In pwMS receiving fumarates, vaccination is generally safe and elicits protective immune responses.

Background: Comorbidity is a current area of interest in multiple sclerosis (MS) and is essential for multidisciplinary management. Although recent studies suggest that patients with MS have an elevated risk of developing inflammatory bowel diseases (IBD), this systematic review and meta-analysis aimed to estimate the overall risk of developing ulcerative colitis (UC), specifically in patients with MS.

Methods: In 2021, a comprehensive literature search was performed on PubMed, Scopus, Embase, and Web of Science to identify studies investigating the association between UC and MS. The selected papers were utilized to estimate the associations, risk ratios (RRs), and a 95% confidence interval (CI).

Results: The analysis revealed a slightly elevated risk of UC incidence in patients with MS compared to controls, but this finding was not statistically significant (RR: 1.27 [95% CI: 0.96-1.67]). In contrast, the study found that patients with UC have a significantly higher risk of developing MS than controls (RR: 1.66 [95% CI: 1.15-2.40]).

Conclusion: Our findings highlight that the presence of UC increases the risk of developing MS by more than 50%, whereas the presence of MS does not increase the risk of UC occurrence. These results underscore the importance of considering the potential development of UC in the clinical management and early diagnosis of patients with MS, as it may contribute to better therapeutic outcomes.

Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.

Background: Differences in pain between subtypes of multiple sclerosis are understudied.

Objective: To compare the prevalence of pain, and the association between pain and: (a) pain interference and (b) social participation in people with relapsing-remitting multiple sclerosis and progressive multiple sclerosis.

Methods: Participants completed the McGill Pain Questionnaire Short-Form-2, Pain Effects Scale and Ability to Participate in Social Roles and Activities-V2.0 questionnaires. We tested the association between multiple sclerosis subtype, pain severity, and pain interference/social participation using quantile regression.

Results: Of 231 participants (relapsing-remitting multiple sclerosis: 161, progressive multiple sclerosis: 70), 82.3% were women. The prevalence of pain was 95.2%, of more than mild pain was 38.1%, and of pain-related limitations was 87%; there were no differences between multiple sclerosis subtypes. Compared to participants with relapsing-remitting multiple sclerosis, those with progressive multiple sclerosis reported higher pain interference (mean (standard deviation) Pain Effects Scale; progressive multiple sclerosis: 15[6.0] vs relapsing-remitting multiple sclerosis: 13[5], p = 0.039) and lower social participation (Ability to Participate in Social Roles and Activities T-scores 45[9.0] vs 48.3[8.9], p = 0.011). However, on multivariable analysis accounting for age, physical disability, mood/anxiety and fatigue, multiple sclerosis subtype was not associated with differences in pain interference or social participation.

Conclusions: Pain was nearly ubiquitous. Over one-third of individuals with relapsing-remitting multiple sclerosis and progressive multiple sclerosis reported pronounced pain, although this did not differ by multiple sclerosis subtype.

Introduction: Mortality is an important feature of the natural history of multiple sclerosis (MS). We report the mortality of all individuals with MS in Iceland, identified in a nationwide population-based study.

Patients and methods: The results are based on a prevalence cohort and an incidence cohort. The prevalence cohort consisted of all patients with MS (n = 526) living in Iceland on the 31 December 2007. The incidence cohort consisted of all residents of Iceland (n = 222) diagnosed with MS during 2002 to 2007. Mortality was determined by following both the incidence cohort (from diagnosis) and the prevalence cohort (from the prevalence day) until death or 31 December 2020. The mortality, associated with MS, was compared with that expected in the Icelandic population (standardized mortality ratio (SMR)).

Results: (a) Prevalence cohort (n = 526). The mean follow up was 12.0 years (range 0.3-13.0). The SMR was 1.6 (95% confidence interval (CI) 1.3-2.0). (b) Incidence cohort (n = 222). The mean follow up was 15.4 years (range 3.7-18.5). The SMR was 1.2 (95% CI 0.6-2.2).

Conclusion: During the follow-up period, there was a substantial increase in mortality among the patients with MS, compared with the general population. There was no increase in mortality among the incidence cohort, when followed for up to 18.5 years following diagnosis.

Background: Anti-CD20 agents are commonly used in MS, NMOSD, and MOGAD. Few studies have compared strategies to address hypogammaglobulinemia.

Objective: To compare strategies to manage secondary hypogammaglobulinemia in neuroimmunology patients, including reducing anti-CD20 dose and dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches.

Methods: All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001 to 2022 were analyzed. The median change in IgG, infection frequency, and infection severity before and after the treatment was calculated.

Results: In total, 257 patients were screened, and 30 had a treatment for hypogammaglobulinemia. IVIG/SCIG yielded the largest increase in IgG per year (674.0 mg/dL), followed by B-cell therapy cessation (34.7 mg/dL), and DMT switch (5.9 mg/dL). Dose reduction had the largest decrease in yearly infection frequency (2.7 fewer infections), followed by IVIG/SCIG (2.5 fewer), DMT switch (2 fewer), and reduced dosing frequency (0.5 fewer). Infection grade decreased by 1.9 for reduced dosing frequency (less severe infections), by 1.3 for IVIG/SCIG, and by 0.6 for DMT switch.

Conclusion: This data suggests that IVIG/SCIG may yield the greatest recovery in IgG while also reducing infection frequency and severity. Stopping anti-CD20 therapy and/or switching DMTs also increase IgG and may lower infection risk.