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

Background: Computerized training in persons with multiple sclerosis (PwMS) seems to enhance working memory (WM)/information processing (IP), but factors associated with the efficacy of the treatment have not been sufficiently explored. Objective: To identify clinical and radiological characteristics associated with positive WM/IP training responses.

Methods: Radiological and neuropsychological assessments were carried out on a sample of 35 PwMs who were divided into "WM/IP-impaired" and "WM/IP-preserved." All participants underwent adaptive n-back training for 10 days and were assessed post-training. Between-group differences ("WM/IP-impaired" vs. "WM/IP-preserved") in training-induced cognitive improvement were assessed and exploratory correlational/ regression-based methods were employed to assess the relationship between cognitive improvement and clinical and radiological variables.

Results: All PwMS exhibited WM/IP benefits after training, but those with preserved WM/IP functions showed greater positive effects as well as transfer effects to other WM/IP tests when compared to the impaired group. Additional analyses revealed that positive response to treatment was associated with WM/IP baseline capabilities and greater gray matter volume (GMVOL) in relevant areas such as the thalamus.

Conclusions: Restorative cognitive training is suitable to improve cognition in PwMS but its effective outcome differs depending on the baseline WM/IP capabilities and GMVOL.

Sleep disturbance is common in people with multiple sclerosis and may worsen fatigue; however, the assessment of sleep-fatigue relationships varies across studies. To better understand sleep-fatigue relationships in this population, we conducted a systematic review and random effects meta-analyses for the associations between fatigue and 10 sleep variables: Sleep-disordered breathing, daytime sleepiness, sleep quality, insomnia, restless legs, number of awakenings, sleep efficiency, sleep latency, sleep duration, and wake after sleep onset. Of the 1062 studies screened, 46 met inclusion criteria and provided sufficient data for calculating Hedges' g. Study quality was assessed using the Newcastle-Ottawa Scale. Sample characteristics did not differ between the 10 analyses. Results indicated that sleep quality and insomnia (assessed via self-report or diagnostic criteria) were strongly associated with fatigue (all gs ≥ 0.80 and all ps < .001). In contrast, the number of awakenings and sleep duration (assessed objectively) were not significantly associated with fatigue. Remaining sleep variables yielded moderate, significant effects. Most effects did not vary based on study quality or sample demographics. Results highlight that insomnia and perceptions of poor sleep have a stronger link than objective sleep duration to fatigue in multiple sclerosis and may represent a more effective target for intervention.

Background: Multiple sclerosis (MS) is a progressively debilitating neurologic disease that poses significant costs to the healthcare system and workforce.

Objective: To evaluate the impact of MS disease progression on societal costs and quality of life (QoL) using data from the German NeuroTransData (NTD) MS registry.

Methods: Cross-sectional cohort study. The cost cohort included patients with MS disability assessed using Expanded Disability Status Scale (EDSS) in 2019 while the QoL cohort included patients assessed using EDSS and EuroQol-5 Dimension 5-Levels between 2009 and 2019. Direct and indirect medical, and non-medical resource use was quantified and costs derived from public sources.

Results: Within the QoL cohort (n = 9821), QoL worsened with increasing EDSS. Within the cost cohort (n = 7286), increasing resource use with increasing EDSS was observed. Societal costs per patient, excluding or including disease-modifying therapies, increased from €5694 or €19,315 at EDSS 0 to 3.5 to €25,419 or €36,499 at EDSS 4 to 6.5, and €52,883 or €58,576 at EDSS 7 to 9.5. In multivariate modeling, each 0.5-step increase in EDSS was significantly associated with increasing costs, and worsening QoL.

Conclusion: This study confirms the major socioeconomic burden associated with MS disability progression. From a socioeconomic perspective, delaying disability progression may benefit patients and society.

Background: People over age 50-55 have historically been excluded from randomized clinical trials for multiple sclerosis (MS). However, more than half of those living with an MS diagnosis are over 55.

Objective: Explore the unique considerations of treating older people with MS (PwMS) using an iterative and structured Delphi-based assessment to gather expert opinions.

Methods: Eight MS neurologists with an interest in older PwMS developed a 2-round survey. Survey respondents were qualified neurologists with ≥3 years' experience, personally responsible for treatment decisions, and treating ≥20 patients per month, of whom ≥10% were ≥50 years old. Consensus was defined as ≥75% agreement on questions with categorical responses or as a mean score ≥4 on questions with numerical responses.

Results: In Survey 1, 224 neurologists responded; 180 of these completed Survey 2. Limited consensus was reached with varying levels of agreement on several topics including identification and assessment of older patients; factors relating to treatment decisions including immunosenescence and comorbidities; considerations for high-efficacy treatments; de-escalation or discontinuation of treatment; effects of COVID-19; and unmet needs for treating this population.

Conclusion: The results of this Delphi process highlight the need for targeted studies to create guidance for the care of older PwMS.

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.