Multiple Sclerosis Journal最新文献

Background: Vaccination in patients with multiple sclerosis (PwMS) presents unique challenges. Disease-modifying therapies (DMTs) can increase infectious risks, though these are largely preventable through immunizations. However, DMTs can also reduce vaccine efficacy.

Aims: This study aimed to identify challenges in achieving effective immunization for PwMS and explore strategies to optimize vaccination practices.

Methods: Recent guidelines and studies on vaccination in PwMS were reviewed to pinpoint challenges, unmet needs, and opportunities for improvement.

Results: Early immunization before DMT initiation is vital for optimal responses, coordinating vaccinations with DMTs' presents challenges. Strategies to enhance vaccine efficacy, such as bridging therapies or more immunogenic formulations, may benefit highly active patients requiring immediate DMT initiation. Although live-attenuated vaccines pose challenges for those on immunosuppressive therapies, emerging evidence suggests safe administration in select cases. Overcoming vaccine hesitancy demands targeted education, personalized counseling, and improved access to services, especially in low- and middle-income countries. Inclusivity is crucial, particularly for groups, such as pediatric, pregnant, and elderly PwMS.

Conclusion: A multifaceted approach is essential to addressing vaccination challenges in PwMS. Collaborative efforts involving multiple stakeholders are crucial for overcoming these obstacles and generating robust evidence. We propose an integrated strategy to ensure effective immunization while maintaining timely DMT administration.

Background: While treatment with ocrelizumab has proven effective in preventing relapse-associated worsening (RAW) in relapsing multiple sclerosis (RMS), a significant number of patients experience progression independent of relapse activity (PIRA).

Objectives: To investigate the association between B-cell depletion status and the risk of disability accumulation in RMS patients receiving ocrelizumab treatment.

Methods: In this monocentric cohort study of 148 RMS patients (2017-2023), we categorized participants into three groups: no evidence of disease activity (NEDA), evidence of disease activity (EDA), and PIRA. B-cell counts were measured every 6-12 months, with suboptimal depletion defined as ⩾10 CD19+ B-cells/µL. Logistic regression and Cox proportional hazards models analyzed the relationship between B-cell depletion and disability progression.

Results: Of 148 patients, 70 (47%) achieved NEDA, 51 (34%) showed EDA, and 25 (17%) developed PIRA. NEDA patients demonstrated significantly lower B-cell counts compared to EDA (p < 0.01) and PIRA (p < 0.001) groups. Insufficient B-cell depletion was the strongest PIRA predictor (OR 3.73, 95% CI: 2.50-5.43, p < 0.001) and increased EDSS progression risk (HR 0.50, 95% CI: 0.26-0.97, p = 0.039).

Conclusions: PIRA occurs in the context of suboptimal B-cell depletion in RMS patients, highlighting the need for close monitoring and potential adjustment of infusion intervals.

Background: Fatigue is a common problem in individuals with multiple sclerosis (MS).

Objective: The objective was to evaluate the effects on fatigue of having 4 weeks of access to audio recordings of therapeutic hypnosis (HYP) and mindfulness meditation (MM) practices.

Methods: A total of 333 individuals with MS and fatigue were randomly assigned to one of the three treatment conditions for 28 weeks: (1) access to therapeutic HYP audio recordings, (2) access to MM audio recordings, or (3) no access to recordings (treatment as usual or TAU). Fatigue impact (primary outcome) and other outcomes were assessed at 4, 16, and 28 weeks after random assignment.

Results: Participants assigned to the HYP and MM conditions reported significantly greater reductions in fatigue impact, sleep disturbance, and depressive symptom severity than participants assigned to the TAU condition after 4 weeks of access to audio recordings of these interventions. These improvements were maintained for 16 and 28 weeks following initial access and did not result in any serious adverse events.

Conclusion: Given the ease with which audio recordings of HYP and MM could be provided to individuals with MS, the findings support the feasibility of a simple approach to have a significant beneficial impact on people with MS-related fatigue.

Background: Spinal cord (SC) imaging is less routinely used for monitoring disease activity in patients with multiple sclerosis (MS), and the frequency of clinically silent breakthrough SC disease remains unclear.

Objective: The objective was to determine the frequency of asymptomatic T2 hyperintense cervical SC (c-SC) lesions in patients with relapsing-remitting MS (RRMS) and identify associated risk factors.

Methods: We included RRMS patients aged 18-65 years followed at the Johns Hopkins MS Center (2014-2019), with up to four brain and c-SC magnetic resonance imaging (MRI) scans considered per patient. New asymptomatic lesions were identified as hyperintense T2 lesions on MRI during routine surveillance. Univariate and multivariate logistic regression identified factors associated with developing asymptomatic lesions on the first scan, and a generalized estimating equations model assessed factors across successive scans.

Results: Among 869 patients included, the proportion of asymptomatic lesions identified ranged from 4.8% to 12.1% across scans. Roughly half of those with c-SC lesions also showed new brain lesions. Patients receiving higher-efficacy therapies were more likely to have an asymptomatic lesion detected (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.16-1.88, p = 0.001), as were Black/African American individuals (OR = 1.64, 95% CI = 1.23-2.18, p = 0.001).

Conclusion: These findings suggest a limited but important role for c-SC imaging, especially for Black/African Americans who may benefit from routine surveillance.

Introduction: Retinal layer thickness measured by optical coherence tomography (OCT) correlates with disability and disease activity in multiple sclerosis (MS), yet there is scarce data on the ability of retinal OCT rates of change to predict subsequent continuous disease stability.

Aims: To investigate whether the rate of change in retinal OCT measures during the first year of monitoring can predict maintenance of continuous "No evidence of disease activity" (c-NEDA) status in MS.

Methods: We conducted a longitudinal study of people with MS (PwMS) from our observational cohort (AMIR) at the American University of Beirut. Cases included had at least three spectral-domain OCT scans at baseline, 12 months, and at the last visit. Mixed effects regression (controlling for age, sex, disease duration, EDSS, gap time from initiation of current DMT to first OCT scan, type of DMT, and history of optic neuritis per eye) was performed to explore the differences between the annualized changes in retinal layer thicknesses (microns/year) during the first year in the c-NEDA group compared to those with evidence of disease activity (EDA) at any point during follow-up.

Results: In total, 222 eyes of 111 RRMS cases (67 females, 60.4%) were included and followed up clinically for a median (min-max) of 5.24 (3-8.64) years. During the study period, 51 (45.9%) cases maintained c-NEDA, and 60 (54.1%) had EDA. In regression models, EDA cases had greater mean retinal thinning rates during the first year of observation compared to c-NEDA cases with an annualized loss (microns/year) in pRNFL of -1.84 versus 0.03 (p < 0.0001); in macular RNFL -1.86 versus -0.76 (p < 0.0001); in GCIPL -0.13 versus 0.53 (p = 0.008); and in retinal thickness -3.81 versus -1.06 (p < 0.0001).

Conclusion: Our data support the potential value of retinal OCT in prospectively identifying PwMS likely to maintain c-NEDA status versus EDA during follow-up, guiding proactive treatment strategies.

Background: Obstructive sleep apnea (OSA) may be more prevalent in people with multiple sclerosis (MS) and previous work suggests possible association with demyelinating brainstem lesions.

Objectives: The objectives of this study were to assess the relationship between demyelinating brainstem lesions in patients with MS referred for polysomnography (PSG) and the severity of the apnea-hypopnea index (AHI).

Methods: A total of 122 people with MS or clinically isolated syndrome (CIS) who underwent PSG due to concern for OSA or hypersomnia at two institutions between 2010 and 2022 were included. AHI was associated with the number of and presence of brainstem demyelinating lesions on magnetic resonance imaging (MRI) obtained within 1 year of PSG after controlling for body mass index (BMI), age, sleep study type, study center, and study year.

Results: Having one brainstem lesion was significantly associated with mildly elevated AHI (5 ⩽ AHI < 15; odds ratio (OR) = 2.71, 95% confidence interval (CI) = 1.29-5.67) and two or more lesions was associated with higher odds of mildly elevated AHI (OR = 3.27, 95% CI = 1.83-5.85) and moderately/severely elevated AHI (AHI > 15; OR = 3.23, 95% CI = 1.91-5.47). The presence of brainstem demyelinating lesion(s) conferred a higher odds of mildly elevated AHI (OR = 3.00, 95% CI = 1.75-5.16) and moderately/severely elevated AHI (OR = 1.65, 95% CI = 1.08-2.52).

Conclusions: These data suggest that brainstem lesions may be associated with elevated AHI in people with MS.

After 1.5 years of treatment with dimethyl fumarate (DMF) for multiple sclerosis, preceded 8 years earlier by intravenous (IV) cladribine and 1 year earlier by natalizumab, our patient developed myelodysplastic syndrome (MDS). The initial manifestation was a severe drop in absolute neutrophil and lymphocyte counts. Repeat bone marrow biopsy demonstrated a new unbalanced translocation (between the chromosome 1 long arm and chromosome 7 short arm). This case report, to our knowledge, is the first linking iatrogenic MDS to DMF and cladribine, while also suggesting caution with immunosuppressants in multiple sclerosis patients.

Background: Mothers with MS face an increased incidence and prevalence of peripartum mental illness as compared to mothers without MS.

Objective: To determine the factors associated with the risk of peripartum mental illness among mothers with MS.

Methods: We identified mothers with MS with live births between 2002 and 2019 using linked population-based administrative data from Ontario, Canada. Using validated definitions, we estimated the incidence of mental illness (depression, anxiety, bipolar disorder) from conception through the first post-partum year (peripartum period). We used multivariable Poisson regression to assess the association between age, delivery year, area-level deprivation (Ontario Marginalization Index), disease duration, disability, and comorbidity and incidence of peripartum mental illness.

Results: Among 1745 mothers with MS, the mean (SD) age at conception was 31.2 (4.8) years. Mothers living in communities that lacked cohesion had increased rates of peripartum depression (incidence rate ratio [IRR] 1.25; 1.11-1.42) and anxiety (IRR 1.20; 1.07-1.33). Elevated MS disability level was associated with elevated peripartum depression rates (IRR 1.51; 1.12-2.04).

Conclusion: Higher area-level deprivation and disability levels are associated with an increased incidence of peripartum mental illness. These findings may assist clinicians in identifying women with MS who may benefit from peripartum mental health support.

Background: The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.

Objectives: To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).

Methods: Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model.

Results: In RMS, ocrelizumab reduced cerebellar volume loss in the double-blind period (DBP) and the difference (30% at DBP end) was maintained in the open-label extension (OLE) after control patients (IFN β-a) were switched to ocrelizumab. In PPMS, there was a small numerical difference in the DBP, but a larger (up to 22%) difference in favor of ocrelizumab in the OLE.

Conclusions: In both RMS and PPMS, early treatment with ocrelizumab helps to prevent additional cerebellar volume loss compared with delayed switching to ocrelizumab. Further analysis is needed to fully understand the clinical impact of cerebellar atrophy.

Background: Clinical trials of disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly incorporate cognitive outcomes, although effects of DMTs on cognition remain unknown.

Methods: In this secondary analysis of data from SPRINT-MS, a phase 2 randomized, placebo-controlled trial of ibudilast for progressive MS, we evaluated performance on Symbol Digit Modalities Test (SDMT) and Selective Reminding Test (SRT) in relation to physical disability, brain volume assessed with magnetic resonance imaging, and retinal nerve fiber layer (RNFL) thickness over 96-week follow-up. We hypothesize that trial participants would show a decline in cognitive test scores over 96 weeks of follow-up, with a possible between-group difference in favor of ibudilast.

Results: Data from 255 participants were analyzed. On average, physical outcome measures, brain parenchymal fraction, and RNFL thickness worsened; average SDMT and SRT scores remained largely unchanged. There were no differences between treatment groups in cognitive outcomes at 96-week follow-up. Practice effects likely contributed to results.

Conclusions: Observed stability of cognitive scores in individuals with progressive MS over 96-week follow-up may reflect true cognitive stability. However, the possibility that current cognitive measurement instruments are psychometrically flawed remains, warranting further research.