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

Introduction: Shared decision-making is advocated in treating patients with multiple sclerosis (pwMS), enabled by the wide range of disease-modifying treatments (DMTs). However, the role of psychological characteristics in treatment decisions remains understudied.

Methods: In a prospective study, pwMS completed the Big Five Trait inventory, UPPS Impulsive Behaviour Scale and Brief COPE at treatment initiation. Associations between choosing high-efficacy DMTs (H-DMT; natalizumab, anti-CD20 monoclonal antibodies) versus low/moderate-efficacy DMTs were analysed using logistic regression, for each dimension separately, then in a multidimensional model. Propensity scoring adjusted for MS-associated determinants of DMT choice (sex, age, disease duration, prior DMT, relapse in previous year, Expanded Disability Status Scale [EDSS]).

Results: Of 148 pwMS (75.7% female, age 36.5 years [SD 9], EDSS 1.0 [IQR, 0-2]) 53.4% initiated H-DMT. Higher active coping (adjusted odds ratio [aOR] 1.59, p = 0.024) and openness (aOR 1.48, p = 0.046) were significantly associated with H-DMT choice, with trends for extraversion (aOR 1.38, p = 0.097), supportive coping (aOR 1.42, p = 0.069), and higher perseverance (aOR 1.43, p = 0.068). In the multidimensional model, neuroticism demonstrated the most substantial association (aOR 2.17, p = 0.005).

Conclusion: Personality structure, particularly neuroticism, active coping and openness may influence treatment decisions among pwMS.

Background: B cell depleting therapy has become a cornerstone in disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS). Given that the maximum blood concentration of ofatumumab (OFA) is two orders of magnitude lower than that of ocrelizumab, it was anticipated that OFA would result in fewer adverse events.

Methods: The study included 38 RRMS patients had received at least 5 months of standard OFA administration. CD3 ⁺ CD20⁺ cell counts were assessed prior to OFA administration.

Results: The number of CD3 ⁺ CD20⁺ cells reached up to 75/μL in the treatment groups other than NTZ, and up to 200/μL in the NTZ-treated group, where B cell levels increased. Lymphopenia classifies as Grade 2 (800/μL or less) was observed in 7/33 cases. Beyond the depletion of CD3 ⁺ CD20⁺ cells, a reduction in CD3⁺ cells was noted in 29 of 33 cases (88%), and with seven cases showing progressive T cell decline for up to 5 months after OFA initiation.

Conclusion: In addition to the expected depletion of B cells, there was a greater-than-anticipated reduction in T cells lacking CD20 expression. Long-term continuous BCDT appears to have a profound impact on the immune system. Adjustments to administration intervals should be considered to mitigate the risk of over-treatment.

Background: Age and sex were shown to influence multiple sclerosis (MS) relapse activity in the 1990s. Whether relapse risk factors are the same with new treatment paradigms is unclear. We evaluate predictors of clinical relapse following the first clinic visit (FV) across different treatment eras in a large, retrospective cohort.

Methods: Adults with clinically isolated syndrome or relapsing-onset MS were divided into cohorts with FV at the Brigham Multiple Sclerosis Center (Boston, MA) from 1997 to 2010 ("early") and 2010 to 2020 ("recent"). Risk factors for relapse in 3 years after the FV were assessed for each cohort using multivariable logistic regression, and interaction terms were evaluated.

Results: 2192 patients were included (early: 1536; recent: 656). Younger age, female sex, relapsing-remitting disease, more prior relapses, and the use of platform therapy were associated with a future relapse in the early cohort. Age, family history of MS, and platform therapy were predictive in the recent cohort. Interaction terms for all variables were not significant. Model accuracy was similar across treatment eras.

Conclusions: Predictors of future relapse did not differ substantially across treatment eras. Younger age and the use of less effective therapies were strong risk factors at FV. However, significant heterogeneity exists in individuals' relapse risk.

This study assessed how neurologists perceive the organization and functioning of multiple sclerosis care units. As a cross-sectional, observational study conducted in collaboration with the Spanish Society of Neurology, an electronic survey of 116 neurologists revealed that 39.7% of participants identified a need for improvement in their unit's care processes based on the Care Process Self-Assessment Tool (CPSET). The primary areas for improvement were collaboration with primary care and patient follow-up. A significant negative correlation was observed between lower CPSET scores and a higher prevalence of clinician occupational stress (p = 0.035), with 28.4% of neurologists reporting burnout. These findings suggest that enhancing care coordination could improve care delivery for patients and help mitigate the risk of burnout for clinicians.

Background: Satralizumab is approved for aquaporin-4 immunoglobulin G-positive (AQP4-IgG⁺) neuromyelitis optica spectrum disorder (NMOSD), but real-world data are limited. This case series aimed to describe real-world experiences with satralizumab in adults with AQP4-IgG⁺ NMOSD.

Methods: Case information for patients with AQP4-IgG⁺ NMOSD who received satralizumab for ≥6 months was obtained from US healthcare providers over 28 months. Patient characteristics, examination findings, diagnostic tests, treatment responses, and adverse events were recorded.

Results: Of 43 patients, 88% were female and 44% self-identified as Black. Median age was 54 (range, 20-82) years, and time since confirmed NMOSD diagnosis was 8 (1-18) years. Reasons for satralizumab initiation included intolerance/safety concerns with existing therapy (30%), new diagnosis (26%), and inadequate disease control (21%). The median duration of satralizumab treatment was 31 (range, 7-104) months, during which three patients (7%) had radiographically confirmed relapses and 15 (35%) experienced a related adverse event. At data cutoff, 35 patients (81%) were receiving satralizumab.

Conclusion: Satralizumab was effective and well tolerated in patients with NMOSD, including those who switched from previous treatments due to inadequate disease control and/or intolerance. These real-world outcomes align with long-term safety and efficacy findings from the Phase III SAkura trials.

Background: Current multiple sclerosis management primarily targets symptom alleviation and immune modulation, with limited success in halting progression or achieving sustained remission. Consequently, the development of novel therapeutic strategies targeting the underlying mechanisms of multiple sclerosis (MS) remains a critical area of research.

Objectives: This study investigated the putative neuroprotective properties of Nigella sativa oil (NSO) in a cuprizone-induced demyelination model in adult male Wistar rats.

Methods: Twenty-four adult male Wistar rats were divided into four groups: Group A (Control) received normal mash feed; Group B received 0.2% cuprizone diet; Group C received 5 ml/kg NSO, while Group D received 0.2% cuprizone diet and 5 ml/kg NSO. After 35 days, rats were tested for memory and behaviour (Y-maze, Morris water maze, open-field test). Rats were euthanized, brains were excised then examined for myelin integrity, oligodendrocyte loss, and microglial activation using immunohistochemistry (antibodies: myelin basic protein, oligodendrocyte transcription factor, ionized calcium-binding adaptor molecule 1).

Results: Cuprizone exposure resulted in impaired memory function, reduced exploratory behaviour, and increased anxiety-like behaviours. Treatment with NSO mitigated these behavioural deficits. Additionally, NSO treatment reduced microglial activation and preserved myelin integrity.

Conclusion: Nigella sativa oil ameliorated behavioural alterations, neuroinflammation and demyelination in cuprizone model of MS, suggesting that NSO may have therapeutic potential for MS.

Background: Visual symptoms are common in people with multiple sclerosis. The revised 2024 McDonald criteria include the optic nerve as a fifth anatomical region, underscoring the need for specific diagnostics. Although optical coherence tomography (OCT) and visual evoked potentials (VEP) are available, the extent of their routine pre-referral use is insufficiently documented. We evaluated pre-referral utilization and hypothesized that specific diagnostics are used less often than non-specific diagnostics and that differences are not explained by demographics alone.

Methods: Retrospective cross-sectional study of 305 patients referred for visual symptoms to a tertiary neuroimmunology clinic in Germany. Analyses focused on people with multiple sclerosis (n = 112) and disease controls with neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein-associated disease (pwNM; n = 36).

Results: In people with multiple sclerosis, only 6.2% received OCT and 33% VEP for their visual complaints, compared to unspecific diagnostics such as cranial magnetic resonance imaging (58%) and lumbar puncture (42%) - independent of demographic factors.

Conclusion: The pre-referral use of specific neurovisual tests in people with multiple sclerosis with visual symptoms was low relative to non-specific procedures. This suggests heterogeneous integration of neurovisual testing across care levels. In light of the revised McDonald Criteria 2024, prospective multicenter studies should examine implementation and clinical impact.

Background: Word-finding deficits are common in persons with relapsing-remitting multiple sclerosis (pwRRMS); this may be related to the inefficient organization of semantic information.

Objective: To understand whether the semantic organization and semantic retrieval are impacted in pwRRMS.

Methods: Semantic fluency data from 64 pwRRMS and 73 controls was utilized to (1) derive standard verbal fluency measures using the Semantic Network and Fluency Utility R package and (2) build semantic networks via the correlation-based network approach in the SemNet R package. Subjective word-finding concerns were assessed in a subgroup of the sample. Group differences were evaluated.

Results: PwRRMS endorsed more frequent word-finding concerns. There were no differences between pwRRMS and controls on standard measures of semantic fluency. PwRRMS semantic networks exhibited differences in topology. Specifically, RRMS networks exhibited reduced efficiency, reduced interconnectivity, and reduced flexibility relative to control networks.

Conclusion: Word-finding concerns are prevalent in pwRRMS; it is important to screen for and address these concerns in clinical settings. Semantic network analysis appears more sensitive in detecting semantic retrieval deficits in pwRRMS relative to standard semantic fluency metrics. Semantic network disorganization and inflexibility may partially underlie word-finding difficulty in pwRRMS. Strategies aimed at improving network structure may assist in managing these deficits.

Background: Optic neuritis (ON) is a common manifestation of multiple sclerosis and related disorders (MSRD) characterized by retinal neurodegeneration, including thinning of ganglion cell-inner plexiform layer (GCIPL). Compared to absolute values, inter-eye differences (IED) account for variation in baseline structure and function before ON.

Objectives: To determine retinal layer IED thresholds associated with multimodal visual dysfunction after unilateral demyelinating ON.

Methods: In this cross-sectional study, MSRD participants with and without a history of unilateral ON, and healthy controls underwent optical coherence tomography, best-corrected visual acuity, 2.5% and 1.25% low-contrast letter acuity (LCLA), standard automated perimetry, and color vision testing.

Results: Sixty-six participants with MSRD (33 with unilateral ON history, 33 without ON history) and 15 healthy controls were included. For the ON cohort, a GCIPL IED threshold of 6.5% was associated with dyschromatopsia (AUC = 0.76, p = 0.011), 11% with 1.25% LCLA IED of >5 letters (AUC = 0.75, p = 0.008), 13% with 2.5% LCLA IED of >5 letters (AUC = 0.86, p < 0.001), 15% with VFMD IED of >2 dB (AUC = 0.75, p = 0.031), and 27% with logarithm of minimum angle of resolution IED of >0.3 (AUC = 1.00, p < 0.001). These associations were more robust compared to other retinal layer IED.

Conclusions: GCIPL IED thresholds more accurately reflect multimodal visual dysfunction after ON compared to other retinal layer IED.

Background: Evaluating safety of emerging interventions is important in clinical trials. To support reporting of safety outcomes, a harms extension of the Consolidated Standards of Reporting Trial (CONSORT) guidelines was published in 2004.

Objective: To examine safety reporting in pivotal trials of disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS).

Methods: Published phase III clinical trials from 1995 to 2022 included in FDA approval material for MS DMTs were compiled and reviewed by two independent examiners. Criteria derived from the CONSORT harms extension were used to evaluate safety reporting. Linear regression was applied to examine associations between quality of safety reporting and study level factors.

Results: 30 publications were included in the analysis. Overall, safety reporting quality was fair with an average score of 10.2 out of 15. Trials examining small molecule versus biologic interventions (p = 0.001) and recent publication (p = 0.005) were associated with higher quality reporting. Items related to laboratory-defined toxicity and defining adverse events were among reporting items notably lacking (present in 53% and 40% of publications, respectively).

Conclusion: While the reporting of phase III clinical trials for DMTs for the treatment of MS has improved with time, there remain gaps and opportunities for further improvement.