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

Background: Cognitive disengagement syndrome (CDS) refers to a set of attentional symptoms comprising daydreaming, mental fogginess, and hypoactivity clearly distinguishable from ADHD-IN and other forms of psychopathological issues.

Objective: The present study: (1) assessed CDS among adults with multiple sclerosis (MS) and healthy controls, and (2) investigated the associations between CDS and depression, insomnia, fatigue, and paresthesia in persons with MS.

Methods: Two-hundred and seven adults with MS (mean age: 36.64 years; 72.5% females) and 213 healthy controls (mean age: 34.19 years; 54.5% females) provided self-ratings of CDS, insomnia, depression, fatigue, and paresthesia.

Results: Compared to healthy controls, adults with MS reported higher scores for CDS (t(418 = 4.29, p < 0.001, d = 0.42), depressive symptoms (t(41) = 2.21, p = 0.014, d = 0.22), and insomnia (t(418) = 1.66, p = 0.049). Among the MS sample, higher levels of CDS were associated with higher depression (r = 0.64), insomnia (r = 0.34), fatigue (r = 0.53), and paresthesia (r = 0.28). Further, higher scores for depression, insomnia, and fatigue were independently associated with higher CDS.

Conclusions: Adults with MS experience greater CDS symptoms than healthy controls. Higher CDS scores were associated with depression, insomnia, fatigue, and paresthesia, which are typical of adults with MS. MS may contribute to or exacerbate CDS symptoms and be a potentially important target for further investigation.

Background: Multiple sclerosis remains under-recognized in Zambia and much of sub-Saharan Africa, often leading to misdiagnosis and delays. Understanding diagnostic pathways and barriers can inform strategies to improve multiple sclerosis recognition and care.

Objectives: This study explores the diagnostic journeys of adults with multiple sclerosis in Zambia, emphasizing the challenges encountered at each stage.

Methods: We conducted a qualitative study using semi-structured interviews with adults diagnosed with multiple sclerosis in Zambia. Thematic analysis identified patterns in diagnostic experiences, enabling the mapping of common pathways and barriers, along with patient perspectives on the impact of diagnostic delays.

Results: Thirteen individuals with relapsing-remitting multiple sclerosis (mean age 34 ± 11 years; 70% female) were enrolled. Diagnostic pathways involved multiple healthcare visits, frequent misdiagnoses, and substantial delays. Key barriers included limited magnetic resonance imaging access, low multiple sclerosis awareness, and financial constraints. Thematic findings highlighted misinterpretation of symptoms, lack of specialists, and systemic health system limitations. Delayed diagnosis had a significantly negative impact on patients' lives.

Conclusion: Multiple sclerosis diagnosis in Zambia is markedly delayed, adversely affecting patients. Greater awareness and policy reforms targeting diagnostic barriers are needed to promote earlier diagnosis and improve outcomes in Zambia and similar resource-limited settings.

Janus kinase inhibitors (JAKis), such as baricitinib, target the Janus kinase/signal transducers and activators of transcription pathway to regulate proinflammatory cytokines and T-helper cell activity, thereby reducing inflammation. Despite their therapeutic benefits, inflammatory demyelinating diseases of the central nervous system (CNS) have been reported in association with JAKi treatment, most previously involving tofacitinib in patients with rheumatoid arthritis. We report the first case of a CNS inflammatory demyelinating disease that was possibly exacerbated by baricitinib, underscoring the need for heightened clinical vigilance and close monitoring of patients receiving JAKi therapy.

Background and objectives: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

Methods: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic resonance imaging (MRI) metrics.

Results: MS-E4 patients exhibited worse outcomes, including thinner RNFL, higher blood glial fibrillary acidic protein (GFAP) and neurofilament light chain levels, slower cognitive reaction times, and more white matter hyperintensities. GFAP had significant interactions between MS and APOE4 status, correlating with neurodegenerative markers.

Discussion: APOE4 exacerbates neurodegeneration and neuroinflammation in MS, evident in retinal OCT, cognitive testing, and MRI findings. Similar effects were observed in healthy APOE4 carriers. These results highlight the utility of multi-domain biomarkers for MS diagnosis and long-term management, emphasizing less invasive tools for monitoring disease progression.

Background: As knowledge is limited about the real-world impact of relapse among patients with neuromyelitis optica spectrum disorder (NMOSD), we aimed to assess the impact of relapse(s) on patient disability, clinical outcomes, and patient and caregiver burden in a real-world setting.

Objective: To assess how NMOSD relapses impacts patient and caregiver burden.

Methods: Data were drawn retrospectively from the Adelphi Real World NMOSD Disease Specific Programme, a cross-sectional survey of neurologists and patients with NMOSD patients in five European countries from January-June 2023. Neurologists reported patients' demographics, caregiver involvement and clinical outcomes. Analyses were bivariate.

Results: Overall, 99 neurologists provided data for 433 patients. In total, 128 patients had a relapse since their initial attack (1 relapse, 64.1%; 2 relapses, 18.8%; ≥ 3 relapses, 17.2%). Patients who had relapsed once had higher rates of control deficit for bladder (40.2% vs. 25.6%, p < .001) and bowel (8.5% vs. 5.6%, p = .042), which increased with additional relapses. Relapsed patients also required more caregiver support (41.4% vs. 31.1%, p = .048), often their partner (41.4% vs. 31.1%, p = .046).

Conclusions: NMOSD relapse occurrence was associated with debilitating symptoms and more caregiver support, highlighting the need for more highly effective interventions to prevent patient and caregiver burden.

Background: Leptomeningeal enhancement (LME) is a putative magnetic resonance imaging (MRI) marker of meningeal inflammation in multiple sclerosis (MS). 3D inversion-prepared fast-spin-echo sequence with real-reconstruction inversion recovery (Real-IR) MRI at 3 tesla (T) is highly sensitive to LME.

Objectives: To assess LME prevalence across brain regions and characterize the relationship between LME and subtle cortical pathology.

Methods: LME distribution patterns across brain regions were recorded for 90 adults (Age: 51 ± 11; women: 57; MS: 78) using 3T Real-IR. A subset of 15 participants had corresponding T₁-maps at 7T. T₁ relaxation times were calculated in the normal-appearing cortex subjacent to the LME, in comparison to the adjacent and homologue cortex.

Results: 243 LME foci were found across 65 participants (73%). One hundred and sixty-one (66.3%) LME foci were posterior to the central sulcus. Three of 15 7T participants had a cortical lesion nearby LME (3/49 foci). Mean T₁ times within cortex beneath LME (1734 ± 135 ms) were elevated compared to homologue (1668 ± 167 ms, p = .0052) and adjacent cortex (1651 ± 133 ms, p < .0001).

Conclusions: Regional variations in LME distribution may point to topographical differences in the blood-meningeal barrier. Alterations in T₁ relaxation time observed in the cortex adjacent to LME may signify subtle tissue changes in the absence of cortical lesions.

Background: Research studies in multiple sclerosis (MS) lack diversity.

Objective: To gain consensus on priorities about how future research in MS in Canada addresses equity, diversity, and inclusion (EDI) using a modified e-Delphi technique.

Methods: We recruited people with lived experience (people with MS (PwMS) or family members); EDI researchers; and clinicians with experience caring for PwMS. The first survey was developed based on a scoping review, EDI literature, and advisory group meetings and included items for five domains: measuring and reporting diversity characteristics, recruiting diverse research populations, role of funders, role of publishers/editors, and training. All items were rated on a 7-point scale with anchors of 1 (aspirational), 4 (achievable), and 7 (core). We undertook three rounds. New items were added after the first round; consensus was defined as a standard deviation ≤1.0.

Results: Ultimately, 87 people (36 with lived experience, 28 EDI researchers, 23 MS clinicians) completed the first survey, of whom 82 (94.2%) completed the second survey and 81 (93.1%) completed the third. Forty-five items reached consensus across the five domains. Nearly all these items were rated as achievable.

Conclusions: This e-Delphi identified priorities for how future MS research in Canada addresses EDI.

Background: Comorbidities are common among people with multiple sclerosis (pwMS) and have been suggested to affect the usage of disease-modifying treatments (DMTs).

Objectives: We investigated the prevalence and types of comorbidities in newly diagnosed pwMS, as well as the associations between comorbidities and the choice and persistence of the initial DMT.

Methods: This retrospective register study used data from the Finnish MS register (85% of national coverage). The inclusion criteria were a diagnosis of relapsing-remitting MS between 2010 and 2022, the first DMT started between 2016 and 2022, and an age of at least 18 years. The exclusion criteria were a diagnosis of secondary progressive MS and initiation of azathioprine or mitoxantrone.

Results: The inclusion criteria were met by 1630 pwMS. At least one comorbidity was present in 50.9% of the pwMS. Respiratory comorbidities were associated with the choice of medium-efficacy DMT over high-efficacy DMT (OR = 0.58, CI = 0.36-0.91). Multicomorbidity was associated with lower persistence on all DMTs. Additionally, lower persistence on medium-efficacy DMTs was associated with autoimmune and psychiatric comorbidities and the injectable administration route.

Conclusions: Comorbidities are prevalent among newly diagnosed pwMS. Clinicians should consider comorbidities carefully, as they are associated with DMT persistence.

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.