Multiple Sclerosis Journal最新文献

Healthcare breakthroughs are extending the lives of multiple sclerosis (MS) patients and cancer survivors, creating a growing cohort of individuals navigating a dual diagnosis. Determining the relationship between MS and cancer risk remains challenging, with inconclusive findings confounded by age, risk exposures, comorbidities, genetics and the ongoing introduction of new MS disease-modifying therapies (DMTs) across study periods.This research places significant emphasis on cancer survival, with less attention given to the impact on MS outcomes. Our review explores the existing literature on MS, cancer risk and the intersection of DMTs and cancer treatments. We aim to navigate the complexities of managing MS in cancer survivors to optimise outcomes for both conditions. Continuous research and the formulation of treatment guidelines are essential for guiding future care. Collaboration between neuro-immunology and oncology is crucial, with a need to establish databases for retrospective and ultimately prospective analysis of outcomes in these rapidly evolving fields.

We report the case of a patient suffering from biopsy-proven relapsing tumefactive demyelinating lesions (TDLs) of the central nervous system who had five relapses in 16 years. No signs/symptoms suggestive of alternative pathologies emerged during the follow-up. A limited benefit was observed with intravenous (IV) high-dose steroids, while both plasma exchange and IV immunoglobulin G (IgG) administration were ineffective. A long-lasting (9 years) but transient clinical stabilization was obtained with cyclophosphamide. Our case supports the view that recurrent TDL is a relapsing brain inflammation not belonging to multiple sclerosis (MS) or myelin oligodendrocyte glycoprotein (MOG)-/AQP4-associated disorders. TDL concept and clinical features should be revised.

The pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.

Background: Cognitive impairment is common in neurologic diseases. Precise measurement of cognitive change over time is necessary for isolating disease-related patterns from normal age-related decline. Existing measures of subjective cognition, however, focus on present status. There is, to our knowledge, no currently available self-report measure of cognitive change. We therefore developed the Cognitive Change Scale (CCS), which assesses perceived cognitive change in neurologic populations.

Methods: A systematic mixed-methods process was followed for the scale design and validation. Associations of CCS responses to demographics, mood, and fatigue were examined in 131 persons with multiple sclerosis. A total of 46 participants also completed a cognitive test battery. Correlations of test scores with CCS responses were calculated.

Results: The 17-item CCS showed good reliability and validity. Results of exploratory and confirmatory factor analyses supported a four-factor structure, with items reflecting change in (1) general cognition, (2) language and executive function, (3) external feedback, and (4) use of coping strategies. Positive relationships of CCS scores with fatigue, depression, and anxiety were observed. Correlations of CCS scores with cognitive test performance did not reach significance.

Conclusion: The CCS may be a useful cognitive outcome tool for treatment trials in neurologic populations.

This comprehensive review aims to explore imaging outcome measures targeting compartmentalized inflammation in Phase 2 clinical trials for multiple sclerosis (MS). The traditional primary imaging outcomes used in Phase 2 MS trials, new or enhancing white matter lesions on MRI, target the effects of peripheral inflammation, but the widespread inflammation behind a mostly closed blood-brain barrier is not captured. This review discusses several emerging imaging technologies that could be used as surrogate markers of compartmentalized inflammation, targeting chronic active lesions, meningeal inflammation, and innate immune activation within the normal-appearing white matter and gray matter. The integration of specific imaging outcomes into Phase 2 trials can provide a more accurate assessment of treatment efficacy, ultimately contributing to the development of more effective therapies for MS.

Background: Scarce data are available on the long-term immunological effects of multiple sclerosis (MS) disease-modifying treatments (DMTs).

Objectives: This study aimed to investigate the long-term modifications of the peripheral immune repertoire on interruption of a sequestering DMT (natalizumab, fingolimod) and switch to another high-efficacy DMT.

Methods: Lymphocyte subpopulations were assessed, every 6 months up to 48 months, in patients switched from fingolimod or natalizumab to ocrelizumab, and in patients switched from fingolimod to natalizumab, compared to patients switched to ocrelizumab or natalizumab from a moderate-efficacy DMT and to naive patients.

Results: We included 389 MS patients (200 ocrelizumab and 189 natalizumab). After adjusting for baseline variables, patients switched from fingolimod to ocrelizumab showed lower CD3 + and CD4 + lymphocytes up to 48 months after switch (with lower percentage of naive CD4 +), and increased odds of total, CD3+, CD4+ lymphopenia. Patients switched from natalizumab to ocrelizumab showed higher CD3 + lymphocytes up to 36 months after switch, and higher CD4+, CD8+ lymphocytes up to 24 months. The frequency of infections was not influenced by previous treatment.

Conclusions: A long-term persistence of the residual effects of the exposure to sequestering DMTs (fingolimod and less natalizumab) on the peripheral immune repertoire was observed after switching to another high-efficacy DMT.

Background: Retrograde trans-synaptic degeneration (TSD) following retro-chiasmal pathology, typically retro-geniculate in multiple sclerosis (MS), may manifest as homonymous hemi-macular atrophy (HHMA) of the ganglion cell/inner plexiform layer (GCIPL).

Objective: To determine the frequency, association with clinical outcomes, and retinal and radiological features of HHMA in people with MS (PwMS).

Methods: In this cross-sectional study, healthy controls (HC) and PwMS underwent retinal optical coherence tomography scanning. For quantitative identification of HHMA, a normalized asymmetry ratio was used, and its normative cutoffs were established from the HC. HHMA PwMS were propensity score matched 1:2 to non-HHMA PwMS. Mixed-effects linear regression models were used in analyses.

Results: Based on normative data from 238 HC (466 eyes), 79 out of 942 PwMS exhibited HHMA (8.4%; 143 eyes). Compared to non-HHMA eyes from matched PwMS (158 PwMS; 308 eyes), HHMA eyes had lower average GCIPL (diff: -5.7 μm (95% CI -7.6 to -3.8); p < 0.001) but also inner nuclear layer (diff: -0.9 μm (95% CI -1.6 to -0.1); p = 0.02), and outer nuclear layer (diff: -1.9 μm (95% CI -3.4 to -0.4); p = 0.02) thicknesses; in further analyses, these differences were exclusive to the homonymous side of HHMA. HHMA participants also exhibited higher expanded disability status scale scores (diff: 0.5 (95% CI 0.1 to 0.9); p = 0.02), worse 100% and 2.5% visual acuity scores (diff: -3.2 (95% CI -4.1 to -1.0); p = 0.002, -5.4 (95% CI -7.5 to -3.5); p < 0.001), and higher frequency of microcystoid macular changes (10.1% vs. 3.2%; p = 0.03) compared to non-HHMA participants.

Conclusions: HHMA, possibly as a marker of TSD, may signify higher disability in MS.