Imaging phenotypic differences in multiple sclerosis: at the crossroads of aging, sex, race, and ethnicity

Frontiers in Global Women s Health, Год журнала: 2024, Номер 5

Опубликована: Июнь 28, 2024

Clear sex differences are observed in clinical and imaging phenotypes of multiple sclerosis (MS), which evolve significantly over the age spectrum, more specifically, during reproductive milestones such as pregnancy menopause. With neuroimaging being an outcome measure also a key subclinical biomarker subsequent phenotype MS, this comprehensive review aims to provide overview hormone structural functional biomarkers including lesion burden location, atrophy, white matter integrity, connectivity, iron distribution. Furthermore, how therapies aimed at altering hormones can impact women men with MS lifespan is discussed. This explores intersection between age, sex, race/ethnicity may affect MS.

Язык: Английский

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PET Beta‐Amyloid Tracer Uptake in Leukoencephalopathies: Comparing Metachromatic Leukodystrophy and CADASIL

European Journal of Neurology, Год журнала: 2025, Номер 32(4)

Опубликована: Апрель 1, 2025

Язык: Английский

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Integrating TSPO-PET imaging with metabolomics for enhanced prognostic accuracy in multiple sclerosis

BMJ Neurology Open, Год журнала: 2025, Номер 7(1), С. e001026 - e001026

Опубликована: Янв. 1, 2025

Background Predicting disease progression in multiple sclerosis (MS) remains challenging. PET imaging with 18 kDa translocator protein (TSPO) radioligands can detect microglial and astrocyte activation beyond MRI-visible lesions, which has been shown to be highly predictive of progression. We previously demonstrated that nuclear magnetic resonance (NMR)-based metabolomics could accurately distinguish between relapsing-remitting (RRMS) secondary progressive MS (SPMS). This study investigates whether combining TSPO enhances accuracy a similar setting. Methods Blood samples were collected from 87 patients undergoing the TSPO-binding radioligand 11 C-PK11195 Finland. Patient disability was assessed using expanded status scale (EDSS) at baseline 1 year later. Serum performed identify biomarkers associated binding Results Greater availability normal-appearing white matter perilesional regions correlated higher EDSS. metabolites glutamate (p=0.02), glutamine (p=0.006), glucose (p=0.008), detected by NMR, effectively distinguished future progressors. These three alone predicted same as TSPO-PET (AUC 0.78; p=0.0001), validated an independent cohort. Combining serum metabolite data significantly improved power, achieving AUC 0.98 (p<0.0001). Conclusion Measuring specific is effective predicting However, integrating analysis substantially accuracy. Given simplicity affordability NMR analysis, this approach lead more personalised, accessible treatment strategies serve valuable tool for clinical trial stratification.

Язык: Английский

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Nasal foralumab treatment of PIRA induces regulatory immunity, dampens microglial activation and stabilizes clinical progression in non-active secondary progressive MS

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 3, 2025

ABSTRACT Background Progression independent of relapses (PIRA) is a major therapeutic challenge in multiple sclerosis (MS). Nasal anti-CD3 treats animal models progressive MS by inducing regulatory T cells (Tregs) that suppress central nervous system (CNS) inflammation and lessen clinical disease. Methods Ten patients with non-active secondary (naSPMS) continued to progress on B cell therapy were treated nasal (foralumab) for minimum six months an open label study. Safety monitoring included otolaryngology evaluation neurologic assessments including Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC-4), Modified Fatigue Impact (MFIS), California Verbal Learning Test (CVLT-II) Low Contract Visual Acuity (LCVA). MRI microglial translocator protein (TSPO)-PET imaging [F-18]PBR06 conducted. Serum cerebrospinal fluid (CSF) proteomic biomarkers single RNA sequencing blood was performed evaluate foralumab-induced immunomodulation. The endpoints our study safety, effects, signal immune measures. Results All stabilized EDSS scores three four continuously 12 had improvement EDSS. Six 10 fatigue the MFIS scale. There no treatment-related serious adverse events (SAEs) or severe AEs new T2 lesions observed MRI. reduction TSPO-PET over (p<0.05). Changes peripheral gene expression occurred as early affected antigen presentation, interferon responses pathways types FoxP3+ Tregs, CD4+ Tcm cells, CD8+ Tem CD14+ CD16+ monocytes cells. TGFβ increased across subsets. Interpretation These findings identify novel, non-toxic based treatment PIRA acts induction dampens inflammation. Double blind placebo-controlled trials are warranted explore foralumab naSPMS.

Язык: Английский

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Biomarkers of Progression Independent of Relapse Activity—Can We Actually Measure It Yet?

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4704 - 4704

Опубликована: Май 14, 2025

Progression independent of relapse activity (PIRA) is increasingly recognized as a key driver disability in multiple sclerosis (MS). However, the concept PIRA remains elusive, with uncertainty surrounding its definition, underlying mechanisms, and methods quantification. This review examines current landscape biomarkers used to predict measure PIRA, focusing on clinical, imaging, body fluid biomarkers. Clinical scores such Expanded Disability Status Scale (EDSS) are widely used, but may lack sensitivity capturing subtle relapse-independent progression. Imaging biomarkers, including MRI-derived metrics (brain spinal cord volume loss, chronic active lesions) optical coherence tomography (OCT) parameters (retinal nerve fiber layer ganglion cell-inner plexiform thinning), offer valuable insights, often reflect both inflammatory neurodegenerative processes. Body neurofilament light chain (NfL) glial fibrillary acidic protein (GFAP), promising indicators axonal damage activation, their specificity for limited. emphasizes distinction between predicting PIRA-identifying individuals at risk future progression-and measuring ongoing PIRA-related real time. We highlight limitations differentiating from relapse-associated call clearer conceptual framework guide research. Advancing precision utility will require multimodal approaches, longitudinal studies, standardized protocols enable clinical integration improve personalized MS management.

Язык: Английский

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