Demyelinating Autoimmune Diseases, CNS Research

Demyelinating Autoimmune Diseases, CNS: current evidence & treatments

Multiple sclerosis (MS) progression and disability are influenced by aging and hormonal factors, but menopause does not appear to be a distinct clinical inflection point for relapse activity or MRI-defined inflammation ¹. In women of childbearing age, global MS incidence rose 48% and prevalence increased 66% from 1990 to 2021, though mortality and DALYs improved ¹⁵. T cell-microglial interactions drive aging-related myelin changes in murine models, with interferon-gamma from CD8+ T cells inducing glial states that limit remyelination ⁴.

Ocrelizumab reduces disability progression risk in primary progressive MS versus placebo ⁶, and in relapsing forms, disability improvement (offset effect) is most prominent ¹². However, high-dose ocrelizumab (1200/1800 mg) shows no significant difference in disability progression compared to 600 mg ⁵. Non-pharmacologic interventions show benefit: acupoint stimulation (especially electroacupuncture with acupoint injection) improves EDSS scores ⁸; aerobic and strength training reduce fatigue ¹⁹; laughter yoga substantially reduces fatigue (Cohen's d=2.785) ²⁰; exercise training improves cognition and fatigue in older adults ²¹; and PLISSIT counseling improves sexual life in women with MS (Hedges' g=0.927, though not statistically significant) ²². Mindfulness improves sleep efficiency ²³, and people with MS show reduced stress-induced autonomic responses compared to controls ²⁴.

Emerging therapies and mechanisms are under investigation. NINJ1 targeting shows potential for MS but faces knowledge gaps ³. PAD4-mediated citrullination and PAD4-directed therapies are being explored for CNS demyelinating disease ⁹. Stem cell-derived extracellular vesicles (SC-EVs) show immunomodulatory and neuroprotective potential in preclinical models ¹⁰. CAR-T and HSC therapies are considered for MS but face challenges including toxicity and limited persistence ¹³. Ferroptosis-immune crosstalk is a proposed therapeutic target in CNS diseases including MS ¹⁶. For trigeminal neuralgia secondary to MS, microvascular decompression has a 30.2% success rate for long-term pain freedom ¹⁴. A case report links pucotenlimab to AQP4-Ab-positive NMOSD ²⁵.

Menopause is not a distinct inflection point for MS progression; aging and T cell-microglial interactions drive myelin changes ¹⁴.

Global MS burden in women of childbearing age rose 48% from 1990 to 2021, but mortality and DALYs improved ¹⁵.

Ocrelizumab reduces disability progression in PPMS and improves disability in relapsing MS; high-dose shows no added benefit ⁵⁶¹².

Non-pharmacologic interventions (acupoint stimulation, exercise, laughter yoga, mindfulness, PLISSIT counseling) improve fatigue, cognition, sleep, and sexual function ⁸¹⁹²⁰²¹²²²³.

Emerging therapies (NINJ1, PAD4, SC-EVs, CAR-T) show promise but face knowledge gaps; MVD for TN-MS has 30.2% success ³⁹¹⁰¹³¹⁴.