視神経脊髄炎

Demyelination of the Central Nervous System (CNS) is a pathological process that causes the destruction of the myelin sheath, the insulating cover that protects the nerve fibres. This serves as one of the major attributes of numerous neurological disorders, such as Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorder (NMOSD), Acute Disseminated Encephalomyelitis (ADEM), Myelin Oligodendrocyte Glycoprotein-related antibody disease (MOGAD), etc. It is usually initiated as an immune-mediated injury to myelin, followed by dysregulation of the immune system and ultimately failure of effective remyelination. Although oligodendrocytes in the CNS have some capacity for regeneration, the surrounding microenvironment severely inhibits their function, which results in a reduced regenerative outcome. Previously referred to as suppressor T cells, regulatory T cells (Tregs) are a subset of T cells that were traditionally thought to have an immunosuppressive function. However, it has just recently been shown that they directly contribute to regeneration and repair. The goal of this review is to demonstrate how Tregs can promote regeneration by balancing a variety of underlying molecular and cellular processes. Recent research shows that Tregs affect oligodendrocyte lineage progression, microglial and astrocytic responses, and the milieu around the demyelination site in order to perform remyelination. These effects are age-dependent and occur both temporally and geographically. In order to offer an evolutionary perspective on the conserved immune-mediated regenerative pathways that may be diminished in mammals and can be further investigated for therapeutic purposes, this review also aims to draw comparisons between the mechanisms used by regeneration-competent and non-competent species.

MOG-antibody-associated disease (MOGAD) is a rare inflammatory demyelinating CNS condition. Diagnosis is based on core clinical symptoms supported by additional clinical/MRI data if necessary, depending on the antibody titer in the blood. The clinical presentation is age-dependent. Due to its recent recognition, management is not clearly defined. Treatment differs from other inflammatory demyelinating CNS diseases such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) despite overlapping symptoms. In this review, we summarise recent knowledge for optimal patient management.

BACKGROUND: To compare relapse and disability outcomes of inebilizumab, azathioprine (AZA), mycophenolate mofetil (MMF) and rituximab (RTX) in maintenance-therapy-naive patients with aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder. METHODS: We prospectively enrolled 566 patients (inebilizumab n=72, AZA n=196, MMF n=170, RTX n=128). Primary effectiveness analyses were conducted in the per-protocol cohort (n=528), with supportive analyses in the full cohort. Both used inverse probability of treatment weighting to estimate the average treatment effect on the treated, with inebilizumab as reference. Primary outcomes were annualised relapse rate (ARR) and time to first relapse; disability progression was secondary. Adverse events (AEs) were assessed in the full cohort. RESULTS: In the per-protocol cohort, median age was 37 years, 477 (90.3%) were female and median follow-up was 21.5 months. Compared with inebilizumab, ARR was higher with AZA (incidence rate ratio (IRR) 4.78), MMF (IRR 4.33) and RTX (IRR 2.26; all p<0.05). Average relapse hazards were higher with AZA (HR 3.77; p=0.006) and MMF (HR 4.05; p=0.003), but not significantly different with RTX (hazard ratio (HR) 2.08; p=0.178). Time-varying analysis suggested a higher relapse hazard with RTX only during the first 6 months. Supportive analyses in the full cohort yielded consistent results. AZA and MMF were associated with greater disability progression than inebilizumab, whereas RTX was not. Severe AEs did not differ across groups. CONCLUSIONS: Inebilizumab was associated with better relapse and disability outcomes than AZA or MMF. Compared with RTX, inebilizumab was associated with lower ARR, whereas no significant differences were detected in time to first relapse or disability progression.

OBJECTIVE: To explore iron and myelin changes in U-fiber regions of relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorders (NMOSD) by susceptibility separation imaging, and to evaluate the clinical relevance of these changes. METHODS: This study included 119 RRMS patients, 47 NMOSD patients, and 93 healthy controls (HC). The U-fiber region was defined as the white matter within 4 mm beneath the gray-white matter boundary. Susceptibility separation imaging was reconstructed from 3D multi-echo gradient echo data, and total susceptibility, positive susceptibility (χpos) and negative susceptibility (χneg) were extracted from each U-fiber subregion. General linear models were performed to compare these metrics among the three groups. Partial correlation analyses were conducted to explore the associations between susceptibility metrics and clinical characteristics. RESULTS: Compared with HC, RRMS patients showed significantly decreased χpos in multiple temporal and limbic U-fiber regions, and significantly increased χneg in widespread U-fiber subregions. However, no significant differences in susceptibility metrics were observed between NMOSD patients and HC in any U-fiber subregion. Notably, after adjusting for potential confounding effects of disease severity and lesion burden, there were no significant differences in susceptibility metrics between RRMS and NMOSD patients. In RRMS patients, χneg in U-fiber subregions was significantly correlated with Expanded Disability Status Scale, particularly in the left superior frontal region. CONCLUSION: Susceptibility separation imaging provided surrogate markers suggestive of iron loss and demyelination in the U-fiber region of RRMS patients. These metrics were closely associated with lesion burden and may hold promise as imaging correlates of clinical disability.