Background and objectives Disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum disease (AQP4-IgG NMOSD) is considered relapse-driven although subclinical injury has been suggested by neuroimaging and visual pathway assessments. We investigated longitudinal changes in serum glial fibrillar acidic protein (sGFAP) and neurofilament light chain (sNfL) during relapse-free periods. Methods We conducted a retrospective longitudinal study (2008–2025) at a UK national referral centre for NMOSD. Patients with ≥3 serum samples collected over ≥3 years were included; samples within 3 months of relapses were excluded. Longitudinal changes in sGFAP and sNfL were assessed using linear mixed-effects models with random intercepts and generalised estimating equations, adjusting for age, sex and time. Results 40 patients (87.5% females; 162 samples; median onset age 40.1 years) and 28 matched controls were included. Over the course of four measurements and a median sampling over 9 years, stability was observed in sGFAP levels (99.2 pg/mL at 0–2.5 years (95% CI 84.2 to 117.0) to 90.3 pg/mL at 7.5–10 years (95% CI 74.7 to 109.0), p=0.65) and sNfL levels (12.0 pg/mL at 0–2.5 years (95% CI 10.8 to 13.3) to 10.4 pg/mL (9.1 to 11.8) at 7.5–10 years, p=0.12) after adjustment for covariates. Discussion In this longitudinal study, mean sGFAP and sNfL levels remained stable over 9 years of sequential measurements during relapse-free periods, supporting the relapse-driven nature of NMOSD pathology.
P. Siriratnam, C. Dunai, Nkongho Egbe Franklyn et al.· Journal of Neurology Neurosu...· 0 citations
The diagnosis and treatment of multiple sclerosis (MS) remain an evolving challenge in modern neurology. Recent advances are reflected in the 2024 revision of the McDonald criteria, which aim to facilitate earlier, more accurate and biologically informed diagnosis of MS. Key updates include expansion of dissemination in space to incorporate the optic nerve, integration of relapsing and progressive onset MS within a unified diagnostic framework, provision for diagnosis in selected asymptomatic individuals, dispensing with the requirement for dissemination of time in certain situations and incorporation of more specific imaging biomarkers. These include specific radiological features such as the central vein sign and paramagnetic rim lesions, visual pathway assessments using optical coherence tomography, magnetic resonance imaging and visual evoked potentials. Furthermore, oligoclonal bands and kappa free light chain index are now acknowledged as alternative cerebrospinal fluid biomarkers of intrathecal immunoglobulin synthesis. These revisions acknowledge the evolving understanding of MS biology alongside the substantial advances in disease modifying therapies. This review uses the 2024 McDonald criteria as an overarching framework to synthesise and contextualise the recent developments in MS diagnosis and treatment, highlighting their clinical implications, current limitations and future directions.
P. Siriratnam, Mineesh Datta, Katherine Buzzard et al.· Autoimmunity Reviews· 0 citations