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Inter-attack serum GFAP and NfL remain stable over 9 years in AQP4 IgG NMOSD

Pakeeran Siriratnam, Cordelia Dunai, Nkongho Egbe Franklyn, Samantha Linaker and 9 more

Journal of Neurology Neurosurgery & Psychiatry | Jul 10, 2026

Abstract

Abstract

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.

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Authors

Researchers on this paper

Pakeeran Siriratnam

first | University of Liverpool | ORCID 0000-0003-4751-2102

Cordelia Dunai

middle | University of Liverpool

Nkongho Egbe Franklyn

middle | University of Liverpool

Samantha Linaker

middle | University of Liverpool

Robb Wesselingh

middle | The Alfred Hospital | ORCID 0000-0002-5898-3287

Anu Jacob

middle | Cleveland Clinic

Edward Joseph Jackson

middle | University of Liverpool | ORCID 0009-0009-3602-2643

Anneke van der Walt

middle | The Alfred Hospital | ORCID 0000-0002-4278-7003

Vilija Jokubaitis

middle | The Alfred Hospital | ORCID 0000-0002-3942-4340

Helmut Butzkueven

middle | The Alfred Hospital

Mastura Monif

middle | The Alfred Hospital | ORCID 0000-0001-6404-9768

Benedict D Michael

middle | University of Liverpool

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Citation

BibTeX

@article{Siriratnam2026Inter,
  title = {Inter-attack serum GFAP and NfL remain stable over 9 years in AQP4 IgG NMOSD},
  author = {Pakeeran Siriratnam and Cordelia Dunai and Nkongho Egbe Franklyn and Samantha Linaker and Robb Wesselingh and Anu Jacob and Edward Joseph Jackson and Anneke van der Walt and Vilija Jokubaitis and Helmut Butzkueven and Mastura Monif and Benedict D Michael and Saif Huda},
  journal = {Journal of Neurology Neurosurgery & Psychiatry},
  year = {2026},
  doi = {10.1136/jnnp-2026-338523},
  url = {https://doi.org/10.1136/jnnp-2026-338523}
}

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