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. 2024 Oct;30(11-12):1423-1435.
doi: 10.1177/13524585241275491. Epub 2024 Sep 11.

Is there a prodrome to NMOSD? An investigation of neurologic symptoms preceding the first NMOSD attack

Sydney Lee  1 , Ruth Ann Marrie  2 , Giulia Fadda  3 , Mark S Freedman  3 , Liesly Lee  4 , Alexandra Muccilli  5 , Manav V Vyas  5 , Andrea Konig  5 , Dalia L Rotstein  5
Affiliations

Is there a prodrome to NMOSD? An investigation of neurologic symptoms preceding the first NMOSD attack

Sydney Lee et al. Mult Scler. 2024 Oct.

Abstract

Background: It is unknown whether people with aquaporin-4 antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) experience a prodrome, although a few cases report AQP4 + serology up to 16 years before the first attack.

Objectives: To evaluate whether individuals with AQP4-IgG + NMOSD have prodromal neurologic symptoms preceding the first attack.

Methods: We reviewed medical records of participants meeting the 2015 diagnostic criteria for AQP4-IgG + NMOSD from four demyelinating disease centres in the Canadian NMOSD cohort study CANOPTICS. We searched for neurologic symptoms occurring at least 30 days before the first attack.

Results: Of 116 participants with NMOSD, 17 (14.7%) had prodromal neurologic symptoms. The median age was 48 years (range 25-83) at first attack; 16 (94.1%) were female. Participants presented with numbness/tingling (n = 9), neuropathic pain (n = 5), visual disturbance (n = 4), tonic spasms (n = 2), Lhermitte sign (n = 2), severe headache (n = 2), incoordination (n = 2), weakness (n = 1), psychosis (n = 1) or seizure (n = 1). Of eight who underwent magnetic resonance imaging (MRI) brain, orbits and/or spinal cord, five had T2 lesions. Within 1.5-245 months (median 14) from the onset of prodromal neurologic symptoms, participants experienced their first NMOSD attack.

Conclusions: One in seven people with NMOSD experienced neurologic symptoms before their first attack. Further investigation of a possible NMOSD prodrome is warranted.

Keywords: Neuromyelitis optica spectrum disorder; demyelinating diseases; neuroinflammatory diseases; prodrome.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.L. has nothing to declare. R.A.M. receives research funding from CIHR, MS Canada, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. G.F. has served as a member of the advisory board for Horizon Therapeutics. M.S.F. has received research or educational grants from Sanofi-Genzyme Canada. He has received consulting fees or honoraria from Alexion/Astra Zeneca, Biogen Idec, EMD Inc./EMD Serono/Merck Serono, Find Therapeutics, Hoffman La-Roche, Horizon Therapeutics, Novartis, Quanterix, Sanofi-Genzyme, Teva Canada Innovation. He has served as a member of a company advisory board, board of directors or other similar group for Alexion/Astra Zeneca, Actelion/Janssen (J&J), Atara Biotherapeutics, Bayer Healthcare, Celestra Health, EMD Inc./Merck Serono, Find Therapeutics, Hoffman La-Roche, Novartis, Sanofi-Genzyme, Setpoint Medical. He has been part of a speaker’s bureau for Hoffman La-Roche, Novartis, and EMD Inc. L.L. is a site investigator for studies funded by Roche, Novartis and Sanofi Aventis. He has received consultation fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Novartis, Roche and Sanofi Aventis. A.M. has received compensation for serving on an advisory board or data safety monitoring board for Biogen, Novartis, EMD Serono and Alexion. M.V.V. has received salary support as a co-investigator from National MS Society. A.K. has nothing to declare. D.L.R. has received research funding from MS Canada, the National MS Society, CMSC, University of Toronto Division of Neurology and Roche Canada. She has received speaker or consultant fees from Alexion, Biogen, EMD Serono, Horizon Therapeutics, Novartis, Roche, Sanofi Aventis and Touch IME.

Figures

Figure 1.
Figure 1.
Select MRI brain and spinal cord images and optical coherence tomography in patients with prodromal neurologic symptoms preceding a diagnosis of AQP4-IgG-positive NMOSD. 1: Case 1, patient with severe right-sided headache and left torso and leg sensory symptoms. (1.a) Axial and (1.b) Sagittal T2 FLAIR show a T2 hyperintense lesion in the right parietal white matter, sparing the cortex. 2: Case 10, patient with prodromal Lhermitte sign and asymptomatic optic disc oedema. (2.a) Axial and (2.b) Sagittal T2 FLAIR at the time of the first NMOSD attack reveal T2 hyperintense lesions in the left cerebral peduncle and splenium of the corpus collosum. (2.c) Optical coherence tomography after asymptomatic left optic disc oedema shows retinal ganglion cell layer thinning in the left eye. 3: Case 11, patient with left inferior quadrantopia. (3.a) Axial T2 FLAIR and (3.b) Axial T1 post-contrast at the time of prodromal neurologic symptoms show a right occipital periventricular lesion with subtle patchy enhancement. (2.c) Diffusion weighted imaging and (2.d) Apparent diffusion coefficient show partial diffusion restriction. OD: right eye; OS: left eye; RNFL: retinal nerve fibre layer; GCL: ganglion cell layer; IPL: inner plexiform layer.
See this image and copyright information in PMC

Comment in

  • Evidence for an NMOSD prodrome.
    Wood H. Wood H. Nat Rev Neurol. 2024 Nov;20(11):643. doi: 10.1038/s41582-024-01030-1. Nat Rev Neurol. 2024. PMID: 39402246 No abstract available.

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