Comparative study of AQP4-NMOSD, MOGAD and seronegative NMOSD: a single-center Belgian cohort

Abstract

Purpose: To emphasize physio-pathological, clinical and prognosis differences between conditions causing serious and sometimes very similar clinical manifestations: anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies related diseases, and seronegative NMOSD (neuromyelitis optica spectrum disorders).

Methods: Based on Wingerchuk et al. (Neurology 85:177-189, 2015) criteria for NMOSD and on those more recently proposed by Jarius et al. (J Neuroinflammation 15:134, 2018) for MOGAD (MOG associated disorders), we retrospectively surveyed 10 AQP4-NMOSD, 8 MOGAD and 2 seronegative NMOSD, followed at the specialized neuroimmunology unit of the CHU Liège.

Results: Female predominance was only observed in AQP4 group. Age at onset was 37.8 and 27.7 years old for AQP4-NMOSD and MOGAD respectively. In both groups, the first clinical event most often consisted of optic neuritis (ON), followed by isolated myelitis. Fifteen of our 20 patients encountered a relapsing course with 90% relapses in AQP4-NMOSD, 62.5% in MOGAD and 50% in seronegative group, and a mean period between first and second clinical event of 7.1 and 4.8 months for AQP4-NMOSD and MOGAD, respectively. In total we counted 54 ON, with more ON per patient in MOGAD. MOG-associated ON mainly affected the anterior part of the optic nerve with a papilledema in 79.2% of cases. Despite a fairly good visual outcome after MOG-associated ON, retinal nerve fibre layer (RNFL) thickness decreased, suggesting a fragility of the optic nerve toward further attacks.

Conclusion: As observed in larger cohorts, our MOGAD and AQP4-NMOSD cases differ by clinical and prognostic features. A better understanding of these diseases should encourage prompt biological screening and hasten proper diagnosis and treatment.

Keywords: AQP4-antibody NMO spectrum disorders; MOG-associated disorders; Neuromyelitis optica; Optic neuritis.

Fig. 1

Clinical relapses in AQP4 NMOSD group (a) and MOGAD group (b). Right-hand side charts represent the proportion of different clinical manifestation

Fig. 2

Patient 1 (N1) brain MRI. Note the central midbrain lesion with contrast enhancement

Fig. 3

Patient 1 (N1) brain MRI (FLAIR on the left and T1 gadolinium on the right) showing progressive reduction of pseudotumoral lesion size and contrast enhancement over time, while receiving rituximab infusions

Fig. 4

Brain MRI showing a lesion of the optic chiasm in a MOGAD patient (M2), with contrast enhancement

Fig. 5

Charts on the left-hand side represent visual acuity of both eyes over time for each MOGAD patients and charts on the right-hand side represent RNFL thickness measured by OCT over time. RNFL thickness is clearly reduced for optic nerves that were injured by inflammation, and this slimming is obvious even when visual acuity shows a good recovery. This is particularly the case for patients M3, M4 and M7 whose visual acuities are bilaterally assessed at 10/10 by the end of follow-up but whose optic nerve thickness are distinctly altered

Fig. 5

Charts on the left-hand side represent visual acuity of both eyes over time for each MOGAD patients and charts on the right-hand side represent RNFL thickness measured by OCT over time. RNFL thickness is clearly reduced for optic nerves that were injured by inflammation, and this slimming is obvious even when visual acuity shows a good recovery. This is particularly the case for patients M3, M4 and M7 whose visual acuities are bilaterally assessed at 10/10 by the end of follow-up but whose optic nerve thickness are distinctly altered