Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up

Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Abneg patients. 37 AQP4-Ab positive (AQP4-Abpos) and 32 AQP4-Ab negative (AQP4-Ab neg) patients (8 with MOG-Ab) were identified. The AQP4-Abneg group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Abneg patients, AQP4-Abpos patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Abneg patients with RION also had poor visual outcome. Up to 35 % of AQP4-Abneg patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Abneg patients (25 %) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0–6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Abneg RION also had a poor visual outcome. Of those without AQP4-Ab, 25 % had MOG-Ab and another 25 % developed MS; thus, MOG-Ab is associated with AQP4-Abneg non-MS ON.