MOGAD: A comprehensive review of clinicoradiological features, therapy and outcomes in 4699 patients globally.

Abstract

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is one of the most common antibody-mediated CNS disorders. Optimal diagnostic and prognostic biomarkers remain unclear. Our aim was to clarify these biomarkers and therapeutic outcomes internationally. We reviewed articles from 2007 to 2022 and identified 194 unique cohorts encompassing 4699 paediatric and adult patients from 31 countries. Where phenotypes were specified, the most common initial presentation overall was optic neuritis (ON; paediatric 34 %; adults 60 %), during which 71 % had papilloedema on fundoscopy. The most common phenotype at latest follow-up was relapsing ON (20 %). Only 47 % of patients with 6-24 months of follow-up exhibited a relapsing course, while this proportion was much higher (72 %) when follow-up was extended beyond 5 years. Despite a similar relapse rate, the time to first relapse was much shorter in paediatric than adult patients (6 vs 17 months). Adult MRI-Brain scans performed at onset were more frequently normal than in paediatric patients (50 % vs 27 %). Abnormal MRI scans showing involvement of deep grey matter, cortico-subcortical, periventricular lesions, leptomeningeal enhancement, H-shaped spinal cord lesions, and bilateral optic nerve abnormalities were more common in paediatric patients compared to adults. Conversely, adults demonstrated higher frequencies of eccentric spinal cord lesions and intraorbital involvement. CSF analysis demonstrated intrathecally restricted oligoclonal bands in 12 %, elevated protein in 35 %, and pleocytosis in 54 %. Peripapillary retinal nerve fibre layer (pRNFL) thickness, measured acutely, frequently demonstrated swelling (weighted-median 145 μm; normal 85-110). Most cohorts demonstrated notable pRNFL atrophy at latest follow-up (weighted-median 67 μm). Follow-up pRNFL thickness was lower when measured at or 6 months after, as opposed to within 6 months of, ON onset (p < 0.001). Therapeutic and outcome data was available for 3031 patients with a weighted-median disease duration of 32 months. Acute immunotherapy was initiated in 97 %, and maintenance immunotherapy in 64 %, with considerable regional variation. Expanded Disability Status Scale (EDSS) scores and visual acuities improved from nadir to latest follow-up in most patients. A negative correlation was noted between follow-up pRNFL thickness and latest follow-up visual acuity (r = -0.56). Based on this unprecedented global aggregation of MOGAD patients, we reveal a higher proportion of relapsing patients than previously recognised. While commonly used measures like EDSS show significant recovery, they underestimate visual disability following optic neuritis, the most frequent clinical presentation. Our findings suggest that RNFL thickness, especially when measured at least 6 months post-ON, may serve as a more sensitive biomarker for long-term visual impairment.