Comparison of Spinal Cord Magnetic Resonance Imaging Features Among Children With Acquired Demyelinating Syndromes

Abstract

IMPORTANCEThe recognition of magnetic resonance imaging (MRI) features associated with distinct causes of myelitis in children is essential to guide investigations and support diagnostic categorization. OBJECTIVE To determine the clinical and MRI features and outcomes associated with spinal cord involvement in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), multiple sclerosis (MS), and seronegative monophasic myelitis. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, participants were recruited between 2004 and 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study, which enrolled youth younger than 18 years presenting within 90 days of an acquired demyelinating syndrome. Of the 430 participants recruited, those with lesions on available spine MRI and anti-MOG testing performed on archived samples obtained close to clinical presentation were selected. Participants with poor-quality images and final diagnoses of nondemyelinating disease, antiaquaporin 4 antibody positivity, and relapsing seronegative myelitis were excluded. Data analysis was performed from December 2019 to November 2020. MAIN OUTCOMES AND MEASURES Spinal cord involvement was evaluated on 324 MRI sequences, with reviewers blinded to clinical, serological, and brain MRI findings. Associated clinical features and disability scores at 5 years of follow-up were retrieved. Results were compared between groups. RESULTS A total of 107 participants (median [IQR] age at onset, 11.14 [5.59-13.39] years; 55 girls [51%]) were included in the analyses; 40 children had MOGAD, 21 had MS, and 46 had seronegative myelitis. Longitudinally extensive lesions were very common among children with MOGAD (30 of 40 children [75%]), less common among those with seronegative myelitis (20 of 46 children [43%]), and rare in children with MS (1 of 21 children [5%]). Axial gray matter T2-hyperintensity (ie, the H-sign) was observed in 22 of 35 children (63%) with MOGAD, in 14 of 42 children (33%) with seronegative myelitis, and in none of those with MS. The presence of leptomeningeal enhancement was highly suggestive for MOGAD (22 of 32 children [69%] with MOGAD vs 10 of 38 children [26%] with seronegative myelitis and 1 of 15 children [7%] with MS). Children with MOGAD were more likely to have complete lesion resolution on serial images (14 of 21 children [67%]) compared with those with MS (0 of 13 children). CONCLUSIONS AND RELEVANCEThese findings suggest that several features may help identify children at presentation who are more likely to have myelitis associated with MOGAD. Prominent involvement of gray matter and leptomeningeal enhancement are common in pediatric MOGAD, although the pathological underpinning of these observations requires further study.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

“…Single or multiple short lesions can occur in MOGAD but are uncommon and should always raise the suspicion for a false MOG-IgG positivity in the context of MS, particularly when the lesions are peripherally located on axial spinal cord MRI (60,76,77). The conus medullaris is more frequently involved in MOGAD compared to AQP4-IgG+NMOSD (53).…”

“…In contrast, optic nerve enhancement is seen during almost all ON attacks and can characteristically involve the optic nerve sheath or peribulbar fat, which has been termed perineural enhancement (56,57). Notably, the initial brain or spinal cord MRI in MOGAD can be normal in up to 10% of cases despite severe acute disability (58)(59)(60). In these patients, somatosensory evoked potentials or repeat MRI within days may help confirm involvement of the affected CNS region (59).…”

“…MOGAD myelitis T2-lesions often predominantly affect the ventral part of the spinal cord on sagittal images ("ventral sagittal line"), and/or the central gray matter on axial images ("H-sign") in about a third (Figure 4) (53). Although highly suggestive of MOGAD, these signs are not 100% specific and can be seen in other myelopathies (e.g., acute flaccid myelitis, viral myelitis, idiopathic myelitis) (60,78). Similar to brain lesions, acute gadolinium enhancement is often nonspecific, differing from other myelitis for which characteristic enhancement patterns have been described (e.g., "elongated ring" in AQP4-IgG+NMOSD, dorsal subpial enhancement and "trident sign" in spinal cord sarcoidosis) (78)(79)(80)(81).…”

“…Similar to brain lesions, acute gadolinium enhancement is often nonspecific, differing from other myelitis for which characteristic enhancement patterns have been described (e.g., "elongated ring" in AQP4-IgG+NMOSD, dorsal subpial enhancement and "trident sign" in spinal cord sarcoidosis) (78)(79)(80)(81). Leptomeningeal enhancement accompanying the myelitis can occur, and may be more common in children (60). -Cerebral cortical encephalitis is a less common phenotype, also known as FLAMES (unilateral cortical FLAIRhyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures), characterized by encephalopathy, seizures, headache, marked CSF pleocytosis, and cortical hyperintensity on FLAIR images (82,83).…”

“…In addition, many patients that are persistently positive can remain monophasic and therefore an exact prediction of the disease course at presentation is not possible based on MOG-IgG titers (23,30,(91)(92)(93)(94). An important characteristic of MOGAD MRI lesions is the tendency to resolve completely after the acute attacks, resulting in a complete normalization of the brain and/or spine MRI in 50-80% of cases (30,55,60). This represents a major difference from AQP4-IgG+NMOSD and MS where complete lesion resolution is extremely rare (Figures 5, 6).…”