Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS

Banks, Samantha A.; Morris, Pearse; Chen, John J.; Pittock, Sean J.; Sechi, Elia; Kunchok, Amy; Tillema, Jan Mendelt; Fryer, James P.; Weinshenker, Brian G.; Krecke, Karl N.; López-Chiriboga, A. Sebastian; Nguyen, Adam; Greenwood, Tammy M.; Lucchinetti, Claudia F.; Zalewski, Nicholas L.; Messina, Steven A.; Flanagan, Eoin P.

doi:10.1136/jnnp-2020-325121

Cited by 81 publications

(65 citation statements)

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“… 12 Also, a recent series of patients with MOGAD with brainstem or cerebellar attacks from our group showed lesion resolution at ≥6 months observed in 6/9 (67%) patients. 21 Accepting differences in study design and follow-up durations, these numbers are in line with our findings and suggest MRI normalization in MOGAD may occur even after multiple attacks. A prior study specifically analyzed brain lesion evolution on MRI in 63 patients with NMOSD (95% with AQP4-IgG), for a total of 211 acute brain lesions, and found complete resolution in 24% of these.…”

Section: Discussionsupporting

confidence: 89%

Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders

et al. 2021

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Background and Objective:There are few studies that compare lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2-lesion evolution in myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS).Methods:In this descriptive study, we retrospectively identified Mayo Clinic patients with MOGAD, AQP4-IgG-NMOSD, or MS and: 1) brain or myelitis attack; 2) available attack MRI within 6 weeks; and 3) follow-up MRI beyond 6 months without interval relapses in that region. Two neurologists identified the symptomatic or largest T2-lesion for each patient (index lesion). MRIs were then independently reviewed by two neuroradiologists blinded to diagnosis to determine resolution of T2-lesions by consensus. The index T2-lesion area was manually outlined acutely and at follow-up to assess variation in size.Results:We included 156 patients (MOGAD, 38; AQP4-IgG-NMOSD, 51; MS, 67) with 172 attacks (brain, 81; myelitis, 91). The age (median [range]) differed between MOGAD (25 [2-74]), AQP4-IgG-NMOSD (53 [10-78]) and MS (37 [16-61]) (p<0.01) and female sex predominated in the AQP4-IgG-NMOSD (41/51 [80%]) and MS (51/67 [76%]) groups but not among those with MOGAD (17/38 [45%]). Complete resolution of the index T2-lesion was more frequent in MOGAD (brain, 13/18[72%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 3/21[14%]; spine, 0/34[0%]) and MS (brain, 7/42[17%]; spine, 0/29[0%]), p<0.001. Resolution of all T2-Lesions occurred most often in MOGAD (brain, 7/18[39%]; spine, 22/28[79%]) than AQP4-IgG-NMOSD (brain, 2/21[10%]; spine, 0/34[0%]), and MS (brain, 2/42[5%]; spine, 0/29[0%]), p< 0.01. There was a larger median (range) reduction in T2-lesion area in mm2 on follow-up axial brain MRI with MOGAD (213[55-873]) than AQP4-IgG-NMOSD (104[0.7-597]) (p=0.02) and MS, 36[0-506]) (p< 0.001) and the reductions in size on sagittal spine MRI follow-up in MOGAD (262[0-888]) and AQP4-IgG-NMOSD (309[0-1885]) were similar (p=0.4) and greater than MS (23[0-152]) (p<0.001).Conclusions:The MRI T2-lesions in MOGAD resolve completely more often than AQP4-IgG-NMOSD and MS. This has implications for diagnosis, monitoring disease activity, and clinical trial design, while also providing insight into pathogenesis of central nervous system demyelinating diseases.

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Section: Discussionsupporting

confidence: 89%

Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders

et al. 2021

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“…We report for the first time, to our knowledge, the high frequency (69%) of spinal cord leptomeningeal enhancement in children with MOGAD. Although leptomeningeal enhancement has thus far been sporadically reported in the spinal cord, [25][26][27] it has been more frequently recognized on brain MRI, with or without associated cortical hyperintensity, [28][29][30][31] supporting meningeal involvement as a possible key feature of MOGAD.…”

Section: Discussionmentioning

confidence: 99%

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

Fadda

O’Mahony

et al. 2021

JAMA Netw Open

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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.

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“…Acute disseminated encephalomyelitis (ADEM) or ADEM-like phenotypes are characterized clinically by encephalitis and/or myelitis accompanied by large T2-hyperintense demyelinating lesions in multiple CNS regions on MRI (spinal cord, brain, and/or optic nerves). Large T2 hyperintensities with indistinct margins can be encountered and involve the middle cerebellar peduncle (Figure 2A1) in the infratentorial region or deep gray matter in the supratentorial region (19,(55)(56)(57). MOG antibodies are found in 30-50% of ADEM patients while AQP4 autoantibodies account for a much smaller proportion of cases (<5%) (2,19,58).…”

Section: Paraneoplastic and Non-demyelinating Syndromes Suggestive For An Antibody-mediated Etiologymentioning

confidence: 99%

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

Sechi

Flanagan

2021

Front. Neurol.

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Antibody-mediated disorders of the central nervous system (CNS) are increasingly recognized as neurologic disorders that can be severe and even life-threatening but with the potential for reversibility with appropriate treatment. The expanding spectrum of newly identified autoantibodies targeting glial or neuronal (neural) antigens and associated clinical syndromes (ranging from autoimmune encephalitis to CNS demyelination) has increased diagnostic precision, and allowed critical reinterpretation of non-specific neurological syndromes historically associated with systemic disorders (e.g., Hashimoto encephalopathy). The intracellular vs. cell-surface or synaptic location of the different neural autoantibody targets often helps to predict the clinical characteristics, potential cancer association, and treatment response of the associated syndromes. In particular, autoantibodies targeting intracellular antigens (traditionally termed onconeural autoantibodies) are often associated with cancers, rarely respond well to immunosuppression and have a poor outcome, although exceptions exist. Detection of neural autoantibodies with accurate laboratory assays in patients with compatible clinical-MRI phenotypes allows a definite diagnosis of antibody-mediated CNS disorders, with important therapeutic and prognostic implications. Antibody-mediated CNS disorders are rare, and reliable autoantibody identification is highly dependent on the technique used for detection and pre-test probability. As a consequence, indiscriminate neural autoantibody testing among patients with more common neurologic disorders (e.g., epilepsy, dementia) will necessarily increase the risk of false positivity, so that recognition of high-risk clinical-MRI phenotypes is crucial. A number of emerging clinical settings have recently been recognized to favor development of CNS autoimmunity. These include antibody-mediated CNS disorders following herpes simplex virus encephalitis or occurring in a post-transplant setting, and neurological autoimmunity triggered by TNFα inhibitors or immune checkpoint inhibitors for cancer treatment. Awareness of the range of clinical and radiological manifestations associated with different neural autoantibodies, and the specific settings where autoimmune CNS disorders may occur is crucial to allow rapid diagnosis and early initiation of treatment.

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Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS

Cited by 81 publications

References 32 publications

Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders

Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders

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

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

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