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Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease
Laura Cacciaguerra1, Omar Abdel-Mannan1, Dimitrios Champsas1
1From the Department of Neurology and Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (L.C., J.J.C., S.B.S.-M., V.R., J.-M.T., S.J.P., E.P.F.), Mayo Clinic, Rochester, MN; Queen Square MS Centre (O.A.-M., D.C., C.H., O.C., Y.H.), UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; Department of Neurology (O.A.-M., D.C., C.H., Y.H.), and Department of Neuroradiology (K.M.), Great Ormond Street Hospital for Children, London, United Kingdom; Department of Radiology (K.N.K.), Department of Ophthalmology (J.J.C.), and Laboratory Medicine and Pathology (S.J.P., E.P.F.), Mayo Clinic, Rochester, MN; Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Department of Neurology (C.V.-S.), Mayo Clinic, Phoenix, AZ; and NIHR University College London Hospitals Biomedical Research Centre (O.C.), United Kingdom.
Background And Objectives:
Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD).
Methods:
This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis.
Results:
Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]).
Discussion:
Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.
Insights
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) attacks show dynamic brain lesion changes, including new lesion formation and resolution, distinguishing them from multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). This aids in diagnosing MOGAD.
Area of Science:
- Neuroimmunology
- Neurology
- Radiology
Background:
- Understanding the evolution of central nervous system (CNS) demyelinating lesions during attacks is crucial for accurate diagnosis.
- Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) presents with diverse clinical and radiological features.
- Differentiating MOGAD from multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD) can be challenging.
Purpose of the Study:
- To evaluate and compare intra-attack lesion dynamics in the brain using MRI in patients with MOGAD, MS, and AQP4+NMOSD.
- To identify imaging characteristics that can help distinguish MOGAD from MS and AQP4+NMOSD during an acute attack.
Main Methods:
- A retrospective, observational, multicenter study involving patients diagnosed with MOGAD, MS, or AQP4+NMOSD.
- Inclusion criteria required at least two brain MRIs within 30 days of attack onset and evidence of brain involvement.
- Analysis focused on changes in T2 lesions (new, resolved, or stable) within a single attack, comparing findings across the three disease groups.
Main Results:
- In MOGAD attacks, 47% showed new T2 lesions, 41% stability, and 7% lesion resolution on follow-up MRI.
- Radiologic lag (normal initial MRI despite symptoms) was observed in 10% of MOGAD attacks.
- Intra-attack MRI changes suggesting active lesion dynamics were significantly more frequent in MOGAD (59%) compared to MS (26%) and AQP4+NMOSD (21%).
- Lesion resolution within an attack was exclusive to MOGAD (12%). Steroid treatment was associated with lesion resolution and reduced new lesion formation.
Conclusions:
- Dynamic brain MRI findings, including lesion appearance and occasional disappearance within a single attack, are characteristic of MOGAD.
- These imaging patterns can aid in differentiating MOGAD from MS and AQP4+NMOSD.
- The findings have significant implications for clinical diagnosis, trial design, and understanding MOGAD pathogenesis.
