Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease

Abstract

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.

Figure 1. Examples of Intra-Attack T2 Lesion Dynamics in Patients With MOGAD

All images are in axial view. Resolving T2 lesions are indicated by arrows on first examination. To improve readability, arrows are not displayed when obvious changes are visible. Patients with initial negative MRIs (i.e., radiologic lag A.a and B.a) developed a cortical lesion in the setting of cerebral cortical encephalitis (A.b, arrowheads) and multiple ill-defined supratentorial lesions (B.b). Patient with bilateral thalamic lesions (C.a), 1 resolving (C.a, right thalamic, arrow) and 1 enlarging (C.b, left thalamic) at follow-up (C.b). Additional lesions are also visible in the right globus pallidus and both internal capsules (C.b). Patient with left thalamic lesions and right subcortical lesion (D.a, arrows) had resolved at follow-up (D.b). T2-FLAIR = fluid-attenuated inversion recovery; T2-w = T2-weighted image.

Figure 2. Examples of Intra-Attack T2 Lesion Dynamics in a Patient With MOGAD With 4 MRI Scans Within a Single Attack

All images are in axial view on T2–fluid-attenuated inversion recovery. The patient had progressive increase in number and size of T2 lesions over a span of 16 days. First MRI (A) was normal. The patient developed new and enlarging ill-defined lesions on subsequent examinations (B, C, and D) mainly located in infratentorial and juxtacortical supratentorial white matter. MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease.

Figure 3. Graphic Representation of MRI Scan Dynamics Over Time in the Study Population

X axis shows the days from symptom onset. Each horizontal line represents 1 attack, with dots corresponding to each MRI scan labeled by its evolution. AQP4+NMOSD = aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease; MS = multiple sclerosis.

Figure 4. Comparison of Intra-Attack T2 Lesion Dynamics in Patients With MOGAD, MS, and AQP4+NMOSD

All images are in axial view on T2–fluid-attenuated inversion recovery. Resolving T2 lesions are indicated by arrows on the first examination. To improve readability, arrows are not displayed when obvious changes are visible. MOGAD: 2 patients who developed multiple new ill-defined lesions at the second intra-attack MRI (A.b, B.b) compared with initial MRI (A.a, B.a). The second patient also had resolution of a single lesion in the left putamen (B.a, arrow). MS: a patient with an unchanged periventricular lesion (C.a, C.b) and a patient who developed multiple new focal periventricular lesions (D.a, D.b). AQP4+NMOSD: 2 patients with stable MRIs (E.b, F.b) compared with initial MRIs (E.a, F.a). AQP4+NMOSD = aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease; MS = multiple sclerosis.