Tumefactive Demyelination in MOG Ab-Associated Disease, Multiple Sclerosis, and AQP-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder

Abstract

Background and objectives: Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD).

Methods: We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD.

Results: We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD (p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R ² = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance.

Discussion: Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.

Figure 1. Pictorial Overview of the MRI Features Evaluated in This Study, With Corresponding Definitions

Lesions are shown by arrows and are displayed on axial T2-FLAIR (left half of each image) and on the most appropriate sequence for the evaluation of each specific feature, indicated by an arrowhead (right half of each image). Exceptions are images E and J, where the second sequence (T2-weighted image in E, and T1-weighted image in J) is reported for descriptive purposes only because the T2-FLAIR sequence is suitable for the visualization of those features. For image I, T2-FLAIR image was unavailable and therefore substituted with T2-weighted sequence. Features were defined as follows: (A) T2-hypointense rim: rim-shaped relative T2-hypointensity compared with the T2-hyperintensity of the lesion center and surrounding edema; (B) T1-hypointensity: hypointensity on T1-weighted images compared with the normal-appearing white matter; (C) Baló-like appearance: the presence of ≥2 concentric rings or a pattern of alternating bands of signal intensity on any MRI sequence; (D) cystic component: T2-weighted or T1-weighted signal of similar intensity to CSF; (E) poorly demarcated borders: fluffy appearance on T2-FLAIR or T2-weighted sequences; (F) restricted diffusion: DWI hyperintensity with corresponding hypointensity on the ADC map; (G) arc/ring of peripheral restricted diffusion: dark peripheral ADC arc or ring with a brighter center; (H) ring enhancement (closed ring shown in this figure): circular border of enhancement, closed if complete, otherwise open; (I) cloud-like enhancement: multiple patchy enhancement with ill-defined margins; (J) mass effect: lesion exerting a secondary effect on adjacent structures such as sulci, ventricles, or midline. ADC = apparent diffusion coefficient map; DWI = diffusion-weighted images; FLAIR = fluid-attenuated inversion recovery; Gd = gadolinium.

Figure 2. Long-term Outcomes of Patients With MOGAD With Tumefactive Lesions

Kaplan-Meier curves of survival probability estimates of not developing relapse or reaching the EDSS disability milestone of 6 in patients with MOGAD up to 120 months from disease onset, according to the presence of tumefactive lesions. EDSS = Expanded Disability Status Scale; IgG = immunoglobulin G; MOGAD = myelin oligodendrocyte glycoprotein-IgG–associated disease.

Figure 3. Examples of Tumefactive Brain Lesions and Relevant MRI Features for the Differential Diagnosis of Patients With MOGAD, MS, and AQP4+NMOSD

Unless otherwise specified, lesions are shown on axial T2-fluid-attenuated inversion recovery (T2-FLAIR). Tumefactive lesions are indicated by white arrows, while specific features are indicated by arrowheads. Panel A (MOGAD): tumefactive lesions in the bilateral hemispheric white matter (A.a, arrows); bilateral tumefactive lesions in the corticospinal tract and thalami (A.b, arrows); tumefactive lesion involving the entire pons (A.c, arrow) without evidence of T2-hypointense rim, diffusion restriction (i.e., no DWI hyperintensity), and no ADC map hypointensity (A.c); bilateral tumefactive lesions in the middle cerebellar peduncles (A.d, arrows), with complete resolution at follow-up MRI (A.e). Panel B (MS): Baló-like tumefactive lesions in the hemispheric white matter (B.a, arrow) and periventricular white matter (B.b, arrow); tumefactive lesion located in the hemispheric white matter, showing a complete T2-hypointense rim (arrowhead) with a corresponding ring of peripheral diffusion restriction, as indicated by the hyperintensity in DWI (arrowhead) and hypointensity on ADC map (arrowhead) (B.c); tumefactive lesion in the left middle cerebellar peduncle (B.d, arrow) undergoing volumetric reduction, but still present at follow-up MRI (B.e, arrow). Panel C (AQP4+NMOSD): tumefactive lesions in the hemispheric white matter (C.a, arrow), corticospinal tract (C.b, arrow); tumefactive periventricular lesion extensively involving the splenium of the corpus callosum in an “arch-bridge” pattern (C.c, arrow); the lesion does not show any T2-hypointense rim and is characterized by DWI hyperintensity of the splenium (arrowhead) with focal diffusion restriction (i.e., corresponding hypointensity on the ADC map, arrowhead); tumefactive lesion involving the entire pons (C.d, arrow), showing residual mild hyperintensity near the fourth ventricle (C.e, arrow). ADC = apparent diffusion coefficient map; AQP4+NMOSD = aquaporin-4-IgG–positive neuromyelitis optica spectrum disorders; DWI = diffusion-weighted images; IgG = immunoglobulin G; MOGAD = myelin oligodendrocyte glycoprotein-IgG–associated disease; MS = multiple sclerosis.