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

Background and objectives: Studies on tumefactive brain lesions in myelin-oligodendrocyte-glycoprotein-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 to multiple sclerosis (MS) and aquaporin-4-IgG-positive-neuromyelitis-optica-spectrum-disorder (AQP4+NMOSD). Methods: We retrospectively searched 194 MOGAD and 359 AQP4+NMOSD patients 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. Tumefactive MS patients 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 tumefactive vs. non-tumefactive MOGAD patients. Results: We included 108 patients with tumefactive demyelination (MOGAD=43; AQP4+NMOSD=16; MS=49). Tumefactive lesions were more frequent among MOGAD (43/194[22%]) than AQP4+NMOSD (16/359[5%]) (p<0.001). Risk of relapse and need for gait aid were similar in tumefactive and non-tumefactive MOGAD. Clinical features more frequent in MOGAD than 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 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, Balo'-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 MOGAD (11/42[26%], p=0.005). Cerebrospinal fluid analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37[5%]) than MS (30/43[70%]) (p<0.001) and higher median white cell count in MOGAD than MS (33 vs. 6 cells/µl, p<0.001). At baseline, independent predictors of MOGAD diagnosis were presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R Squared=0.67). Tumefactive lesion resolution was more common in MOGAD than MS or AQP4+NMOSD and improved model performance. Discussion: Tumefactive lesions are frequent in MOGAD but are not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from tumefactive MS, and are more similar to tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.