Exploring the Paradox: The Role of TNF-α Inhibitors in the Emergence of FLAIR-Hyperintense Lesions and Seizures in Anti-MOG Encephalitis — A Case-Based Review

Abstract

Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) encompasses a spectrum of demyelinating disorders of the central nervous system, including a rare subtype known as FLAMES (FLAIR-hyperintense Lesions in Anti-MOG–associated Encephalitis with Seizures). FLAMES typically presents with unilateral cortical lesions, seizures, and elevated inflammatory markers in cerebrospinal fluid (CSF). Although the pathophysiology remains incompletely understood, recent reports have suggested potential immunologic triggers, including biologic agents. Herein, we present a case of a 17-year-old male adolescent with long-standing psoriasis, treated with the tumor necrosis factor α (TNF-α) inhibitor adalimumab, who developed FLAMES. The patient initially presented with focal seizures and severe headache, followed by neuropsychiatric symptoms and magnetic resonance imaging (MRI) findings consistent with cortical fluid-attenuated inversion recovery (FLAIR) hyperintensities. Diagnostic workup revealed positive anti-MOG antibodies, elevated CSF protein, and pleocytosis, whereas infectious etiologies were excluded. High-dose corticosteroids led to partial improvement, but behavioral disturbances and steroid-induced psychiatric effects necessitated a switch to intravenous immunoglobulin, which resulted in further clinical recovery. Due to the uncertain safety of other TNF-α inhibitors in similar contexts, alternative psoriasis treatment was considered. This case emphasizes the importance of recognizing FLAMES as a potential adverse event associated with TNF-α inhibitors and supports the need for individualized immunotherapy. Clinicians should be vigilant when patients receiving biologics present with new-onset seizures and cortical lesions. Further research is needed to elucidate the underlying mechanisms linking TNF-α inhibitor therapy and MOGAD.