Background: Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system, characterized by inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI) is central to diagnosis, disease monitoring, and differentiation from other neurological conditions. Tumefactive multiple sclerosis (TMS), a rare variant, presents with large, tumor-like lesions that can mimic neoplasms, posing diagnostic challenges. Methods: This retrospective cohort study included 15 patients diagnosed with MS according to the 2017 revised McDonald criteria. Clinical presentations were documented, and all patients underwent MRI using conventional sequences (T1, T2, FLAIR) and advanced techniques, including diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and magnetic resonance spectroscopy (MRS). Lesions were evaluated for size, enhancement patterns, and perilesional features, and imaging findings were correlated with clinical symptoms and treatment outcomes. Results: Among the cohort, 12 patients (80%) exhibited typical MS features, predominantly periventricular and juxtacortical lesions, while 3 patients (20%) demonstrated tumefactive lesions (>2 cm) with open-ring enhancement, perilesional edema, and mild mass effect. Seizures occurred exclusively in the tumefactive subgroup. Advanced imaging modalities aided differentiation from neoplasms, with MRS showing elevated choline and reduced N-acetylaspartate levels, supporting a demyelinating process. Conclusions: MRI remains central to diagnosing and monitoring MS, particularly in distinguishing typical from rare tumefactive variants. Seizures may serve as a clinical correlate of TMS. A multimodal imaging approach, integrating conventional and advanced MRI with clinical correlation, enhances diagnostic accuracy, minimizes unnecessary invasive procedures, and informs optimal patient management.

Central Nervous system (CNS), Multiple sclerosis (MS), Tumefactive MS (TMS), Relapsing-remitting MS (RRMS), Secondary progressive MS (SPMS), Primary progressive MS (PPMS), Progressive-relapsing MS (PRMS)