Abstract
Diffuse gliomas represent a heterogeneous group of infiltrative central nervous system tumors that may resemble inflammatory disorders in early stages. We report a rare case of an IDH-wildtype diffuse glioma initially mimicking autoimmune limbic encephalitis. A 49-year-old male presented with subacute neuropsychiatric symptoms, including confusion, hallucinations, and memory disturbances. MRI revealed widespread FLAIR hyperintensities involving the cingulate gyri, insula, basal ganglia, thalamus, corpus callosum, and frontal operculum, without contrast enhancement or perfusion abnormalities. MR spectroscopy showed increased Cho/Cr and Cho/NAA ratios, decreased NAA/Cr ratio, and elevated myo-inositol peak, suggesting a neoplastic process. The patient received corticosteroids, intravenous immunoglobulin, and plasmapheresis for presumed autoimmune encephalitis, but no clinical or radiological improvement was observed. Subsequent biopsy confirmed IDH-wildtype diffuse glioma. This case highlights the diagnostic overlap between encephalitis and gliomas, especially when radiological findings lack mass effect or enhancement. Extralimbic involvement, abnormal metabolic profiles on spectroscopy, and failure to respond to immunotherapy should raise suspicion for neoplasia. Awareness of these red flags is essential, as misclassification may delay biopsy and oncologic treatment. Early histopathological confirmation remains the only definitive step to secure accurate diagnosis and initiate timely therapy.