To address the diagnostic challenges in differentiating anti-Ma2 antibody encephalitis from CJD when both antibodies coexist, this case aims to: (a) Characterize the clinico-radiological phenotype of anti-Ma2 encephalitis with coexisting 14-3–3 protein in CSF, (b) Systematically evaluate differential diagnoses through antibody testing (Western blot), FLAIR MRI, and prion-specific assays (RT-QuIC, PRNP analysis), and (c) Contextualize these findings within literature on antibody-coexisting neurological syndromes. This evidence concerns the gene PNMA2 and viral encephalitis.