ADEM is demyelinating immune-mediated inflammatory disease affecting the CNS white matter following infection or vaccination. It is associated with influenza, rabies, measles, mumps, rubella, smallpox, pertussis, diphtheriatetanus- polio (DPT), Japanese B encephalitis, pertussis, and hepatitis B infection/and vaccine. Case definitions for ADEM is based on existence of multifocal neurologic deficit, MRI findings of diffuse white matter lesions, the monophasic course of the disease with no relapse for 3 months, and absence of evidences for other acute demyelinating disorders of CNS. Early diagnosis and treatment carry advantageous of preventing severe residual neurological deficits. Our case study suggests ADEM as the patient encountered level-1 criteria for its diagnosis. Detailed vaccination history when assessing patients with neurological manifestations should be obtained. Also, physicians should be aware of developing ADEM following seasonal influenza vaccination.