Active neurosyphilis is uncommon after the introduction of penicillin. We evaluated the pathology of a case of untreated neurosyphilis that was diagnosed as a manic episode. Examinations were performed before and after high-dose penicillin G treatment. Evaluations included the Mini-Mental State Examination (MMSE), the Neurobehavioral Cognitive Status Examination (Cognistat), the Bender Gestalt Test, an electroencephalogram, and brain magnetic resonance imaging/angiography. The most obvious improvements after treatment with penicillin G were the constructive ability and the ability to draw two- and three-dimensional designs. A paradoxical deterioration in several items on the Cognistat after treatment suggested an impairment in working memory. The clinical and psychological abnormalities observed in this case were speculated to be due to disturbed visual cognition related to encephalitis and impaired working memory related to temporofrontal lobe pathology. Current diagnostic tools were useful for precisely diagnosing and assessing the prognosis of older patients with late-onset mania.