A 55-year-old Hispanic woman was brought to the psychiatry unit with increasingly bizarre behavior lasting 1 year and recent inability to recognize family members. Previously in good health, she developed irritability and inappropriateness that led to a brief psychiatric admission and treatment with benzodiazepines. She approached men inappropriately, became sexually preoccupied and emotionally blunted, and explored objects orally. Family members reported alternating episodes of compulsive fasting and eating along with incessant smoking; she had no contributory family or medical history, in particular any diarrhea, fever, headache, or weight loss. On admission, she was unkempt, disorganized, inappropriate, and uncooperative. Neurological examination showed easy distractibility, pressured speech, and prosopagnosia. She followed commands but performed poorly on concentration and memory tasks. Within 3 weeks, she developed right-sided hemiparesis and sensory aphasia. Subsequently, she was withdrawn and apathetic. Brain magnetic resonance imaging demonstrated bilateral medial temporal lesions with ring enhancement and surrounding edema (Figure). Her cerebrospinal fluid protein level was 80 mg/dL with a normal cell count and glucose value. Results of workup for systemic malignancy and paraneoplastic syndrome were negative. Ultimately, a brain biopsy specimen demonstrated granulomatous process and macrophages loaded with intracellular periodic acid–Schiff–positive microorganisms (Figure), diagnostic of Whipple disease (WD). Results of a subsequent duodenal biopsy were normal. The patient was given parenteral ceftriaxone sodium for 2 weeks followed by long-term trimethoprim-sulfamethoxazole. She was less withdrawn, followed simple commands, and spoke few words following treatment. She was eventually transferred to a long-term care facility.