Probable tirzepatide-associated limbic encephalitis with status epilepticus in a patient with extreme obesity: a case report.

A 59-year-old man (240 kg, BMI ≈ 100 kg/m2) with type 2 diabetes developed progressive drowsiness, confusion, behavioral changes (irritability and aggressive behavior), coma and status epilepticus 72 h after the third weekly dose of tirzepatide 2.5 mg subcutaneously. Brain MRI showed left mesial temporal (hippocampal–amygdalar) swelling and restricted diffusion without contrast enhancement; cerebrospinal fluid was acellular with normal biochemistry and negative multiplex PCR and antibody panel. Seizures were partially controlled with benzodiazepines, levetiracetam and lacosamide. High-dose intravenous methylprednisolone (2 g/day × 3 days, then tapered) granted complete control of seizures within 24 h. Tirzepatide was permanently discontinued. Naranjo score was 8 (probable adverse drug reaction). Follow-up MRI at 16 days revealed persistent mesial temporal signal abnormality. Emerging reports describe tirzepatide-associated autoimmune encephalitis with seizures and psychiatric/behavioral symptoms, as well as seizures secondary to metabolic complications such as SIADH-related hyponatremia; to our knowledge this is among the first reports of probable tirzepatide-associated steroid-responsive limbic encephalitis with status epilepticus in a patient with extreme obesity, highlighting that serious neurological adverse events, although rare, warrant neurological vigilance when using dual GLP-1/GIP receptor agonists.