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<p>A 59-year-old man (240&#xa0;kg, BMI ≈ 100&#xa0;kg/m<sup>2</sup>) with type 2 diabetes developed progressive drowsiness, confusion, behavioral changes (irritability and aggressive behavior), coma and status epilepticus 72&#xa0;h after the third weekly dose of tirzepatide 2.5&#xa0;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&#xa0;g/day × 3&#xa0;days, then tapered) granted complete control of seizures within 24&#xa0;h. Tirzepatide was permanently discontinued. Naranjo score was 8 (probable adverse drug reaction). Follow-up MRI at 16&#xa0;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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Andrea Mazzeo,
  • Valerio Alaimo,
  • Luigi M. Grimaldi

摘要

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.