Diagnostic challenge of GAD65-associated autoimmune encephalitis mimicking post-traumatic complications in an older adult: a case report

Abstract

Introduction Glutamic acid decarboxylase 65 (GAD65) antibody-associated autoimmune encephalitis is an uncommon immune-mediated neurological disorder with heterogeneous neuropsychiatric manifestations. Diagnosis is particularly challenging in older adults when symptoms of recent traumatic brain injury (TBI) overlap with structural or metabolic conditions. Case presentation We report a 79-year-old man who developed recurrent headache, progressive confusion, abnormal behavior, poor oral intake, intermittent myoclonic jerks, and low-grade fever after TBI complicated by chronic subdural hematoma. Initial laboratory testing revealed hyponatremia, and the working diagnosis was post-traumatic brain syndrome with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Although serum sodium was corrected and nocturnal agitation partially improved, persistent daytime confusion, cognitive impairment, behavioral abnormalities, and low-grade fever prompted further investigation. Cerebrospinal fluid (CSF) analysis showed mild inflammatory changes with pleocytosis and elevated protein. CSF metagenomic next-generation sequencing (mNGS) and paraneoplastic antibody testing were negative, whereas the autoimmune encephalitis panel was positive for GAD65 antibody at a titer of 1:32. Whole-body positron emission tomography-computed tomography (PET-CT) did not reveal malignancy. The diagnosis was therefore revised to GAD65 antibody-associated autoimmune encephalitis. Because high-dose corticosteroids were considered unsuitable owing to his history of gastric ulcer and previous gastrointestinal bleeding, he was treated with intravenous immunoglobulin (IVIG) at a total dose of 2 g/kg divided over 3 consecutive days followed by oral azathioprine 50 mg daily. His fever resolved within 1 week, and his mental status and responsiveness gradually improved. At 6-month follow-up, he had achieved near-baseline mental status, was able to walk with a cane, and was almost fully independent in daily activities, without relapse or serious treatment-related adverse events. Discussion This case highlights the diagnostic difficulty of recognizing autoimmune encephalitis after TBI. The clinical overlap between post- traumatic syndrome and immune-mediated brain injury often delays diagnosis, emphasizing the value of targeted CSF autoantibody testing in atypical cases. Conclusion Traumatic brain injury may obscure the onset of GAD65-associated autoimmune encephalitis. Early recognition and a corticosteroid-sparing immunotherapy strategy (IVIG and azathioprine) can yield favorable outcomes in elderly patients with medical comorbidities.