Abstract
BACKGROUND: Anti-Dipeptidyl-peptidase-like protein-6 (DPPX) antibody-associated encephalitis is a rare autoimmune condition that affects the central and enteric nervous systems. It often presents with neuropsychiatric symptoms, cerebellar ataxia, and gastrointestinal dysmotility, though clinical manifestations can vary widely. CASE PRESENTATION: We report the case of a 38-year-old woman with psychiatric symptoms who developed severe cognitive impairment, seizures, and a profound weight loss of 100 pounds over one year. Her symptoms initially led to multiple psychiatric diagnoses and treatments, delaying recognition of the underlying autoimmune process. Ultimately, cerebrospinal fluid analysis revealed high-titer anti-DPPX antibodies (1:1000). Despite aggressive immunotherapy—including corticosteroids, plasmapheresis, IVIG, and rituximab—the patient’s condition deteriorated, and she died under hospice care. DISCUSSION: This case expands the known clinical spectrum of anti-DPPX encephalitis by documenting the most extreme reported case of weight loss associated with the disease. The prodromal presentation with isolated weight loss underscores the diagnostic challenges when neuropsychiatric symptoms emerge late. Our case highlights the importance of maintaining clinical suspicion for autoimmune encephalitis in patients with unexplained weight loss and neurocognitive decline. CONCLUSION: Profound, unexplained weight loss may be an early and under-recognized manifestation of anti-DPPX encephalitis. Early recognition and immunotherapy are critical, but the potential for rapid progression and relapse demands heightened clinical vigilance and further research into optimal treatment strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-025-04337-8.