Objective: To describe a case of DPPX antibody-associated encephalitis to facilitate early diagnosis and treatment.

Background: DPPX antibody-associated encephalitis can be challenging to diagnose due to its insidious onset and heterogenous presentation.¹ The most common presentation is a triad of gastrointestinal symptoms (predominately diarrhea), cognitive-psychiatric dysfunction, and manifestation of CNS hyperexcitability in 44.6% of cases.² Here we describe a case of DPPX encephalitis with ataxia and nystagmus that was challenging to diagnose due to the delay between symptom onset and neurological manifestations.

Method: A 26-year-old male presented with sudden onset vertigo and torsional nystagmus. Exam was significant for mild bilateral dysmetria with finger to nose testing and bilateral, severe torsional nystagmus when looking in both the horizontal and vertical directions. Cranial nerves were otherwise intact. There was no evidence of myoclonus on exam. Gait was ataxic. Cognition, strength, reflexes, and sensory exam were normal. He had unintentionally lost 110 pounds over the prior 9 months. Patient retrospectively reported having had hyperekplexia, sleep disturbance, and anxiety during that time.

Results: Brain MRI demonstrated no evidence of cerebellar degeneration or injury. Due to the weight loss, extensive malignancy workup was completed, including upper and lower endoscopies, thyroid and scrotal ultrasound (US), CT chest/abdomen/pelvis, and full-body CT PET scan, all of which were unrevealing. A nutritional cause of the symptoms was considered due to the extensive weight loss, so supplemental B1 and B12 were provided until the baseline thiamine level later returned normal. Serum paraneoplastic panel showed fluorescence on monkey cerebellum and rat hippocampus substrates. Cerebrospinal fluid showed mild elevation in protein without pleocytosis, and encephalitis antibody panel was positive for anti-DPPX antibody. A short course of high-dose steroids led to resolution of his nystagmus and improvement in his ataxia.

Conclusion: DPPX antibody-associated encephalitis can present with ambiguous symptoms and subtle neurological changes that can be missed initially. Patients that present with unintentional weight loss with a negative comprehensive malignancy work-up should be evaluated for DPPX encephalitis, so they can receive timely and appropriate treatment.

References: 1. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404. doi:10.1016/S1474-4422(15)00401-9

2. Li E-C, Zhang T-Y, Cai M-T, et al. Clinical and Paraclinical Characterizations, Management, and Prognosis in DPPX Antibody-Associated Encephalitis: A Systematic Review. Neurol Neuroimmunol neuroinflammation. 2025;12(2):e200350. doi:10.1212/NXI.0000000000200350

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-rare-case-of-dipeptidyl-peptidase-like-protein-6-dppx-antibody-associated-encephalitis/