Pearls & Oy-sters: DPPX Antibody-Associated Encephalitis in a Patient With Diarrhea, Tremor, Ocular Flutter, and Cognitive-Psychiatric Changes

Dipeptidyl-peptidase-like protein-6 antibody-associated encephalitis (DPPXE) is an autoimmune, multisystem disorder characterized by a triad of gastrointestinal prodrome, cognitive-psychiatric change, and CNS hyperexcitability. We report a 57-year-old man with 2 months of progressive gastrointestinal symptoms despite extensive normal gastrointestinal evaluation. He then developed tremor, myoclonus, gait ataxia, hyperekplexia, insomnia, emotional lability, memory impairment, and abnormal eye movements. Examination showed ocular flutter, tremor, ataxia, and cognitive impairment. Brain MRI revealed bilateral T2/fluid-attenuated inversion recovery hyperintensities in the brainstem and limbic regions. CSF demonstrated lymphocytic pleocytosis and 10 unique oligoclonal bands. DPPX-immunoglobulin G was detected in serum and CSF, confirming the diagnosis of DPPXE. Acute immunotherapy with intravenous methylprednisolone and plasma exchange followed by maintenance treatment with rituximab led to dramatic improvement of his symptoms, with residual memory impairment and tremor at 3 months. This case underscores the characteristic gastrointestinal prodrome and syndromic breadth of DPPXE, highlights the diagnostic value of panel-based screening, and supports treatment with immunomodulation.