Describe a case of anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis with attention to hematologic-oncologic comorbidities.

Anti-DPPX encephalitis is a rare autoimmune encephalitis with prodromal features of weight loss and gastrointestinal symptoms, followed by cognitive impairment and central nervous system hyperexcitability. Due to atypical and variable presentation, diagnosis is frequently delayed. Autoimmune encephalitis is associated with malignancies, and three cases of anti-DPPX encephalitis have been linked to hematologic malignancies.

Consent was obtained from patient’s wife. PubMed and Ovid databases were searched using terms (“DPPX” and “lymphoma”) as well as “DPPX”.

A 54-year-old male presented with two months of metallic taste and unintentional weight loss followed by confusion, memory impairment, hallucinations, and sleep disturbances. Neurologic exam was significant for encephalopathy, ataxia, and stimulus-induced myoclonus. Initial workup revealed mildly elevated protein in cerebrospinal fluid but no pleocytosis, MRI brain with nonspecific white matter hyperintensities, and electroencephalogram without epileptiform activity. Initial basic chemistries were within normal limits, and no vitamin deficiencies were identified. Intravenous methylprednisolone (1000 mg) was initiated for suspected autoimmune encephalitis. After anti-DPPX antibody returned positive, he received additional first- and second-line treatment with intravenous immunoglobulins, plasmapheresis and rituximab with modest improvements in encephalopathy and myoclonus. The patient had a history of monoclonal gammopathy of undetermined significance (MGUS) and tobacco use. He underwent serum protein electrophoresis, confirming IgM MGUS with low to intermediate risk of malignant transformation. However, peripheral flow cytometry revealed an indeterminate kappa monotypic restricted B cell population (CD19 positive, CD5 and CD10 negative) without corresponding findings in the CSF or lymphadenopathy. In discussion with hematology-oncology, the B cell population was favored to be reactive to the anti-DPPX encephalitis, rather than a primary malignant hematologic condition. Other malignancy screening was performed and negative.

This case highlights the challenges of determining association of anti-DPPX encephalitis with hematologic malignancy and importance of interdisciplinary collaboration.