To describe long term outcomes in anti-DPPX encephalitis.

Dipeptidyl-peptidase-like protein 6 (DDPX) antibody-associated encephalitis is a rare type of immune-mediated encephalitis characterized by cognitive disorder, neuropsychiatric symptoms, and CNS hyperexcitability, preceded by prodromal weight loss and diarrhea. Although anti-DPPX encephalitis has been described to be immunotherapy responsive, data regarding long-term outcomes is lacking.

We retrospectively identified anti-DPPX encephalitis patients across all three Mayo Clinic sites using the neuroimmunology lab database with the following inclusion criteria: 1) DPPX cell-based assay positive samples in serum and CSF; 2) duration of follow up of at least 36 months from symptom onset to last follow up.

Six anti-DDPX patients were included (median age, 56.5 years; range, 28-70 years) with a median follow up of 70.5 months (range 42-144 months). Of these 67% (4/6) were males. Median time from symptom onset to initiation of treatment was 15.5 months (range 4-48 months). Only 16% (1/6) had a malignancy identified (CLL). All patients had prodromal weight loss and gastrointestinal (GI) symptoms. All patients had cognitive impairment ranging from mild symptoms to dementia. One had neuropsychiatric symptoms including agitation, paranoia, and delusions. Seizures were documented in 33% (2/6), none were drug resistant. All patients had resolution of GI symptoms at last follow up, but all had persistence of sleep disturbances. 100% (6/6) had relapses. One patient died who had severe dysautonomia, but cause of death is unknown. The rest had stability or improvement in symptoms determined objectively with Kokmen mental status exam, ambulatory status (5/6) and ability to return to work (1/6).  33% (2/6) were able to discontinue immunotherapy and remained stable.

Overall long-term outcomes are good in anti-DPPX encephalitis. Relapses are common, particularly in the setting of weaning off immunotherapy. Patients can improve symptoms on treatment, but full resolution and return to premorbid baseline is unlikely.