What Determines the Clinical Course and Outcome of <scp>DPPX</scp> Encephalitis? A Systematic Review

BACKGROUND: Dipeptidyl peptidase like protein 6 (DPPX) encephalitis is a rare type of autoimmune encephalitis. It presents with a plethora of clinical manifestations and variable disease course. OBJECTIVES: The aim of this systematic review is to study the course of DPPX encephalitis, response to various immunotherapies and determine factors that can predict clinical outcome and relapse. METHODS: Search was performed in the PUBMED and Web of Science database for studies published until December 15, 2025. Univariate analysis and multiple regression modeling were used to analyze predictors affecting the outcome and relapse. RESULTS: Treatment details were available in 66 patients. Favorable clinical improvement was observed in 74.24% (n = 49) patients. Among these patients, 18 patients recovered completely with first line immunotherapy and short course of steroids with no relapse until the last follow up while 48 patients were treated with long term immunotherapy. Stratified multivariable regression analysis revealed that, among patients who lacked hyperekplexia, good response to first line immunotherapy (OR = 13.20, 95% CI = 1.89-91.91, p = 0.009) was associated with favorable clinical outcome. However, among patients with hyperekplexia, presence of good response to first line immunotherapy did not predict favorable outcome. CSF abnormality (OR = 14.00, 95% CI: 1.69-115.79, p = 0.02) and hyperekplexia (OR = 4.40, 95% CI: 1.37-14.11, p = 0.01) predicted higher propensity for relapse. CONCLUSION: Recognition of hyperekplexia could be imperative in prognosticating patients with respect to need for long term immunotherapy and course of illness. This study also postulates the possibility of monophasic illness in a subgroup of patients with DPPX encephalitis.