Anti-Zic4 encephalitis in endometrial cancer: Autoimmunity triggered by PD-1 inhibitor or recent CMV encephalitis?

Background

Autoimmune encephalitis has been well described in oncological patients treated with immune checkpoint inhibitors (ICIs), as a paraneoplastic neurological syndrome. Central nervous system (CNS) infections from herpes viruses are also known to trigger secondary neurologic autoimmunity.

Case Presentation

We hereby describe a patient with a recent history of cytomegalovirus (CMV) CNS infection and ongoing immunotherapy with the programmed-cell-death-protein-1(PD-1) inhibitor pembrolizumab for metastatic endometrial cancer. The patient presented with progressive encephalopathy along with cerebellar signs, rapidly evolving to status epilepticus requiring mechanical ventilation and advanced care unit (ACU) support. A serum paraneoplastic antibody panel revealed strongly positive anti-Zic4 antibodies. Despite first-line immunotherapy and aggressive anticonvulsant treatment, the patient died a few days postintubation.

Conclusion

In anti-Zic4 encephalitis, both PD-1 inhibitor treatment and recent CMV viral insult may contribute to the development of neurological autoimmunity. Further research is needed to identify ways of predicting neurological damage in oncological patients treated with ICIs.