Necessary Treatment Standardization in Pediatric Refractory Autoimmune Encephalitis

Authors

• Marlene Fernandez, University of LynchburgFollow

Specialty

Pediatric Neurology

Abstract

Pediatric autoimmune encephalitis (AE) is a complex neuroinflammatory disease process affecting children worldwide. Although its widespread recognition has improved, clinical management remains a challenge. Current treatment protocols are derived from retrospective studies, anecdotal evidence, or case reports. The proposed pathophysiology involves the production of autoantibodies against the neuronal cell surface, leading to the propagation of central nervous system inflammation. The umbrella term AE encompasses different subtypes of encephalitis, some of which are specific to certain neurotransmitters or cell proteins, the most commonly reported being N-methyl-D-aspartate receptor (NMDAR) encephalitis. The key clinical features are psychotic symptoms, sleep disturbances, seizures, memory problems, movement disorders, autonomic dysfunction and encephalopathy. Severity ranges from mild to severe, with no identified factors associated with refractoriness. Prompt immunotherapy is initiated based on clinical suspicion, as diagnostic test results may take weeks to return. Third-line therapy, used in moderate-severe cases, consists of a combination of immunotherapeutic agents, with no universally agreed upon escalation algorithm. Refractory cases can yield long-term neurological deficits including autonomic dysfunction and even death from complications. This researcher performed a comprehensive literature search using Google Scholar and Pubmed databases and reviewed the most recent relevant studies from December 2021-2026. There is currently only one randomized controlled trial in progress evaluating the effects of inebilizumab, a B-cell depleting agent, in older children and adults with moderate to severe NMDAR encephalitis. Guidelines on escalation of therapy are still lacking for all AE subtypes. The purpose of this literature review is to highlight the urgent need for treatment standardization for all subtypes of refractory AE and propose new treatment options based on ideas acquired from the most recent literature.

Recommended Citation

Fernandez M. Necessary Treatment Standardization in Pediatric Refractory Autoimmune Encephalitis. University of Lynchburg DMSc Doctoral Project Assignment Repository. 2026; 8(1).