Peripheral Blood Cell Ratios, Promising Predictive Biomarkers for the Diagnosis of Pediatric Autoimmune Encephalitis

Background: Autoimmune encephalitis (AE) is an increasingly well recognized disorder in the past decade both in adults and in children, yet pediatric data are still limited. A full peripheral blood cell count is a routine examination that provides valuable information regarding the immune system. Thus, there are peripheral blood cell count (PBCC)- derived ratios that reflect systemic inflammatory activity and have been associated with disease severity in adults: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratios (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI). Methods: This study is a retrospective chart review of children under 18 years diagnosed with definite or probable AE and treated in our institution from January 1, 2018 until December 1, 2025. Only patients with available PBCC results prior to any immunomodulatory therapy were included. An age-matched control group was created by selecting results of PBCC of patients presenting for routine pediatric follow-ups with normal inflammatory and hematologic parameters. Group means were compared using independent samples t-test or the Mann Whitney U test for non-normally distributed data. Analysis of the receiver operating characteristics curve (ROC curve) was conducted followed by the area under the curve ROC curve (AUC). Results: 45 children with AE and 150 controls were included in the study. NLR, PLR, SII, SIRI and AISI values were significantly higher in AE patients compared with controls, suggesting an overall pro-inflammatory profile at presentation. Concerning the platelet indices, a trend tower higher medium platelet volume and platecrit was observed in the AE group. These findings point to distinct peripheral immune alterations in pediatric AE, consistent with reports in adult patients. Conclusions: Our results suggest that at the time of the initial hospitalization, children with AE already show altered peripheral immune cell profiles compared to their age-matched peers The high specificity and the low sensitivity of the inflammatory indices make them more suitable for supporting the AE diagnosis in suggestive clinical circumstances, but not for screening. These results represent a foundation for further investigating the roles that these indices have both as diagnostic and prognostic factors for these children.