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 they have been associated with disease severity in adults: the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI), and 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 1 January 2018 until 1 December 2025. Only patients with available PBCC results at the time of the first hospital admission after neurological/psychiatric symptom onset were included. An age-matched control group was created by selecting the results of PBCC of patients presenting for routine pediatric follow-ups with normal inflammatory and hematologic parameters. The group means were compared using an 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: A total of 45 children with AE and 150 controls were included in the study. Of these, 22 patients (49%) had probable AE and 23 patients (51%) had definite AE. The NLR, PLR, SII, SIRI and AISI values were significantly higher in AE patients compared with the controls, but the AUC values (~0.58–0.66) indicate poor-to-fair discriminative ability. Youden’s index-based cut-off values were associated with high specificity and modest sensitivity. The likelihood ratios in the range of 2–3 (LR+) and 0.6–0.7 (LR−) suggest weak rule-in capacity and limited rule-out utility. 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 investigation of the roles that these indices have both as diagnostic and prognostic factors for these children.