Epidemiology of Potential Missed Diagnosis of Pediatric Central Nervous System Infections in the Emergency Department

BACKGROUND: Pediatric CNS infections (CNSi)-meningitis, encephalitis, and craniospinal abscess-are uncommon, high-morbidity conditions in which timely emergency department (ED) diagnosis is critical and challenging. This study aimed to characterize the epidemiology of potential missed diagnosis (PMD) of CNSi and assess its association with acute neurological complications. METHODS: Cross-sectional analysis of 2018 to 2019 Healthcare Cost and Utilization Project State ED and Inpatient datasets from California, Florida, Maryland, New York, and Wisconsin. Children aged 0 to 17 years with an admission for CNSi were included; those missing the linkage variable, birth hospitalizations, and with pre-existing intracranial devices were excluded. PMD was defined as a prior 7-day ED visit with a high-risk diagnosis, defined using Symptom-Disease Pair Analysis of Diagnostic Error methodology. Descriptive statistics and multivariable logistic regression were used to assess predictors of PMD and neurological complications. RESULTS: Among 2686 CNSi cases, 284 (10.6%) had PMD with a median revisit interval of 2 days (IQR 1 to 3). In children >90 days with PMD, over 75% had isolated ED diagnoses of flu-like symptoms (fever, headache, vomiting, or fatigue), while 6% had CNSi "red flags" of altered mental status or neck pain. Potential missed diagnosis was more common in all age groups >90 days of age (aOR range: 4.19 to 4.78) and patients who were Asian (aOR 1.83, 95% CI: 1.06-3.16), Black (aOR 1.87, 95% CI: 1.30-2.70), and Hispanic (aOR 1.53, 95% CI: 1.1-2.13) relative to White children. In addition, patients initially presenting to lower annual pediatric volume quartile EDs (aOR 3.7, 95% CI: 2.6-5.3) and minor (aOR 1.49, 95% CI: 1.11-1.98) or nonteaching hospitals (aOR 2.08, 95% CI: 1.27-3.41) had higher risk of PMD. Among the subset of bacterial CNSi cases, PMD was associated with increased risk of neurological complications (aOR 2.49, 95% CI: 1.41-4.39). CONCLUSIONS: One in 10 children with CNSi had a potential missed diagnosis, most often after an initial ED visit for nonspecific flu-like symptoms. Risk of PMD was greater in children >90 days of age and those seen at lower-pediatric volume and nonacademic EDs. In addition, PMD in bacterial CNSi was associated with increased risk of severe neurological complications. These findings highlight the need for targeted diagnostic support tools to improve timely recognition of pediatric CNS infections, particularly in older infants and children.