Epilepsy and Neurodevelopmental Outcomes in Children With Etiologically Diagnosed Central Nervous System Infections: A Retrospective Cohort Study

Abstract

Background: Central nervous system (CNS) infection in childhood can lead to neurological sequelae, including epilepsy, and neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). This study investigated the association of etiologically diagnosed childhood brain infections with the subsequent risks of epilepsy and neurodevelopmental disorders. Objectives: We retrospectively analyzed the data of children aged <18 years who had definite brain infections with positive cerebrospinal fluid cultures from January 1, 2005, to December 31, 2017. These patients were followed to evaluate the risks of epilepsy and neurodevelopmental disease (ADHD and ASD) after brain infections (group 1) in comparison with the risks in those without brain infections (group 2). Results: A total of 145 patients with an average age of 41.2 months were included in group 1. Enterovirus accounted for the majority of infections, followed by group B Streptococcus, S. pneumoniae, and herpes simplex virus. A total of 292 patients with an average age of 44.8 months were included in group 2. The 12-year risk of epilepsy in group 1 was 10.7 (95% confidence interval [CI], 2.30-49; p < 0.01). Compared with group 2 (reference), the risk of ASD in the age interval of 2-5 years in group 1 was 21.3 (95% CI, 1.33-341.4; p = 0.03). The incidence of ADHD in group 1 was not significantly higher than that in group 2. Conclusions: This study identified the common etiological causes of brain infections in Taiwanese children. The highest-risk neurodevelopmental sequelae associated with brain infections was epilepsy. Children who had a diagnosis of brain infection (specially Enterovirus) should be followed since they are at greater risk of developing epilepsy and ASD.

Keywords: brain infections; central nervous system infections; children; epilepsy; neurodevelopmental outcomes.

Figure 1

Flowchart of the study. *The patients who were screened from the medical records and contacted by the our case managers.

Figure 2

Common pathogens of central nervous system infections among 145 affected subjects (A) and their stratification by age (B). The pathogenic organisms of “others” included Adenovirus (n = 2), HHV-6 (n = 2), HHV-7 (n = 1), Parvovirus (n = 1), Varicella-zoster virus (n = 1), Citrobacter koseri (n = 1), Enterobacter hormaechei (n = 1), Enterococcus casseliflavus (n = 1), Escherichia coli (n = 2), Haemophilus influenzae (n = 2), Neisseria meningitidis (n = 1), Listeria monocytogenes (n = 1), Mycobacteria tuberculosis complex (n = 1), Staphylococcus aureus (n = 2), Streptococcus constellatus (n = 2).

Figure 3

Subclassification of enteroviruses among 78 affected individuals.

Figure 4

Possible risk factors during admission for subsequent NDDs among 145 study children. PGCS, Pediatric Glasgow Coma Scale; F, focal; G, generalized; F to G, focal seizures evolving to secondarily generalized seizures; Infection type 1: meningitis; Infection type 2: Encephalitis; Infection type 3: meningoencephalitis; Infection type 4: Encephalomyelitis; Infection type 5: other brain infections types. ** Seizure patterns were classified into focal, generalized, focal to generalized, according to their clinical features of seizures and electroencephalographic data.