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.

Determination of Free Valproic Acid Concentration in 569 Clinical Samples by LC-MS/MS After Hollow Fiber Centrifugal Ultrafiltration Treatment

“…The highest risk was conferred by central nervous system infections. A Taiwanese study 28 showed that systematic infection was an independent risk factor for epileptic seizures, conferring a 10.7-fold higher risk compared with the control group. In addition, human herpesvirus 6 (HHV-6), 29 Epstein-Barr virus (EBV), 29,30 respiratory syncytial virus infections, 31 and urinary tract infections 32 could increase epilepsy risk.…”

Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes

“…Neurodevelopmental disorders (NDDs)[ 1 ] are a group of conditions that interfere with the central nervous system (CNS) development at an early age. Developmental brain dysfunction causes later neuropsychiatric problems that persist into adulthood, including the attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning disabilities, and intellectual disability[ 2 ]. Numerous epidemiological reports[ 3 ] suggest an association between NDDs and prenatal exposure to viral pathogens.…”

CYP2C9*3/*3 Gene Expression Affects the Total and Free Concentrations of Valproic Acid in Pediatric Patients with Epilepsy

“…The risk of epilepsy increased by 78% due to infection (HR=1.78, 95% CI 1.73–1.83), with central nervous system infection showing the highest risk (HR=4.97, 95% CI 4.42–5.59). A study performed in Taiwan 29 indicated that central nervous system infection is an independent risk factor for epilepsy, increasing its odds by 10.7 times versus the control group. Furthermore, when infection-related epilepsy in children is not well cured, the in-hospital mortality rate could reach 16%.…”

“…24 Besides, genetic mutation is also one of the pathogenetic factors of epilepsy and mental/developmental disorders, with ion channel and synapse related genes being most commonly mutated. [25][26][27] Infectious Diseases and Epilepsy 29 indicated that central nervous system infection is an independent risk factor for epilepsy, increasing its odds by 10.7 times versus the control group. Furthermore, when infection-related epilepsy in children is not well cured, the in-hospital mortality rate could reach 16%.…”