Endocrinologic Dysfunctions and Neuropsychiatric Sequelae in Pediatric Patients With a History of Central Nervous System Infection (ENDLESS): A Prospective Monocentric Study

Introduction: Central nervous system (CNS) infections represent some of the most critical pediatric health challenges, characterized by high mortality rates and a notable risk of long-term complications. Despite their significance, standardized guidelines for endocrinological follow-up of CNS infection survivors are lacking, leading to reliance on the expertise of individual centers and clinicians.

Materials and methods: Prospective monocentric observational study conducted at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy. It included patients with a history of CNS infection, admitted to various pediatric departments of the hospital. The participants were selected based on a coded diagnosis of CNS infection and had completed their follow-up at the Pediatric Endocrinology Day Hospital after October 2019.

Results: Eighty participants were included, comprising 53 patients with a prior CNS infection and 27 healthy controls, with a median age of 7.4 years (range 3.6-12.3 years). Endocrinologic alterations were detected in 13 patients, with 8 cases in those who had meningitis, 4 in encephalitis survivors, and 1 in a patient with a cerebral abscess. Patients with a history of CNS infections were shorter compared with healthy controls (P = 0.027). Moreover, those who had meningitis exhibited an increased risk of developing epilepsy (P = 0.01), neurosensory disabilities (P = 0.034) and the need for ventriculoperitoneal shunt insertion (P = 0.006). Patients with bacterial CNS infections were more prone to neurosensory and endocrine dysfunctions compared to those with viral or other infections. Significant differences were observed in hormone levels between previously infected patients and controls, specifically in TSH (P < 0.001), ACTH (P = <0.001), and cortisol (P = 0.019). IGF-1 levels were considerably lower in the infection group, both in absolute terms and when adjusted for sex and age (P < 0.001). The regression analysis suggested that the reduction in IGF-1 was more pronounced the earlier the CNS infection occurred, irrespective of infection type.

Conclusions: Our study found several endocrinologic imbalances in children who survived CNS infections.