Adenovirus Infection-associated Central Nervous System Disease in Children

Abstract

Background: Adenovirus (Adv) is a frequent etiology of acute respiratory tract infections. Although rare, neurologic manifestations are known to occur during Adv infection. Methods: We retrospectively analyzed clinical, laboratory, outcome and the relationship between clinical characteristics and viral detection results in the cerebrospinal fluid (CSF) in children with Adv-associated central nervous system (CNS) dysfunction. Results: Twenty-one (1.5%) cases had Adv-associated CNS manifestations. The median age was 1.4 years and 20 (95%) were less than 5 years of age. Six (28%) were male. The most frequently cited CNS symptoms were altered consciousness (100%) and seizure (14.3%). Fourteen cases (73.7%) had abnormal electroencephalogram examination and 6 cases (37.5%) had abnormal imaging. None of the patients had received cidofovir administration. Twenty children recovered without sequelae and 1 patient died of respiratory failure. Patients with positive Adv polymerase chain reaction (n = 11) presented lower onset age compared with that of patients with negative Adv polymerase chain reaction (n = 10) in the CSF. Clinical manifestation, laboratory findings, imaging studies and electroencephalogram showed no significant difference between the 2 groups. Conclusion: Adv is a rare cause of CNS disease in children, mainly causing altered consciousness. Adv was detected in more cases in the respiratory tract than the CSF, but the majority of patients had the virus detected in both. The lack of Adv in the CSF does not exclude CNS involvement. Furthermore, the viral detection results in the CSF do not seem useful as an indicator of the severity of CNS disease.

Neurological Complications in Children Hospitalized With Seizures and Respiratory Infections: A Comparison Between SARS-CoV-2 and Other Respiratory Infections

“…Neurological symptoms were associated with adenovirus, which has been observed in other children. 14 In a pediatric cohort with adenovirus infection, a subset (1.5%, 21/1,360) had evidence of encephalitis, encephalopathy, or meningitis. In this subset, 100% (21/21) had encephalopathy, with seizures (9.5%, 3/21), weakness (9.5%, 3/21), gait disturbance (5%, 1/21), and 1 patient (5%) died).…”

“…In this subset, 100% (21/21) had encephalopathy, with seizures (9.5%, 3/21), weakness (9.5%, 3/21), gait disturbance (5%, 1/21), and 1 patient (5%) died). 14 One study using a mouse model with adenoviral infection may shed some light on a potential pathophysiological mechanism for how adenovirus can cause neurological symptoms. This mouse model of neuroinflammation related to adenoviral infection demonstrates hemorrhagic encephalomyelitis, with microglial activation and blood-brain barrier dysfunction.…”

Clinical epidemiology and disease burden of adenoviral encephalitis in hospitalized children in China: A nationwide cross‐sectional study

“…Previous studies have documented a low incidence of complications and a favorable prognosis for individuals with adenovirus encephalitis. 14,23 Our study revealed that slightly over half of the children did not develop any complications, while nearly 40% experienced complications such as pneumonia or acute bronchitis, followed by myocardial damage. Only a small percentage of children, approximately 1%, suffered from neurological complications such as epilepsy, cerebral hernia, or paralysis.…”

“…Adenovirus encephalitis typically presents with symptoms such as fever, headache, convulsions, disturbance of consciousness, and meningeal irritation. In severe cases, the disease may lead to varying degrees of neurological sequelae 14 . This highlights the severity of the disease and the significant threat it poses to children's health.…”

A fatal case of viral sepsis and encephalitis in a child caused by human adenovirus type 7 infection

“…Adenovirus-related central nervous system (CNS) diseases cover a wide range, including meningitis, encephalitis, and encephalopathy. The prognosis of adenovirus-related CNS involvement is usually good [ 6 ], and risk factors associated with adverse clinical outcomes include seizures, coagulopathy, and young age [ 7 ]. No fatal cases of HAdV type 7-related encephalitis have been reported in this decade.…”