Neurodevelopment and cognition in children after enterovirus 71 infection

N Engl J Med. 2007 Mar 22;356(12):1226-34. doi: 10.1056/NEJMoa065954.


Background: Enterovirus 71 is a common cause of hand, foot, and mouth disease and encephalitis in Asia and elsewhere. The long-term neurologic and psychiatric effects of this viral infection on the central nervous system (CNS) are not well understood.

Methods: We conducted long-term follow-up of 142 children after enterovirus 71 infection with CNS involvement - 61 who had aseptic meningitis, 53 who had severe CNS involvement, and 28 who had cardiopulmonary failure after CNS involvement. At a median follow-up of 2.9 years (range, 1.0 to 7.4) after infection, the children received physical and neurologic examinations. We administered the Denver Developmental Screening Test (DDST II) to children 6 years of age or younger and the Wechsler intelligence test to children 4 years of age or older.

Results: Nine of the 16 patients with a poliomyelitis-like syndrome (56%) and 1 of the 5 patients with encephalomyelitis (20%) had sequelae involving limb weakness and atrophy. Eighteen of the 28 patients with cardiopulmonary failure after CNS involvement (64%) had limb weakness and atrophy, 17 (61%) required tube feeding, and 16 (57%) required ventilator support. Among patients who underwent DDST II assessment, delayed neurodevelopment was found in only 1 of 20 patients (5%) with severe CNS involvement and in 21 of 28 patients (75%) with cardiopulmonary failure (P<0.001 for the overall comparison). Children with cardiopulmonary failure after CNS involvement scored lower on intelligence tests than did children with CNS involvement alone (P=0.003).

Conclusions: Enterovirus 71 infection with CNS involvement and cardiopulmonary failure may be associated with neurologic sequelae, delayed neurodevelopment, and reduced cognitive functioning. Children with CNS involvement without cardiopulmonary failure did well on neurodevelopment tests. ( number, NCT00172393 [].).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child Development
  • Child, Preschool
  • Cognition
  • Cognition Disorders / etiology*
  • Developmental Disabilities / etiology*
  • Encephalitis, Viral / complications*
  • Encephalitis, Viral / mortality
  • Encephalitis, Viral / psychology
  • Encephalitis, Viral / virology
  • Enterovirus Infections / complications*
  • Enterovirus Infections / psychology
  • Enterovirus Infections / virology
  • Enterovirus*
  • Female
  • Follow-Up Studies
  • Heart Arrest / etiology
  • Humans
  • Infant
  • Intelligence Tests
  • Male
  • Meningitis, Aseptic / complications*
  • Meningitis, Aseptic / psychology
  • Meningitis, Aseptic / virology
  • Regression Analysis
  • Respiratory Insufficiency / etiology

Associated data