Source:Chang L-Y, Huang L-M, Gau SS-F, et al. Neurodevelopment and cognition in children after Enterovirus 71 infection.
N Engl J Med.
–1234; doi:10.1056/ NEJMoa065954

Enterovirus 71 (EV71) is a common cause of both hand-foot-and-mouth syndrome and aseptic meningitis, particularly in Asia. EV71 may also invade the ventral brain stem, cerebellum, and spinal cord producing a spectrum of disorders, including aseptic meningitis, encephalitis, encephalomyelitis, or a polio-like syndrome with acute flaccid paralysis and can also cause cardiopulmonary failure. Investigators from the National Taiwan University Hospital and the Chang Gung Children’s Hospital, Taiwan, followed 142 children up to six years after an EV71 infection with central nervous system (CNS) involvement to assess the long-term neurodevelopmental consequences of EV71 CNS infection in children hospitalized between 1998 and 2003. Isolation of the virus, a positive EV71 IGM, or a four-fold increase in EV71-neutralizing acute body titers were used to confirm EV71 infection. A total of 621 patients had EV71 infection, and of these 232 (37.4%) had CNS involvement. The median age at disease onset was 1.8 years (range 0.1 to 13.5), the median interval from disease onset to assessment was 2.9 years, and the median age at the time of assessment was five years (range 1.3–20.8). Sixty-one had aseptic meningitis, 53 had severe CNS involvement, and 28 had cardiopulmonary failure after the CNS involvement. Among this group of 232 children, 25 (10.8%) died of cardiopulmonary failure and brain stem encephalitis during the acute illness, and 14 (6%) died one month or longer after onset of the disease. There were 51 eligible patients who declined to participate in the current study or could not be located. Neurologic and cognitive functions in the remaining 142 patients were evaluated using the DDST II and/or the Wechsler Intelligence Scale for Children III in addition to a complete physical and neurologic examination. All of the patients with mild CNS involvement (aseptic meningitis) recovered completely. Among those with severe CNS involvement, 1 of 32 patients (3%) who had presented with encephalitis had a mild facial nerve palsy, and 9 of 16 (56%) who initially had a poliomyelitis-like syndrome and one of five (20%) who presented with encephalomyelitis had unilateral limb weakness and atrophy. Twenty-one of 28 (75%) patients who had acute cardiopulmonary failure after manifestations of E71 CNS infection had significant sequelae including limb weakness (64%), hypoventilation and ventilator dependency (57%), and delayed neurodevelopment (75%). The authors conclude that EV71 infection with CNS involvement and cardiopulmonary failure may eventuate in severe long-term sequelae.

Dr. Millichap has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does not contain a discussion of an unapproved/ investigative use of a commercial product/device.

Enterovirus, an RNA nonpoliovirus, causes significant and frequent illnesses in infants and children worldwide. Clinical manifestations of EV71 are protean and include hand-foot-and-mouth syndrome, brainstem encephalitis, and polio-like paralysis. Outbreaks have occurred in Japan, Taiwan, and Australia. In the US and other temperate...

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