International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

Elevated cerebrospinal fluid endothelin 1 associated with neurogenic pulmonary edema in children with enterovirus 71 encephalitis.

PMID 25820093


Neurogenic pulmonary edema (NPE) is a fatal complication in children with enterovirus 71 (EV71) encephalitis. Endothelin 1 (ET-1), a potent vasoconstrictor, can induce pulmonary edema in rats via intrathecal injections. Thus, it was hypothesized that ET-1 in the central nervous system may correlate with NPE in children with EV71 encephalitis. Clinical data and ET-1 in the cerebrospinal fluid (CSF) were compared between three groups: (1) EV71 encephalitis with NPE; (2) EV71 encephalitis without NPE; and (3) non-EV71 aseptic meningitis. ET-1 immunostaining was performed on the brainstem of autopsy patients. The EV71 with NPE group showed significantly increased CSF levels of ET-1 compared to the EV71 without NPE and the non-EV71 aseptic meningitis groups (both p<0.01). The optimum cut-off point of ET-1 to predict NPE in EV71 patients, based on the receiver operating characteristic curve, was 0.5 pg/ml (sensitivity 83%, specificity 100%). Immunostaining in the brainstem showed increased ET-1 expression, mainly in the oligodendrocytes, in EV71 with NPE patients compared with control patients. ET-1 in the central nervous system may play a role in the development of NPE in children with EV71 infection and could be used as a biomarker or therapeutic target for NPE in EV71 encephalitis.