Pathologic Studies of Fatal Encephalomyelitis in Children Caused by Enterovirus 71

Abstract

OBJECTIVES: Enterovirus 71 (EV71) is the major pathogen of hand, foot, and mouth disease and can cause death; however, its pathogenesis remains elusive. METHODS: We performed a detailed systematic histopathologic examination and molecular studies on six autopsy cases of EV71 infection using H&E, immunohistochemistry, double immunofluorescence staining, and nested reverse transcription polymerase chain reaction. RESULTS: Characteristic features of acute encephalomyelitis were observed. Viral antigens were mainly detected in neuronal cytoplasm and processes in the different brainstem nuclei and spinal cord, including the anterior and posterior horn cells. Viral antigens were also positive in the nerve roots of spinal cord and autonomic ganglia of intestines. CONCLUSIONS: Our study revealed direct pathologic evidence supporting viral entry into the central nervous system (CNS) through peripheral nerves. In addition to the major motor pathway, EV71 can also enter the CNS via peripheral sensory and autonomic pathways in retrograde axonal transport.