Enterovirus 71 infection and neurological complications

Abstract

Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.

Keywords: Brain stem; Human enterovirus 71; Neurological manifestations; Pulmonary edema; Vaccines.

Fig. 1. Chest radiograph of a patient with enterovirus 71 infection presenting with pulmonary hemorrhage and shock. Note the diffuse haziness on both lungs.

Fig. 2. Brain magnetic resonance imaging findings in a patient with enterovirus 71 brainstem encephalitis. (A) Note the high signal-intensity lesion in the posterior aspect of the midbrain (arrow). (B) Note the high signal-intensity lesion in the posterior aspect of the pons and the bilateral dentate nuclei of the cerebellum (arrowheads).

Fig. 3. Spine magnetic resonance imaging findings in a 4-month-old infant. The patient presented with acute motor weakness of the left lower extremity along with enterovirus 71 infection. (A, B) Note the strong enhancement of the left anterior horn of the spinal cord (arrow) and the left ventral nerve roots (arrowhead) on gadolinium-enhanced T1-weighted images.