Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA

Abstract

(2012) Neuropathology and Applied Neurobiology 38, 443-453 Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA Aims: To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished. Methods: Tissue sections from the central nervous system of infected cases were examined by light microscopy, immunohistochemistry and in situ hybridization. Results: All 13 cases of EV71 encephalomyelitis collected from Asia and France invariably showed stereotyped distribution of inflammation in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus and, to a lesser extent, cerebral cortex and meninges. Anterior pons, corpus striatum, thalamus, temporal lobe, hippocampus and cerebellar cortex were always uninflamed. In contrast, the eight JE cases studied showed inflammation involving most neuronal areas of the central nervous system, including the areas that were uninflamed in EV71 encephalomyelitis. Lesions in both infections were nonspecific, consisting of perivascular and parenchymal infiltration by inflammatory cells, oedematous/necrolytic areas, microglial nodules and neuronophagia. Viral inclusions were absent. Conclusions: Immunohistochemistry and in situ hybridization assays were useful to identify the causative virus, localizing viral antigens and RNA, respectively, almost exclusively to neurones. The stereotyped distribution of inflammatory lesions in EV71 encephalomyelitis appears to be very useful to help distinguish it from JE.

Viral neuronotropism is important in the pathogenesis of Murray Valley encephalitis

“…Macroscopically evident thalamic ‘degeneration’ similar to the necrolytic lesions in our case has been reported previously in chronic stages of MVE [8]. Although nonspecific, these necrolytic lesions may be more common or prominent in JE virus infection [9,10]. Brain MRI had also shown striking inflammation‐associated, thalamic hyperintensity in MVE, JE, TBE and WN encephalitis [11].…”

An approach for differentiating echovirus 30 and Japanese encephalitis virus infections in acute meningitis/encephalitis: a retrospective study of 103 cases in Vietnam

“…However, it is difficult to conduct these expensive examinations in a resource limiting setting in the rural areas of Asian countries. Neuropathological findings in fatal JEV cases showed that the virus caused broad inflammation in the central nervous system [33]. JEV infects neurons and causes direct damage [10,33] that consequently leads to many severe neurological symptoms.…”

“…Neuropathological findings in fatal JEV cases showed that the virus caused broad inflammation in the central nervous system [33]. JEV infects neurons and causes direct damage [10,33] that consequently leads to many severe neurological symptoms. Thus, in areas where E30 and JEV outbreaks are overlapping, severe neurological symptoms could provide strong evidence of JEV infection.…”

Transgenic mouse model for the study of enterovirus 71 neuropathogenesis

“…However, in some infants and young children, after a few days of prodromal illness, HFMD caused predominantly by EV71 can be complicated by neurological manifestations, including ataxia, tremor, myoclonus, polio-like paralysis, encephalomyelitis, cardiopulmonary failure, and death (3,4). In humans with fatal EV71 encephalomyelitis, inflammation and viral antigens in neurons were observed mainly in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus, and cerebrum (5,6). Since the 1970s, HFMD outbreaks with significant mortality have been reported throughout the world, including in Bulgaria in 1975 [44 deaths (7)], Hungary in 1978 [47 deaths (8) Appropriate animal models are needed to better understand EV71 neuropathogenesis and to facilitate the development of effective vaccines and drugs.…”