White matter injury following rotavirus infection in neonates: new aspects to a forgotten entity, 'fifth day fits'?

Abstract

That rotavirus infection can cause neurological symptoms in young children has been well established. However, it is surprising why rotavirus infection has been overlooked as a cause of neonatal seizures for many years, despite significant research interest in neonatal rotavirus infection. Neonates are the age group most vulnerable to seizures, which are typically attributed to a wide range of causes. By contrast, because rotavirus infection is usually asymptomatic, it has been difficult to identify an association between this virus and neonatal seizures. The conventional wisdom has been that, although neonates are commonly infected with rotavirus, neurological complications are rare in this age. However, recent studies using diffusion-weighted imaging (DWI) have suggested a connection between rotavirus infection and neonatal seizures and that rotavirus infection can induce diffuse white matter injury without direct invasion of the central nervous system. The clinical features of white matter injury in rotavirus-infected neonates include the onset of seizures at days 4–6 of life in apparently healthy term infants. The recent findings seem to contradict the conventional wisdom. However, white matter injury might not be a completely new aspect of rotavirus infection in neonates, considering the forgotten clinical entity of neonatal seizures, 'fifth day fits'. With increased use of DWI in neonatal seizures, we are just starting to understand connection between viral infection and white matter injury in neonates. In this review, we discuss the historical aspects of rotavirus infection and neonatal seizures. We also present the clinical features of white matter injury in neonatal rotavirus infection.

Clinical Findings and Neurologic Outcome in Neonatal Encephalopathy With White Matter Injury Accompanied by Rotavirus

“…The characteristic white matter injury in newborns described here is not specific to encephalopathy associated with rotavirus infection. 7,23 White matter damage has also been observed in neonatal enterovirus and parechovirus encephalitis. 7,[23][24][25][26] The pathogenesis of white matter damage in viral infections is uncertain.…”

“…7,23 White matter damage has also been observed in neonatal enterovirus and parechovirus encephalitis. 7,[23][24][25][26] The pathogenesis of white matter damage in viral infections is uncertain. Previous studies have suggested that white matter injury in newborns is related to a vulnerability of specific developmentally regulated cells, premyelinating oligodendrocytes, which are prevalent in white matter and are highly vulnerable to systemic infection or inflammation.…”

“…Moreover, there is a higher signal intensity on T2-weighted MRI sequences in enterovirus and human parechovirus encephalitis than in encephalopathy associated with rotavirus. 7,11,[24][25][26] Enterovirus and parechovirus are usually isolated in the cerebrospinal fluid or blood, which is not the case for rotavirus. Furthermore, in our study, no neonates with rotavirus-associated encephalopathy had cerebrospinal fluid pleocytosis or sepsis-like conditions, such as fever or rash, accompanied by hepatitis, coagulopathy, or thrombocytopenia, which are usually observed in enterovirus and parechovirus encephalitis.…”

Febrile encephalopathy and diarrhoea in infancy: do not forget this culprit

“…During infancy, the concomitant presence of febrile encephalopathy and gastroenteritis should raise the suspicion of rotavirus infection. The classical neuroimaging findings are ‘subtle or no change in T1 and T2 weighted sequences, but marked symmetric diffusion restriction in periventricular white matter, corpus callosum or thalamus’ 4. This pattern of white matter injury can be seen in parecho and enterovirus encephalopathy as well but, overtly restricting signals on diffusion sequences with no/subtle changes on conventional T1 and T2 weighted spin echo sequences is quite specific for rotavirus encephalopathy and gives an edge over the other two differentials 4.…”

Monocyte Chemoattractant Protein (MCP)-1 in Rotavirus-Associated White Matter Injury in Newborns

“…[1][2][3] The pattern of WMI is evident on diffusion-weighted images as symmetrical restricted diffusion in the periventricular white matter and along entire fiber tracts, including the corpus callosum. 1,4 The high positive rate of rotavirus infection in neonatal seizures with WMI [1][2][3] suggests that these two features are linked. For this hypothesis to be widely accepted, further studies are needed to elucidate the mechanisms of this phenomenon as well as the causal relationship.…”