Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities

Abstract

ObjectiveTo evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs).MethodsMulticentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability.ResultsNeuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia.ConclusionsCategorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.

Congenital cytomegalovirus in Sub-Saharan Africa—a narrative review with practice recommendations

“…One of the limitations of this categorisation is the wide range of manifestations that fall into the category of CNS disease, whereby microcephaly, calcification and white matter changes are given the same significance as polymicrogyria, lissencephaly, cortical, and cerebellar malformations. Neuroradiological scoring systems are being developed to better understand the significance of these findings ( 34 , 35 ). However, the extent of developmental delay may not be fully appreciated until 4–6 years of age when social, communication and learning difficulties become evident ( 28 ).…”

“…Several studies have recorded around half of infants identified through screening have abnormal brain imaging including abnormal white matter and even polymicrogyria ( 34 , 55 ). It is discussed whether infants with less severe disease might have a greater benefit from treatment than those more severely affected, however there are no randomised controlled trials to currently support treating infants with mild disease or isolated SNHL.…”

“Minimally symptomatic” congenital cytomegalovirus infection: latest data and emerging concepts

“…Central nervous system manifestations include microcephaly (occipital frontal circumference <10%) as well as periventricular calcifications, lenticulostriate vasculopathy, subependymal cysts, and ventricular dilatation that can be seen on cranial ultrasonography [23,24]. The most relevant neuroimaging findings that negatively impact neurodevelopmental outcomes pertain to the neuronal migrational disorders that result from fetal infection early in gestation [25–28,29 ▪▪ ]. These brain abnormalities are only detected by brain MRI and consist of focal or generalized cortical dysplasias such as lissencephaly, schizencephaly, pachygyria, and microgyria [30].…”

“…In addition, ophthalmologic examination as well as cranial ultrasound should be performed at the time of diagnosis. If findings suggest central nervous system disease, brain MRI should be obtained [28,29 ▪▪ ,50 ▪▪ ,62,63]. Brain MRI provides the optimal evaluation for neuronal migrational disorders, but its expense and availability make its routine performance impractical.…”