Fetal Brain Magnetic Resonance Imaging Findings In Congenital Cytomegalovirus Infection With Postnatal Imaging Correlation
Introduction
Cytomegalovirus (CMV) is an endemic herpesvirus that is spread by close contact with bodily fluids, with up to 90% of individuals infected by late adulthood.1 In children and adults, CMV infection is typically asymptomatic or produces a mild, flulike illness. Special groups, though, are susceptible to severe illness caused by the virus, including immunocompromised patients, newborns (especially when premature), and fetuses. Congenital CMV infection occurs through transplacental transmission, most commonly in women who acquire a primary infection during pregnancy, although transmission during secondary infection can also occur.2 Congenital CMV infection is seen in approximately 0.6%-0.7% of all live births in industrialized countries, with 11%-13% of those being symptomatic at birth.3, 4
Clinical findings of congenital CMV infection in the newborn are varied, with more severe features associated with first and second trimester infection.5 Intrauterine growth restriction, hydrops, thrombocytopenic purpura, jaundice, hepatosplenomegaly, hepatitis, pneumonitis, chorioretinitis, microcephaly, poor tone and suck, sensorineural hearing loss, and seizures have all been described.2 Outcomes for these newborns are varied as well. Long-term neurologic sequelae are seen in approximately 50% of symptomatic newborns including sensorineural hearing loss, visual impairment, cognitive impairment, seizures, cerebral palsy, and developmental delay.3 An additional 5%-15% of asymptomatic newborns will develop neurodevelopmental sequelae, most commonly hearing loss, although developmental delay and seizures are also seen. Sensorineural hearing loss due to congenital CMV infection can be unilateral or bilateral and may not be detected with routine newborn screening owing to its often progressive or fluctuating course.6 It is estimated that congenital CMV infection is responsible for 10%-25% of cases of sensorineural hearing loss diagnosed by 4 years of age.7, 8
Serologic screening for CMV infection is not part of routine prenatal or neonatal care in the United States. If performed, maternal primary infection can be established by conversion from IgG-negative to IgG-positive status, or positive IgM with low IgG. Fetal infection can be confirmed with positive viral culture or polymerase chain reaction (PCR) of amniotic fluid. In the newborn, confirmation of congenital CMV infection with blood, urine, or saliva viral culture or PCR must be performed within the first 3 weeks of life to exclude postnatal infection.2 It is possible to perform PCR testing on the dried blood spot of the newborn screening card later.9
Brain abnormalities seen on prenatal ultrasound (US) are often the first indication of congenital CMV infection. Ventriculomegaly is most commonly seen, with microcephaly and periventricular calcification also commonly noted.10 Other features that can be detected with targeted US include subependymal cysts, intraventricular synechiae, white matter hyperechogenicity, callosal hypoplasia, lenticulostriate vasculopathy, sulcation and gyral abnormalities, and cerebellar and cisterna magna anomalies.11 When 1 or more of these features is detected, magnetic resonance imaging (MRI) is often pursued for more detailed evaluation, as the addition of MRI increases the sensitivity and positive predictive value for the diagnosis of symptomatic congenital CMV infection.10, 12 New developments in prenatal and postnatal antiviral treatments add to the importance of accurate and timely diagnosis.
In this article, we review the prenatal brain MRI findings seen in congenital CMV infection and provide postnatal imaging correlation, highlighting the evolution of findings at different times in prenatal and postnatal development (Box 1).
Section snippets
Fetal Brain MRI Features of Congenital CMV
As for most fetal MRI examinations, multiplanar T2-weighted images (eg, single-shot fast spin echo or half-fourier acquisition single-shot turbo spin-echo [HASTE]) are the workhorse for structural evaluation of the brain. Steady-state free precession images (eg, fast imaging employing steady-state acquisition [FIESTA] or true fast imaging with steady-state precession [TruFISP]) can be a useful adjunct for structural evaluation. T1-weighted and gradient-recalled echo images aid in detection of
Clinical Perspective
MRI provides superior image quality of the fetal brain and allows for detailed evaluation of possible features of congenital CMV infection. In already suspected cases, MRI findings may build a case for prenatal or postnatal antiviral therapy or possibly termination of pregnancy in severely affected fetuses. Findings on fetal brain MRI may also be the first clue to making the diagnosis.
A study by Doneda et al12 correlated prenatal US and MRI findings with CMV infection-related neurologic
Conclusions
CMV is the most common prenatally acquired infection and can be seen in 0.6%-0.7% of all live births. Infection may be completely asymptomatic or cause severe lifelong neurologic impairment. Fetal brain MRI is a powerful tool in the diagnosis of symptomatic congenital CMV infection, with greater sensitivity compared with prenatal US. In any fetus evaluated for ventriculomegaly, microcephaly, or intrauterine growth restriction, a detailed search for specific features of congenital CMV infection
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Cited by (38)
Evolution of the intracranial features of congenital cytomegalovirus on MRI
2023, Clinical RadiologyNewer Updates in Pediatric Intracranial Infection
2023, Seminars in RoentgenologyCitation Excerpt :On a cellular level, CMV affects the germinal matrix, leading to neuronal cell loss and disruption of migration when the insult occurs before 18 weeks of gestation. Insults occurring between 18 and 24 weeks often cause polymicrogyria (particularly in the frontal and perisylvian regions) which is the most observed migrational abnormality; fetuses affected in the third trimester usually have a normal gyration pattern.10,12,14-16 Vascular injury is associated with fetal brain disruption sequence, such as schizencephaly and porencephaly.
Is it not time for international guidelines to combat congenital cytomegalovirus infection? A review of central nervous system manifestations
2020, Clinical RadiologyCitation Excerpt :Histologically, the white matter changes have been attributed to oedema and increased vascularity with an oedematous plump endothelium.28 Ventriculitis leading to the development of septa and cysts (Figs 3 and 4a,b, 5) may similarly develop as a result of second trimester infection; these are seen as thin bands crossing the ventricles and visualised best on MRI and ultrasound imaging.53,54 Cysts are particularly specific for cCMV when associated with white matter signal abnormalities.55
Fetal Neuroimaging Update
2020, Seminars in Pediatric NeurologyCitation Excerpt :US and MRI are complementary in the diagnosis.91 Classical fetal imaging findings in CMV include one or more of the following: caudothalamic groove germinolytic cysts, temporal polar white matter pathology (gliosis, necrosis, cysts, dysmorphic and/or abnormally developed temporal horns), malformations of cortical development, ventriculomegaly, and decreased brain volume (Fig. 18).92 ZIKA virus infection may also cause malformations of cortical development and ventriculomegaly, as well as associated severe frontal lobe hypoplasia,93-95 and/or posterior fossa destructive processes.93,94,96
Neonatal HCMV-related polymicrogyria in seroimmune women: What is the optimal pregnancy management?
2018, Journal of Clinical VirologyCitation Excerpt :However, the immune response in reinfected women is performed for diagnostic purposes in a research setting only, and limited so far to the detection of strain-specific IgG antibodies to gH and gB polymorphic sites [23,24]. When maternal infection is assessed, fetal cMRI is a powerful tool to diagnose symptomatic congenital HCMV infection, with greater sensitivity than prenatal cUS, and should be recommended to help reaching a highly realistic diagnosis [25,26]. A spectrum of cortical migration abnormalities can be seen in congenital infection.
Viral, Protozoan, and Related Intracranial Infections
2018, Volpe's Neurology of the Newborn