Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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October 28, 2021
Congenital Cytomegalovirus Infection
- Background:
- Cytomegalovirus (CMV) is a DNA virus belonging to the Herpesviridae family. It is a part of TORCH infections (toxoplasmosis, others, rubella, CMV, and herpes simplex virus) associated with a propensity to cause intrauterine infections.
- Congenital CMV is the most common cause of nongenetic congenital hearing loss and neurodevelopmental delay.
- The mode of infection in infants may be primary, where the mother seroconverts during pregnancy (rate of transmission: 30%), or secondary, where the mother has a recurrence of an existing infection or reinfection during pregnancy (rate of transmission: 1.5%).
- The fetal injury in the setting of congenital CMV is because of gene products that modify the cell cycle interface with apoptosis and induce an inflammatory response.
- Clinical Presentation:
- About 10–15% of the babies with congenital CMV infection are symptomatic at birth. Around 10–15% of asymptomatic neonates at birth may develop sensorineural hearing loss in later life.
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The key presentation of a symptomatic infant is microcephaly, developmental delay, hepatosplenomegaly, thrombocytopenic purpura, sensorineural hearing loss, abnormal dentition, and ocular manifestations such as chorioretinitis.
- Key Diagnostic Features:
- The timing of gestational infection determines the degree of brain insult. Early gestational infection is typically more severe, with malformation of cortical development. Germinal zone necrosis with subependymal cysts and dystrophic calcifications are also features of early infection.
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CMV presents with a wide spectrum of imaging findings:
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Intracranial calcifications: These patients have periventricular calcifications with a predilection for the germinal matrix, particularly the caudostriatal region. However, the absence of calcifications does not exclude CMV. CT has the best sensitivity to detect these areas of calcification but requires exposure to ionizing radiation. Ultrasonography (USG) can be instrumental in detecting intracranial calcification in patients with CMV infection. USG has better sensitivity than MRI for detection of calcification. Calcification on MRI appears as T2-hypointense foci with blooming on SWI.
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Migration abnormalities: Lissencephaly, pachygyria, and diffuse or focal polymicrogyria are the most common migrational abnormalities. These abnormalities are best depicted on high-resolution volume-gradient T1-weighted MR images, and they may be focal or diffuse.
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White matter abnormalities: T2 and FLAIR images show focal patchy or confluent white matter involvement. There is predominant parietal or posterior white matter involvement with a rim of spared periventricular and subcortical white matter. Delay in myelination is also a feature, though not specific.
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Periventricular and pretemporal cysts: Cystic areas with T1 and T2 prolongation adjacent to the ventricles are seen. Intraparenchymal cysts are seen, the characteristic location being the anterior temporal region. Vacuolization of the anterior temporal lobes precedes frank cyst formation. White matter changes with anterior temporal cysts can suggest CMV infection in an appropriate clinical setting.
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Cerebral atrophy: This is seen in the form of microcephaly, ventriculomegaly, or generalized loss of volume in the cerebrum or cerebellum. Early infection leads to neuronal volume loss and substantial brain atrophy. Cerebellar dysplasia can occur in about 67% of patients with CMV infection.
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Others: Lenticulostriate vasculopathy and ventricular adhesions are other imaging findings seen.
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- Diagnosis is established by polymerase chain reaction (PCR) analysis of urine, saliva, or blood to determine if CMV DNA is present within 3 weeks of birth. In this infant, the diagnosis was established by PCR.
- Differential Diagnoses:
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The differential diagnoses depend on the imaging features.
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Intracranial calcification can be seen in:
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Toxoplasmosis: Shows scattered parenchymal calcifications; they have a greater chance of hydrocephalus than CMV.
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Zika virus infection: Endemic infection/history of travel; calcification is usually seen at the gray-white matter junction with severe microcephaly, migration anomaly.
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Pseudo-TORCH syndromes may also mimic congenital CMV, including Aicardi-Goutieres syndrome (microcephaly with basal ganglia calcification).
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Other conditions causing bilateral temporal white matter cysts such as:
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Megalencephalic or nonmegalencephalic leukoencephalopathy with subcortical cysts: These patients have more extensive white matter changes than CMV infection. Microcephaly present in congenital CMV infection is the chief differentiating feature.
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Migration anomalies: Can be seen in isolation with numerous genetic mutations (LIS1/DCX) or as a part of syndromes (such as Zellweger). Lissencephaly generally is associated with a thickened cortical mantle; however, in patients with congenital CMV infection, the cortex may be thin if associated neuronal loss is present.
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Treatment:
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Currently, no FDA-approved vaccine is available to prevent the spread.
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Symptomatic infants are treated with oral valganciclovir or intravenous ganciclovir for 6 months.
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Early maternal hyperimmunoglobulin therapy improves the outcome of fetuses from women with primary CMV infections.
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