Answer for BIR CoW 02 March 2025
Congenital Cytomegalovirus infection sequelae
Findings
T2 hyperintense areas noted in white matter of bilateral anterior temporal lobe . Multiple well defined T2 hyperintense cystic areas noted in bilateral anterior temporal lobe . Bilateral temporal horns appear prominent. T2 FLAIR periventricular hyperintensities noted bilaterally.
Discussion
Congenital cytomegalovirus infection is a serious public health concern. It is the most commonly acquired congenital viral infection, a major cause of neurological disability in children, and the leading cause of non-genetic SNHL in infants. Clinically, majority of the infants are asymptomatic at birth ,symptomatic infants are often premature and have hepatosplenomegaly, jaundice, thrombocytopenia, chorioretinitis and progressive sensorineural hearing loss. Long‐term sequelae are expected in 40%‐60% of symptomatic survivors, and 10%‐20% of asymptomatic children. CMV is part of the Herpesviridae family. It is transmitted via smear infection, through direct contact of mucous surfaces with infectious body fluids,establishing a lifelong latent infection in the host, with periodic reactivations which can be a source of disease. Pathophysiology and clinical features CMV is a neurotropic virus and predominantly affects and replicates in ependymal cells and the germinal matrix of the developing brain resulting in varying degrees of neurological abnormalities. The severity of the disease depends on the gestational age of affection. Infants affected early in mid 2nd trimester (<18 weeks) suffer from cerebral atrophy, microcephaly, cerebellar hypoplasia and pachygyria-lissencephaly. Infants affected in the late 2nd trimester predominantly have migrational abnormalities such as polymicrogyria, cerebellar hypoplasia and schizencephaly. Infants affected in the 3rd trimester (after 26 Weeks) show delayed myelination, dysmyelination and white matter abnormalities since neuronal migration and organization are usually complete by this time. Role of imaging Imaging in cCMV has two main objectives: detection of structural anomalies for correct diagnosis and provision of prognostic information. While US is the method of choice for fetal imaging, MRI has an established added value in the detection of fetal brain anomalies with a high negative predictive value (96.8%‐99%) for neurological impairment and SNHL. Imaging Features MRI findings in cCMV are often unspecific, with ventriculomegaly and white matter (WM) signal abnormalities being the most commonly described CNS anomalies. More characteristic (but less frequently observed) features include temporal lobe lesions (abnormal WM, cysts, and enlargement of the temporal horns), ventriculitis and intracranial calcification. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to USG in their detection .Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. White matter lesions may appear as multifocal patchy or confluent parietal and occipital white matter hyperintensities, periventricular subependymal cysts, temporal pole cysts and delayed myelination. Migrational abnormalities include Lissencephaly, pachygyria, cortical dysplasia, polymicrogyria and schizencephaly. Calcifications are usually thick and chunky when in periventricular locations and appear faint and punctate in basal ganglia. This common imaging finding can be seen in any trimester infection.However, the absence of calcifications does not exclude a diagnosis of congenital CMV infection List of possible magnetic resonance imaging (MRI) findings in fetuses with congenital cytomegalovirus (cCMV) include: • WM hyperintensities • Ventriculomegaly • Cysts/pseudocysts(Most often periventricular-temporal pole cyst-characteristic ) • Ventriculitis • Intraventricular septations/adhesions • Cortical malformations/polymicrogyria • Clefts (schizencephaly/porencephaly) • Calcifications(Periventricular > deep gray nuclei > white matter) • Cerebellar hypoplasia/dysplasia(Small vermis and/or hemispheres • Increased infra/retrocerebellar space (megacisterna magna >8 mm-Rare in fetal MRI ,Common in postnatal imaging) • Hippocampal dysplasia(dilated temporal horns,v erticalization of the hippocampal with or without internal temporal lobe atrophy which are often not described in fetal MRI but common in postnatal imaging.) • Lenticullostriate vasculopathy(Calcification of basal ganglia -Late finding on MRI) The differential for white matter signal change in neonates and infants is broad and in isolation includes ischaemia, metabolic disorders, leukoencephalopathies, other TORCH (T, toxoplasmosis from Toxoplasma gondii; O, other infections; R, rubella; C, CMV; H, herpes simplex virus-2 or neonatal herpes simplex infections) and pseudo-TORCH syndromes (the clinical picture and presence of additional radiological findings will narrow the differential). Subependymal cysts (also referred to as periventricular cysts, germinolytic cysts, and pseudocysts) are likely to progressively involute over time. Cysts can also be seen in pseudo-TORCH syndromes, mitochondrial disorders (e.g., PNPT1 and RMND1 related leukoencephalopathies), RNASET-2 deficient leukoencephalopathy, megalencephalic leukoencephalopathy with subcortical cysts, and certain dystroglycanopathies. The differential diagnosis of leukoencephalopathy with anterior temporal cysts is limited and includes congenital CMV infection, megalencephalic leukoencephalopathy (Van der Knaap Disease), and vanishing white matter disease However ,Macrocephaly is present at birth or develops within the first year of life in megalencephalic leukoencephalopathy. Cerebellar ataxia and normal or near normal psychomotor development is usually present in vanishing white matter disease with severe to mild cerebellar atrophy, typically involving the vermis is seen along with white matter abnormalities. Outcome Neurodevelopmental outcome is generally poor leading to severe psychomotor retardation, cerebral palsy, sensorineural hearing loss and chorioretinitis. The mainstay of management is early detection by serial antenatal USG and foetal MRI at 28-32 weeks. Early institution of antiviral therapy in symptomatic neonates also improves neurological outcomes In conclusion, imaging has an important role to play in the diagnosis of cCMV, which may first be suggested by radiologists assessing the intracranial imaging of children referred for neurocognitive abnormalities or hearing loss. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.
References:
Evolution of the intracranial features of congenital cytomegalovirus on MRI.Garnham, J. et al.-Clinical Radiology, Volume 78, Issue 5, e451 - e457 Vanbuggenhout, L., Aertsen, M., De Catte, L. et al. Pre- and postnatal brain magnetic resonance imaging in congenital cytomegalovirus infection: a case report and a review of the literature. BMC Pediatr 22, 293 (2022). https://doi.org/10.1186/s12887-022-03334-x https://www.eurorad.org/case/17232 10.35100/eurorad/case.17232 Rangankar V, Dongre A, Hadgaonkar M, Singh H. Subcortical cysts in anterior temporal regions: Unusual imaging finding in congenital cytomegalovirus infection. Med J Armed Forces India. 2015 Jul;71(Suppl 1):S230-3. doi: 10.1016/j.mjafi.2014.04.014. Epub 2014 Aug 4. PMID: 26265842; PMCID: PMC4529571.
Findings
T2 hyperintense areas noted in white matter of bilateral anterior temporal lobe . Multiple well defined T2 hyperintense cystic areas noted in bilateral anterior temporal lobe . Bilateral temporal horns appear prominent. T2 FLAIR periventricular hyperintensities noted bilaterally.
Discussion
Congenital cytomegalovirus infection is a serious public health concern. It is the most commonly acquired congenital viral infection, a major cause of neurological disability in children, and the leading cause of non-genetic SNHL in infants. Clinically, majority of the infants are asymptomatic at birth ,symptomatic infants are often premature and have hepatosplenomegaly, jaundice, thrombocytopenia, chorioretinitis and progressive sensorineural hearing loss. Long‐term sequelae are expected in 40%‐60% of symptomatic survivors, and 10%‐20% of asymptomatic children. CMV is part of the Herpesviridae family. It is transmitted via smear infection, through direct contact of mucous surfaces with infectious body fluids,establishing a lifelong latent infection in the host, with periodic reactivations which can be a source of disease. Pathophysiology and clinical features CMV is a neurotropic virus and predominantly affects and replicates in ependymal cells and the germinal matrix of the developing brain resulting in varying degrees of neurological abnormalities. The severity of the disease depends on the gestational age of affection. Infants affected early in mid 2nd trimester (<18 weeks) suffer from cerebral atrophy, microcephaly, cerebellar hypoplasia and pachygyria-lissencephaly. Infants affected in the late 2nd trimester predominantly have migrational abnormalities such as polymicrogyria, cerebellar hypoplasia and schizencephaly. Infants affected in the 3rd trimester (after 26 Weeks) show delayed myelination, dysmyelination and white matter abnormalities since neuronal migration and organization are usually complete by this time. Role of imaging Imaging in cCMV has two main objectives: detection of structural anomalies for correct diagnosis and provision of prognostic information. While US is the method of choice for fetal imaging, MRI has an established added value in the detection of fetal brain anomalies with a high negative predictive value (96.8%‐99%) for neurological impairment and SNHL. Imaging Features MRI findings in cCMV are often unspecific, with ventriculomegaly and white matter (WM) signal abnormalities being the most commonly described CNS anomalies. More characteristic (but less frequently observed) features include temporal lobe lesions (abnormal WM, cysts, and enlargement of the temporal horns), ventriculitis and intracranial calcification. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to USG in their detection .Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. White matter lesions may appear as multifocal patchy or confluent parietal and occipital white matter hyperintensities, periventricular subependymal cysts, temporal pole cysts and delayed myelination. Migrational abnormalities include Lissencephaly, pachygyria, cortical dysplasia, polymicrogyria and schizencephaly. Calcifications are usually thick and chunky when in periventricular locations and appear faint and punctate in basal ganglia. This common imaging finding can be seen in any trimester infection.However, the absence of calcifications does not exclude a diagnosis of congenital CMV infection List of possible magnetic resonance imaging (MRI) findings in fetuses with congenital cytomegalovirus (cCMV) include: • WM hyperintensities • Ventriculomegaly • Cysts/pseudocysts(Most often periventricular-temporal pole cyst-characteristic ) • Ventriculitis • Intraventricular septations/adhesions • Cortical malformations/polymicrogyria • Clefts (schizencephaly/porencephaly) • Calcifications(Periventricular > deep gray nuclei > white matter) • Cerebellar hypoplasia/dysplasia(Small vermis and/or hemispheres • Increased infra/retrocerebellar space (megacisterna magna >8 mm-Rare in fetal MRI ,Common in postnatal imaging) • Hippocampal dysplasia(dilated temporal horns,v erticalization of the hippocampal with or without internal temporal lobe atrophy which are often not described in fetal MRI but common in postnatal imaging.) • Lenticullostriate vasculopathy(Calcification of basal ganglia -Late finding on MRI) The differential for white matter signal change in neonates and infants is broad and in isolation includes ischaemia, metabolic disorders, leukoencephalopathies, other TORCH (T, toxoplasmosis from Toxoplasma gondii; O, other infections; R, rubella; C, CMV; H, herpes simplex virus-2 or neonatal herpes simplex infections) and pseudo-TORCH syndromes (the clinical picture and presence of additional radiological findings will narrow the differential). Subependymal cysts (also referred to as periventricular cysts, germinolytic cysts, and pseudocysts) are likely to progressively involute over time. Cysts can also be seen in pseudo-TORCH syndromes, mitochondrial disorders (e.g., PNPT1 and RMND1 related leukoencephalopathies), RNASET-2 deficient leukoencephalopathy, megalencephalic leukoencephalopathy with subcortical cysts, and certain dystroglycanopathies. The differential diagnosis of leukoencephalopathy with anterior temporal cysts is limited and includes congenital CMV infection, megalencephalic leukoencephalopathy (Van der Knaap Disease), and vanishing white matter disease However ,Macrocephaly is present at birth or develops within the first year of life in megalencephalic leukoencephalopathy. Cerebellar ataxia and normal or near normal psychomotor development is usually present in vanishing white matter disease with severe to mild cerebellar atrophy, typically involving the vermis is seen along with white matter abnormalities. Outcome Neurodevelopmental outcome is generally poor leading to severe psychomotor retardation, cerebral palsy, sensorineural hearing loss and chorioretinitis. The mainstay of management is early detection by serial antenatal USG and foetal MRI at 28-32 weeks. Early institution of antiviral therapy in symptomatic neonates also improves neurological outcomes In conclusion, imaging has an important role to play in the diagnosis of cCMV, which may first be suggested by radiologists assessing the intracranial imaging of children referred for neurocognitive abnormalities or hearing loss. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.
References:
Evolution of the intracranial features of congenital cytomegalovirus on MRI.Garnham, J. et al.-Clinical Radiology, Volume 78, Issue 5, e451 - e457 Vanbuggenhout, L., Aertsen, M., De Catte, L. et al. Pre- and postnatal brain magnetic resonance imaging in congenital cytomegalovirus infection: a case report and a review of the literature. BMC Pediatr 22, 293 (2022). https://doi.org/10.1186/s12887-022-03334-x https://www.eurorad.org/case/17232 10.35100/eurorad/case.17232 Rangankar V, Dongre A, Hadgaonkar M, Singh H. Subcortical cysts in anterior temporal regions: Unusual imaging finding in congenital cytomegalovirus infection. Med J Armed Forces India. 2015 Jul;71(Suppl 1):S230-3. doi: 10.1016/j.mjafi.2014.04.014. Epub 2014 Aug 4. PMID: 26265842; PMCID: PMC4529571.
Note:
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!