Apparent diffusion coefficient values of the white matter in magnetic resonance imaging of the neonatal brain may help predict outcome in congenital cytomegalovirus infection.

BACKGROUND: White matter change is a well-known abnormality in congenital cytomegalovirus (cCMV) infection, but grading remains challenging and clinical relevance unclear. OBJECTIVE: To investigate if quantitative measurement of white matter apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI) of the neonatal brain can predict outcome in cCMV. MATERIALS AND METHODS: A retrospective, single-center observational study, including patients with cCMV who had a neonatal brain MRI with diffusion-weighted imaging, was performed between 2007 and 2020. Regions of interest were systematically placed in the white matter on the ADC maps. Two pediatric radiologists independently scored additional brain abnormalities. Outcome measures were neonatal hearing and cognitive and motor development. Statistical analysis included simple and penalized elastic net regression. RESULTS: Neonatal brain MRI was evaluated in 255 patients (median age 21 days, 25-75 percentiles: 14-28 days, 121 male). Gyral abnormalities were noted in nine patients (3.5%), ventriculomegaly in 24 (9.4%), and subependymal cysts in 58 (22.7%). General white matter ADC was significantly higher in patients with neonatal hearing loss and cognitive and motor impairment (P< 0.05). For neonatal hearing loss, simple logistic regression using only general white matter was the best prediction model, with a receiver operating characteristic area under the curve (AUC)=0.76. For cognitive impairment, interacting elastic net regression, including other brain abnormalities and frontoparietal white matter ADC, performed best, with AUC=0.89. For motor impairment, interacting elastic net regression, including other brain abnormalities and deep anterior frontal white matter performed best, with AUC=0.73. CONCLUSION: Neonatal white matter ADC was significantly higher in patients with clinical impairments. Quantitative ADC measurement may be a useful tool for predicting clinical outcome in cCMV.

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

OBJECTIVE: To 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). METHODS: Multicentre 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. RESULTS: Neuroimaging 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. CONCLUSIONS: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.

Implications of isolated white matter abnormalities on neonatal MRI in congenital CMV infection: a prospective single-centre study.

OBJECTIVE: Investigating the clinical implications of isolated white matter abnormalities on neonatal brain MRI in congenital cytomegalovirus (CMV). DESIGN: Prospective, observational. PATIENTS/INTERVENTIONS: Two paediatric radiologists, blinded to clinical data, independently scored the white matter in 286 newborns with congenital CMV. After assessing interobserver variability, mean score was used to categorise white matter (normal, doubtful or abnormal). Patients with other brain abnormalities were excluded. MAIN OUTCOME MEASURES: Hearing and neuromotor evaluation. RESULTS: Cohen's weighted kappa was 0.79 (95% CI 0.73 to 0.84). White matter was normal in 121 patients, doubtful in 62, abnormal in 28. Median clinical follow-up was 12.0 months (IQR 12.0-27.7 months). Neonatal hearing loss occurred in 4/27 patients (14.8%) with abnormal, 1/118 patients (0.8%) with normal and 1/62 patients (1.6%) with doubtful white matter (p<0.01). Impaired cognitive development was seen in 3/27 patients (11.1%) with abnormal, 3/114 patients (2.6%) with normal and 1/59 patients (1.7%) with doubtful white matter (p=0.104). Alberta Infant Motor Scale (AIMS) was below P75 in 21/26 patients (80.8%) with abnormal, 73/114 patients (64.0%) with normal and 36/57 patients (63.2%) with doubtful white matter (p=0.231). In a subgroup of patients with minimal clinical follow-up of 18 months, AIMS score was below P75 in 10/13 patients (76.9%) with abnormal, 13/34 patients (38.2%) with normal and 7/20 patients (35.0%) with doubtful white matter (p<0.05). CONCLUSIONS: Abnormal white matter was associated with neonatal hearing loss and mild, lower motor scores. A tendency towards impaired cognitive development was seen. Patients with doubtful white matter did not show worse clinical outcome.

Enlarging 18 F-FDG-Avid Solitary Pulmonary Nodule: A Distinctly Unusual Presentation of Cytomegalovirus Infection in a Patient Receiving Chemotherapy.

ABSTRACT: Rapidly growing lung lesions, particularly in immunocompromised patients, invoke consideration of an infectious etiology. Aspergillomas, for example, can appear as round nodules with soft tissue attenuation, often associated with cavitation, and are variably 18 F-FDG avid. In contrast, cytomegalovirus, which may also evidence 18 F-FDG uptake, typically manifests as ground-glass opacities, symmetrically distributed small pulmonary nodules, or confluent consolidations, with lower lobe predilection. We describe a patient treated for lymphoma presenting with a solitary enlarging FDG-avid lung nodule, which was determined on resection to be focal cytomegalovirus infection, a distinctly uncommon presentation of this pathogen, more typical of fungal or mycobacterial disease.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age.

INTRODUCTION: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. METHODS: Infants <32 gestational weeks (02/2011-11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. RESULTS: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. CONCLUSION: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Myocardial Function in Fetuses with Congenital Cytomegalovirus Infection.

INTRODUCTION: The objective of this study was to investigate myocardial deformation of left (LV) and right ventricle (RV) using 2-dimensional speckle-tracking echocardiography (2D-STE) in fetuses with and without congenital cytomegalovirus (CMV) infection. METHODS: This was a prospective single-center study. Vertical transmission was defined by a positive CMV polymerase chain reaction (PCR) test on the amniotic fluid or on the neonate's urine. Fetuses were divided into group 1 and group 2 if CMV-PCR was positive or negative, respectively. LV and RV global longitudinal strain (GLS) values were obtained and adjusted for gestational age by calculating Z-scores. Univariate analysis was carried out to compare cardiac indices between group 1 and group 2. RESULTS: Fetuses from group 1 (n = 11) had a significantly lower LV myocardial shortening than those from group 2 (n = 32). GLS was -20.7 ± 5.2% and -26.3 ± 4.1%, respectively (p = 0.001). Similarly, GLS Z-score was lower (0.02 ± 0.72) in group 1 than in group 2 (-0.80 ± 0.59) (p = 0.001). Similarly, RV GLS Z-score was significantly impaired in group 1 compared to group 2 (-0.44 ± 1.03 vs. -1.04 ± 0.71, p = 0.041). CONCLUSION: Fetuses with congenital CMV showed subclinical biventricular myocardial dysfunction. Further studies are needed to confirm the potential role of 2D-STE in identifying fetuses with congenital CMV at risk of postnatal cardiovascular morbidities.

Fetal brain imaging provides valuable information in cCMV infected infants.

BACKGROUND: Congenital CMV infection (cCMV) is the most common congenital infection with 10-15% of cases developing symptomatic disease. Early antiviral treatment is of essence when symptomatic disease is suspected. Recently, the use of neonatal imaging has been implicated as a prognostic tool for long term sequalae among asymptomatic newborns at high risk. Even though neonatal MRI is commonly used in neonatal symptomatic cCMV disease, it is less often used in asymptomatic newborns, mainly due to cost, access and difficulty to perform. We have therefore developed an interest in assessing the use of fetal imaging as an alternative. Our primary aim was to compare the fetal and neonatal MRIs in a small cohort 10 asymptomatic neonates with congenital CMV infection. METHODS: We performed a single-center retrospective cohort study (case-series) on a convenience sample of children born from January 2014 to March 2021 with confirmed congenital CMV infection who had undergone both fetal and neonatal MRIs. We created a checklist of relevant cerebral abnormalities and asked 4 blinded radiologists to assess the MRIs (2 for each, namely fetal and neonatal) and then compared the findings between the fetal and neonatal imaging as well as the concordance in reporting of abnormalities within each category. FINDINGS: Overall concordance between prenatal and postnatal scans was high (70%). When comparing the two blinded reports for each MRI, we found high levels of concordance: 90% concordance for fetal MRIs and 100% for neonatal MRIs. The most common abnormalities identified in both fetal and neonatal scans were "abnormal white matter hyperintensity" and "subependymal cysts." INTERPRETATION: Even though this is a small descriptive study, it indicates that fetal MRI could potentially provide us with similar information as neonatal imaging. This study could form the basis for subsequent larger future studies.

Halo sign in fetal cytomegalovirus infection: cerebral imaging abnormalities and postmortem histopathology in 35 infected fetuses.

OBJECTIVE: To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection. METHODS: This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal-fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non-isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin-eosin-stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0-3) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions. RESULTS: Thirty-five CMV-infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non-isolated CNS finding (22.6 vs 24.4 weeks; P = 0.10). In fetuses with a non-isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10/18 (56%) vs 1/8 (13%); P = 0.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non-isolated halo sign (21/26 (81%)) and those without a periventricular echogenic halo (2/3 (67%); P = 0.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white-matter necrosis or cortical injury. On the other hand, 25/26 fetuses with a non-isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non-isolated halo, histological brain lesions did not progress with gestational age, although white-matter necrosis was more frequent, albeit non-significantly, in fetuses diagnosed in the second vs the third trimester (10/15 (67%) vs 3/11 (27%); P = 0.06). CONCLUSIONS: In CMV-infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white-matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow-up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Prognostic Value of Amniotic Fluid Viral Load to Predict Adverse Outcome in Pregnancies Complicated by Congenital Cytomegalovirus Infection: A Multicenter Study.

INTRODUCTION: The aim of the study was to report the prognostic value of cytomegalovirus (CMV) viral load in the amniotic fluid (AF) in predicting the outcome of infected pregnancies. METHODS: Multicenter retrospective study involving 11 Italian referral centers from 2012 to 2021 was conducted. Inclusion criteria were fetuses with confirmed congenital CMV infection. The primary outcome was the prognostic value accuracy of CMV quantitative polymerase chain reaction (qPCR) in AF in predicting the risk of additional anomalies detected either at follow-up ultrasound or fetal magnetic resonance imaging (MRI). The secondary outcome was prediction of postnatal clinical symptoms related to CMV infection. Multivariate logistic regression and area under the curve (AUC) analyses were used to analyze the data. RESULTS: 104 fetuses were included. Associated anomalies detected at follow-up ultrasound or fetal MRI were detected in 14.4% of cases (15/104). Mean AF CMV viral load was significantly higher in fetuses with additional anomalies compared to those without additional anomalies at follow-up ultrasound or fetal MRI (3,346,634.27 ± 402,582.95 vs. 761,934 ± 222513,2 p < 0.001). At multivariate logistic regression analysis, CMV AF viral load was independently associated with the presence of additional anomalies at follow-up ultrasound or MRI, with an OR of 1.07 (p = 0.010), while maternal age (p = 0.24), trimester at maternal infection (p = 0.97), and type of infection (primary vs. non-primary) (p = 0.12) were not. CMV AF viral load had AUC of 0.755 for the occurrence of anomalies due to CMV infection, with an optimal cut-off point of >1,310,520 copies/mL, a sensitivity of 66.7%, a specificity of 84.3%, and a positive likelihood ratio of 4.24. Once excluding fetuses with anomalies at ultrasound or MRI, the diagnostic performance of qPCR in identifying fetuses with symptomatic infection after birth was low, with an AUC of 0.586. CONCLUSION: CMV viral load at second trimester amniocentesis has a moderate accuracy for the occurrence of CMV-related anomalies in fetuses with congenital infection and normal ultrasound at the initial diagnosis. Conversely, prediction of symptomatic infection is low.

Predicting Outcome of Congenital Cytomegalovirus Infection by Differentiating and Revisiting Severe versus Mild Prenatal Imaging Features.

INTRODUCTION: Our objective was to evaluate the outcome of fetuses with first- and second-trimester fetal cytomegalovirus infection (CMVi) according to prenatal imaging patterns, especially fetuses presenting with mild imaging features (MF), being currently of uncertain prognosis. MATERIAL AND METHODS: In a retrospective study of 415 suspected CMVi cases, 59 cases were confirmed. Among prenatal imaging features, microcephaly, cortical disorder, and cerebellar hypoplasia as well as severe IUGR and fetal hydrops were considered as severe imaging features (SF). Other imaging features were considered as MF. Postnatal outcome was classified as "normal outcome," "mild sequelae" characterized mainly by sensorineural disorder (SND) and "severe sequelae" characterized by cognitive impairment. RESULTS: Only first-trimester (T1) and second-trimester (T2) CMVi cases were included in our study (n = 49) since all third-trimester cases (n = 10) had normal imaging and outcome. Sixteen fetuses had normal prenatal imaging and normal outcome, except one showing SND. Abnormal ultrasound findings were present in 33 fetuses, including SF noted in 16 fetuses, related exclusively to first-trimester CMVi. Termination of pregnancy was performed in 18 cases. Twelve first-trimester infected fetuses presented SF, whereas 6 fetuses (T1: n = 5, T2: n = 1) presented isolated MF. Four fetal deaths were encountered. Live-born babies with abnormal imaging included 10 fetuses with MF and one with SF. Among the 10 live babies with isolated MF, SND was encountered in 5 cases, whereas 5 children demonstrated normal outcome. Overall, 50% of our babies showing MF suffered from SND. No case of cognitive disorders was reported in babies showing only MF. CONCLUSION: SF were encountered only in first-trimester CMVi and should be distinguished from MF. Among our 10 live babies with prenatal MF following first- or second-trimester infection, 50% showed SND, whereas none presented severe sequelae. In 16 fetuses displaying normal fetal imaging, SND was encountered in one first-trimester case (6%).

Evolution of the intracranial features of congenital cytomegalovirus on MRI.

AIM: To describe the evolution of the intracranial features of congenital cytomegalovirus (cCMV) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixteen infants with polymerase chain reaction (PCR)-confirmed cCMV who had undergone at least two MRI examinations of the brain were identified. Two paediatric neuroradiologists reviewed the baseline studies retrospectively for intracranial features of cCMV, including white matter signal abnormalities, subependymal cysts, malformations of cortical development, and intracranial calcification. The subsequent MRI studies were then reviewed and directly compared to the baseline examinations. RESULTS: White matter signal abnormalities were seen on all 16 baseline studies (100%); these persisted on all subsequent examinations but were patchier, more focal, and associated with an interval reduction in white matter volume. Subependymal cysts were present on 11 (69%) of the baseline scans; these almost universally regressed (in 10 of the 11 cases [91%]), with no new cysts appreciable on subsequent imaging. Malformations of cortical development, exclusively in the form of polymicrogyria, were seen in six (38%) patients and persisted, unchanged, on subsequent imaging. Intracranial calcification was seen in a minority of baseline studies (4 [25%]) and remained stable on subsequent scans. CONCLUSION: Children with cCMV who present later in life without an established or suspected underlying pathology can pose a challenge to the assessing radiologist. The radiological sequelae of cCMV can be non-specific; in some cases, white matter signal abnormalities and focal loss of white matter volume may be the only intracranial features. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.

Do Filling Defects of the Vestibule Represent a Neuroradiological Marker for Congenital Cytomegalovirus? A Retrospective Case Series.

INTRODUCTION: The aim of this study was to investigate whether radiological marker(s) of the inner ear can be detected in congenital cytomegalovirus (cCMV) patients with severe-profound sensorineural hearing loss. METHODS: A retrospective imaging review of confirmed cCMV paediatric patients that had undergone consecutive cochlear implantation was performed at a tertiary hospital. Available pre- and postoperative imaging was examined, and abnormalities of the labyrinth were catalogued by a consultant neuroradiologist in the study group and control group. RESULTS: Twenty-eight paediatric patients with cCMV having undergone cochlear implantation were identified between the ages of 1-15 years (mean 4.7 years) at the time of implantation. Increased density of the vestibule on computed tomography (CT) or filling defects of the vestibule on magnetic resonance imaging (MRI) were identified in 11 and 4 patients, respectively, of the 24 in the case series. No filling defects were identified in any of the 48 CT and MRI control group. CONCLUSION: This study demonstrates a potential novel radiological finding of the inner ear of patients with cCMV. With more research, greater onus placed on MRI and CT for inner ear assessment may facilitate early detection and treatment for patients at risk of significant hearing loss. Further prospective studies in this area will help to validate radiological markers in order to establish a comprehensive inner ear classification system for neuroradiological features in cCMV.

Brain cortical maturation assessed by magnetic resonance imaging in unaffected or mildly affected fetuses with cytomegalovirus infection.

OBJECTIVES: To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. METHODS: This was a retrospective case-control study of consecutive pregnancies with a CMV-infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low-risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV-DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto-occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non-parametric trend analysis. RESULTS: Twenty-four CMV-infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV-infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9-9.9) mm vs 3.9 (IQR, 2.6-5.3) mm; left side, 7.5 (IQR, 6.0-10.9) mm vs 4.2 (IQR, 3.2-5.3) mm), significantly decreased parieto-occipital sulcus depth (right side, 12.6 (IQR, 11.3-13.5) mm vs 15.9 (IQR, 13.5-17.3) mm; left side, 12.3 (IQR, 10.6-13.5) mm vs 16.0 (IQR, 13.3-17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4-16.3) mm vs 17.5 (IQR, 16.1-18.7) mm; left side, 14.6 (IQR, 14.1-15.6) mm vs 16.7 (IQR, 15.6-18.9) mm) (P < 0.001 for all). Compared with controls, CMV-infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8-45.8°) vs 48.9° (IQR, 38.4-64.7°); left side, 40.9° (IQR, 34.2-45.8°) vs 48.2° (IQR, 41.9-60.7°)) and lower (right side, 41.6° (IQR, 34.4-49.2°) vs 48.9° (IQR, 40.6-60.9°); left side, 42.2° (IQR, 38.8-46.9°) vs 48.9° (IQR, 39.5-57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV-infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto-occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small-for-gestational age as a confounding factor. CONCLUSIONS: Unaffected and mildly affected CMV-infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non-severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal predictors of adverse perinatal outcome in congenital cytomegalovirus infection: a retrospective multicenter study.

OBJECTIVES: To identify predictors of adverse perinatal outcome in congenital cytomegalovirus (CMV) infection. METHODS: In a multicenter study fetuses with congenital CMV infection diagnosed by PCR on amniotic fluid and normal prenatal imaging at the time of diagnosis were included. Primary outcome was the occurrence of structural anomalies at follow-up ultrasound or prenatal magnetic resonance imaging (MRI). Secondary outcomes were the occurrence of anomalies detected exclusively postnatally and the rate of symptomatic infection. RESULTS: One hundred and four fetuses with congenital CMV were included in the study. Anomalies were detected at follow-up ultrasound or MRI in 18.3% (19/104) cases. Additional anomalies were found after birth in 11.9% (10/84) of cases and 15.5% (13/85) of newborns showed clinical symptoms related to CMV infection. There was no difference in either maternal age (p=0.3), trimester (p=0.4) of infection and prenatal therapy (p=0.4) between fetuses with or whiteout anomalies at follow-up. Conversely, median viral load in the amniotic fluid was higher in fetuses with additional anomalies at follow-up (p=0.02) compared to those without. At multivariate logistic regression analysis, high viral load in the amniotic fluid, defined as ≥100,000 copies/mL was the only independent predictor for the occurrence of anomalies detected exclusively at follow-up ultrasound assessment or MRI, with an OR of 3.12. CONCLUSIONS: Viral load in the amniotic fluid is a strong predictor of adverse perinatal outcome in congenital CMV infection. The results of this study emphasize the importance of adequate follow up even in case of negative neurosonography to better predict postnatal adverse outcomes of infected newborns, especially in amniotic fluid high viral load.

Role of fetal magnetic resonance imaging in fetuses with congenital cytomegalovirus infection: multicenter study.

OBJECTIVE: To investigate the role of fetal brain magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses with congenital cytomegalovirus (CMV) infection and normal neurosonography. METHODS: This was a multicenter, retrospective cohort study of patients examined between 2012 and 2021 in 11 referral fetal medicine centers in Italy. Inclusion criteria were fetuses with congenital CMV infection diagnosed by polymerase chain reaction analysis of amniotic fluid, pregnancies that underwent detailed multiplanar ultrasound assessment of the fetal brain as recommended by the International Society of Ultrasound in Obstetrics and Gynecology, maternal age ≥ 18 years, normal fetal karyotype and MRI performed within 3 weeks after the last ultrasound examination. The primary outcome was the rate of central nervous system (CNS) anomalies detected exclusively on MRI and confirmed after birth or autopsy in fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography at diagnosis. Additional CNS anomalies were classified into anomalies of the ventricular and the periventricular zone, intracranial calcifications in the basal ganglia or germinal matrix, destructive encephalopathy in the white matter, malformations of cortical development, midline anomalies, posterior fossa anomalies and complex brain anomalies. We evaluated the relationship between the incidence of structural CNS malformations diagnosed exclusively on fetal MRI and a number of maternal and gestational characteristics. Univariate and multivariate logistic regression analyses were used to identify and adjust for potential independent predictors of the MRI diagnosis of fetal anomalies. RESULTS: The analysis included 95 fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography referred for prenatal MRI. The rate of structural anomalies detected exclusively at fetal MRI was 10.5% (10/95). When considering the type of anomaly, malformations of cortical development were detected on MRI in 40.0% (4/10) of fetuses, destructive encephalopathy in 20.0% (2/10), intracranial calcifications in the germinal matrix in 10.0% (1/10) and complex CNS anomalies in 30.0% (3/10). On multivariate logistic regression analysis, only CMV viral load in the amniotic fluid, expressed as a continuous variable (odds ratio (OR), 1.16 (95% CI, 1.02-1.21); P = 0.02) or categorical variable (> 100 000 copies/mL) (OR, 12.0 (95% CI, 1.2-124.7); P = 0.04), was independently associated with the likelihood of detecting fetal anomalies on MRI. Associated anomalies were detected exclusively at birth and missed by both prenatal neurosonography and fetal MRI in 3.8% (3/80) of fetuses with congenital CMV infection. CONCLUSIONS: Fetal brain MRI can detect additional anomalies in a significant proportion of fetuses with congenital CMV infection and negative neurosonography. Viral load in the amniotic fluid was an independent predictor of the risk of associated anomalies in these fetuses. The findings of this study support a longitudinal evaluation using fetal MRI in congenital CMV infection, even in cases with negative neurosonography at diagnosis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Pre- and postnatal brain magnetic resonance imaging in congenital cytomegalovirus infection: a case report and a review of the literature.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is the most common known viral cause of neurodevelopmental delay in children. The risk of severe cerebral abnormalities and neurological sequelae is greatest when the infection occurs during the first trimester of pregnancy. Pre- and postnatal imaging can provide additional information and may help in the prediction of early neurological outcome. CASE PRESENTATION: This report presents the case of a newborn with cCMV infection with diffuse parenchymal calcifications, white matter (WM) abnormalities and cerebellar hypoplasia on postnatal brain imaging after magnetic resonance imaging (MRI) and neurosonogram (NSG) at 30 weeks showing lenticulostriate vasculopathy, bilateral temporal cysts and normal gyration pattern according to the gestational age (GA). No calcifications were seen on prenatal imaging. CONCLUSION: cCMV infection can still evolve into severe brain damage after 30 weeks of GA. For this reason, a two-weekly follow-up by fetal NSG with a repeat in utero MRI (iuMRI) in the late third trimester is recommended in cases with signs of active infection.

Cytomegalovirus Infection Associated with Smaller Total Cortical Surface Area in Schizophrenia Spectrum Disorders.

OBJECTIVES: Cytomegalovirus (CMV) congenital infection and in immunodeficiency can have deleterious effects on human cortex. In immunocompetent adults, the putative association between CMV infection and cortical measures has not been explored. We hypothesized that CMV exposure is associated with smaller cortical surface area or cortical thinning mainly in patients with schizophrenia spectrum disorders. STUDY DESIGN: We included 67 adult patients with schizophrenia spectrum disorders and 262 adult healthy controls. We measured circulating CMV IgG antibody concentrations with solid-phase immunoassay techniques. We measured the total cortical surface area, regional cortical surface areas and the overall mean cortical thickness based on T1-weighted MRI scans processed in FreeSurfer v6.0. STUDY RESULTS: In the whole sample analysis, we found a significant diagnostic group-by-CMV status interaction on the total surface area (P = .020). Among patients, CMV antibody positivity was significantly associated with smaller total surface area (P = .002, partial eta2 = 0.138) whereas no such association was found in healthy controls (P = .059). Post hoc analysis among patients showed that higher CMV antibody concentrations were also significantly associated with smaller total surface area (P = .038), and that CMV antibody positivity was significantly inversely associated with 14 left and 16 right regional surface areas mainly in the frontal and temporal lobes. CMV infection was not associated with the overall mean cortical thickness. CONCLUSIONS: The results are indicative of a cortical surface area vulnerability to CMV infection in patients with schizophrenia spectrum disorders but not in healthy controls. CMV infection may contribute to the established cortical surface area aberrations in schizophrenia.

18F-FDG PET/CT Findings in HIV-Positive Patient With Primary Pancreas Lymphoma and CMV Pancreatitis.

ABSTRACT: A 35-year-old HIV-positive man with abdominal pain was referred to 18F-FDG PET/CT for metabolic characterization of mass in pancreas. PET/CT images showed intense FDG uptake in head of the pancreas, as well as diffuse moderate uptake throughout body and tail of the pancreas. Histopathological results revealed Epstein-Barr virus (EBV) associated large B-cell lymphoma and pancreatitis caused by cytomegalovirus.