In the intricate landscape of pediatric neurology, congenital cytomegalovirus (cCMV) infection remains a particularly challenging area for clinicians and researchers alike. The recent article by de Vries, Steggerda, and Alarcon, published in Pediatric Research in 2025, peels back the layers of complexity surrounding neuroimaging in cCMV infection, offering a clarion call for standardization in the interpretation and reporting of imaging findings. As we delve into the nuances of neuroimaging within this domain, the significance of speaking a unified language becomes not only evident but imperative to advance patient care and research outcomes.
Congenital cytomegalovirus stands out as the most common congenital infection worldwide and a leading non-genetic cause of neurological disabilities in infants. Early diagnosis and accurate neuroimaging evaluation are critical to understanding the extent of central nervous system (CNS) involvement and anticipating neurodevelopmental prognosis. Despite numerous studies highlighting characteristic imaging features, the heterogeneity in terminology and interpretation has hindered cohesive clinical decision-making, often leaving clinicians navigating a fog of ambiguity.
At the heart of this challenge lies the interpretation of neuroimaging modalities such as cranial ultrasound (cUS), magnetic resonance imaging (MRI), and computed tomography (CT) scans. Each brings a unique vantage point to reveal the diverse neuropathological manifestations of cCMV, ranging from intracranial calcifications to cortical malformations and white matter abnormalities. However, the lack of standardized descriptors and consensus guidelines means that what one center may define as “white matter abnormalities” might differ subtly in definition or severity from another, complicating comparisons across studies and institutions.
The authors emphasize the critical role of MRI, particularly advanced sequences, in delineating the extent and nature of brain injury in affected neonates. High-resolution MRI not only visualizes the classic periventricular calcifications but also uncovers subtle findings such as ventriculomegaly, polymicrogyria, and delayed myelination patterns, each of which correlates variably with clinical outcomes. Standardized reporting frameworks, analogous to those used in adult stroke or multiple sclerosis imaging, are posited as essential tools to bring clarity and consistency to neonatal neuroimaging in cCMV.
Further complicating the diagnostic landscape is the timing of imaging studies. The neonatal brain is at a dynamic stage of development, and the progression of injury from the prenatal period through the first months of life influences the radiologic appearance. Early imaging may show limited abnormalities, whereas delayed scans might reveal evolving changes such as cystic encephalomalacia or volume loss. Thus, not only the choice of modality but the timing and repeat imaging protocols must be harmonized to maximize diagnostic yield.
De Vries and colleagues advocate for a multidisciplinary approach, intertwining the expertise of radiologists, neonatologists, infectious disease specialists, and neurologists. The ability to decode imaging findings within the broader clinical and virological context enhances diagnostic accuracy and informs tailored interventions. Moreover, standardized neuroimaging lexicons could facilitate the development of robust, multicenter databases, driving research into prognostic markers and novel therapeutic strategies.
From a technical perspective, the article delves into the intricacies of imaging sequences optimal for detecting cCMV-related pathology. T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI) are underscored for their utility in identifying edema, gliosis, and hemorrhagic components, respectively. Diffusion tensor imaging (DTI), an advanced MRI technique, is spotlighted for its promise in quantifying microstructural white matter integrity, which may correlate with neurodevelopmental outcomes beyond what conventional imaging reveals.
Another dimension tackled by the authors is the need to reconcile disparate terminologies such as “periventricular leukomalacia,” “white matter injury,” and “hypoxic-ischemic patterns” when applied to cCMV. Misclassification or imprecise usage not only muddles clinical communication but also impedes research reproducibility. The proposal for establishing a consensus nomenclature rooted in pathophysiological mechanisms aims to unify the lexicon, fostering clearer understanding and research collaboration.
Furthermore, the article touches upon the role of prenatal imaging in antenatal diagnosis of cCMV. While ultrasound remains the frontline modality, MRI offers superior sensitivity in detecting cortical malformations and migrational anomalies during gestation. However, the challenge lies in standardizing prenatal imaging protocols and signs suggestive of cCMV, which would empower obstetricians and pediatricians to optimize postnatal care pathways and parental counseling.
In the context of therapeutic implications, timely and precise neuroimaging characterization can influence eligibility for antiviral treatment and monitoring strategies. Given emerging data on valganciclovir therapy’s efficacy in mitigating hearing loss and neurodevelopmental deficits, identifying neonates with significant CNS involvement becomes a clinical imperative. Thus, a reproducible imaging framework directly impacts clinical decision-making paradigms.
De Vries et al. also emphasize the influence of evolving neuroimaging technologies in enriching the understanding of cCMV neuropathology. Beyond conventional MRI metrics, functional MRI (fMRI) and magnetic resonance spectroscopy (MRS) may offer insights into cerebral metabolism and functional connectivity alterations, serving as potential biomarkers for neurodevelopmental prognosis. These modalities, however, call for standardization akin to routine structural imaging to avoid variable interpretations across centers.
Multiplicity of findings inherent to cCMV, such as cortical dysplasia coexisting with calcifications and white matter injury, underlines a complex pathogenesis involving viral cytotoxicity, inflammatory cascades, and disrupted neurodevelopmental processes. Understanding this multifaceted injury requires integrated imaging approaches informed by consistent terminology that faithfully represent pathological substrates.
The call to action by the authors extends toward establishing international working groups tasked with developing consensus guidelines and imaging atlases. Such initiatives would, ideally, encompass training modules to promote uniform interpretation across radiologists irrespective of experience, thereby elevating diagnostic reliability globally. The ultimate beneficiary of these strides would be the affected infants and their families, who depend on accurate prognosis and interventions to optimize long-term outcomes.
The broader implications of standardizing neuroimaging language transcend cCMV, serving as a model for handling other congenital infections and developmental disorders where imaging subtleties carry substantial weight in clinical trajectories. This unified approach facilitates meta-analyses, comparative research, and the rapid dissemination of findings integral to evidence-based medicine.
In summation, the 2025 publication by de Vries, Steggerda, and Alarcon shines a spotlight on a pivotal yet under-addressed aspect of cCMV research and clinical management. By underscoring the necessity of a common neuroimaging language, it lays the foundation for improved diagnostic clarity, enhanced interdisciplinary collaboration, and ultimately, better patient care in this vulnerable population. As imaging technology continues to evolve, embracing standardization remains an essential step toward unraveling the intricate neuropathological puzzle presented by congenital cytomegalovirus infection.
Subject of Research: Neuroimaging in congenital cytomegalovirus (cCMV) infection and the need for standardized terminology and interpretation.
Article Title: Neuro-imaging in cCMV infection: let’s try and speak the same language.
Article References:
de Vries, L.S., Steggerda, S.J. & Alarcon, A. Neuro-imaging in cCMV infection: let’s try and speak the same language. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04407-0
Image Credits: AI Generated
