Hydrocephalus is a complex neurological condition marked by abnormal cerebrospinal fluid (CSF) accumulation, often leading to elevated intracranial pressure and structural brain damage. Despite advances in surgical treatment, diagnostic precision and prognosis remain challenging, especially in idiopathic normal pressure hydrocephalus (iNPH). This narrative review aims to synthesize the current knowledge regarding molecular and neuroimaging biomarkers that hold diagnostic, prognostic, and therapeutic significance in hydrocephalus. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar. The inclusion criteria encompassed peer-reviewed studies involving congenital or acquired hydrocephalus and reporting on mechanistic, diagnostic, or monitoring biomarkers. Both established and emerging biomarkers were included, and preclinical findings were considered when translational relevance was apparent. The review highlights a broad spectrum of molecular markers including aquaporins, vascular endothelial growth factor, neurofilaments, glial fibrillary acidic protein, matrix metalloproteinases, and neuroinflammatory markers. The genetic markers associated with ciliogenesis also show promise in subtyping disease. Parallel to molecular advances, neuroimaging techniques, ranging from classic markers like Evans’ index to advanced modalities such as diffusion tensor imaging (DTI), arterial spin labeling (ASL), and glymphatic MRI, provide functional perspectives on hydrocephalus diagnosis and management, while artificial intelligence may further enhance diagnostic algorithms. Molecular and imaging markers could not only increase diagnostic confidence, but also provide information on disease causes and progression. As research progresses, merging various methodologies may result in more accurate diagnoses.

Background/Objectives: Hydrocephalus is a complex neurological disorder marked by abnormal cerebrospinal fluid dynamics and ventricular enlargement. Despite breakthroughs in neuroimaging, diagnosis and longitudinal the application of imaging markers for the diagnosis and longitudinal monitoring of hydrocephalus remains challenging in routine clinical practice. The present study examines the behavior and cross-modality agreement of commonly used linear ventricular measurements under routine imaging conditions, at a single Romanian tertiary-care center characterized by heterogeneous acquisition protocols and limited availability of advanced volumetric techniques. Methods: We conducted a single-center retrospective observational study of 68 adults with hydrocephalus. Linear ventricular metrics, including Evans index and third-ventricle width, were measured on all available CT and MRI scans. CT–MRI agreement was assessed using paired examinations within a 90-day window. Longitudinal changes were analyzed using first–last and pre–post VP shunt comparisons. Associations between baseline imaging features and VP shunt placement were evaluated using rule-based and odds ratio analyses. Results: CT and MRI measurements demonstrated strong agreement for both Evans index (r = 0.93) and third-ventricle width (r = 0.90), with minimal systematic bias. Longitudinal analyses demonstrated small-magnitude changes in ventricular size following intervention, with substantial inter-individual variability. VP utilization increased across Evans index strata, reaching 100% in patients with values ≥0.50. Transependymal cerebrospinal fluid exudation showed the strongest association with subsequent VP shunting. Imaging-based rules exhibited expected trade-offs between sensitivity and specificity. Conclusions: Standard linear ventricular parameters exhibited adequate cross-modality agreement and clinically important longitudinal behavior in this cohort. While insufficient as standalone predictors, these readily available imaging markers remain important tools when combined with a comprehensive clinical assessment.

Background/Objectives: Ventricular enlargement is a common finding on non-contrast computed tomography (CT) in acute neurological presentations, occurring in hydrocephalus, stroke, and traumatic brain injury. This study evaluated whether routinely available CT-based ventricular morphometric parameters can distinguish hydrocephalus from stroke and traumatic brain injury using initial imaging examinations. Methods: This retrospective observational study included 186 adults (68 with hydrocephalus, 64 with stroke, and 54 with TBI) who underwent index non-contrast cranial CT. Quantitative ventricular parameters included Evans index and third ventricle width, alongside temporal horn dilation and periventricular edema. Multivariable logistic regression models were developed to assess diagnostic performance. A primary morphometric model and a distortion-controlled model incorporating midline shift, mass lesions, and hemorrhage burden were analyzed. Discrimination was evaluated using receiver operating characteristic (ROC) curves. Results: Patients with hydrocephalus showed significantly greater ventricular enlargement, with higher Evans index and third ventricle width compared with stroke and traumatic brain injury groups. The primary model demonstrated moderate discrimination (AUC 0.71). After adjustment for intracranial distortion variables, model performance improved substantially (AUC 0.91), with balanced sensitivity and specificity at optimized thresholds. Evans index and third ventricle width were the strongest independent predictors. Conclusions: CT-derived ventricular morphometrics provide a practical and reproducible approach for differentiating hydrocephalus from stroke and traumatic brain injury on first-presentation CT, supporting objective interpretation in routine neuroimaging practice.