Doppler Ultrasound Flow Reversal in the Superior Sagittal Sinus to Detect Cerebral Venous Congestion in Vein of Galen Malformation

Vein of Galen (aneurysmal) malformation (VGAM) is a rare congenital cerebrovascular malformation characterized by arteriovenous (AV) fistulas between the persistent median prosencephalic vein of Markowski (MPV) and arterial feeding vessels. This abnormal connection leads to reduced cerebral arterial perfusion and increased cerebral venous pressure, significantly contributing to brain parenchymal damage. The high mortality rate (approximately 40%) and poor neurodevelopmental outcomes (50% of survivors) highlight the need for effective monitoring and treatment strategies. Increased cerebral venous pressure results from arterialization of the MPV and cerebral sinuses, causing outflow obstruction, congestion, venous ischemia, and hydrocephalus. This venous hypertension can be worsened by high venous return due to excessive shunt volumes and potential jugular bulb stenosis. Cerebral venous congestion primarily causes white matter injury and subependymal atrophy, making it a critical factor in progressive brain damage. Currently, cerebral MR imaging (cMRI) is the primary diagnostic tool; however, it only reveals indirect signs and damage resulting from chronic venous congestion. This study aimed to explore the potential of serial venous ultrasound (US) Doppler measurements as a noninvasive method for early detection and monitoring of cerebral venous congestion in VGAM.

Existing literature emphasizes the significant impact of increased cerebral venous pressure in VGAM pathogenesis and its contribution to poor patient outcomes. Studies have shown correlations between venous congestion and neurological damage, highlighting the need for non-invasive monitoring tools. While cMRI is the current standard, its limitations (indirect signs, late detection, cost, and need for sedation/anesthesia) necessitate the search for alternative methods. Previous research on Doppler ultrasound in other cerebrovascular conditions suggests its potential for assessing venous hemodynamics, prompting the current investigation into its application in VGAM.

This retrospective monocentric study included 7 neonates with VGAM admitted to a neonatal intensive care unit between January and June 2022. All patients underwent standardized US Doppler flow profile (FP) measurements at four time points: before the first cMRI (T1), after the first cMRI/embolization (T2), 5-7 days post-embolization (T3), and before discharge (T4). High-end ultrasound machines with high-resolution linear transducers were used. Doppler FPs in the SSS were recorded using a median sagittal section, with angle-corrected pulsed Doppler time-frequency analysis. FPs in cortical veins were measured similarly. Based on Ikeda et al., FPs were categorized into six types (FP1-FP6) representing increasing degrees of retrograde flow. The Bicêtre Neonatal Evaluation Score (BNES) was used to assess disease severity before the first cMRI. Endovascular therapy (primarily transarterial embolization) was performed based on clinical and sonographic findings. cMRI assessments were performed by a blinded neuroradiologist using a structured report and scoring system for parenchymal damage. Statistical analysis included descriptive statistics and Spearman correlation to assess the association between FPs and BNES.

The study included 44 SSS and 36 cortical vein Doppler US examinations. Before intervention, Doppler FPs significantly correlated with disease severity (BNES) (r = -0.97, P < .001). 4 of 7 patients (57.1%) showed retrograde flow in the SSS pre-intervention, while none showed it post-embolization. Only the two patients with severe venous congestion damage on cMRI exhibited high (≥ one-third) or complete retrograde flow. In one patient with persistent retrograde flow post-discharge, further investigation revealed bilateral jugular bulb stenosis, successfully treated with balloon dilation and stent implantation. Serial Doppler measurements showed a strong correlation between flow reversal and venous congestion as detected by cMRI. In patients with successful VGAM occlusion, US Doppler FPs normalized, demonstrating a potential correlation between the embolization success and normalization of flow pattern.

This study demonstrates the potential of US Doppler FPs in the SSS and cortical veins as a noninvasive method for detecting and monitoring cerebral venous congestion in VGAM. The strong correlation between retrograde flow and disease severity, as well as the normalization of FPs following successful embolization, supports the clinical utility of this approach. Retrograde flow is likely attributed to fluctuations in right atrial pressure, arterialized pressure in the confluence of sinuses, or mechanical outflow obstruction. The study highlights the limitations of cMRI, as it often reveals damage only after significant congestion has occurred. The real-time monitoring capability of Doppler US offers a significant advantage over cMRI for managing VGAM therapy. While acknowledging the limitations of this retrospective study (small sample size), this work suggests the potential integration of US Doppler assessments into routine care for VGAM.

This study demonstrates that flow reversal in the SSS, measured with spectral Doppler US, is a promising diagnostic parameter for assessing venous congestion in VGAM. The presence of significant retrograde flow may indicate cerebral venous outflow obstruction and should prompt further investigation. Future prospective studies with larger cohorts are needed to validate these findings and explore the role of cerebral venous Doppler measurements in intensive care and endovascular therapy management of VGAM. Further research should also investigate the broader applicability of this technique in assessing cerebral venous hemodynamics in neonates with other complex hemodynamic conditions.

The study's limitations include its retrospective design and small sample size due to the rarity of VGAM. The retrospective nature introduces selection bias and limits the ability to draw definitive causal conclusions. The reliance on cMRI as the criterion standard for venous congestion also introduces a temporal lag, as cMRI might not detect early congestion. Furthermore, interpretation of Doppler US findings may be influenced by factors such as central venous pressure, cardiac function, and supportive medical therapies.