Reversal of Fetal Compromise Following In Utero Treatment of Vein of Galen Malformation Using Glue.

OBJECTIVE: To treat the fetus presenting with in utero compromise due to a large vein of Galen malformation (VOGM) using glue embolization. METHODS: The fetus that was referred for termination of pregnancy at 30 weeks of gestation due to severe cardiomegaly, mild pericardial effusion and large VOGM was evaluated using ultrasound. There was reversed end diastolic flow in the umbilical artery Doppler indicating imminent fetal demise in the premature fetus weighing <1200 g. Considering the request of parents, a treatment similar to recently reported cases of VOGM embolization in utero was attempted as an emergency procedure to salvage the baby. Due to unavailability of coils, financial constraints and urgent need for intervention, n-butyl cyanoacrylate glue with lipiodol was used to embolize the venous outflow of VOGM outflow under ultrasonographic guidance. RESULTS: There was immediate correction of the umbilical artery Doppler waveform with the establishment of a normal flow pattern. The cardiomegaly resolved over 3 weeks and fetal MRI done 2 weeks later showed normal brain architecture with no evidence of hemorrhage or infarction. Pregnancy was continued for 4 weeks after the procedure and terminated at 36 weeks. A female baby weighing 1900 g was delivered by Cesarean section with an Apgar of 8/10. Though initially the baby did well, with mild ventriculomegaly reported on postnatal day 5, she eventually presented at 3 months of age with cardiac failure. As the MRI showed encephalomalacia, due to uncertainty of neurological outcome, further treatment was not pursued by the parents and the baby died a few days later. CONCLUSION: To our knowledge, this is the first report on the use of glue to treat VOGM prenatally. Though technically successful in correcting the in utero compromise, the baby eventually expired. Cases of in utero embolization using coils and glue have shown success in reversing prenatal pathology and improving survival. However, long-term outcomes including neurological status are yet to be reported.

Vein of galen malformations: for patients and caregivers.

Vein of Galen malformations (VOGMs), also known as Vein of Galen Aneurysmal Malformations (VGAMs), are rare and complex cerebrovascular anomalies that pose significant diagnostic and therapeutic challenges. These malformations result from abnormal arteriovenous shunts during embryonic development, leading to a range of severe clinical manifestations, including high-output cardiac failure and hydrocephalus. Advances in prenatal imaging, particularly fetal MRI, have improved early detection, allowing for timely intervention. Endovascular techniques, especially transarterial embolization, have become the primary treatment modality, often preferred over surgical approaches due to their effectiveness and lower risk. However, challenges remain, particularly in managing these malformations in neonates and infants, where the risk of complications is high. Gamma Knife radiosurgery offers a non-invasive alternative for select cases, though its effects are gradual and may carry delayed risks. Despite advancements, the management of VOGMs continues to require a multidisciplinary approach, with ongoing research focused on improving outcomes through a better understanding of the genetic and molecular underpinnings of the disease. Future directions include the integration of genetic studies into clinical practice and the refinement of treatment strategies to optimize outcomes for this complex condition.

MV-flow in the assessment of fetal vein of Galen aneurysmal malformation.

MV-Flow is a tool enables to acquire spatially and temporally coherent data on low-speed blood flow information. In our case, it allowed a better definition of vein of Galen aneurysmal malformation morphology, venous drainage and feeder vessels than standard ultrasound techniques.

Neonatal intracranial haemorrhage secondary to vein of Galen aneurysmal dilatation.

Paediatric neurovascular anomalies associated with the vein of Galen (VG) comprise of a spectrum of rare, complex, and life-threatening conditions. In this group, the "vein of Galen aneurysmal dilatation" (VGAD) is a distinct entity that often presents with progressive neurological symptoms in older children. Acute haemorrhage in VGAD is uncommon. We present an unusual presentation of VGAD in a neonate and discuss the challenges faced in the management.

Comparing Vascular Morphology and Hemodynamics in Patients with Vein of Galen Malformations Using Intracranial 4D Flow MRI.

BACKGROUND AND PURPOSE: Vein of Galen malformation (VOGM) is the most common congenital cerebrovascular malformation, and many patients have high mortality rates and poor cognitive outcomes. Quantitative diagnostic tools are needed to improve clinical outcomes, and the purpose of this study was to characterize intracranial blood flow in VOGM using quantitative 4D flow MRI. MATERIALS AND METHODS: A prospective study of children with VOGM was conducted by acquiring 4D flow MRI to quantify total blood inflow to the brain, flow in the pathologic falcine sinus, and flow in the superior sagittal sinus. Linear regression was used to test the relationships between these flows and age, clinical status, and the mediolateral diameter of the outflow tract of the lesion through the falcine or straight sinus diameter, which is a known morphologic prognostic metric. RESULTS: In all 11 subjects (mean age, 22 [SD,17 ] weeks), total blood flow to the brain always exceeded normal levels (mean, 1063 [SD, 403] mL/minute). Significant correlations were observed between falcine sinus flow and the mediolateral diameter of the straight or falcine sinus, the posterior cerebral artery/MCA flow ratio and age at scanning, and superior sagittal sinus flow proximal to malformation inflow and age at scanning. CONCLUSIONS: Using 4D flow MRI, we established the hemodynamic underpinnings of the mediolateral diameter of the straight or falcine sinus and investigated metrics representing parenchymal venous drainage that could be used to monitor the normalization of hemodynamics during embolization therapy.

Vein of Galen Malformations.

Significant efforts have been made over the last few decades to improve the diagnosis and management of patients with vein of Galen malformations (VOGMs). The mainstays of treatment remain focused on primary endovascular management by staged transarterial embolizations with adjunctive use of transvenous embolization, medical therapy, and neurosurgical intervention for symptom control in select patients. Innovation in endovascular technology and techniques as well as promising new genomic research elucidating potential therapeutic targets hold significant promise for the future of VOGM treatment.

Spontaneous thrombosis of type II vein of Galen aneurysmal malformation: a case report.

Vein of Galen malformations (VGAMs) are rare and complex congenital brain vascular anomalies that pose significant diagnostic and treatment challenges. The natural history of this type of vascular anomaly is very poor, with many patients succumbing to complications such as congestive heart failure, hydrocephalus, and brain parenchymal injury. Although the clinical course of most VGAMs was considered unfortunate, with meticulous imaging, a group of lesions with a more placid presentation and course can be identified.

Vein of Galen aneurysmal malformation: does size affect outcome?

PURPOSE: To validate a semiautomated method for segmenting vein of Galen aneurysmal malformations (VGAM) and to assess the relationship between VGAM volume and other angioarchitectural features, cardiological findings, and outcomes. METHODS: In this retrospective study, we selected all subjects with VGAM admitted to the Gaslini Children's Hospital between 2009 and 2022. Clinical data were retrieved from electronic charts. We compared 3D-Slicer segmented VGAM volumes obtained by two independent observers using phase-contrast MR venography to those obtained with manual measurements performed on T2-weighted images. The relationship between VGAM volumes and clinical and neuroimaging features was then explored. RESULTS: Forty-three subjects with VGAM (22 males, mean age 6.56 days) were included in the study. Manual and semiautomated VGAM volumes were well correlated for both readers (r = 0.86 and 0.82, respectively). Regarding reproducibility, the inter-rater interclass correlation coefficients were 0.885 for the manual method and 0.992 for the semiautomated method (p < 0.001). The standard error for repeated measures was lower for the semiautomated method (0.04 versus 0.40 of manual method). Higher VGAM volume was associated with superior sagittal sinus narrowing, jugular bulb stenosis, and aqueductal stenosis (p < 0.05). A weak correlation was found between VGAM volume and straight sinus dilatation (r = 0.331) and superior sagittal sinus index (r = - 0.325). No significant associations were found with cardiac findings, post-embolization complications, and outcome (p > 0.05). CONCLUSIONS: Semiautomated VGAM volumetry is feasible and reliable with improved reproducibility compared to the manual method. VGAM volume is not a prognostic factor for clinical outcome, but it is related to other venous findings with potential hemodynamic effects.

Aortic Steal Correlates with Acute Organ Dysfunction and Short-Term Outcomes in Neonates with Vein of Galen Malformation.

INTRODUCTION: Vein of Galen aneurysmal malformation (VGAM) is a rare, congenital cerebrovascular malformation with high morbidity and mortality. Parameters to foresee clinical progression and allow individualized parent counseling are lacking. The aim of this study was to evaluate aortic steal measured by Doppler ultrasound as a prognostic parameter in these neonates. METHODS: A retrospective monocentric analysis of cardiac ultrasound exams before embolization in neonates with VGAM was conducted. Percentage of aortic steal measured by time-averaged maximum velocity above and below the zero flow baseline by pulsed Doppler ultrasound at the preductal aortic isthmus was calculated. Association of aortic steal with parameters of acute organ dysfunction (Bicêtre neonatal evaluation score [BNES], neonatal multiple organ dysfunction score [NeoMODS]) and mortality and determination of correlation between aortic steal and cerebral damage on initial and follow-up cerebral magnetic resonance imaging (cMRI) were evaluated. RESULTS: Twelve neonates were included, of which 3 died. Per 10 percentage point increase of aortic steal, BNES decreased by 1.64 (95% confidence interval [CI]: 1.28-2.0) points and the maximum observed NeoMODS increased by 1.25 (CI: 0.94-1.57) points. The odds for mortality increased by 2.3 (CI: 1.14-13.67) per 10 percentage point increase of aortic steal. There was a correlation between aortic steal and cerebral damage at baseline (white matter ρ [rho] = 0.34, gray matter ρ = 0.81) and follow-up (white matter ρ = 0.80, gray matter ρ = 0.72). CONCLUSION: The degree of aortic steal in neonates with VGAM was highly associated with the severity of organ dysfunction, disease progression on cMRI, and mortality.

Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10-7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (17.5-fold, p = 1.22 x 10-5), which cooperates with p120 RasGAP to regulate vascular development. Additional probands had damaging variants in ACVRL1, NOTCH1, ITGB1, and PTPN11. ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant (Phe867Leu) exhibited disrupted developmental angiogenesis and impaired hierarchical development of arterial-capillary-venous networks, but only in the presence of a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have implications for patients and their families.

Direct Transverse Sinus Puncture for Transvenous Coil Embolization of Vein of Galen Malformations: Innovating Existing Techniques.

BACKGROUND AND IMPORTANCE: Vein of Galen malformations (VOGMs) are complex arteriovenous malformations in neonates and young children. Recent advances in endovascular interventions have drastically improved treatment and clinical outcomes in what was previously high-morbidity, high-mortality disease. The high-flow shunt pathophysiology in VOGMs can lead to dynamic changes in the malformation angioarchitecture, and over time patients can develop jugular bulb stenosis. In the setting of inaccessible transvenous access to the malformation for endovascular embolization in cases where transarterial embolization is inadequate, a combined surgical and endovascular technique must be used. We present the first successful modern-day application of direct puncture through transverse sinus for transvenous embolization of a VOGM. CLINICAL PRESENTATION: We present 2 unique cases of complex VOGM malformations in patients who had previously undergone staged endovascular embolization for reduction of flow within the malformation. On follow-up, in both cases, there was development of severe sigmoid sinus and jugular bulb stenosis, increasing intracranial venous congestion and causing marked clinical deterioration. The stenosis prevented traditional transvenous access and treatment. We describe a direct puncture transverse sinus access using a burr hole approach for endovascular transvenous embolization in both cases with successful clinical outcomes. CONCLUSION: Direct access using burr hole craniotomy to the transverse sinus for transvenous endovascular embolization is a safe approach in the setting of severe jugular bulb stenosis for treatment of VOGMs. This technique can be done efficiently to achieve complete flow elimination in the malformation, in cases where that is called for, without significant risks or complications related to the approach.

That which is unseen: 3D printing for pediatric cerebrovascular education.

INTRODUCTION: Pediatric cerebrovascular lesions are very rare and include aneurysms, arteriovenous malformations (AVM), and vein of Galen malformations (VOGM). OBJECTIVE: To describe and disseminate a validated, reproducible set of 3D models for optimization of neurosurgical training with respect to pediatric cerebrovascular diseases METHODS: All pediatric cerebrovascular lesions treated at our institution with adequate imaging studies during the study period 2015-2020 were reviewed by the study team. Three major diagnostic groups were identified: aneurysm, AVM, and VOGM. For each group, a case deemed highly illustrative of the core diagnostic and therapeutic principles was selected by the lead and senior investigators for printing (CSG/JM). Files for model reproduction and free distribution were prepared for inclusion as Supplemental Materials. RESULTS: Representative cases included a 7-month-old female with a giant left MCA aneurysm; a 3-day-old male with a large, complex, high-flow, choroidal-type VOGM, supplied from bilateral thalamic, choroidal, and pericallosal perforators, with drainage into a large prosencephalic vein; and a 7-year-old male with a left frontal AVM with one feeding arterial vessel from the anterior cerebral artery and one single draining vein into the superior sagittal sinus CONCLUSION: Pediatric cerebrovascular lesions are representative of rare but important neurosurgical diseases that require creative approaches for training optimization. As these lesions are quite rare, 3D-printed models and open source educational materials may provide a meaningful avenue for impactful clinical teaching with respect to a wide swath of uncommon or unusual neurosurgical diseases.

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

BACKGROUND AND PURPOSE: Vein of Galen malformation is a rare congenital cerebrovascular malformation. In affected patients, increased cerebral venous pressure constitutes an important etiologic factor for the development of brain parenchymal damage. The aim of this study was to investigate the potential of serial cerebral venous Doppler measurements to detect and monitor increased cerebral venous pressure. MATERIALS AND METHODS: This was a retrospective monocentric analysis of ultrasound examinations within the first 9 months of life in patients with vein of Galen malformation admitted at <28 days of life. Categorization of perfusion waveforms in the superficial cerebral sinus and veins into 6 patterns was based on antero- and retrograde flow components. We performed an analysis of flow profiles across time and correlation with disease severity, clinical interventions, and congestion damage on cerebral MR imaging. RESULTS: The study included 44 Doppler ultrasound examinations of the superior sagittal sinus and 36 examinations of the cortical veins from 7 patients. Doppler flow profiles before interventional therapy correlated with disease severity determined by the Bicêtre Neonatal Evaluation Score (Spearman ρ = -0.97, P = < .001). At this time, 4 of 7 patients (57.1%) showed a retrograde flow component in the superior sagittal sinus, whereas after embolization, none of the 6 treated patients presented with a retrograde flow component. Only patients with a high retrograde flow component (equal or more than one-third retrograde flow, n = 2) showed severe venous congestion damage on cerebral MR imaging. CONCLUSIONS: Flow profiles in the superficial cerebral sinus and veins appear to be a useful tool to noninvasively detect and monitor cerebral venous congestion in vein of Galen malformation.

Spontaneous thrombosis of vein of Galen malformation managed with surgical resection: a case­based review.

INTRODUCTION: Vein of Galen malformation (VOGM) is an exceptionally uncommon form of congenital intracranial vascular malformations. It is highly unusual for this lesion to spontaneously thrombose. The clinical presentation of a patient may range from being asymptomatic to critically ill. The underlying pathophysiological mechanisms that cause spontaneous thrombosis are still poorly understood. METHODS AND RESULTS: The literature on spontaneous thrombosis of VOGM was systematically reviewed, analyzed, and summarized with a focus on its pathophysiology, types, clinical presentations, diagnosis, management, and outcomes. It was also illustrated with a case presentation. The case presents an unusual presentation and location of a VOGM in a 2-year-old boy who was successfully treated with surgical resection. CONCLUSIONS: A handful of cases of thrombosed VOGM have been reported worldwide where surgery was used to treat the condition. Low-flow fistulas of the mural type are prone to spontaneous thrombosis, have delayed clinical presentations, and are typically diagnosed in young children. Among the many possible manifestations, hydrocephalus is by far the most common. In the absence of blood flow, MRI is the diagnostic test of choice. Depending on the patient's symptoms, surgery to either remove the aneurysm or divert the cerebrospinal fluid usually results in a good prognosis.

Pulmonary Hypertension in Infants and Children with Vein of Galen Malformation and Association with Clinical Outcomes.

OBJECTIVE: To assess the extent and resolution of pulmonary hypertension (PH), cardiovascular factors, and echocardiographic findings associated with mortality in infants and children with vein of Galen malformation (VOGM). STUDY DESIGN: We performed a retrospective review of 49 consecutive children with VOGM admitted to Boston Children's Hospital from 2007 to 2020. Patient characteristics, echocardiographic data, and hospital course were analyzed for 2 cohorts based on age at presentation to Boston Children's Hospital: group 1 (age ≤60 days) or group 2 (age >60 days). RESULTS: Overall hospital survival was 35 of 49 (71.4%); 13 of 26 (50%) in group 1 and 22 of 23 (96%) in group 2 (P < .001). High-output PH (P = .01), cardiomegaly (P = .011), intubation (P = .019), and dopamine use (P = .01) were significantly more common in group 1 than group 2. Among patients in group 1, congestive heart failure (P = .015), intubation (P < .001), use of inhaled nitric oxide (P = .015) or prostaglandin E1 (P = .030), suprasystemic PH (P = .003), and right-sided dilation were significantly associated with mortality; in contrast, left ventricular volume and function, structural congenital heart disease, and supraventricular tachycardia were not associated. Inhaled nitric oxide achieved no clinical benefit in 9 of 11 treated patients. Resolution of PH was associated with overall survival (P < .001). CONCLUSIONS: VOGM remains associated with substantial mortality among infants presenting at ≤60 days of life owing to factors associated with high output PH. Resolution of PH is an indicator associated with survival and a surrogate end point for benchmarking outcomes.

Vein of Galen Malformations in adults.

OBJECTIVE: Vein of Galen Malformations (VoGM) are rare vascular malformations, typically seen in pediatric age groups. Even more rarely, VoGM's may be seen later in adulthood. In this case report and systematic review, we provide a thorough description of the current literature as well as provide a case example exploring the diagnosis, imaging, treatment, and management of VoGM in adults. METHODS: In accordance with PRISMA guidelines, we performed a systematic literature search for all relevant cases and case series of VoGM in adult patients. The reference list of all articles were reviewed for additional relevant cases. Articles were included if they described a VoGM of a patient over the age of 18 years old and published in English. 149 articles were originally identified and 26 described cases met our inclusion criteria. RESULTS: In our literature review we found 26 patients that met our inclusion criteria. We found 14 male patients and 12 female patients. The mean age at presentation was 37.2 years (median=34 years, SD= 13.6 years). The most common presenting symptoms of patient were headache (n = 9), seizure (n = 6), and vomiting (n = 4). Of the 12 cases which clearly reported the subtype of VoGM, the choroidal type was more frequently seen (n = 10) compared to the mural type (n = 2). In 3 patients, the VoGM was thrombosed at time of diagnosis. Of the 26 patients, endovascular treatment was performed most frequently (n = 8) but some received microsurgical treatment (n = 4) or were treated conservatively (n = 6). Other treatment modalities included (ventriculoperitoneal shunt, ventriculostomy) (n = 5). In 3 cases treatment was not specified. In comparison to VoGM seen in pediatric or neonatal populations, VoGM in adults generally resulted in more favorable outcomes with only 2 patients reported to have passed away following treatment. CONCLUSION: VoGM remains a rare finding amongst the adult population. Hence, we described the clinical presentation, treatment modalities, and outcomes of the cases described in the English literature. Perhaps due to the rate of thrombosis and the unique angioarchitecture seen in adult VoGM patients, outcomes were generally more favorable than those described in the literature in pediatric or neonate VoGM patients.