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.

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.

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.

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.

Overcoming roadblocks in clinical innovation via high fidelity simulation: use of a phantom simulator to achieve FDA and IRB approval of a clinical trial of fetal embolization of vein of Galen malformations.

BACKGROUND: Vein of Galen malformation (VOGM) is a rare, life-threatening vascular malformation in neonates and is treated with embolization. However, even at the most experienced centers, patients face high mortality and morbidity. In utero treatment options have been limited by lack of animal models or simulations. OBJECTIVE: To create a novel ultrasound phantom simulator for a preclinical feasibility study of in utero fetal intervention for VOGM. METHODS: Novel phantoms were designed and built in two configurations of spherical and windsock shape from cryogel material to mimic the salient vasculature of the fetal VOGM, based on real-patient fetal MR imaging dimensions. Critical anatomy was realistically mimicked within this model and transtorcular ultrasound-guided coil deployment was simulated. Each phantom model was assessed before and after treatment to evaluate coil mass deposition within the target. RESULTS: The two phantoms underwent pretreatment T2-weighted MR imaging assessment, ultrasound-guided embolization, post-treatment MR and fluoroscopic imaging, and visual inspection of the sliced phantoms for target embolization verification. Postoperative MR scans confirmed realistic compact deposition of the coil masses within the central cavity. Phantom embolization results were submitted as part of the institutional review board and US Food and Drug Administration investigative device exemption approval for a first-in-humans clinical trial of fetal intervention for VOGM. CONCLUSIONS: A phantom simulator for fetal intervention of VOGM produces lifelike results during trial interventions, removing obstacles to feasibility and safety evaluations, typically precluded by non-availability of appropriate animal models. The study provides a proof of concept for potentially wider applications of medical simulation to enable novel procedural advancements in neurointerventions.

Rapid Ventricular Pacing Facilitates Transarterial Embolization in Vein of Galen Malformations.

Background: Mural type vein of Galen malformation (mVOGM) is a congenital high flow arteriovenous shunt between choroidal arteries and the prosencephalic vein of Markowski leading to heart failure and hydrovenous disorder in children. Embolizing fistulous connections can be challenging and typically requires adjunctive techniques such as induced hypotension, balloon-assisted flow control, and creation of a coil basket. These maneuvers add time, complexity, and unpredictability. Rapid ventricular pacing (RVP) has been proposed as an alternative strategy with fewer drawbacks, but has not been well studied. The approach involves catheterizing the right ventricle with a pacing catheter connected to a temporary external pacemaker. Prior to embolization, RVP is initiated to lower cardiac output. Following embolization, pacing is discontinued, and the heart returns to sinus rhythm. Methods: We performed RVP in five mVOGM patients from 4/2020 through 7/2021. Accounting for multiple procedures, RVP was utilized in ten cases and twenty-six pedicles. Results: Ventricular capture was achieved in all instances and was well tolerated, without arrhythmia. Casting the arterial pedicle with liquid embolic immediately adjacent to, or traversing, the fistulous point was achieved in 9/10 cases. There were no procedural complications. In 1 case, creation of a coil basket in the venous pouch was required to achieve a stable arterial cast Conclusions: This report describes the largest case series utilizing RVP in mVOGM. The technique appears safe and well tolerated.

Vein of Galen aneurysmal malformation: rationalizing medical management of neonatal heart failure.

Neonates who present in high output heart failure secondary to vein of Galen aneurysmal malformation can be difficult to manage medically due to the complex physiology that results from the large shunt through the malformation. Though the cardiac function is often normal, right ventricular dilation, severe pulmonary hypertension, and systemic steal can result in inadequate organ perfusion and shock. This report recommends medical management for stabilization of neonates prior to definitive management with endovascular embolization. IMPACT: Vein of Galen aneurysmal malformation (VGAM) is a rare intracranial arteriovenous malformation, which can present in the neonatal period with high output heart failure. Heart failure secondary to VGAM is often difficult to manage and is associated with high mortality and morbidity. Despite optimal medical management, many patients require urgent endovascular embolization for stabilization of their heart failure. This report offers discrete recommendations that can be used by clinicians as guidelines for the medical management of heart failure in newborns with VGAM.

Evolution of transvenous embolization in vein of Galen malformation: case series and review of the literature.

BACKGROUND: Treatment of vein of Galen malformations (VOGMs) has improved greatly since the inception of endovascular treatment. Transvenous embolization (TVE) is an attractive option to achieve complete obliteration. OBJECTIVE: To review the literature on TVE of VOGM and then analyze our practice's unique experience and evolving treatment strategies over 30 years. METHODS: A retrospective review of our clinical database for patients with the diagnosis of VOGM treated between January 2004 and August 2021 was performed. A literature review of 49 relevant articles was also carried out. RESULTS: TVE in VOGM has evolved with initial introduction as a transtorcular (TT) approach, which then lost favor to transarterial embolization (TAE). TAE has been considered the more favorable approach in most high-volume centers. In more recent times, the transvenous embolization (TVE) approach has been revisited as a last treatment to achieve a cure after a series of TAE treatments. We presently favor beginning treatment with staged TAE to reduce flow to the lesion and, importantly, shrink the draining vein. This then allows for the performance of TVE with the Chapot pressure cooker technique (CPCT) with coils and liquid embolic embolization. CONCLUSIONS: TT TVE itself carries a high degree of risk and is most highly associated with long-term morbidities and mortality. Traditional transfemoral/transjugular TVE approaches are safe and effective in simple fistulas with a small venous pouch; however, we believe that the CPCT is the safest technique as a last-stage treatment for its security in avoiding reflux and obtaining occlusion of the small perforators.

The composition of landmark vein of Galen malformation research: the emergence of endovascular treatments.

BACKGROUND: Since the advent of endovascular treatment, the long-term prognosis of vein of Galen malformation (VOGM) has markedly improved; however, the nature of research leading to this point is unclear. The objective of this study was to define the composition of VOGM research to date, by means of a bibliometric analysis of the 100 most cited VOGM articles. METHODS: An electronic search of Elsevier's Scopus database was performed to identify the 100 most cited articles on VOGM screened against predetermined criteria. Data were then compared. RESULTS: The 100 most cited VOGM articles were published between 1974 and 2017 in 38 unique journals and originated from 16 unique countries. Mean citation count and rate were 59.4 citations and 2.9 citations/year, respectively. The USA (n = 42); Hôpital de Bicêtre, France (n = 15); and Dr. Pierre Lasjaunias (n = 16) were the largest individual country, institutional, and author contributors. Compared to the older articles (published < 2000), key differences for newer articles were statistically higher citation rates (P < 0.01), more authors (P < 0.01), higher proportion of endovascular treatment descriptions (P = 0.01), and more originating from Asia Pacific (P < 0.01). CONCLUSIONS: From the 100 most cited VOGM articles to date, there has been a noticeable shift from diagnosing VOGM based on the foundational work by Dr. Lasjaunias to understanding how we can model clinical outcomes now that endovascular treatment has become the standard of care. Significant shifts in prognosis are pending, and the current bibliometric data implicate we are on the precipice of more recent works making an impact in the near future.

Vein of Galen Aneurysmal Malformation with Anomalous Right Superior Vena Cava to the Left Atrium Leading to Atypical Clinical and Echocardiographic Findings.

Vein of Galen aneurysmal malformation (VGAM) is a rare intracranial vascular malformation which typically presents in a critically ill newborn with intractable heart failure, severe pulmonary hypertension, and right heart dilation. We report two unusual cases of neonates with VGAM and anomalous connection of right superior vena cava to the left atrium. Both neonates were diagnosed with VGAM in utero and were clinically stable after birth with dilation of the left atrium and left ventricle and no evidence of pulmonary hypertension. One case with hydrocephalus underwent transcatheter embolization at 1 week of age. The other case without hydrocephalus underwent elective transcatheter embolization at 4 months. We postulate that the presence of a right superior vena cava to the left atrium provides a physiological advantage and counters the left-to-right shunt from the arteriovenous malformation. This provides insight to a potential treatment strategy to improve outcomes in patients with severe heart failure and pulmonary hypertension secondary to VGAM.