Increasing Access to High Value Care: Preventing Complications in Common Disorders.

Most infantile hemangiomas (IHs), the most common vascular tumors of childhood, evolve without complications; however 10% to 12% require specialty referral for treatment. To emphasize the complications of late referral, we present a case of necrotizing infection within a segmental IH leading to sepsis. Early evaluation by a pediatric dermatologist could have prevented this life-threatening and disfiguring complication. We discuss how teledermatology would enable rapid triage of such critical cases in underserved areas, increasing access to high-value care and optimizing outcomes for our most vulnerable patients.

Emergency Carotid Thrombo-Endarterectomy after Failed Endovascular Recanalization for Acute Complete Carotid Occlusion: A Case Report.

Rapid identification of the type and origin of a stroke is crucial for prompt and appropriate treatment, which can significantly influences patient outcomes. We report a multidisciplinary management case involving a 76-year-old man who presented with left-sided weakness and mild dysarthria. Imaging revealed a completely occluded right internal carotid artery. Despite multiple endovascular recanalization attempts, adequate flow could not be achieved, leading to the decision to perform an open thrombo-endarterectomy. The patient underwent carotid endarterectomy with microsurgical techniques under general anesthesia. The atheroma plaque and central thrombus were removed, which reestablished flow. Continuous intraoperative neuromonitoring was utilized to ensure patient safety. The patient woke up without new deficits and was discharged for rehabilitation. Follow-up imaging confirmed arterial patency, and the patient eventually made an excellent recovery, including being independent over one and a half years. Emergent recanalization with carotid endarterectomy following a failed endovascular recanalization is both safe and feasible, emphasizing the need for collaboration between different treatment providers to ensure optimal patient outcomes. Our report highlights the importance of a multidisciplinary approach and the advantages of a hybrid operating room in the treatment of acute complete carotid artery occlusion.

Extensive sinovenous thrombosis and hemorrhagic infarction during therapy for T-cell acute lymphoblastic leukemia.

Sinovenous thrombosis (SVT) is a well-recognized and serious complication in children treated for acute leukemia. This frequently occurs during or immediately upon completion of induction therapy and is commonly attributed to asparaginase therapy.Headache is the first and most common clinical symptom to occur during the early development of SVT. With advancement of the thrombosis, the clinical symptoms can progress to increased sleepiness, focal neurological deficit, seizures, and altered consciousness. We report the case of a 4-year-old girl who presented after several days of headaches and anorexia, which then progressed to seizures, left-sided weakness, and altered consciousness. She was later found to have a widespread and occlusive SVT with right cerebral hemorrhagic infarction. This case is notable for the extensive nature of the cerebral SVT and the child's complete clinical recovery from the neurological event. The report discusses the relation of the thrombosis and leukemia and also emphasizes the importance of early recognition and prompt management, while incorporating a collaborative multidisciplinary approach to prevent long-term consequences.

Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification.

BACKGROUND: The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale. METHODS: PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated. RESULTS: As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series. CONCLUSIONS: The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture. TRIAL REGISTRATION: NCT02186561.

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.

Genetic dysregulation of an endothelial Ras signaling network in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, 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 (p=4.79×10 -7 ). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 ( EPHB4 ) (p=1.22×10 -5 ), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants in ACVRL1 , NOTCH1 , ITGB1 , and PTPN11 . ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.

Low profile sheaths in pediatric neurointervention: a multicenter experience.

BACKGROUND: Pediatric neurointervention is challenged by the appropriateness of adult catheters and devices. This multicenter report on the smallest groin access sheaths offers technical notes and clinical outcomes in the pediatric neurointerventional population. METHODS: All pediatric neurointerventional cases from 2019 to 2021 were reviewed for use of a 3.3F Pediavascular or a 4F Merit Prelude Ideal low profile sheath. Hospital records were reviewed for complications and technical notes and compared with arterial groin access with the 4F Terumo Pinnacle in infants less than 1 year old, before the low profile sheaths at one author's institution were introduced. RESULTS: From January 1, 2019 to March 31, 2021 there were 347 procedures performed at Boston Children's Hospital and University of Wisconsin. Forty-four procedures in 26 patients were identified in which a 3.3F (38 cases, 20 patients) or 4F (6 cases, 6 patients) sheath was used. The average age was 2.2 years (1.5 days to 18 years). Retinoblastoma intra-arterial chemotherapy infusion (18 of 44) was the most common indication. The remaining procedures comprised vein of Galen embolization (12), diagnostic cerebral angiography (13), and one preoperative tumor embolization. Morbidity included a groin hematoma and decreased pulses (4.5%). No major groin complications occurred. There was no statistically significant difference compared with the historical cohort (132 procedures), which had seven instances of decreased pulses (5.3%, p>0.05). CONCLUSION: The 3.3F Pediavascular and 4F Merit Prelude Ideal sheaths are easily incorporated into the pediatric neurointerventionalist's armamentarium for infants and readily accommodate various microcatheters for distal embolization and catheterization.

Wide Arterial Sparing Encephalo-Duro-Synangiosis for Moyamoya: Surgical Technique and Outcomes.

BACKGROUND: Moyamoya is managed by surgical revascularization, but no standardized method has yet been universally adopted. OBJECTIVE: To describe a new indirect bypass technique for pediatric moyamoya, wide arterial sparing encephalo-duro-synangiosis (WASEDS), which provides a much wider area of revascularization with minimal compromise to the middle meningeal arterial tree compared with traditional procedures. Initially used as a salvage technique after failed encephalo-duro-arterio-synangiosis, its success later motivated its use as a first-line procedure. METHODS: Clinical and radiographic records of patients who underwent WASEDS for moyamoya from 2009 to 2020 were reviewed. Brain perfusion relative cerebral blood volume on the side of the WASEDS procedure was calculated. Two-tailed paired t tests were performed to identify the statistically significant differences ( P ≤ .05). RESULTS: WASEDS was successfully performed on 8 patients for a total of 14 cerebral hemispheres. Age ranged from 2 to 25 years. There were no mortalities. The average clinical and radiographic follow-up was 49.79 months (range 2-126 months), demonstrating improvement in neurological condition and no postoperative stroke and significant diminution or cessation of transient ischemic attacks in all patients. Relative cerebral blood volume increased 9.24% after the WASEDS procedure ( P = .012). There were no neurological complications. There were 2 pseudomeningoceles related to the extensive dural openings. CONCLUSION: WASEDS is a safe and effective indirect revascularization technique for both primary and salvage techniques. It provides an extensive area of cortical revascularization with no compromise of the middle meningeal vasculature and subjective reports of early improvement in cognition and behavior. The main disadvantage is elevated risk of pseudomeningocele secondary to the large craniotomy.

Angiography suite cone-beam CT perfusion for selection of thrombectomy patients: A pilot study.

BACKGROUND AND PURPOSE: The availability of cone-beam CT perfusion (CBCTP) in angiography suites may improve large-vessel occlusion (LVO) triage and reduce reperfusion times for patients presenting during extended time window. We aim to evaluate the perfusion maps correlation and agreement between multidetector CT perfusion (MDCTP) and CBCTP when obtained sequentially in patients undergoing endovascular therapy. METHODS: This is a prospective, pilot, single-arm interventional cohort study of consecutive patients with anterior circulation LVO. All patients underwent MDCTP and CBCTP prior to endovascular therapy, generating cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-maximum/time to peak contrast concentration maps. We compared the two imaging modalities using three different methods: (1) six regions of interest (ROIs) placed in the anterior circulation territory; (2) ROIs placed in all 10 Alberta Stroke Program Early CT Score regions; and (3) ROI drawn around the entire ischemic area. ROI ratios (unaffected/affected area) were compared for all sequences in each method. We used the intraclass correlation coefficient to calculate the correlation between the studies. Bland-Altman plots were also created to measure the degree of agreement. Finally, a sensitivity analysis was done comparing both modalities in patients with low infarct growth rate. RESULTS: Fourteen patients were included (median age 81 years [74-87], 50% males, median National Institutes of Health Stroke Scale 19 [14-22]). Median time between studies was 42 minutes (interquartile range 29-61). Independently of the method used, we found moderate to excellent correlation in CBF, CBV, and MTT between modalities. CBF correlation further improved in patients with low infarct growth. CONCLUSION: These results demonstrate promising accuracy of CBCTP in evaluating ischemic tissue in patients presenting with LVO ischemic stroke.

U.S. Wingspan Registry: 12-month follow-up results.

BACKGROUND AND PURPOSE: The purpose of this study is to present 12-month follow-up results for a series of patients undergoing percutaneous transluminal angioplasty and stenting with the Gateway-Wingspan stenting system (Boston Scientific) for the treatment of symptomatic intracranial atherostenosis. METHODS: Clinical and angiographic follow-up results were recorded for patients from 5 participating institutions. Primary end points were stroke or death within 30 days of the stenting procedure or ipsilateral stroke after 30 days. RESULTS: During a 21-month study period, 158 patients with 168 intracranial atherostenotic lesions (50% to 99%) were treated with the Gateway-Wingspan system. The average follow-up duration was 14.2 months with 143 patients having at least 3 months of clinical follow-up and 110 having at least 12 months. The cumulative rate of the primary end point was 15.7% for all patients and 13.9% for patients with high-grade (70% to 99%) stenosis. Of 13 ipsilateral strokes occurring after 30 days, 3 resulted in death. Of these strokes, 76.9% (10 of 13) occurred within the first 6 months of the stenting procedure and no events were recorded after 12 months. An additional 9 patients experienced ipsilateral transient ischemic attack after 30 days. Most postprocedural events (86%) could be attributed to interruption of antiplatelet medications (n=6), in-stent restenosis (n=12), or both (n=1). In 3 patients, the events were of uncertain etiology. CONCLUSIONS: After successful Wingspan percutaneous transluminal angioplasty and stenting, some patients continued to experience ipsilateral ischemic events. Most of these ischemic events occurred within 6 months of the procedure and were associated with the interruption of antiplatelet therapy or in-stent restenosis.

Time resolved contrast enhanced intracranial MRA using a single dose delivered as sequential injections and highly constrained projection reconstruction (HYPR CE).

Time-resolved contrast-enhanced magnetic resonance angiography of the brain is challenging due to the need for rapid imaging and high spatial resolution. Moreover, the significant dispersion of the intravenous contrast bolus as it passes through the heart and lungs increases the overlap between arterial and venous structures, regardless of the acquisition speed and reconstruction window. An innovative technique is presented that divides a single dose contrast into two injections. Initially a small volume of contrast material (2-3 mL) is used to acquiring time-resolved weighting images with a high frame rate (2 frames/s) during the first pass of the contrast agent. The remaining contrast material is used to obtain a high resolution whole brain contrast-enhanced (CE) magnetic resonance angiography (0.57 × 0.57 × 1 mm(3) ) that is used as the spatial constraint for Local Highly Constrained Projection Reconstruction (HYPR LR) reconstruction. After HYPR reconstruction, the final dynamic images (HYPR CE) have both high temporal and spatial resolution. Furthermore, studies of contrast kinetics demonstrate that the shorter bolus length from the reduced contrast volume used for the first injection significantly improves the arterial and venous separation.

Intraoperative application of a new-generation 3D IV-DSA technology in resection of a hemorrhagic cerebellar AVM.

Although intravenous digital subtraction angiography (IV-DSA), cone-beam CT, and rotational angiography are well-established technologies, using them in a single system in the hybrid operating room to acquire high-quality noninvasive 3D images is a recent development. This video demonstrates microsurgical excision of a ruptured cerebellar arteriovenous malformation (AVM) in a 66-year-old male followed by intraoperative IV-DSA acquisition using a new-generation system (Artis Icono). IV-DSA confirmed in real time that no residual remained following excision without the need to reposition the patient. To the best of the authors' knowledge, this is the first surgical video to demonstrate the simplified workflow and application of this technology in neurovascular surgery. The video can be found here: https://youtu.be/bo5ya9DQQPw.

Achievable aspiration flow rates with large balloon guide catheters during carotid artery stenting.

BACKGROUND: Emergency carotid artery stenting (CAS) is a frequent endovascular procedure, especially in combination with intracranial thrombectomy. Balloon guide catheters are frequently used in these procedures. Our aim was to determine if mechanical aspiration through the working lumen of a balloon occlusion catheter during the steps of a carotid stenting procedure achieve flow rates that may lead to internal carotid artery (ICA) flow reversal which consecutively may prevent distal embolism. METHODS: Aspiration experiments were conducted using a commercially available aspiration pump. Aspiration flow rates/min with 6 different types of carotid stents inserted into a balloon guide catheter were measured. Measurements were repeated three times with increasing pressure in the phantom. To determine if the achieved aspiration flow rates were similar to physiologic values, flow rates in the ICA and external carotid artery (ECA) in 10 healthy volunteers were measured using 4D-flow MRI. RESULTS: Aspiration flow rates ranged from 25 to 82 mL/min depending on the stent model. The pressure in the phantom had a significant influence on the aspiration volume. Mean blood flow volumes in volunteers were 210 mL/min in the ICA and 101 mL/min in the ECA. CONCLUSIONS: Based on the results of this study, flow reversal in the ICA during common carotid artery occlusion is most likely achieved with the smallest diameter stent sheath and the stent model with the shortest outer stent sheath maximum diameter. This implies that embolic protection during emergency CAS through aspiration is most effective with these models.

Difference in imaging biomarkers between transient and permanent neurological deficits after endovascular treatment of cerebrovascular aneurysms.

OBJECTIVE: The literature suggests that blood-brain barrier disruption (BBBD) plays a significant role in the development of neurological events in patients with diffusion-weighted imaging (DWI) that is negative for lesions. In this prospective, single-center cohort study, the authors compared the imaging characteristics of patients suffering transient neurological events (TNEs) with those in patients suffering permanent neurological events (PNEs) after having undergone elective embolization of unruptured intracranial aneurysms. METHODS: This prospective cohort study was conducted between July 2016 and June 2019. Inclusion criteria were adults undergoing elective neuroendovascular procedures and the absence of contraindications to MRI. All subjects underwent brain MRI including postcontrast FLAIR (pcFLAIR) sequences for evaluation of BBBD within 24 hours postprocedure. RESULTS: In total, 128 patients harboring 133 unruptured aneurysms were enrolled, 109 of whom (85.2%) showed some degree of BBBD on pcFLAIR MRI and 50 of whom (39.1%) suffered an ischemic insult per DWI. In total, 23 patients (18%) suffered neurological complications, 16 of which (12.5%) were TNEs and 7 of which (5.5%) were PNEs. The median extent of BBBD was focal in asymptomatic patients as compared to hemispheric and lobar in the TNE and PNE groups, respectively (p < 0.001). The American Society of Anesthesiologists physical status classification predicted the extent of BBBD (p = 0.046). Lesions on DWI were noted in 34 asymptomatic patients (32.4%) compared to 9 patients (56.3%) with TNEs and all 7 patients (100%) with PNEs (p < 0.001). The median number of DWI lesions was 0 (range 0-18 lesions) in the asymptomatic group compared to 1.5 (range 0-8 lesions) and 8 (range 1-13 lesions) in the TNE and PNE groups, respectively (p < 0.001). Smoking (p = 0.008), older age (p = 0.002), and longer surgery (p = 0.006) were positively associated with the number of lesions on DWI. On multivariate analysis, intraarterial verapamil (p = 0.02, OR 8.01, 95% CI 1.35-47.43) and extent of BBBD (p < 0.001, OR 58.58, 95% CI 9.48-361.84) were positively associated with the development of TNEs, while intravenous infusion of midazolam during surgery (p = 0.02, OR 6.03, 95% CI 1.29-28.20) was negatively associated. An increased number of lesions on DWI was the only significant predictor for the development of PNEs (p < 0.001, OR 49.85, 95% CI 5.56-447.10). CONCLUSIONS: An increasing extent of BBBD was associated with the development of TNEs, whereas an increasing number of lesions on DWI was significantly associated with the development of PNEs. BBBD imaging using pcFLAIR may serve as a valuable biomarker for detecting subtle cerebral ischemia and stratifying the risk for ischemic events.

Prospective study on embolization of intracranial aneurysms with the pipeline device: the PREMIER study 1 year results.

BACKGROUND: Preliminary clinical studies on the safety and efficacy of the pipeline embolization device (PED) for the treatment of small/medium aneurysms have demonstrated high occlusion rates with low complications. OBJECTIVE: To evaluate the safety and effectiveness of the PED for treatment of wide necked small and medium intracranial aneurysms. METHODS: PREMIER is a prospective, multicenter, single arm trial. Patients were treated with the PED for unruptured wide necked aneurysms, measuring ≤12 mm along the internal carotid artery or vertebral artery, between July 2014 and November 2015. At 1 year post-procedure, the primary effectiveness endpoint was complete occlusion (Raymond grade 1) without major parent vessel stenosis (≤50%) or retreatment, and the primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death. RESULTS: A total of 141 patients were treated with PEDs (mean age 54.6±11.3 years, 87.9% (124/141) women). Mean aneurysm size was 5.0±1.92 mm, and 84.4% (119/141) measured <7 mm. PED placement was successful in 99.3% (140/141) of patients. Mean number of PEDs implanted per patient was 1.1±0.26; a single PED was used in 92.9% (131/141) of patients. At 1 year, 97.9% (138/141) of patients underwent follow-up angiography with 76.8% (106/138) of patients having met the study's primary effectiveness endpoint. The combined major morbidity and mortality rate was 2.1% (3/140). CONCLUSIONS: Treatment of wide necked small/medium aneurysms with the PED results in high rates of complete occlusion without significant parent vessel stenosis and low rates of permanent neurologic complications. TRIAL REGISTRATION: NCT02186561.

Outcome of symptomatic intracranial atherosclerotic disease.

BACKGROUND AND PURPOSE: Patients with intracranial atherosclerotic disease have a 3.6% to 22% annual risk of stroke. In this study, we sought to evaluate the natural history and prognosis of patients with symptomatic intracranial atherosclerotic disease who received medical therapy versus percutaneous transluminal angioplasty and stenting (PTAS) at our institution. METHODS: Charts of all patients with symptomatic intracranial atherosclerotic disease from July 2004 to September 2007 were reviewed and assessed for history of transient ischemic attack or stroke. Patients were either treated with "best medical therapy" (Medical Therapy Group) or PTAS plus antiplatelet agents (PTAS Group) and followed prospectively. A favorable outcome was defined as the absence of transient ischemic attacks, strokes, or vascular death; modified Rankin Scale of < or =3; and no endovascular reintervention of symptomatic in-stent restenosis. RESULTS: One hundred eleven patients fulfilled entry criteria, with 58 (52.3%) and 53 patients (47.7%) enrolled in the Medical Therapy and PTAS Groups, respectively. Thirty-eight patients of the Medical Therapy Group (65.5%) had a favorable outcome compared with 37 patients of the PTAS Group (69.8%). Combined ischemic end point data for the occurrence of transient ischemic attack, stroke, and vascular death was similar with 14 (24%) events in the Medical Therapy Group versus 15 (28.3%) events in the PTAS Group. CONCLUSIONS: Overall, the combined ischemic end point was the same in the Medical Therapy and PTAS Groups.

Target lesion revascularization after wingspan: assessment of safety and durability.

BACKGROUND AND PURPOSE: In-stent restenosis (ISR) occurs in approximately one-third of patients after the percutaneous transluminal angioplasty and stenting of intracranial atherosclerotic lesions with the Wingspan system. We review our experience with target lesion revascularization (TLR) for ISR after Wingspan treatment. METHODS: Clinical and angiographic follow-up results were recorded for all patients from 5 participating institutions in our US Wingspan Registry. ISR was defined as >50% stenosis within or immediately adjacent (within 5 mm) to the implanted stent and >20% absolute luminal loss. RESULTS: To date, 36 patients in the registry have experienced ISR after percutaneous transluminal angioplasty and stenting with Wingspan. Of these patients, 29 (80.6%) have undergone TLR with either angioplasty alone (n=26) or angioplasty with restenting (n=3). Restenting was performed for in-stent dissections that occurred after the initial angioplasty. Of the 29 patients undergoing TLR, 9 required >/=1 interventions for recurrent ISR, for a total of 42 interventions. One major complication, a postprocedural reperfusion hemorrhage, was encountered in the periprocedural period (2.4% per procedure; 3.5% per patient). Angiographic follow-up is available for 22 of 29 patients after TLR. Eleven of 22 (50%) demonstrated recurrent ISR at follow-up angiography. Nine patients have undergone multiple retreatments (2 retreatments, n=6; 3 retreatments, n=2; 4 retreatments, n=1) for recurrent ISR. Nine of 11 recurrent ISR lesions were located within the anterior circulation. The mean age for patients with recurrent anterior circulation ISR was 57.9 years (vs 81 years for posterior circulation ISR). CONCLUSIONS: TLR can be performed for the treatment of intracranial Wingspan ISR with a relatively high degree of safety. However, the TLR results are not durable in approximately 50% of patients, and multiple revascularization procedures may be required in this subgroup.

Differences in Pressure Within the Sac of Human Ruptured and Nonruptured Cerebral Aneurysms.

BACKGROUND: Hemodynamics plays a critical role in the development, growth, and rupture of intracranial aneurysms. This data could be vital in determining individual aneurysm rupture risk and could facilitate our understanding of aneurysms. OBJECTIVE: To present the largest prospective cross-sectional cohort study of intrasaccular pressure recordings of ruptured and nonruptured intracranial aneurysms and describe the hemodynamic differences that exist between ruptured and nonruptured aneurysms. METHODS: During endovascular treatment, a standard 1.8-Fr 200 m length microcatheter was navigated into the dome of the aneurysm prior to coil embolization. With the microcatheter centralized within the dome of the aneurysm, an arterial pressure transducer was attached to the proximal end of the microcatheter to measure the stump pressure inside the aneurysm dome. RESULTS: In 68 aneurysms (28 ruptured, 40 nonruptured), we observed that ruptured cerebral aneurysms had a lower systolic and mean arterial pressure compared to nonruptured cohort (P = .0008). Additionally, the pulse pressures within the dome of ruptured aneurysms were significantly more narrow than that of unruptured aneurysms (P = .0001). These findings suggest that there may be an inherent difference between ruptured and nonruptured aneurysms and such recordings obtained during routine digital subtraction angiography could potentially become a widely applied technique to augment risk stratification of aneurysms. CONCLUSION: Our preliminary data present new evidence distinguishing ruptured from unruptured aneurysms that may have a critical role as a predictive parameter to stratify the natural history of nonruptured intracranial aneurysms and as a new avenue for future investigation.

Serial Quantitative and Qualitative Measurements of Flow in Vein of Galen Malformations Using 4-Dimensional Flow Magnetic Resonance Imaging (Phase Contrast Vastly undersampled Isotropic PRojection).

BACKGROUND: Vein of Galen malformations (VoGMs) induce cerebrovascular dysfunction through arterial steal and venous hypertension resulting, if untreated, in severe neurologic morbidity and mortality. Noninvasive techniques for quantitative, serial evaluation of cerebrovascular hemodynamics in VoGMs are lacking. This proof of concept study using quantitative blood flow measurements from 4-dimensional flow magnetic resonance imaging may be useful as a noninvasive biomarker to guide timing of intervention and assess disease progression and treatment outcomes. CASE DESCRIPTION: Between July 2016 and July 2018, 4 patients harboring VoGMs underwent Phase Contrast Vastly undersampled Isotropic PRojection (PCVIPR) imaging at the University of Wisconsin Hospitals and Clinics. We applied PCVIPR imaging to assess its potential for obtaining anatomic and physiologic flow data before and after surgical embolization of VoGMs. Hemodynamic pressure parameters obtained from PCVIPR imaging were compared with stump pressures recorded in vivo. We found a decrease in mean arterial pressure from 97 mm Hg pretreatment to 65 mm Hg post treatment. These findings corroborate the decrement in venous pressure gradients documented on PCVIPR imaging. For all patients, pressure gradient changes on PCVIPR imaging correlated with in vivo arterial pressures and aided in clinical decision related to cerebrovascular evaluation, treatment planning, and clinical course. CONCLUSIONS: Four-dimensional flow magnetic resonance imaging/PCVIPR imaging has a potential role in determining endovascular embolization and therapeutic outcomes on the basis of objective and reproducible hemodynamic characteristics of the vascular lesion. It represents a novel, noninvasive approach that may guide the extent and timing of therapeutic intervention and treatment of cerebrovascular diseases in pediatric patients.

Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.

Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.