Posterior cerebral territory ischemia in pediatric moyamoya: Surgical techniques and long-term clinical and radiographic outcomes.

PURPOSE: To describe a surgical technique for posterior cerebral revascularization in pediatric patients with moyamoya arteriopathy. Here, we describe the clinical characteristics, surgical indications, operative techniques, and clinical and radiographic outcomes in a series of pediatric patients with moyamoya disease affecting the posterior cerebral artery (PCA) territory. METHODS: A retrospective single-center series of all pediatric patients with moyamoya disease who presented to our institute between July 2009 through August 2019 were reviewed. The clinical characteristics, surgical indications, operative techniques, and long-term clinical and radiographic outcomes of pediatric moyamoya patients with PCA territory ischemia were collected and analyzed. RESULTS: A total of 10 PCA revascularization procedures were performed in 9 patients, 5 female, ages 1 to 11.1 years (average 5.2 years). Complications included 1 stroke, with no infections, hemorrhages, seizures, or deaths. One patient had less than 1 year of radiographic and clinical follow-up. In 8 of 9 patients with at least 1 year of radiographic follow-up, there was engraftment of surgical vessels present in all cases. No new strokes were identified on long-term follow-up despite the radiographic progression of the disease. In the 8 cases available for analysis, the average follow-up was 50.8 months with a range of 12 to 117 months. CONCLUSIONS: PCA territory ischemia in patients with progressive moyamoya disease can be surgically treated with indirect revascularization. Here, we describe our experience with PCA revascularization procedures for moyamoya disease, including pial pericranial dural (PiPeD) revascularization and pial synangiosis utilizing the occipital artery. These surgical options may be useful for decreasing the risk of stroke in pediatric moyamoya patients with severe posterior circulation disease.

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.

Intracranial venous malformation masquerading as a meningioma in PI3KCA-related overgrowth spectrum disorder.

Gain of function PIK3CA pathogenic variants have been identified in overgrowth syndromes collectively termed "PIK3CA-related overgrowth spectrum" (PROS). There are no previously reported cases of cerebrovascular venous malformations in PROS syndromes, though somatic activating PIK3CA variants have been identified in extracranial venous malformation. This study was approved by the Institutional Review Boar at Boston Children's Hospital. A 14-year-old female mosaic for the de novo p.R108H pathogenic variant in the PIK3CA gene was found to have a large tumor involving the superior sagittal sinus with mass effect on the motor cortex most consistent with a parafalcine meningioma. She underwent surgical resection with pathology demonstrating a venous malformation. PIK3CA pathogenic variants have been identified in nonsyndromic extracranial venous and lymphatic malformations as well in brain tumors, including glioma and meningioma. However, PIK3CA variants have not previously been identified in purely intracranial venous malformations. This distinction is relevant to treatment decisions, given that mTOR inhibitors may provide an alternative option for noninvasive therapy in cases of suspected venous malformation.

Adverse effects of erenumab on cerebral proliferative angiopathy: A case report.

BACKGROUND: Cerebral proliferative angiopathy is a vascular malformation associated with compromised blood-brain barrier and with migraine-like headache. Treating blood-brain barrier-compromised patients with erenumab, an anti-calcitonin gene-related peptide receptor monoclonal antibody, may be risky. CASE: We describe a case of a 22-year-old chronic migraine patient with cerebral proliferative angiopathy who presented to our hospital in status epilepticus 2 d after his first dose of erenumab. Serial magnetic resonance imaging (MRI) studies demonstrated progressive areas of diffusion restriction including the brain tissue adjacent to the cerebral proliferative angiopathy, bilateral white matter and hippocampi. His 6-month post-presentation magnetic resonance imaging was notable for white matter injury, encephalomalacia surrounding cerebral proliferative angiopathy and bilateral hippocampal sclerosis. He remains clinically affected with residual symptoms, including refractory epilepsy and cognitive deficits. CONCLUSION: The evidence presented in this case supports further investigation into potential deleterious side effects of erenumab in patients with compromised blood-brain barrier, such as individuals with intracranial vascular malformations.

Congenital Disseminated Pyogenic Granuloma: Characterization of an Aggressive Multisystemic Disorder.

OBJECTIVE: To describe the clinical, radiologic, and histopathologic features of "congenital disseminated pyogenic granuloma" involving various organs with high morbidity related to cerebral hemorrhagic involvement. STUDY DESIGN: We searched the database of the Vascular Anomalies Center at Boston Children's Hospital from 1999 to 2019 for patients diagnosed as having multiple vascular lesions, visceral vascular tumors, congenital hemangiomatosis, multiple pyogenic granulomas, or multiple vascular lesions without a definite diagnosis. A retrospective review of the medical records, photographs, histopathologic, and imaging studies was performed. Only patients with imaging studies and histopathologic diagnosis of pyogenic granuloma were included. RESULTS: Eight children (5 male, 3 female) had congenital multifocal cutaneous vascular tumors. Lesions also were found in the brain (n = 7), liver (n = 4), spleen (n = 3), muscles (n = 4), bone (n = 3), retroperitoneum (n = 3), and intestine/mesentery (n = 2). Less commonly affected were the spinal cord, lungs, kidneys, pancreas, and adrenal gland (n = 1 each). The mean follow-up period was 21.8 months. The cerebral and visceral lesions were hemorrhagic with severe neurologic sequelae. The histopathologic diagnosis was pyogenic granuloma with prominent areas of hemorrhage and necrosis. The endothelial cells had enlarged nuclei, pale cytoplasm and were immunopositive for CD31 and negative for D2-40 and glucose transporter 1. CONCLUSIONS: Congenital disseminated pyogenic granuloma is a distinct multisystemic aggressive disorder that primarily affects the skin, brain, visceral organs, and musculoskeletal system. Differentiation of this entity from other multiple cutaneous vascular lesions is critical because of possible cerebral hemorrhagic involvement.

Survey of practice patterns and preparedness for endovascular therapy in acute pediatric stroke.

PURPOSE: Endovascular therapy benefits selected adults with acute stroke while data are lacking for children. The purpose of this study was to assess physician practice and institutional preparedness for endovascular therapy in pediatric stroke. METHODS: A link to an anonymous online survey was sent to members of the International Pediatric Stroke Study (IPSS) group about physician experience with endovascular therapy, likelihood of treatment for provided clinical vignettes, and institutional readiness for the delivery of endovascular therapy to children. RESULTS: Thirty-one pediatric physicians with a mean of 11 years (SD 7.1) of experience responded. All but two would consider endovascular therapy in a child, and 20 (64.5%) had recommended endovascular therapy for a child in the preceding year. Most (n = 19, 67.9%) did not commit to an age minimum for endovascular therapy. Sixteen (57.1%) would consider treatment up to 24 h after symptom onset with 19 (67.9%) respondents reporting that their practice changed after the 2018 American Heart Association guidelines extended the time window for endovascular therapy in adults. Seventeen (60.7%) preferred imaging that included perfusion in children presenting beyond 6 h. Nineteen (70.4%) had institutional endovascular therapy criteria. Physicians in larger pediatric groups had more "likely to treat" responses on the clinical vignettes than physicians working in smaller groups (11.7 vs. 6.1, p < 0.05). CONCLUSION: Pediatric stroke physicians are largely willing to consider endovascular therapy with most changing their practice according to adult guidelines, though experience and selection criteria varied. These findings may help to inform consensus guidelines and clinical trial development.

Direct neural current imaging in an intact cerebellum with magnetic resonance imaging.

The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR=100ms) at 4.7T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1mm(3), (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27-0.37°, corresponding to local magnetic field changes of 0.67-0.93nT (for TE=26ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents.

Considerations in Applying a New Stent Retriever in Pediatric Endovascular Cerebral Thrombectomy for Acute Ischemic Stroke.

Acute ischemic stroke (AIS) in children has been difficult to diagnose, treat and study, due to atypical clinical presentation, imaging challenges and the rarity of large-vessel embolic occlusion as the etiology of acute neurological change in children. With endovascular thrombectomy showing success in randomized trials of adult AIS, the technique is increasingly being extrapolated to pediatric stroke. However, there is little evidence regarding the safety or efficacy of applying in children these devices developed and tested in adults. There is concern about a vessel-to-device size mismatch that may result in a different complication and benefit profile than typically seen. We report on the successful application in pediatric stroke of a newer-generation, smaller stent retriever, designed to be delivered through relatively smaller and more navigable microcatheters than the prior generation of this device.

Magnetic resonance imaging of ionic currents in solution: the effect of magnetohydrodynamic flow.

PURPOSE: Reliably detecting MRI signals in the brain that are more tightly coupled to neural activity than blood-oxygen-level-dependent fMRI signals could not only prove valuable for basic scientific research but could also enhance clinical applications such as epilepsy presurgical mapping. This endeavor will likely benefit from an improved understanding of the behavior of ionic currents, the mediators of neural activity, in the presence of the strong magnetic fields that are typical of modern-day MRI scanners. THEORY: Of the various mechanisms that have been proposed to explain the behavior of ionic volume currents in a magnetic field, only one-magnetohydrodynamic flow-predicts a slow evolution of signals, on the order of a minute for normal saline in a typical MRI scanner. METHODS: This prediction was tested by scanning a volume-current phantom containing normal saline with gradient-echo-planar imaging at 3 T. RESULTS: Greater signal changes were observed in the phase of the images than in the magnitude, with the changes evolving on the order of a minute. CONCLUSION: These results provide experimental support for the MHD flow hypothesis. Furthermore, MHD-driven cerebrospinal fluid flow could provide a novel fMRI contrast mechanism.

Interventional neuroradiology in children: diagnostics and therapeutics.

PURPOSE OF REVIEW: To highlight the spectrum of pediatric neurovascular conditions typically referred for diagnostic or interventional neuroangiography, the range of techniques available in contemporary pediatric neurointerventional practice, and the specific considerations relating to radiation and contrast dosing applicable to pediatric neurointerventional procedures. RECENT FINDINGS: Neurointerventional procedures are increasingly utilized in children for a variety of indications, with continuous emphasis on improving safety and treatment effectiveness. Numerous steps can be taken to mitigate the potential risks of pediatric neurointerventional procedures, with recent data from high-volume centers suggesting similar, if not lower, complication rates in children compared with adults. Judicious patient selection and clarity of goals are critically important, however, because children undergoing complex and lengthy neurointerventional procedures are particularly vulnerable to the effects of ionizing radiation, vessel injury, and contrast overload. SUMMARY: With continued advances in endovascular technology, neurointerventionalists stand to play an important and expanding role in the multidisciplinary management of pediatric neurovascular disease.

Pediatric central nervous system vascular malformations.

Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations.

Intracranial aneurysms in the youngest patients: characteristics and treatment challenges.

BACKGROUND: Characteristics and treatment challenges of aneurysms in young children differ from those in older pediatric patients. METHODS: Records of children undergoing cerebral or spinal angiography by the senior neurointerventionalist (D.B.O.) from October 2006 to January 2014 were reviewed to identify patients with digital subtraction angiography-confirmed intracranial aneurysms. Demographics, presentation, subtype of aneurysm, treatment strategy, and outcome were evaluated. RESULTS: Of 763 pediatric cases, 33 were of children harboring cerebral aneurysms. Overall, 48% were male, 24% presented with hemorrhage and 67% harbored fusiform/dissecting aneurysms. Patients aged 0-10 years were significantly more likely to harbor nonsaccular, dissecting/fusiform aneurysms (84 vs. 43%, p = 0.02). A total of 13/22 pediatric patients harboring dissecting/fusiform aneurysms were male (59%) compared to 3/11 with saccular aneurysms (27%, p = 0.14). Overall, 15 patients underwent endovascular treatment (45%) and 8 underwent microsurgical treatment (24%). There was no significant difference in treatment approach based on patient age or aneurysm morphology. Overall, 19/23 aneurysms were occluded after initial treatment (83%); there were 2 procedure-related complications with neurological sequelae (9%). CONCLUSION: We demonstrate that the youngest patients (10 years and under) have aneurysms even more distinct and less similar to adult aneurysms than those in the larger pediatric cohort.

Transarterial embolization of mandibular arteriovenous malformations using ONYX.

PURPOSE: To document the efficacy of ethylene vinyl alcohol copolymer (ONYX; ev3/Covidien, Irvine, CA) in the treatment of arteriovenous malformations (AVMs) of the mandible. MATERIALS AND METHODS: A retrospective consecutive series of patients with facial AVMs isolated to the mandible and immediate perimandibular tissue was identified at 2 institutions. The primary treatment modality of transarterial embolization using ONYX was performed by way of the external carotid artery branches. Staged procedures were accomplished until no arteriovenous shunt remained. A 1-year follow-up angiogram was obtained for each patient. RESULTS: Three patients, aged 8 (patient 1), 16 (patient 2), and 17 (patient 3) years presented with bleeding from facial AVMs isolated to the mandible. Patient 1 was female and patients 2 and 3 were male. The 2 older patients had loose molar or canine dentition. Transarterial embolization with ONYX achieved complete angiographic closure of the arteriovenous shunt in each patient. A total of 1, 6, and 3 staged embolization procedures were performed in the 3 patients. Patient 2 had mild transient facial numbness after embolization that completely resolved. Patient 3 had loose molars associated with the AVM that were extracted for treatment of intraprocedural bleeding. The 1-year angiographic follow-up data demonstrated durable closure of all 3 lesions. CONCLUSIONS: Transarterial embolization of high-flow intraosseus mandibular AVMs was safely accomplished with ONYX in our small retrospective cohort. Complete, durable occlusion was found on the angiogram at 1 year, with clinical stability extending to an average of 3 years. Surgical resection of the AVM was avoided in all 3 patients.

Infantile dural arteriovenous fistula: a reconsideration.

BACKGROUND: Infantile-type dural arteriovenous shunts (IDAVS) are rare and heterogeneous vascular lesions, complicating their classification and management. The current tripartite classification of pediatric dural arteriovenous shunts (DAVS) into dural sinus malformation, infantile-type, and adult-type, does not stand up to scrutiny, given the variable presentations of the latter two types in children. We estimate the prevalence of IDAVS and evaluate the long term outcomes after endovascular treatment (EVT). METHODS: A retrospective review of a pediatric cerebrovascular database between 2006 and 2023 was conducted. Clinical and radiographic data were analyzed to evaluate the presentation and long term outcomes of IDAVS. RESULTS: IDAVS were identified in 8 (0.5%) of 1463 patients, with mean age at diagnosis of 34.7 months; male infants comprised 62.5%. The most common clinical presentations included macrocephaly (37.5%), seizures (25%), and dilated scalp veins (25%). EVT was performed in 87.5% of cases, averaging 5.8 procedures per patient. Radiographic obliteration was observed in 28.6%. Good clinical outcomes (modified Rankin Scale score of ≤2) were achieved in 85.7%. Our findings showcased discrepancies and limitations in the current classification of pediatric DAVS, prompting a re-evaluation. CONCLUSION: IDAVS accounted for a small proportion of pediatric cerebrovascular pathologies, with markedly heterogeneous presentations. Stepwise selective embolization was associated with favorable outcomes, and is recommended over an aggressive approach with the goal of complete angiographic obliteration. Our proposed revised classification system bifurcates pediatric DAVS into dural sinus malformations and all other DAVS that are manifest in children, thereby enhancing diagnostic clarity and therapeutic approaches.

Imaging Assessment of Fetal Cerebrovascular Anomalies.

Four distinct vascular anomalies can be seen to affect the brain on fetal imaging: vein of Galen malformations, non-galenic arteriovenous pial fistulas, dural sinus malformations, and intracranial venous malformations. These congenital disorders affect the arteries and veins of the developing brain and are rarely seen beyond the neonatal stage. The four fetal cerebrovascular anomalies are associated with quite disparate natural histories and prognoses. MRI plays a pivotal role in the evaluation of fetuses with these conditions due to its ability to definitively establish the diagnosis, to detect subtle parenchymal injuries, to delineate the course of abnormal vessels in detail and to some extent the nature of vascular flow, and to identify ischemic, thrombotic, and hemorrhagic complications. Recently, an investigational transurterine embolization procedure targeted at treating fetuses with vein of Galen malformations who are at high risk for neonatal decompensation has emerged as a promising alternative to expectant management and post-natal embolization, with imaging being used to identify suitable patients for the intervention and in pre-procedural planning. This manuscript reviews the essential imaging and clinical features of these four fetal neurovascular anomalies and underscores the practical aspects related to counseling, prognosis, and the multidisciplinary management of these entities.ABBREVIATIONS: ACVRL1= activin A receptor like type 1; b-SSFP=Balanced Steady State Free precession; DSM= Dural Sinus Malformation; Ephrin B4= Ephrin type-B receptor 4; icVM= Intracranial Venous Malformation; ITGB1= Integrin Subunit Beta 1; NOTCH1= Neurogenic locus notch homolog protein 1; PTPN11= Protein Tyrosine Phosphatase Non-Receptor Type 11; RASA1= RAS P21 Protein Activator 1; SSFSE= Single-shot fast spin echo; VOGM=Vein of Galen Malformation.

Low-profile mechanical thrombectomy devices for large vessel occlusion in pediatric ischemic stroke.

BACKGROUND: Mechanical thrombectomy (MT) is a well-established treatment modality for large vessel occlusion (LVO) in adults, but there are limited data in the pediatric population. The rarity of the condition makes prospective trial design difficult, and therefore evaluation of MT devices and outcomes is sparse. In pediatric LVO cases, some newer devices may be appropriate for use in revascularization procedures. Furthermore, illustrative specific device-access combinations have rarely been presented in young patients under the age of 5 years. METHODS: This was a single institution experience in intracranial MT procedures for pediatric acute ischemic stroke (AIS). A given procedure was included if there was an attempt at MT between 2015 and 2023. RESULTS: Sixteen endovascular procedures were performed in 15 patients with AIS, with a mean age of 7.4 years; eight patients were <5 years of age. MT was attempted in 15/16 (93.7%) procedures, including 11 (73.3%) in the anterior circulation and four (26.7%) in the posterior circulation; one case recanalized after medical treatment. The most common MT techniques were combined aspiration with a stentriever (n=10, 66.7%) and aspiration alone (n=3, 20%). Traditional stentrievers (4-6 mm) were used in seven cases and low-profile stentrievers in four cases. Improved reperfusion was achieved in all low-profile stentriever cases. Reperfusion of modified Thrombolysis in Cerebral Infaction ≥2b was obtained in 73.3% of cases, including 72.7% of those in which a stentriever was used. CONCLUSIONS: Low-profile thrombectomy devices may achieve similar revascularization results to other approaches in challenging clinical scenarios observed in younger children.

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 suffer high mortality rates and poor cognitive outcomes. Quantitative diagnostic tools are needed to improve clinical outcomes. 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 lesion's outflow tract through the falcine or straight sinus (MD), which is a known morphological prognostic metric. RESULTS: In all 11 subjects (mean age 22±17 weeks [SD]), total blood flow to the brain always exceeded normal levels (1063±403 ml/min [mean±SD]). Significant correlations were observed between falcine sinus flow and MD, the posterior/middle cerebral artery flow ratio and age at scan, and between superior sagittal sinus flow proximal to malformation inflow and age at scan. CONCLUSIONS: Using 4D flow MRI we established the hemodynamic underpinnings of MD, and investigated metrics representing parenchymal venous drainage that could be used to monitor the normalization of hemodynamics during embolization therapy. ABBREVIATIONS: ACA = anterior cerebral artery; BA = basilar artery; MD = falcine or straight sinus mediolateral diameter; NAR = neonatal at risk; PCA = posterior cerebral artery; PCom = posterior communicating artery; SSS = superior sagittal sinus; VOGM = vein of Galen malformation.