Cerebrovascular Surgery and Interventions Center | Selected Papers

There is evidence to suggest that the formation of pediatric brain aneurysms is different than those in adults. Our research looks at the unique characterizes of aneurysms in children.

• Penn DL; Lanpher AB; Klein JM; Kozakewich HPW; Kahle KT; Smith ER; Orbach DB. Multimodal treatment approach in a patient with multiple intracranial myxomatous aneurysms. Journal of Neurosurgery: Pediatrics. 2018 Mar 1;21(3):315-21.
• Gross BA; Smith ER; Scott RM; Orbach DB. Intracranial aneurysms in the youngest patients: Characteristics and treatment challenges. Pediatr Neurosurg. 2015;50(1):18-25.

Our research into arteriovenous malformations (AVMs) includes new approaches to treating these tangles of arteries and veins in the brain. To learn more about AVMs, watch our video series.

• Gross BA; Storey A; Orbach DB; Scott MR; Smith ER. Microsurgical treatment of arteriovenous malformations in pediatric patients: the Boston Children's Hospital experience. J Neurosurg Pediatr 2015 Jan; 15:71-7. A review of 94 children with cerebral AVMs who underwent microsurgical resection finds high efficacy and low complications.
• Fehnel KP; Penn DL; Duggins-Warf M; Gruber M; Pineda S; Sesen J; Moses-Gardner A; Shah N; Driscoll J; Zurakowski D; Orbach DB; Smith ER. Dysregulation of the EphrinB2-EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients. Exp Mol Med. 2020 Apr;52(4):658-671. doi: 10.1038/s12276-020-0414-0. Epub 2020 Apr 14. PubMed PMID: 32286515; PubMed Central PMCID: PMC7210966.
• See AP; Mohammaden MH; Rizko M; Stapleton CJ; Amin-Hanjani S; Charbel FT; Aletich V; Alaraj A. Morbidity and mortality associated with sequential flow reduction embolization technique of cerebral arteriovenous malformations using n-butyl cyanoacrylate. J Neurointerv Surg. 2021 Mar;13(3):237-241. doi: 10.1136/neurintsurg-2020-016223. Epub 2020 Aug 14. PMID: 32801122
• Riordan CP; Orbach DB; Smith ER; Scott RM. Acute fatal hemorrhage from previously undiagnosed cerebral arteriovenous malformations in children: a single-center experience. J Neurosurg Pediatr. 2018 Jun 1:1-7. PMID: 29856294.

Our work with arteriovenous fistulas (AVFs) includes innovative ways to adopt; enhance; and create minimally invasive strategies and devices to safely treat even the youngest of children.

• See AP; Kochis MA; Orbach DB. Republished: Segmental upper mid-basilar artery sacrifice in a child using a Micro Vascular Plug device for treatment of a basilar arteriovenous fistula compressing the brainstem. Journal of Neurointerventional Surgery. 2017 Oct 1;9(10): e37.
• Ashour R; Orbach DB. Lower vertebral-epidural spinal arteriovenous fistulas: a unique subtype of vertebrovertebral arteriovenous fistula; treatable with coil and Penumbra Occlusion Device embolization. Journal of Neurointerventional surgery. 2016 Jun 1;8(6):643-7.
• Gross BA; Akgoz A; Orbach DB. Dural arteriovenous shunts in children. J Pediatr Neuroradiol 2013 Oct 2:263-8. A review of dural AVFs in children; including subtypes (dural sinus malformations; infantile dural arteriovenous shunts; and adult-type dural arteriovenous shunts) and prognosis.
• Duran D; Karschnia P; Gaillard JR; Karimy JK; Youngblood MW; DiLuna ML; Matouk CC; Aagaard- Kienitz B; Smith ER; Orbach DB; Rodesch G; Berenstein A; Gunel M; Kahle KT. Human genetics and molecular mechanisms of vein of Galen malformation. J Neurosurg Pediatr. 2018 Apr; 21 (4):367-374. PMID: 29350590.
• Duran D; Zeng X; Jin SC; Choi J; Nelson-Williams C; Yatsula B; Gaillard J; Furey CG; Lu Q; Timberlake AT; Dong W; Sorscher MA; Loring E; Klein J; Allocco A; Hunt A; Conine S; Karimy JK; Youngblood MW; Zhang J; DiLuna ML; Matouk CC; Mane S; Tikhonova IR; Castaldi C; Lopez- Giraldez F; Knight J; Haider S; Soban M; Alper SL; Komiyama M; Ducruet AF; Zabramski JM; Dardik A; Walcott BP; Stapleton CJ; Aagaard-Kienitz B; Rodesch G; Jackson E; Smith ER; Orbach DB; Berenstein A; Bilguvar K; Vikkula M; Gunel M; Lifton RP; Kahle KT. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron. 2019 Feb 6; 101 (3):429-443 e424. PMID: 30578106.
• Arko L; Lambrych M; Montaser A; Zurakowski D; Orbach DB. Fetal and neonatal MRI predictors of aggressive early clinical course in vein of Galen malformation. AJNR 2020 Jun;41(6):1105-1111. PMID: 32467186.

We feel a responsibility to our patients to learn as much as possible about vascular malformations and tumors in children as well as adults. Our work includes the development of effective therapies as well as research that may lead to ways to prevent these anomalies.

• Desai SB; O'Brien C; Shaikh R; Hedequist D; Proctor M; Orbach DB; Padua H. Multidisciplinary management of spinal aneurysmal bone cysts: A single-center experience. Interv Neuroradiol. 2019 Oct;25(5):564-569. PMID: 31088242
• Chen KS; Montaser A; Ashour R; Orbach DB. Intracranial venous malformations: Incidence and characterization in a large pediatric cohort. Interv Neuroradiol. 2021 Feb; 27 (1):6-15 DOI:10.1177/1591019920943752. PMID:32689840.
• Alomari MH; Shahin MM; Fishman S; Kerr CL; Smith ER; Eng W; Ruiz-Gutierrez M; Adams D; Orbach DB; Chaudry G; Shaikh R; Chewning R; Alomari AI. Cerebrospinal fluid leak in epidural venous malformations and blue rubber bleb nevus syndrome. J Neurosurg Spine. 2021. In press

Cavernous malformation are small masses made up of abnormal, thin-walled blood vessels. While they can occur anywhere in the body, they usually only cause serious problems when in the brain and spinal cord. Our research has focused on ways to better understand CMs in hopes of treating and preventing potentially life-threatening neurologic symptoms.

• Gross BA; Du R; Orbach DB; Scott RM; Smith ER. The natural history of cerebral cavernous malformations in children. J Neurosurg Pediatr. 2015:1-6. PMID: 26474098.

Our work with dural sinus malformations (DSM) includes innovative approaches to fetal imaging and prognosing these vascular malformations while a child is utero.

• Yang E; Storey A; Olson HE; Soul; J; Estroff JA; Trenor CC; Cooper BK; Smith ER; Orbach DB. Imaging features and prognostic factors in fetal and postnatal torcular dural sinus malformations; part I: review of experience at Boston Children’s Hospital. Journal of neurointerventional surgery. 2018 May 1;10(5):467-70.
• Yang E; Storey A; Olson HE; Soul J; Estroff JA; Trenor CC; Cooper BK; Smith ER; Orbach DB. Imaging features and prognostic factors in fetal and postnatal torcular dural sinus malformations; part II: synthesis of the literature and patient management. Journal of neurointerventional surgery. 2018 May 1;10(5):471-5.
• Orbach D; Storey A; Morash D; Estroff J; Smith E; Trenor C; Olson H. Pathogenesis of dural sinus malformations as demonstrated by fetal imaging: a decision-making crucible for parents and clinicians. J Neurointerv Surg 2014 Jul; 6 Suppl 1:A69-70. A study of all 9 cases of dural sinus malformation seen prenatally over the past five years by Boston Children’s Hospital’s Advanced Fetal Care Center.

Our research into vein of Galen malformations looks to pave the way for advances in the diagnosis and treatment of patients and includes investigating early neonatal and fetal imaging to accurately assess risk and time treatment decisions.

• Arko L; Lambrych M; Montaser A; Zurakowski D; Orbach; DB. Fetal and neonatal MRI predictors of aggressive early clinical course in vein of Galen malformation. Am Journal Neurorad Jun 2020; 41 (6) 1105-1111. This study found that early neonatal and fetal MRI can accurately predict which fetuses with vein of Galen malformations will go on to have heart failure after birth.
• Duran D; Zeng X; Chih Jin S; Choi J; Nelson-Williams C; Yatsula B; Gaillard J; Furey CG; Qiongshi Lu Q; Timberlake AT; Dong W; Sorscher MA; Loring E; Klein J; Allocco A; Hunt A; Conine S; Karimy JK; Youngblood MW; Zhang J; DiLuna ML; Matouk CC; Mane S; Tikhonova IR; Castaldi C; López-Giráldez F; Knight J; Haider S; Soban M; Alper SL; Komiyama M; Ducruet AF; Zabramski JM; Dardik A; Walcott BP; Stapleton CJ; Aagaard-Kienitz B; Rodesch G; Jackson E; Smith ER; Orbach DB; Berenstein A; Bilguvar K; Vikkula M; Gunel M; Lifton RP; Kahle KT. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron. 2019 02 06; 101(3):429-443.e4
• Daniel Duran D; Karschnia P; Gaillard JR; Karimy JK; Youngblood MW; DiLuna ML; Matouk CC; Aagaard-Kienitz B; Smith ER; Orbach DB; Rodesch G; Berenstein A; Gunel M; Kahle KT. Human genetics and molecular mechanisms of vein of Galen malformation. J Neurosurg Pediatr. 2018 04; 21(4):367-374.

The Boston Children’s Moyamoya Program is the largest center of its kind in the country — and our team of experts are the most experienced in caring for children and adolescents with this rare condition and have played a key role in developing the American Heart Association’s (AHA) guidelines for management of moyamoya and stroke. To learn more about moyamoya disease, watch our video series.

• Pinard A; Guey S; Guo D; Cecchi AC; Kharas N; Wallace S; Regalado ES; Hostetler EM; Sharrief AZ; Bergametti F; Kossorotoff M; Hervé D; Kraemer M; Bamshad MJ; Nickerson DA; Smith ER; Tournier-Lasserve E; Milewicz DM. The pleiotropy associated with de novo variants in CHD4; CNOT3; and SETD5 extends to moyamoya angiopathy. Genetics in Medicine. 2019 Sep 2:1-5.
• Riordan CP; Storey A; Cote DJ; Smith ER; Scott MR. Results of more than 20 years of follow-up in pediatric patients with moyamoya disease undergoing pial synangiosis. Journal of Neurosurgery: Pediatrics. 2019 Mar 1;23(5):586-92.
• Penn DL; Wu KC; Presswood KR; Riordan CP; Scott MR; Smith ER. General principles for pial synangiosis in pediatric moyamoya patients: 2-dimensional operative video. Operative Neurosurgery. 2019 Jan 1;16(1):E14-5.
• Ganesan V; Smith ER. Moyamoya: defining current knowledge gaps. Dev Med Child Neurol 2015 Feb 13 (DOI: 10.1111/dmcn.12708).
• See; AP; Ropper; AE; Underberg; DL; Robertson; RL; Scott MR ; Smith ER. Down syndrome and moyamoya: Clinical presentation and surgical management. J Neurosurg Pediatr. 2015 Jul 1;16(1):58-63.
• Baird LC; Smith ER; Ichord R; Piccoli DA; Bernard TJ; Spinner NB; Scott MR; Kamath BM. Moyamoya syndrome associated with Alagille syndrome: Outcome after surgical revascularization. J Pediatr 2015 Feb; 166:470-3. A case report of five children with ALGS with moyamoya who underwent revascularization surgery.
• Kundishora AJ; Peters ST; Pinard A; Duran D; Panchagnula S; Barak T; Miyagishima DF; Dong W; Smith H; Ocken J; Dunbar A; Nelson-Williams C; Haider S; Walker RL; Li B; Zhao H; Thumkeo D; Marlier A; Duy PQ; Diab NS; Reeves BC; Robert SM; Sujijantarat N; Stratman AN; Chen YH; Zhao S; Roszko I; Lu Q; Zhang B; Mane S; Castaldi C; López-Giráldez F; Knight JR; Bamshad MJ; Nickerson DA; Geschwind DH; Chen SL; Storm PB; Diluna ML; Matouk CC; Orbach DB; Alper SL; Smith ER; Lifton RP; Gunel M; Milewicz DM; Jin SC; Kahle KT. DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease. JAMA Neurol. 2021 Jun 14;. doi: 10.1001/jamaneurol.2021.1681. [Epub ahead of print] PubMed PMID: 34125151; PubMed Central PMCID: PMC8204259.
• Sesen J; Driscoll J; Moses-Gardner A; Orbach DB; Zurakowski D; Smith ER. Non-invasive Urinary Biomarkers in Moyamoya Disease. Front Neurol. 2021;12:661952. doi: 10.3389/fneur.2021.661952. eCollection 2021. PubMed PMID: 33868159; PubMed Central PMCID: PMC8047329.
• Pinard A; Guey S; Guo D; Cecchi AC; Kharas N; Wallace S; Regalado ES; Hostetler EM; Sharrief AZ; Bergametti F; Kossorotoff M; Hervé D; Kraemer M; Bamshad MJ; Nickerson DA; Smith ER; Tournier-Lasserve E; Milewicz DM. The pleiotropy associated with de novo variants in CHD4; CNOT3; and SETD5 extends to moyamoya angiopathy. Genet Med. 2020 Feb;22(2):427-431. doi: 10.1038/s41436-019-0639-2. Epub 2019 Sep 2. PubMed PMID: 31474762; PubMed Central PMCID: PMC7673309.
• Rosi A; Riordan CP; Smith ER; Scott RM; Orbach DB. Clinical status and evolution in moyamoya: which angiographic findings correlate? Brain Commun. 2019;1(1):fcz029. doi: 10.1093/braincomms/fcz029. eCollection 2019. PubMed PMID: 32954269; PubMed Central PMCID: PMC7425301.
• Riordan CP; Storey A; Cote DJ; Smith ER; Scott RM. Results of more than 20 years of follow-up in pediatric patients with moyamoya disease undergoing pial synangiosis. J Neurosurg Pediatr. 2019 Mar 1: 1-7. doi: 10.3171/2019.1.PEDS18457. [Epub ahead of print] PubMed PMID: 30835683.
• Jernigan S; Storey A; Hammer C; Riordan C; Orbach DB; Scott RM; Smith E. Moyamoya syndrome and PHACE syndrome: clinical and radiographic characterization of the intracranial arteriopathy and response to surgical revascularization. J Neurosurg Pediatr. 2019 Feb 1:1-5. PMID: 30717056.
• Bolar DS; Gagoski B; Orbach DB; Smith ER; Adalsteinsson E; Rosen BR; Grant PE; Robertson RL. Comparison of CBF measured with velocity selective ASL and pulsed ASL to blood flow patterns assessed by conventional angiography in pediatric moyamoya. AJNR. 2019 Nov;40(11):1842-1849. PMID: 31694821.
• Rosi A; Riordan C; Smith ER; Scott RM; Orbach DB. Clinical status and evolution in moyamoya: which angiographic findings correlate? Brain Communications. 2019 1(1):fcz029. doi:10.1093/braincomms/fcz029. PMID: 32954269
• Sesen J; Driscoll J; Moses-Gardner A; Orbach DB; Zurakowski D; Smith ER. Non-invasive Urinary Biomarkers in Moyamoya Disease. Front Neurol. 2021 12:661952 DOI:10.3389/fneur.2021.661952. PMID:33868159.
• Kundishora AJ; Peters ST; Pinard A; Duran D; Panchagnula S; Barak T; Miyagishima DF; Dong W; Smith H; Ocken J; Dunbar A; Nelson-Williams C; Haider S; Walker RL; Li B; Zhao H; Thumkeo D; Marlier A; Duy PQ; Diab NS; Reeves BC; Robert SM; Sujijantarat N; Stratman AN; Chen YH; Zhao S; Roszko I; Lu Q; Zhang B; Mane S; Castaldi C; Lopez-Giraldez F; Knight JR; Bamshad MJ; Nickerson DA; Geschwind DH; Chen SL; Storm PB; Diluna ML; Matouk CC; Orbach DB; Alper SL; Smith ER; Lifton RP; Gunel M; Milewicz DM; Jin SC; Kahle KT. DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease. JAMA Neurol. 2021 Jun 14; DOI:10.1001/jamaneurol.2021.1681. PMID:34125151.
• Montaser A*; Driscoll J; Smith H; Karsten MB; Day E; Mounlavongsy T; Orbach DB; Smith ER. Long-term clinical and radiographic outcomes after pial pericranial dural revascularization: a hybrid surgical technique for treatment of anterior cerebral territory ischemia in pediatric moyamoya disease. J Neurosurg Pediatr. 2021 Jul 2:1-9 DOI:10.3171/2021.2.PEDS20743. PMID:34214976.
• Scott RM; Smith ER. Moyamoya disease and moyamoya syndrome [review]. N Engl J Med 2009; 360:1226-37. This comprehensive review of moyamoya disease covers who is at risk; presenting features; diagnosis; treatment and outcomes.
• Montaser; AS; Srinavasan HL; Staffa SJ; Zurakowski D; Slingerland A; Orbach DB; Hausman- Kedem M; Roth J; Smith ER. Ivy sign: A diagnostic and prognostic biomarker for pediatric moyamoya. J Neurosurg Ped. 2021. In press.

The Stroke and Cerebrovascular Center at Boston Children’s is one of a few specialized programs in the country dedicated to understanding, preventing, and treating childhood strokes. We are one of the most active pediatric stroke research centers in the world — both clinically and in the laboratory — working to improve treatments.

• Ferriero DM; Fullerton HJ; Bernard TJ; Billinghurst L; Daniels SR; DeBaun MR; deVeber G; Ichord RN; Jordan LC; Massicotte P; Meldau J; Roach ES; Smith ER. Management of stroke in neonates and children: a scientific statement from the American Heart Association/American Stroke Association. Stroke. 2019 Mar;50(3):e51-96.
• See AP; Kochis MA; Khandelwal P; Orbach DB. Considerations in applying a new stent retriever in pediatric endovascular cerebral thrombectomy for acute ischemic stroke. Pediatric neurosurgery. 2016 May ;51(5):263-8.

• Wilson JL; Amlie-Lefond C; Abruzzo T; Orbach DB; Rivkin MJ; deVeber GA; Pergami P. Survey of practice patterns and preparedness for endovascular therapy in acute pediatric stroke. Child's nervous system: ChNS : official journal of the International Society for Pediatric Neurosurgery. 2019 Dec;35(12):2371-2378. PMID: 31482313
• Gadgil N; Aldave G; Whitehead WE; Dmytriw AA; Chen K; Orbach DB; Maier I; Behme D; Fargen KM; Elijovich L; Dornbos D; 3rd; Spiotta A; Kan P. Endovascular Intervention for Refractory Pediatric Cerebral Venous Sinus Thrombosis. Pediatr Neurol. 2021 Aug; 121:45-50 DOI:10.1016/j.pediatrneurol.2021.05.004. PMID:34147818.

• Chen K; Dawkins D; Orbach DB; Aagaard-Kienitz B. Low-profile sheaths in pediatric neurointervention: a multicenter experience. J Neurointerv Surg 2021. In press.
• Burch EA; Orbach DB. Pediatric CNS vascular anomalies. Pediatric Radiology. 2015 Sep 1;45(3):463-72.
• Lin N; Smith ER; Scott RE; Orbach DB. Safety of neuroangiography and embolization in children: Complication analysis in 697 consecutive procedures in 394 patients. J Neurosurg Pediatr. 2015 Oct 1; 16 (4):432-8.
• Gross BA; Orbach DB. Addressing challenges in 4 F and 5 F arterial access for neurointerventional procedures in infants and young children. J Neurointerv Surg 2014 May; 6:308-313. With creative strategies for accessing tiny vessels; complex endovascular neurointerventions are possible even in the youngest infants.
• Weinstock P; Prabhu SP; Flynn K; Orbach DB; Smith ER. Optimizing cerebrovascular surgical and endovascular procedures in children via personalized 3-dimensional printing. J Neurosurg Pediatr. 2015 Nov 1;16(5):584-9. A small case series describes the use of 3D printing models based on patients’ brain scans to prepare for cerebrovascular procedures. A collaboration between the Cerebrovascular Surgery and Interventions Center and Boston Children’s SimPeds program.
• See AP; Stapleton CJ; Du X; Charbel FT; Amin-Hanjani S; VERiTAS Study Group. Perfusion-MRI is a Poor Indicator of Hemodynamic Compromise in Vertebrobasilar Disease in the VERiTAS Study. J Neuroimaging. 2021 Jan;31(1):151-154. doi: 10.1111/jon.12802. Epub 2020 Nov 4.
• Amin-Hanjani S; See AP; Du X; Rose-Finnell L; Pandey DK; Chen YF; Elkind MSV; Zipfel GJ; Liebeskind DS; Silver FL; Kasner SE; Gorelick PB; Charbel FT; Derdeyn CP; VERiTAS Study Group. Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort. Stroke. 2020 Nov;51(11):3295-3301. doi: 10.1161/STROKEAHA.120.029909. Epub 2020 Oct 9. PMID: 33032489
• See AP; Pandey DK; Du X; Rose-Finnell L; Charbel FT; Derdeyn CP; Amin-Hanjani S; VERiTAS Study Group*. Optimized Hemodynamic Assessment to Predict Stroke Risk in Vertebrobasilar Disease: Analysis from the VERiTAS Study. J Am Heart Assoc. 2020 Jun 16;9(12):e016406. doi: 10.1161/JAHA.120.016406. Epub 2020 Jun 5. PMID: 32500810