Antiangiogenic agent as a novel treatment for pediatric intracranial arteriovenous malformations: case report

Ken Maynard MD1,2,3, Melissa LoPresti MD1,2, Ionela Iacobas MD4,5,6, Peter Kan MD, MPH2, and Sandi Lam MD, MBA1,2,3
View More View Less
  • 1 Pediatric Neurosurgery, Texas Children’s Hospital, Houston;
  • | 2 Department of Neurosurgery, Baylor College of Medicine, Houston;
  • | 3 Department of Neurosurgery, University of Texas Medical Branch, Galveston;
  • | 4 Division of Hematology/Oncology, Department of Pediatrics, and
  • | 5 Vascular Anomalies Center, Texas Children’s Hospital, Houston; and
  • | 6 Baylor College of Medicine, Houston, Texas
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online

Intracerebral arteriovenous malformations (AVMs) are high-flow collections of abnormal vessels and a common cause of pediatric intracranial hemorrhage. There are few treatment options available for AVMs not amenable to surgical resection, endovascular embolization, radiosurgery, or multimodality treatment. The authors sought to review the molecular and genetic pathways that have been implicated in the formation of AVMs, focusing on the possibility of medically targeting these pathways in the treatment of AVMs. In the novel case presented here, a pediatric patient who was diagnosed with an intracranial AVM unamenable to conventional treatments underwent alternative treatment with molecular pathway inhibitors.

ABBREVIATIONS

AKT = protein kinase b; AVM = arteriovenous malformation; ERK = extracellular signal–regulated kinase; MAPK = mitogen-activated protein kinase; MEK = mitogen-activated protein kinase kinase; mTOR = mammalian target of rapamycin; PI3K = phosphatidylinositol 3-kinase; PLCϒ = phospholipase C ϒ; TIA = transient ischemic attack; VEGF = vascular endothelial growth factor; VEGFR = VEGF receptor.

Illustration from Proctor and Meara (pp 622–631). Copyright Mark Proctor. Used with permission.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1

    Al-Olabi L, Polubothu S, Dowsett K, Andrews KA, Stadnik P, Joseph AP, et al.: Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy. J Clin Invest 128:14961508, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Balestri R, Neri I, Patrizi A, Angileri L, Ricci L, Magnano M: Analysis of current data on the use of topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis complex. J Eur Acad Dermatol Venereol 29:1420, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Benedito R, Hellström M: Notch as a hub for signaling in angiogenesis. Exp Cell Res 319:12811288, 2013

  • 4

    Blatt J, McLean TW, Castellino SM, Burkhart CN: A review of contemporary options for medical management of hemangiomas, other vascular tumors, and vascular malformations. Pharmacol Ther 139:327333, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Blauwblomme T, Bourgeois M, Meyer P, Puget S, Di Rocco F, Boddaert N, et al.: Long-term outcome of 106 consecutive pediatric ruptured brain arteriovenous malformations after combined treatment. Stroke 45:16641671, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Chelliah MP, Do HM, Zinn Z, Patel V, Jeng M, Khosla RK, et al.: Management of complex arteriovenous malformations using a novel combination therapeutic algorithm. JAMA Dermatol 154:13161319, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Colletti G, Dalmonte P, Moneghini L, Ferrari D, Allevi F: Adjuvant role of anti-angiogenic drugs in the management of head and neck arteriovenous malformations. Med Hypotheses 85:298302, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Dalton A, Dobson G, Prasad M, Mukerji N: De novo intracerebral arteriovenous malformations and a review of the theories of their formation. Br J Neurosurg 32:305311, 2018

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Darsaut TE, Guzman R, Marcellus ML, Edwards MS, Tian L, Do HM, et al.: Management of pediatric intracranial arteriovenous malformations: experience with multimodality therapy. Neurosurgery 69:540556, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Fish JE, Wythe JD: The molecular regulation of arteriovenous specification and maintenance. Dev Dyn 244:391409, 2015

  • 11

    Gross BA, Du R: Natural history of cerebral arteriovenous malformations: a meta-analysis. J Neurosurg 118:437443, 2013

  • 12

    Hammill AM, Wentzel M, Gupta A, Nelson S, Lucky A, Elluru R, et al.: Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 57:10181024, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Lackner H, Karastaneva A, Schwinger W, Benesch M, Sovinz P, Seidel M, et al.: Sirolimus for the treatment of children with various complicated vascular anomalies. Eur J Pediatr 174:15791584, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Laplante M, Sabatini DM: mTOR signaling in growth control and disease. Cell 149:274293, 2012

  • 15

    Lekwuttikarn R, Lim YH, Admani S, Choate KA, Teng JMC: Genotype-guided medical treatment of an arteriovenous malformation in a child. JAMA Dermatol 155:256257, 2019

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Ma L, Chen XL, Chen Y, Wu CX, Ma J, Zhao YL: Subsequent haemorrhage in children with untreated brain arteriovenous malformation: higher risk with unbalanced inflow and outflow angioarchitecture. Eur Radiol 27:28682876, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Matsuki M, Adachi Y, Ozawa Y, Kimura T, Hoshi T, Okamoto K, et al.: Targeting of tumor growth and angiogenesis underlies the enhanced antitumor activity of lenvatinib in combination with everolimus. Cancer Sci 108:763771, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Mizuno T, Emoto C, Fukuda T, Hammill AM, Adams DM, Vinks AA: Model-based precision dosing of sirolimus in pediatric patients with vascular anomalies. Eur J Pharm Sci 109S:S124S131, 2017

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Moftakhar P, Hauptman JS, Malkasian D, Martin NA: Cerebral arteriovenous malformations. Part 1: cellular and molecular biology. Neurosurg Focus 26(5):E10, 2009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Morales-Valero SF, Bortolotti C, Sturiale C, Lanzino G: Are parenchymal AVMs congenital lesions? Neurosurg Focus 37(3):E2, 2014 (Erratum in Neurosurg Focus 39[1]:E14, 2015)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Morgan MK, Davidson AS, Assaad NNA, Stoodley MA: Critical review of brain AVM surgery, surgical results and natural history in 2017. Acta Neurochir (Wien) 159:14571478, 2017

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Nikolaev SI, Vetiska S, Bonilla X, Boudreau E, Jauhiainen S, Rezai Jahromi B, et al.: Somatic activating KRAS mutations in arteriovenous malformations of the brain. N Engl J Med 378:250261, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Pimpalwar S, Yoo R, Chau A, Ashton D, Margolin J, Iacobas I: Temporal evolution and management of fast flow vascular anomalies in PTEN hamartoma tumor syndrome. Int J Angiol 27:158164, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Rangel-Castilla L, Russin JJ, Martinez-Del-Campo E, Soriano-Baron H, Spetzler RF, Nakaji P: Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment. Neurosurg Focus 37(3):E1, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Saxton RA, Sabatini DM: mTOR signaling in growth, metabolism, and disease. Cell 168:960976, 2017

  • 26

    Simanshu DK, Nissley DV, McCormick F: RAS proteins and their regulators in human disease. Cell 170:1733, 2017

  • 27

    Thomas JM, Surendran S, Abraham M, Rajavelu A, Kartha CC: Genetic and epigenetic mechanisms in the development of arteriovenous malformations in the brain. Clin Epigenetics 8:78, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Triana P, Dore M, Cerezo VN, Cervantes M, Sánchez AV, Ferrero MM, et al.: Sirolimus in the treatment of vascular anomalies. Eur J Pediatr Surg 27:8690, 2017

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Zhao Y, Adjei AA: The clinical development of MEK inhibitors. Nat Rev Clin Oncol 11:385400, 2014

  • 30

    ZhuGe Q, Zhong M, Zheng W, Yang GY, Mao X, Xie L, et al.: Notch-1 signalling is activated in brain arteriovenous malformations in humans. Brain 132:32313241, 2009

Metrics

All Time Past Year Past 30 Days
Abstract Views 1712 610 45
Full Text Views 370 115 8
PDF Downloads 301 131 13
EPUB Downloads 0 0 0