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Multiple brain arteriovenous malformations: systematic review and individual patient data meta-analysis

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Abstract

Multiple brain arteriovenous malformations (bAVM) are rare neurovascular lesions usually related to genetic syndromes. Its management is not well established given its rarity. The objective of this study was to describe the clinical and angiographic features of published cases and to explore their associations with treatment outcomes. We performed a literature search of published cases in Medline and the Regional Index Medici. Additional cases were searched in our single-center registry. Data on the proportions of patients and clinical and angiographic characteristics were extracted. The study outcomes were nidal instability in patients who underwent staged treatment and radiological cure in patients who underwent treatment using any treatment modality. Logistic regression models for the study outcomes were analyzed. Data on the proportions of multiple bAVM patients were summarized with meta-analyses of proportions. We included 118 patients (reported in 68 studies) from the literature and 6 cases identified in our registry. A total of 124 patients harboring 339 bAVM nidi were included in the analyses. Differences between syndromic and non-syndromic cases were observed. The logistic regression analyses showed that angiographically occult untreated bAVM was associated (OR 14.37; 95% CI 2.17 to 95.4) with nidal instability after staged treatment, and deep (OR 5.11; 95% CI 1.51 to 17.27) and eloquent (OR 3.91; 95% CI 1.22 to 12.52) locations were associated with residual disease after treatment. Inconsistent reporting of relevant data throughout the included studies undermined the planned analyses. Some prognostic factors were found to be related to the study outcomes. Study Registration: The protocol of the systematic review was registered in PROSPERO as CRD42021245814

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The authors will share the anonymized database used to obtain the results presented in this manuscript upon reasonable request.

References

  1. Kim H, Pawlikowska L, Chen Y, Su H, Yang GY, Young WL (2009) Brain arteriovenous malformation biology relevant to hemorrhage and implication for therapeutic development. Stroke 40(3 Suppl):S95–S97. https://doi.org/10.1161/STROKEAHA.108.533216

    Article  PubMed  CAS  Google Scholar 

  2. Laakso A, Hernesniemi J (2012) Arteriovenous malformations: epidemiology and clinical presentation. Neurosurg Clin N Am 23:1–6. https://doi.org/10.1016/j.nec.2011.09.012

    Article  PubMed  Google Scholar 

  3. Ogino A, Tonetti D, Flickinger JC, Lunsford LD, Kano H (2020) Clinico-radiologic outcomes after stereotactic radiosurgery for patients with complex high-risk multiple arteriovenous malformations. World Neurosurg 144:e244–e252. https://doi.org/10.1016/j.wneu.2020.08.099

    Article  PubMed  Google Scholar 

  4. Stein KP, Wanke I, Oezkan N, Zhu Y, Sandalcioglu IE, Forsting M, Sure U (2016) Multiple cerebral arterio-venous malformations: impact of multiplicity and hemodynamics on treatment strategies. Acta Neurochir (Wien) 158:2399–2407. https://doi.org/10.1007/s00701-016-2989-8

    Article  PubMed  Google Scholar 

  5. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  Google Scholar 

  6. Boone CE, Caplan JM, Yang W, Ye X, Colby GP, Coon AL, Tamargo RJ, Huang J (2016) Hemorrhage risk and clinical features of multiple intracranial arteriovenous malformations. J Clin Neurosci 23:51–57. https://doi.org/10.1016/j.jocn.2015.07.008

    Article  PubMed  Google Scholar 

  7. Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 91:66–67. https://doi.org/10.1002/(sici)1096-8628(20000306)91:1<66::aid-ajmg12>3.0.co;2-p

  8. Patel U, Gupta SC (1990) Wyburn-Mason syndrome. A case report and review of the literature. Neuroradiology 31:544–546. https://doi.org/10.1007/BF00340139

    Article  PubMed  CAS  Google Scholar 

  9. Eerola I, Boon LM, Mulliken JB, Burrows PE, Dompmartin A, Watanabe S, Vanwijck R, Vikkula M (2003) Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am J Hum Genet 73(6):1240–1249. https://doi.org/10.1086/379793

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Lawton MT (2014) Seven AVMs. Thieme Medical Publishers, USA, Tenets and techniques for resection

    Book  Google Scholar 

  11. Sugita K, Takemae T, Kobayashi S (1987) Sylvian fissure arteriovenous malformations. Neurosurgery 21(1):7–14. https://doi.org/10.1227/00006123-198707000-00003

    Article  PubMed  CAS  Google Scholar 

  12. Spetzler RF, Martin NA (1986) A proposed grading system for arteriovenous malformations. J Neurosurg 65(4):476–483. https://doi.org/10.3171/jns.1986.65.4.0476

    Article  PubMed  CAS  Google Scholar 

  13. Ogilvy CS, Heros RC, Ojemann RG, New PF (1988) Angiographically occult arteriovenous malformations. J Neurosurg 69(3):350–355. https://doi.org/10.3171/jns.1988.69.3.0350

    Article  PubMed  CAS  Google Scholar 

  14. Nagai Y, Anan M, Fujiki M (2020) Cerebral arteriovenous malformations as acquired lesions: case reports and review of the literature. J Stroke Cerebrovasc Dis 29(10):105157. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105157

    Article  PubMed  Google Scholar 

  15. Guo B, Moga C, Harstall C, Schopflocher D (2016) A principal component analysis is conducted for a case series quality appraisal checklist. J Clin Epidemiol 69:199–207.e2. https://doi.org/10.1016/j.jclinepi.2015.07.010

    Article  PubMed  Google Scholar 

  16. Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C (2013) Assessing bias in studies of prognostic factors. Ann Intern Med 158(4):280–286. https://doi.org/10.7326/0003-4819-158-4-201302190-00009

    Article  PubMed  Google Scholar 

  17. R Development Core Team (2018) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org. Accessed 11 Feb 2021

  18. Unnithan A (2020) Overview of the current concepts in the management of arteriovenous malformations of the brain. Postgrad Med J 96(1134):212–220. https://doi.org/10.1016/j.neucir.2014.11.004

    Article  PubMed  Google Scholar 

  19. Gelabert-González M, Santin-Amo JM, Román-Pena P, Vázquez Herrero F (2015) Malformación arteriovenosa intracraneal múltiple. Neurocirugia (Astur) 26(4):200–204. https://doi.org/10.1136/postgradmedj-2019-137202

    Article  PubMed  Google Scholar 

  20. Dumont AS, Lanzino G, Sheehan JP (2018) Brain arteriovenous malformations and arteriovenous fistulas. Thieme Medical Publishers, USA

    Google Scholar 

  21. Geibprasert S, Pongpech S, Jiarakongmun P, Shroff MM, Armstrong DC, Krings T (2010) Radiologic assessment of brain arteriovenous malformations: what clinicians need to know. Radiographics 30(2):483–501. https://doi.org/10.1148/rg.302095728

    Article  PubMed  Google Scholar 

  22. Yang W, Liu A, Hung AL, Braileanu M, Wang JY, Caplan JM, Colby GP, Coon AL, Tamargo RJ, Ahn ES, Huang J (2016) Lower risk of intracranial arteriovenous malformation hemorrhage in patients with hereditary hemorrhagic telangiectasia. Neurosurgery 78:684–693. https://doi.org/10.1227/NEU.0000000000001103

    Article  PubMed  Google Scholar 

  23. Gamboa NT, Joyce EJ, Eli I, Park MS, Taussky P, Schmidt RH, McDonald J, Whitehead KJ, Kalani MYS (2018) Clinical presentation and treatment paradigms of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia. J Clin Neurosci 51:22–28. https://doi.org/10.1016/j.jocn.2018.01.019

    Article  PubMed  Google Scholar 

  24. Bharatha A, Faughnan ME, Kim H, Pourmohamad T, Krings T, Bayrak-Toydemir P, Pawlikowska L, McCulloch CE, Lawton MT, Dowd CF, Young WL, Terbrugge KG (2012) Brain arteriovenous malformation multiplicity predicts the diagnosis of hereditary hemorrhagic telangiectasia: quantitative assessment. Stroke 43:72–78. https://doi.org/10.1161/STROKEAHA.111.629865

    Article  PubMed  Google Scholar 

  25. Goldberg J, Raabe A, Bervini D (2018) Natural history of brain arteriovenous malformations: systematic review. J Neurosurg Sci 62:437–443. https://doi.org/10.23736/S0390-5616.18.04452-1

    Article  PubMed  Google Scholar 

  26. Gross BA, Du R (2013) Natural history of cerebral arteriovenous malformations: a meta-analysis. J Neurosurg 118:437–443. https://doi.org/10.3171/2012.10.JNS121280

    Article  PubMed  Google Scholar 

  27. Brinjikji W, Iyer VN, Wood CP, Lanzino G (2017) Prevalence and characteristics of brain arteriovenous malformations in hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis. J Neurosurg 127:302–310. https://doi.org/10.3171/2016.7.JNS16847

    Article  PubMed  Google Scholar 

  28. Abecassis IJ, Xu DS, Batjer HH, Bendok BR (2014) Natural history of brain arteriovenous malformations: a systematic review. Neurosurg Focus 37:E7. https://doi.org/10.3171/2014.6.FOCUS14250

    Article  PubMed  Google Scholar 

  29. Utsuki S, Kurata A, Miyasaka Y, Takano M, Ootaka H, Fujii K (2002) Multiple arteriovenous malformations with hemorrhage. Acta Neurochir (Wien) 144:97–101. https://doi.org/10.1007/s701-002-8279-0

    Article  PubMed  CAS  Google Scholar 

  30. van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ (2011) Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306(18):2011–2019. https://doi.org/10.1001/jama.2011.1632

    Article  PubMed  Google Scholar 

  31. Robert T, Blanc R, Botta D, Ciccio G, Smajda S, Redjem H, Fahed R, Piotin M (2016) Management of multiple cerebral arteriovenous malformations in a non-pediatric population. Acta Neurochir (Wien) 158:1019–1025. https://doi.org/10.1007/s00701-016-2785-5

    Article  PubMed  Google Scholar 

  32. Cezayirli PC, Türe H, Türe U (2022) Microsurgical Treatment of Deep and Eloquent AVMs. Adv Tech Stand Neurosurg 44:17–53. https://doi.org/10.1007/978-3-030-87649-4_2

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru

    Juan E. Basilio-Flores & Joel A. Aguilar-Melgar

  2. Department of Neurology, Neurosurgery and Radiology, University of Iowa Hospitals and Clinics, Iowa City, USA

    Cynthia B. Zevallos & Santiago Ortega-Gutierrez

  3. Department of Neurosurgery, Hospital Nacional Daniel Alcides Carrión, Callao, Peru

    Remy Aguirre-Carbajo & Henry Pacheco-Fernandez Baca

Authors
  1. Juan E. Basilio-Flores
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  2. Joel A. Aguilar-Melgar
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  3. Cynthia B. Zevallos
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  4. Remy Aguirre-Carbajo
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  5. Santiago Ortega-Gutierrez
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  6. Henry Pacheco-Fernandez Baca
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Contributions

All authors contributed to the study conception and design. Literature review and data collection were performed by Juan Basilio, Joel Aguilar, and Remy Aguirre. Data analysis was performed by Juan Basilio. The first draft of the manuscript was written by Juan Basilio and Cynthia Zevallos, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Henry Pacheco-Fernandez Baca.

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Ethics approval

The IRB approval was waived given that the study is a systematic review with de-identified patient data.

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Formal consent was waived given the study design.

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No identifiable patient data was published.

Competing interests

Santiago Ortega is a consultant for Medtronic and Stryker. The other authors declare that they have no relevant financial or non-financial interests to disclose.

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Basilio-Flores, J.E., Aguilar-Melgar, J.A., Zevallos, C.B. et al. Multiple brain arteriovenous malformations: systematic review and individual patient data meta-analysis. Neurosurg Rev 46, 44 (2023). https://doi.org/10.1007/s10143-023-01951-3

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  • DOI: https://doi.org/10.1007/s10143-023-01951-3

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