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Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations

  • Conference paper
Cerebral Hemorrhage

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 105))

Abstract

Brain arteriovenous malformations (AVMs) cause intracranial hemorrhage (ICH), especially in young adults. Molecular characterization of lesional tissue provides evidence for involvement of both angiogenic and inflammatory pathways, but the pathogenesis remains obscure and medical therapy is lacking. Abnormal expression patterns have been observed for proteins related to angiogenesis (e.g., vascular endothelial growth factor, angiopoietin-2, matrix metalloproteinase-9), and inflammation (e.g., interleukin-6 [IL-6] and myeloperoxidase). Macrophage and neutrophil invasion have also been observed in the absence of prior ICH. Candidate gene association studies have identified a number of germline variants associated with clinical ICH course and AVM susceptibility. A single nucleotide polymorphism (SNP) in activin receptor-like kinase-1 (ALK-1) is associated with AVM susceptibility, and SNPs in IL-6, tumor necrosis factor-a (TNF-a), and apolipoprotein-E (APOE) are associated with AVM rupture. These observations suggest that even without a complete understanding of the determinants of AVM development, the recent discoveries of downstream derangements in vascular function and integrity may offer potential targets for therapy development. Further, biomarkers can now be established for assessing ICH risk. These data will generate hypotheses that can be tested mechanistically in model systems, including surrogate phenotypes, such as vascular dys-plasia and/or models recapitulating the clinical syndrome of recurrent spontaneous ICH.

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Authors and Affiliations

  1. Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA

    H. Kim, L. Pawlikowska, Y. Chen, H. Su, G. Y. Yang & W. L. Young MD

  2. Institute for Human Genetics, University of California, San Francisco, CA, USA

    H. Kim & W. L. Young MD

  3. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA

    D. A. Marchuk

  4. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    G. Y. Yang

  5. Department of Neurology, University of California, San Francisco, CA, USA

    W. L. Young MD

  6. UCSF Department of Anesthesia and Perioperative Care, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA, 94110, USA

    W. L. Young MD

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Editors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Huashan Hospital, Fudan University, Shanghai, China

    Liang-Fu Zhou , Xian-Cheng Chen  & Feng-Ping Huang ,  & 

  2. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Guohua Xi , Richard F. Keep , Ya Hua  & Karin Muraszko , ,  & 

  3. Department of Neurosurgery, Shanghai Changzheng Hospital, Shanghai, China

    Yi-Cheng Lu

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Kim, H. et al. (2008). Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations. In: Zhou, LF., et al. Cerebral Hemorrhage. Acta Neurochirurgica Supplementum, vol 105. Springer, Vienna. https://doi.org/10.1007/978-3-211-09469-3_38

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