Cavernous angioma future or investigational therapies: Difference between revisions

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==Future Investigations==
==Future Investigations==
=== Insights ===


*Several insights on development of cavernous angioma exist.
*Several insights on development of cavernous angioma exist.
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***lipopolysaccharide can stimulate the toll-like receptor 4 (TLR4) found on walls of endothelium <ref name="pmid28489816">{{cite journal| author=Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N | display-authors=etal| title=Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. | journal=Nature | year= 2017 | volume= 545 | issue= 7654 | pages= 305-310 | pmid=28489816 | doi=10.1038/nature22075 | pmc=5757866 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28489816  }} </ref>
***lipopolysaccharide can stimulate the toll-like receptor 4 (TLR4) found on walls of endothelium <ref name="pmid28489816">{{cite journal| author=Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N | display-authors=etal| title=Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. | journal=Nature | year= 2017 | volume= 545 | issue= 7654 | pages= 305-310 | pmid=28489816 | doi=10.1038/nature22075 | pmc=5757866 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28489816  }} </ref>


=== Possible Medications that can Reduce Risk of Bleeding ===
* Some drugs have been identified to be able to reduce risk of hemorrhage, and possible development of new lesions. <ref name="pmid30909834">{{cite journal| author=Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL | display-authors=etal| title=Familial Cerebral Cavernous Malformations. | journal=Stroke | year= 2019 | volume= 50 | issue= 5 | pages= 1294-1301 | pmid=30909834 | doi=10.1161/STROKEAHA.118.022314 | pmc=6924279 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30909834  }} </ref> <ref name="pmid27639680">{{cite journal| author=Retta SF, Glading AJ| title=Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin. | journal=Int J Biochem Cell Biol | year= 2016 | volume= 81 | issue= Pt B | pages= 254-270 | pmid=27639680 | doi=10.1016/j.biocel.2016.09.011 | pmc=5155701 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27639680  }} </ref><ref name="pmid22710379">{{cite journal| author=Witiw CD, Abou-Hamden A, Kulkarni AV, Silvaggio JA, Schneider C, Wallace MC| title=Cerebral cavernous malformations and pregnancy:  hemorrhage risk and influence on obstetrical management. | journal=Neurosurgery | year= 2012 | volume= 71 | issue= 3 | pages= 626-30; discussion 631 | pmid=22710379 | doi=10.1227/NEU.0b013e31825fd0dc | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22710379  }} </ref><ref name="pmid30476961">{{cite journal| author=Chohan MO, Marchiò S, Morrison LA, Sidman RL, Cavenee WK, Dejana E | display-authors=etal| title=Emerging Pharmacologic Targets in Cerebral Cavernous Malformation and Potential Strategies to Alter the Natural History of a Difficult Disease: A Review. | journal=JAMA Neurol | year= 2019 | volume= 76 | issue= 4 | pages= 492-500 | pmid=30476961 | doi=10.1001/jamaneurol.2018.3634 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30476961  }} </ref><ref name="pmid25486933">{{cite journal| author=Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J | display-authors=etal| title=Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. | journal=Circulation | year= 2015 | volume= 131 | issue= 3 | pages= 289-99 | pmid=25486933 | doi=10.1161/CIRCULATIONAHA.114.010403 | pmc=4356181 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25486933  }} </ref>
* These include:
** rapamycin <ref name="pmid30556006">{{cite journal| author=De Luca E, Pedone D, Moglianetti M, Pulcini D, Perrelli A, Retta SF | display-authors=etal| title=Multifunctional Platinum@BSA-Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation. | journal=ACS Omega | year= 2018 | volume= 3 | issue= 11 | pages= 15389-15398 | pmid=30556006 | doi=10.1021/acsomega.8b01653 | pmc=6288776 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30556006  }} </ref>
** sorafenib <ref name="pmid20616044">{{cite journal| author=Wüstehube J, Bartol A, Liebler SS, Brütsch R, Zhu Y, Felbor U | display-authors=etal| title=Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 28 | pages= 12640-5 | pmid=20616044 | doi=10.1073/pnas.1000132107 | pmc=2906569 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20616044  }} </ref>
** sulindac (NSAID) <ref name="pmid26109568">{{cite journal| author=Bravi L, Rudini N, Cuttano R, Giampietro C, Maddaluno L, Ferrarini L | display-authors=etal| title=Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice. | journal=Proc Natl Acad Sci U S A | year= 2015 | volume= 112 | issue= 27 | pages= 8421-6 | pmid=26109568 | doi=10.1073/pnas.1501352112 | pmc=4500248 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26109568  }} </ref>
** TLR4-blocking agents <ref name="pmid28489816">{{cite journal| author=Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N | display-authors=etal| title=Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. | journal=Nature | year= 2017 | volume= 545 | issue= 7654 | pages= 305-310 | pmid=28489816 | doi=10.1038/nature22075 | pmc=5757866 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28489816  }} </ref>
** fasudil <ref name="pmid22034008">{{cite journal| author=McDonald DA, Shi C, Shenkar R, Stockton RA, Liu F, Ginsberg MH | display-authors=etal| title=Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease. | journal=Stroke | year= 2012 | volume= 43 | issue= 2 | pages= 571-4 | pmid=22034008 | doi=10.1161/STROKEAHA.111.625467 | pmc=3265629 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22034008  }} </ref><ref name="pmid27879448">{{cite journal| author=Shenkar R, Shi C, Austin C, Moore T, Lightle R, Cao Y | display-authors=etal| title=RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations. | journal=Stroke | year= 2017 | volume= 48 | issue= 1 | pages= 187-194 | pmid=27879448 | doi=10.1161/STROKEAHA.116.015013 | pmc=5183488 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27879448  }} </ref><ref name="pmid28586486">{{cite journal| author=Weiner GM, Ducruet AF| title=Fasudil Slows Development of Cavernous Malformations. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= N25-N27 | pmid=28586486 | doi=10.1093/neuros/nyx100 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28586486  }} </ref>
** vitamin D <ref name="pmid25486933">{{cite journal| author=Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J | display-authors=etal| title=Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. | journal=Circulation | year= 2015 | volume= 131 | issue= 3 | pages= 289-99 | pmid=25486933 | doi=10.1161/CIRCULATIONAHA.114.010403 | pmc=4356181 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25486933  }} </ref>
** tempol <ref name="pmid25486933">{{cite journal| author=Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J | display-authors=etal| title=Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. | journal=Circulation | year= 2015 | volume= 131 | issue= 3 | pages= 289-99 | pmid=25486933 | doi=10.1161/CIRCULATIONAHA.114.010403 | pmc=4356181 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25486933  }} </ref>
** simvastatin <ref name="pmid28586486">{{cite journal| author=Weiner GM, Ducruet AF| title=Fasudil Slows Development of Cavernous Malformations. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= N25-N27 | pmid=28586486 | doi=10.1093/neuros/nyx100 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28586486  }} </ref>
** bevacizumab <ref name="pmid30610500">{{cite journal| author=Apra C, Dumot C, Bourdillon P, Pelissou-Guyotat I| title=Could propranolol be beneficial in adult cerebral cavernous malformations? | journal=Neurosurg Rev | year= 2019 | volume= 42 | issue= 2 | pages= 403-408 | pmid=30610500 | doi=10.1007/s10143-018-01074-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30610500  }} </ref> <ref name="pmid23804539">{{cite journal| author=Berti I, Marchetti F, Skabar A, Zennaro F, Zanon D, Ventura A| title=Propranolol for cerebral cavernous angiomatosis: a magic bullet. | journal=Clin Pediatr (Phila) | year= 2014 | volume= 53 | issue= 2 | pages= 189-90 | pmid=23804539 | doi=10.1177/0009922813492885 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23804539  }} </ref><ref name="pmid27423555">{{cite journal| author=Reinhard M, Schuchardt F, Meckel S, Heinz J, Felbor U, Sure U | display-authors=etal| title=Propranolol stops progressive multiple cerebral cavernoma in an adult patient. | journal=J Neurol Sci | year= 2016 | volume= 367 | issue=  | pages= 15-7 | pmid=27423555 | doi=10.1016/j.jns.2016.04.053 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27423555  }} </ref><ref name="pmidhttps://doi.org/10.3171/ 2017.12.JNS172404.">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://doi.org/10.3171/ 2017.12.JNS172404. | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }} </ref><ref name="pmid26578351">{{cite journal| author=Zabramski JM, Kalani MYS, Filippidis AS, Spetzler RF| title=Propranolol Treatment of Cavernous Malformations with Symptomatic Hemorrhage. | journal=World Neurosurg | year= 2016 | volume= 88 | issue=  | pages= 631-639 | pmid=26578351 | doi=10.1016/j.wneu.2015.11.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26578351  }} </ref>
** propanolol <ref name="pmid30610500">{{cite journal| author=Apra C, Dumot C, Bourdillon P, Pelissou-Guyotat I| title=Could propranolol be beneficial in adult cerebral cavernous malformations? | journal=Neurosurg Rev | year= 2019 | volume= 42 | issue= 2 | pages= 403-408 | pmid=30610500 | doi=10.1007/s10143-018-01074-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30610500  }} </ref> <ref name="pmid23804539">{{cite journal| author=Berti I, Marchetti F, Skabar A, Zennaro F, Zanon D, Ventura A| title=Propranolol for cerebral cavernous angiomatosis: a magic bullet. | journal=Clin Pediatr (Phila) | year= 2014 | volume= 53 | issue= 2 | pages= 189-90 | pmid=23804539 | doi=10.1177/0009922813492885 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23804539  }} </ref><ref name="pmid27423555">{{cite journal| author=Reinhard M, Schuchardt F, Meckel S, Heinz J, Felbor U, Sure U | display-authors=etal| title=Propranolol stops progressive multiple cerebral cavernoma in an adult patient. | journal=J Neurol Sci | year= 2016 | volume= 367 | issue=  | pages= 15-7 | pmid=27423555 | doi=10.1016/j.jns.2016.04.053 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27423555  }} </ref><ref name="pmidhttps://doi.org/10.3171/ 2017.12.JNS172404.">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://doi.org/10.3171/ 2017.12.JNS172404. | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }} </ref><ref name="pmid26578351">{{cite journal| author=Zabramski JM, Kalani MYS, Filippidis AS, Spetzler RF| title=Propranolol Treatment of Cavernous Malformations with Symptomatic Hemorrhage. | journal=World Neurosurg | year= 2016 | volume= 88 | issue=  | pages= 631-639 | pmid=26578351 | doi=10.1016/j.wneu.2015.11.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26578351  }} </ref>
<br />
==References==
==References==



Revision as of 07:33, 26 February 2022

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Edzel Lorrraine F. Co, D.M.D., M.D.

Future Investigations

Insights

  • Several insights on development of cavernous angioma exist.
  • Factors other than genetic mutation are considered such as: [1][2]
    • oxidative stress
    • inflammation
    • alterations in angiogenesis
    • gut microbiome involvement
      • lipopolysaccharide can stimulate the toll-like receptor 4 (TLR4) found on walls of endothelium [3]

Possible Medications that can Reduce Risk of Bleeding


References

  1. Fischer A, Zalvide J, Faurobert E, Albiges-Rizo C, Tournier-Lasserve E (2013). "Cerebral cavernous malformations: from CCM genes to endothelial cell homeostasis". Trends Mol Med. 19 (5): 302–8. doi:10.1016/j.molmed.2013.02.004. PMID 23506982.
  2. 2.0 2.1 Retta SF, Glading AJ (2016). "Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin". Int J Biochem Cell Biol. 81 (Pt B): 254–270. doi:10.1016/j.biocel.2016.09.011. PMC 5155701. PMID 27639680.
  3. 3.0 3.1 Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N; et al. (2017). "Endothelial TLR4 and the microbiome drive cerebral cavernous malformations". Nature. 545 (7654): 305–310. doi:10.1038/nature22075. PMC 5757866. PMID 28489816.
  4. Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL; et al. (2019). "Familial Cerebral Cavernous Malformations". Stroke. 50 (5): 1294–1301. doi:10.1161/STROKEAHA.118.022314. PMC 6924279 Check |pmc= value (help). PMID 30909834.
  5. Witiw CD, Abou-Hamden A, Kulkarni AV, Silvaggio JA, Schneider C, Wallace MC (2012). "Cerebral cavernous malformations and pregnancy: hemorrhage risk and influence on obstetrical management". Neurosurgery. 71 (3): 626–30, discussion 631. doi:10.1227/NEU.0b013e31825fd0dc. PMID 22710379.
  6. Chohan MO, Marchiò S, Morrison LA, Sidman RL, Cavenee WK, Dejana E; et al. (2019). "Emerging Pharmacologic Targets in Cerebral Cavernous Malformation and Potential Strategies to Alter the Natural History of a Difficult Disease: A Review". JAMA Neurol. 76 (4): 492–500. doi:10.1001/jamaneurol.2018.3634. PMID 30476961.
  7. 7.0 7.1 7.2 Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J; et al. (2015). "Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation". Circulation. 131 (3): 289–99. doi:10.1161/CIRCULATIONAHA.114.010403. PMC 4356181. PMID 25486933.
  8. De Luca E, Pedone D, Moglianetti M, Pulcini D, Perrelli A, Retta SF; et al. (2018). "Multifunctional Platinum@BSA-Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation". ACS Omega. 3 (11): 15389–15398. doi:10.1021/acsomega.8b01653. PMC 6288776. PMID 30556006.
  9. Wüstehube J, Bartol A, Liebler SS, Brütsch R, Zhu Y, Felbor U; et al. (2010). "Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling". Proc Natl Acad Sci U S A. 107 (28): 12640–5. doi:10.1073/pnas.1000132107. PMC 2906569. PMID 20616044.
  10. Bravi L, Rudini N, Cuttano R, Giampietro C, Maddaluno L, Ferrarini L; et al. (2015). "Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice". Proc Natl Acad Sci U S A. 112 (27): 8421–6. doi:10.1073/pnas.1501352112. PMC 4500248. PMID 26109568.
  11. McDonald DA, Shi C, Shenkar R, Stockton RA, Liu F, Ginsberg MH; et al. (2012). "Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease". Stroke. 43 (2): 571–4. doi:10.1161/STROKEAHA.111.625467. PMC 3265629. PMID 22034008.
  12. Shenkar R, Shi C, Austin C, Moore T, Lightle R, Cao Y; et al. (2017). "RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations". Stroke. 48 (1): 187–194. doi:10.1161/STROKEAHA.116.015013. PMC 5183488. PMID 27879448.
  13. 13.0 13.1 Weiner GM, Ducruet AF (2017). "Fasudil Slows Development of Cavernous Malformations". Neurosurgery. 80 (5): N25–N27. doi:10.1093/neuros/nyx100. PMID 28586486.
  14. 14.0 14.1 Apra C, Dumot C, Bourdillon P, Pelissou-Guyotat I (2019). "Could propranolol be beneficial in adult cerebral cavernous malformations?". Neurosurg Rev. 42 (2): 403–408. doi:10.1007/s10143-018-01074-0. PMID 30610500.
  15. 15.0 15.1 Berti I, Marchetti F, Skabar A, Zennaro F, Zanon D, Ventura A (2014). "Propranolol for cerebral cavernous angiomatosis: a magic bullet". Clin Pediatr (Phila). 53 (2): 189–90. doi:10.1177/0009922813492885. PMID 23804539.
  16. 16.0 16.1 Reinhard M, Schuchardt F, Meckel S, Heinz J, Felbor U, Sure U; et al. (2016). "Propranolol stops progressive multiple cerebral cavernoma in an adult patient". J Neurol Sci. 367: 15–7. doi:10.1016/j.jns.2016.04.053. PMID 27423555.
  17. 17.0 17.1 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID 2017.12.JNS172404. https://doi.org/10.3171/ 2017.12.JNS172404. Check |pmid= value (help).
  18. 18.0 18.1 Zabramski JM, Kalani MYS, Filippidis AS, Spetzler RF (2016). "Propranolol Treatment of Cavernous Malformations with Symptomatic Hemorrhage". World Neurosurg. 88: 631–639. doi:10.1016/j.wneu.2015.11.003. PMID 26578351.