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ISSN (Print): 2210-2981
ISSN (Online): 2210-2914

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Review Article Section: Neuroscience

Role of Genetics and Surgical Interventions for the Management of Cerebral Cavernous Malformations (CMM)

Author(s): Anjali Patel, Daisy Valle, Andrew Nguyen, Eduardo Molina and Brandon Lucke-Wold*

Volume 3, Issue 5, 2023

Published on: 08 September, 2023

Page: [386 - 395] Pages: 10

DOI: 10.2174/2210298103666230823094431

Price: $65

Abstract

Cerebral cavernous malformations (CCMs) are comprised of tissue matter within the brain possessing anomalous vascular architecture. In totality, the dilated appearance of the cavernoma takes on a mulberry-like shape contributed by the shape and relation to vascular and capillary elements. Analyzing its pathophysiology along with its molecular and genetic pathways plays a vital role in whether or not a patient receives GKRS, medical management, or Surgery, the most invasive of procedures. To avoid neurological trauma, microsurgical resection of cavernomas can be guided by the novel clinical application of a 3D Slicer with Sina/MosoCam. When cavernomas present in deep lesions with poor accessibility, gamma knife stereotactic radiosurgery (GKSR) is recommended. For asymptomatic and non-multilobal lesions, medical and symptom management is deemed standard, such as antiepileptic therapy. The two-hit hypothesis serves to explain the mutations in three key genes that are most pertinent to the progression of cavernomas: CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10. Various exon deletions and frameshift mutations can cause dysfunction in vascular structure through loss and gain of function mutations. MEKK3 and KLF2/4 are involved in a protein kinase signaling cycle that promotes abnormal angiogenesis and cavernoma formation. In terms of potential treatments, RhoKinase inhibitors have shown to decrease endothelial to mesenchymal transition and CCM lesion development in mice models. All in all, understanding the research behind the molecular genetics in CCMs can foster personalized medicine and potentially create new neurosurgical and medicative treatments.

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Graphical Abstract

[1]
McCormick, W.F. The pathology of vascular (“arteriovenous”) malformations. J. Neurosurg., 1966, 24(4), 807-816.
[http://dx.doi.org/10.3171/jns.1966.24.4.0807] [PMID: 5934138]
[2]
Gonzalez, L.F.; Lekovic, G.P.; Eschbacher, J.; Coons, S.; Porter, R.W.; Spetzler, R.F. Are cavernous sinus hemangiomas and cavernous malfor-mations different entities. Neurosurg. Focus, 2006, 21(1), e6.
[http://dx.doi.org/10.3171/foc.2006.21.1.7]
[3]
Flemming, K.D.; Lanzino, G. Cerebral cavernous malformation: What a practicing clinician should know. Mayo Clin. Proc., 2020, 95(9), 2005-2020.
[http://dx.doi.org/10.1016/j.mayocp.2019.11.005] [PMID: 32605781]
[4]
Brinjikji, W.; El-Masri, A.E.R.; Wald, J.T.; Flemming, K.D.; Lanzino, G. Prevalence of cerebral cavernous malformations associated with developmental venous anomalies increases with age. Childs Nerv. Syst., 2017, 33(9), 1539-1543.
[http://dx.doi.org/10.1007/s00381-017-3484-0] [PMID: 28643038]
[5]
Batra, S.; Lin, D.; Recinos, P.F.; Zhang, J.; Rigamonti, D. Cavernous malformations: Natural history, diagnosis and treatment. Nat. Rev. Neurol., 2009, 5(12), 659-670.
[http://dx.doi.org/10.1038/nrneurol.2009.177] [PMID: 19953116]
[6]
Flemming, K.D.; Graff-Radford, J.; Aakre, J.; Kantarci, K.; Lanzino, G.; Brown, R.D., Jr; Mielke, M.M.; Roberts, R.O.; Kremers, W.; Knopman, D.S.; Petersen, R.C.; Jack, C.R., Jr Population-based prevalence of cerebral cavernous malformations in older adults. JAMA Neurol., 2017, 74(7), 801-805.
[http://dx.doi.org/10.1001/jamaneurol.2017.0439] [PMID: 28492932]
[7]
Choquet, H.; Pawlikowska, L.; Lawton, M.T.; Kim, H. Genetics of cerebral cavernous malformations: Current status and future prospects. J. Neurosurg. Sci., 2015, 59(3), 211-220.
[PMID: 25900426]
[8]
Cox, E.M.; Bambakidis, N.C.; Cohen, M.L. Pathology of cavernous malformations. Handb. Clin. Neurol., 2017, 143, 267-277.
[http://dx.doi.org/10.1016/B978-0-444-63640-9.00025-4] [PMID: 28552149]
[9]
D’Angelo, R.; Marini, V.; Rinaldi, C.; Origone, P.; Dorcaratto, A.; Avolio, M.; Goitre, L.; Forni, M.; Capra, V.; Alafaci, C.; Mareni, C.; Garrè, C.; Bramanti, P.; Sidoti, A.; Retta, S.F.; Amato, A. Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian pa-tients with cerebral cavernous malformation. Brain Pathol., 2011, 21(2), 215-224.
[http://dx.doi.org/10.1111/j.1750-3639.2010.00441.x] [PMID: 21029238]
[10]
Awad, I.A.; Polster, S.P. Cavernous angiomas: Deconstructing a neurosurgical disease. J. Neurosurg., 2019, 131(1), 1-13.
[http://dx.doi.org/10.3171/2019.3.JNS181724] [PMID: 31261134]
[11]
Zyck, S.; Gould, G.C. Cavernous Venous Malformation.StatPearls; StatPearls Publishing: Treasure Island, FL, 2022.
[12]
Ruan, D.; Yu, X.B.; Shrestha, S.; Wang, L.; Chen, G. The role of hemosiderin excision in seizure outcome in cerebral cavernous malformation surgery: A systematic review and meta-analysis. PLoS One, 2015, 10(8), e0136619.
[http://dx.doi.org/10.1371/journal.pone.0136619]
[13]
Flemming, K.D. Clinical management of cavernous malformations. Curr. Cardiol. Rep., 2017, 19(12), 122.
[http://dx.doi.org/10.1007/s11886-017-0931-1]
[14]
Morrison, L.; Akers, A. Cerebral cavernous malformation, familial. In: Gene Reviews®; Adam, M.P.; Everman, D.B.; Mirzaa, G.M., Eds.; University of Washington, Seattle: Seattle, WA, , 2003.
[15]
Zafar, A.; Quadri, S.A.; Farooqui, M.; Ikram, A.; Robinson, M.; Hart, B.L.; Mabray, M.C.; Vigil, C.; Tang, A.T.; Kahn, M.L.; Yonas, H.; Lawton, M.T.; Kim, H.; Morrison, L. Familial cerebral cavernous malformations. Stroke, 2019, 50(5), 1294-1301.
[http://dx.doi.org/10.1161/STROKEAHA.118.022314] [PMID: 30909834]
[16]
Agosti, E.; Flemming, K.D.; Lanzino, G. Symptomatic cavernous malformation presenting with seizure without hemorrhage: Analysis of factors influencing clinical presentation. World Neurosurg., 2019, 129, e387-e392.
[http://dx.doi.org/10.1016/j.wneu.2019.05.157] [PMID: 31132505]
[17]
Flemming, K.D.; Kumar, S.; Brown, R.D., Jr; Lanzino, G. Predictors of initial presentation with hemorrhage in patients with cavernous malformations. World Neurosurg., 2020, 133, e767-e773.
[http://dx.doi.org/10.1016/j.wneu.2019.09.161] [PMID: 31605843]
[18]
Taslimi, S.; Modabbernia, A.; Amin-Hanjani, S.; Barker, F.G., II; Macdonald, R.L. Natural history of cavernous malformation. Neurology, 2016, 86(21), 1984-1991.
[http://dx.doi.org/10.1212/WNL.0000000000002701] [PMID: 27164680]
[19]
Horne, M.A.; Flemming, K.D.; Su, I.C.; Stapf, C.; Jeon, J.P.; Li, D.; Maxwell, S.S.; White, P.; Christianson, T.J.; Agid, R.; Cho, W.S.; Oh, C.W.; Wu, Z.; Zhang, J.T.; Kim, J.E.; ter Brugge, K.; Willinsky, R.; Brown, R.D., Jr; Murray, G.D.; Salman, R.A-S. Clinical course of un-treated cerebral cavernous malformations: A meta-analysis of individual patient data. Lancet Neurol., 2016, 15(2), 166-173.
[http://dx.doi.org/10.1016/S1474-4422(15)00303-8] [PMID: 26654287]
[20]
Gross, B.A.; Lin, N.; Du, R.; Day, A.L. The natural history of intracranial cavernous malformations. Neurosurg. Focus, 2011, 30(6), E24.
[http://dx.doi.org/10.3171/2011.3.FOCUS1165] [PMID: 21631226]
[21]
Mouchtouris, N.; Chalouhi, N.; Chitale, A.; Starke, R.M.; Tjoumakaris, S.I.; Rosenwasser, R.H.; Jabbour, P.M. Management of cerebral cavernous malformations: from diagnosis to treatment. ScientificWorldJournal, 2015, 2015, 1-8.
[http://dx.doi.org/10.1155/2015/808314] [PMID: 25629087]
[22]
Bauman, M.M.J.; Bocanegra-Becerra, J.E.; Patra, D.P.; Meyer, J.H.; Meyer, F.B.; Sands, K.A.; Bendok, B.R. Commentary: Precuneal interhemispheric, transtentorial approach to a dorsal pontine cavernous malformation: 2-dimensional operative video. Oper. Neurosurg., 2022, 23(6), e403-e404.
[http://dx.doi.org/10.1227/ons.0000000000000467] [PMID: 36377912]
[23]
Kalani, M.Y.S.; Yagmurlu, K.; Martirosyan, N.L.; Cavalcanti, D.D.; Spetzler, R.F. Approach selection for intrinsic brainstem pathologies. J. Neurosurg., 2016, 125(6), 1596-1607.
[http://dx.doi.org/10.3171/2016.6.JNS161043] [PMID: 27662530]
[24]
Giliberto, G.; Lanzino, D.J.; Diehn, F.E.; Factor, D.; Flemming, K.D.; Lanzino, G. Brainstem cavernous malformations: Anatomical, clini-cal, and surgical considerations. Neurosurg. Focus, 2010, 29(3), E9.
[http://dx.doi.org/10.3171/2010.6.FOCUS10133] [PMID: 20809767]
[25]
Srinivasan, V.M.; Karahalios, K.; Shlobin, N.A.; Koester, S.W.; Nguyen, C.L.; Rumalla, K.; Rahmani, R.; Catapano, J.S.; Labib, M.A.; Mitha, A.P.; Spetzler, R.F.; Lawton, M.T. Residual and recurrent spinal cord cavernous malformations: Outcomes and techniques to opti-mize resection and a systematic review of the literature. Oper. Neurosurg., 2023, 24(1), 44-54.
[http://dx.doi.org/10.1227/ons.0000000000000456] [PMID: 36519878]
[26]
Dukatz, T.; Sarnthein, J.; Sitter, H.; Bozinov, O.; Benes, L.; Sure, U.; Bertalanffy, H. Quality of life after brainstem cavernoma surgery in 71 patients. Neurosurgery, 2011, 69(3), 689-695.
[http://dx.doi.org/10.1227/NEU.0b013e31821d31b7] [PMID: 21508880]
[27]
Gunawan, P.Y.; Islam, A.A.; July, J.; Patellongi, I.; Nasrum, M.; Aninditha, T. Karnofsky performance scale and neurological assessment of neuro-oncology scale as early predictor in glioma. Asian Pac. J. Cancer Prev., 2020, 21(11), 3387-3392.
[http://dx.doi.org/10.31557/APJCP.2020.21.11.3387]
[28]
Zhang, D.; Chen, J.; Han, K.; Yu, M.; Hou, L. Management of penetrating skull base injury: A single institutional experience and review of the literature. BioMed Res. Int., 2017, 2017, 2838167.
[http://dx.doi.org/10.1155/2017/2838167] [PMID: 28828384]
[29]
Zhou, L.; Wang, W. Wei, H Clinical application of 3D Slicer combined with Sina/MosoCam multimodal system in preoperative planning of brain lesions surgery. Sci. Rep., 2022, 12, 19258.
[http://dx.doi.org/10.1038/s41598-022-22549-7]
[30]
Jun, M.; Shaobo, S.; Shuyuan, Y.; Yan, Z.; Yonggang, L.; Xiaochen, C.; Hui, M. Preoperative visualization of cranial nerves in skull base tumor surgery using diffusion tensor imaging technology. Turk Neurosurg., 2015, 26(6), 805-812.
[http://dx.doi.org/10.5137/1019-5149.JTN.13655-14.1] [PMID: 27476917]
[31]
Eftekhar, B. A smartphone app to assist scalp localization of superficial supratentorial lesions—technical note. World Neurosurg., 2016, 85, 359-363.
[http://dx.doi.org/10.1016/j.wneu.2015.09.091] [PMID: 26455767]
[32]
Gao, X.; Yue, K.; Sun, J. Treatment of cerebral cavernous malformations presenting with seizures: A systematic review and meta-analysis. Front. Neurol., 2020, 11, 590589.
[http://dx.doi.org/10.3389/fneur.2020.590589]
[33]
Günel, M.; Awad, I.A.; Finberg, K.; Anson, J.A.; Steinberg, G.K.; Batjer, H.H.; Kopitnik, T.A.; Morrison, L.; Giannotta, S.L.; Nelson-Williams, C.; Lifton, R.P. A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. N. Engl. J. Med., 1996, 334(15), 946-951.
[http://dx.doi.org/10.1056/NEJM199604113341503] [PMID: 8596595]
[34]
Bertalanffy, H.; Benes, L.; Miyazawa, T.; Alberti, O.; Siegel, A.M.; Sure, U. Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients. Neurosurg. Rev., 2002, 25(1-2), 1-53.
[http://dx.doi.org/10.1007/s101430100179] [PMID: 11954761]
[35]
Desai, R.; Rich, K.M. Therapeutic role of gamma knife stereotactic radiosurgery in neuro-oncology. Mo. Med., 2020, 117(1), 33-38.
[PMID: 32158047]
[36]
Harris, L.; Das, M. Stereotactic radiosurgery.StatPearls; StatPearls Publishing: Treasure Island, FL, 2022.
[37]
Gloyd, J.S. Veterinary prescription drugs--good things do happen. J. Am. Vet. Med. Assoc., 1988, 193(12), 1483.
[PMID: 3215804]
[38]
Hauck, E.F.; Barnett, S.L.; White, J.A.; Samson, D. Symptomatic brainstem cavernomas. Neurosurgery, 2009, 64(1), 61-71.
[http://dx.doi.org/10.1227/01.NEU.0000335158.11692.53] [PMID: 19050659]
[39]
Akers, A.; Al-Shahi Salman, R.; A. Awad, I. Dahlem, K.; Flemming, K.; Hart, B.; Kim, H.; Jusue-Torres, I.; Kondziolka, D.; Lee, C.; Mor-rison, L.; Rigamonti, D.; Rebeiz, T.; Tournier-Lasserve, E.; Waggoner, D.; Whitehead, K. Synopsis of guidelines for the clinical management of cerebral cavernous malformations: Consensus recommendations based on systematic literature review by the angioma alliance scientific advisory board clinical experts panel. Neurosurgery, 2017, 80(5), 665-680.
[http://dx.doi.org/10.1093/neuros/nyx091] [PMID: 28387823]
[40]
Régis, J.; Bartolomei, F.; Kida, Y.; Kobayashi, T.; Vladyka, V.; Liscàk, R.; Forster, D.; Kemeny, A.; Schröttner, O.; Pendl, G. Radiosurgery for epilepsy associated with cavernous malformation: retrospective study in 49 patients. Neurosurgery, 2000, 47(5), 1091-1097.
[http://dx.doi.org/10.1097/00006123-200011000-00013] [PMID: 11063101]
[41]
Karaaslan, B.; Gülsuna, B.; Erol, G. Stereotactic radiosurgery for cerebral cavernous malformation: Comparison of hemorrhage rates before and after stereotactic radiosurgery. J. Neurosurg., 2021, 136(3), 655-661.
[http://dx.doi.org/10.3171/2021.2.JNS21138]
[42]
Hasegawa, T.; McInerney, J.; Kondziolka, D.; Lee, J.Y.K.; Flickinger, J.C.; Lunsford, L.D. Long-term results after stereotactic radiosurgery for patients with cavernous malformations. Neurosurgery, 2002, 50(6), 1190-1198.
[http://dx.doi.org/10.1097/00006123-200206000-00003] [PMID: 12015835]
[43]
Dalyai, R.T.; Ghobrial, G.; Awad, I.; Tjoumakaris, S.; Gonzalez, L.F.; Dumont, A.S.; Chalouhi, N.; Randazzo, C.; Rosenwasser, R.; Jab-bour, P. Management of incidental cavernous malformations: A review. Neurosurg. Focus, 2011, 31(6), E5.
[http://dx.doi.org/10.3171/2011.9.FOCUS11211] [PMID: 22133177]
[44]
Rigamonti, D.; Hadley, M.N.; Drayer, B.P.; Johnson, P.C.; Hoenig-Rigamonti, K.; Knight, J.T.; Spetzler, R.F. Cerebral cavernous malfor-mations. Incidence and familial occurrence. N. Engl. J. Med., 1988, 319(6), 343-347.
[http://dx.doi.org/10.1056/NEJM198808113190605] [PMID: 3393196]
[45]
Kivelev, J.; Niemelä, M.; Blomstedt, G.; Roivainen, R.; Lehecka, M.; Hernesniemi, J. Microsurgical treatment of temporal lobe caverno-mas. Acta Neurochir. (Wien), 2011, 153(2), 261-270.
[http://dx.doi.org/10.1007/s00701-010-0812-5] [PMID: 20872256]
[46]
Baumann, C.R.; Acciarri, N.; Bertalanffy, H.; Devinsky, O.; Elger, C.E.; Lo Russo, G.; Cossu, M.; Sure, U.; Singh, A.; Stefan, H.; Ham-men, T.; Georgiadis, D.; Baumgartner, R.W.; Andermann, F.; Siegel, A.M. Seizure outcome after resection of supratentorial cavernous mal-formations: A study of 168 patients. Epilepsia, 2007, 48(3), 559-563.
[http://dx.doi.org/10.1111/j.1528-1167.2006.00941.x] [PMID: 17346251]
[47]
Cerebral Cavernous Malformations StatPearls 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538144/
[48]
Al-Shahi Salman, R.; Berg, M.J.; Morrison, L.; Awad, I.A. Hemorrhage from cavernous malformations of the brain: Definition and report-ing standards. Stroke, 2008, 39(12), 3222-3230.
[http://dx.doi.org/10.1161/STROKEAHA.108.515544] [PMID: 18974380]
[49]
Zawistowski, J.S.; Stalheim, L.; Uhlik, M.T.; Abell, A.N.; Ancrile, B.B.; Johnson, G.L.; Marchuk, D.A. CCM1 and CCM2 protein interac-tions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum. Mol. Genet., 2005, 14(17), 2521-2531.
[http://dx.doi.org/10.1093/hmg/ddi256] [PMID: 16037064]
[50]
Akers, A.L.; Johnson, E.; Steinberg, G.K.; Zabramski, J.M.; Marchuk, D.A. Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): Evidence for a two-hit mechanism of CCM pathogenesis. Hum. Mol. Genet., 2009, 18(5), 919-930.
[http://dx.doi.org/10.1093/hmg/ddn430] [PMID: 19088123]
[51]
Washington, C.W.; McCoy, K.E.; Zipfel, G.J. Update on the natural history of cavernous malformations and factors predicting aggressive clinical presentation. Neurosurg. Focus, 2010, 29(3), E7.
[http://dx.doi.org/10.3171/2010.5.FOCUS10149] [PMID: 20809765]
[52]
Campbell, B.A.; Lasocki, A.; Oon, S.F.; Bressel, M.; Goroncy, N.; Dwyer, M.; Wiltshire, K.; Seymour, J.F.; Mason, K.; Tange, D.; Xu, M.; Wheeler, G. Evaluation of the impact of magnetic resonance imaging with susceptibility-weighted imaging for screening and surveillance of radiation-induced cavernomas in long-term survivors of malignancy. Clin. Oncol., 2021, 33(10), e425-e432.
[http://dx.doi.org/10.1016/j.clon.2021.04.010] [PMID: 34024699]
[53]
Couteulx, S.L.; Jung, H.H.; Labauge, P.; Houtteville, J.P.; Lescoat, C.; Cecillon, M.; Marechal, E.; Joutel, A.; Bach, J.F.; Tournier-Lasserve, E. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat. Genet., 1999, 23(2), 189-193.
[http://dx.doi.org/10.1038/13815] [PMID: 10508515]
[54]
Sahoo, T.; Johnson, E.W.; Thomas, J.W.; Kuehl, P.M.; Jones, T.L.; Dokken, C.G.; Touchman, J.W.; Gallione, C.J.; Lee-Lin, S.Q.; Kosof-sky, B.; Kurth, J.H.; Louis, D.N.; Mettler, G.; Morrison, L.; Gil-Nagel, A.; Rich, S.S.; Zabramski, J.M.; Boguski, M.S.; Green, E.; Marchuk, D.A. Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum. Mol. Genet., 1999, 8(12), 2325-2333.
[http://dx.doi.org/10.1093/hmg/8.12.2325] [PMID: 10545614]
[55]
Liquori, C.L.; Berg, M.J.; Siegel, A.M.; Huang, E.; Zawistowski, J.S.; Stoffer, T.P.; Verlaan, D.; Balogun, F.; Hughes, L.; Leedom, T.P.; Plummer, N.W.; Cannella, M.; Maglione, V.; Squitieri, F.; Johnson, E.W.; Rouleau, G.A.; Ptacek, L.; Marchuk, D.A. Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am. J. Hum. Genet., 2003, 73(6), 1459-1464.
[http://dx.doi.org/10.1086/380314] [PMID: 14624391]
[56]
Denier, C.; Goutagny, S.; Labauge, P.; Krivosic, V.; Arnoult, M.; Cousin, A.; Benabid, A.L.; Comoy, J.; Frerebeau, P.; Gilbert, B.; Houtteville, J.P.; Jan, M.; Lapierre, F.; Loiseau, H.; Menei, P.; Mercier, P.; Moreau, J.J.; Nivelon-Chevallier, A.; Parker, F.; Redondo, A.M.; Scarabin, J.M.; Tremoulet, M.; Zerah, M.; Maciazek, J.; Tournier-Lasserve, E. Mutations within the MGC4607 gene cause cerebral cav-ernous malformations. Am. J. Hum. Genet., 2004, 74(2), 326-337.
[http://dx.doi.org/10.1086/381718] [PMID: 14740320]
[57]
Bergametti, F.; Denier, C.; Labauge, P.; Arnoult, M.; Boetto, S.; Clanet, M.; Coubes, P.; Echenne, B.; Ibrahim, R.; Irthum, B.; Jacquet, G.; Lonjon, M.; Moreau, J.J.; Neau, J.P.; Parker, F.; Tremoulet, M.; Tournier-Lasserve, E. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am. J. Hum. Genet., 2005, 76(1), 42-51.
[http://dx.doi.org/10.1086/426952] [PMID: 15543491]
[58]
Labauge, P.; Denier, C.; Bergametti, F.; Tournier-Lasserve, E. Genetics of cavernous angiomas. Lancet Neurol., 2007, 6(3), 237-244.
[http://dx.doi.org/10.1016/S1474-4422(07)70053-4] [PMID: 17303530]
[59]
Denier, C.; Labauge, P.; Bergametti, F.; Marchelli, F.; Riant, F.; Arnoult, M.; Maciazek, J.; Vicaut, E.; Brunereau, L.; Tournier-Lasserve, E. Genotype–phenotype correlations in cerebral cavernous malformations patients. Ann. Neurol., 2006, 60(5), 550-556.
[http://dx.doi.org/10.1002/ana.20947] [PMID: 17041941]
[60]
Laurans, M.S.H.; DiLuna, M.L.; Shin, D.; Niazi, F.; Voorhees, J.R.; Nelson-Williams, C.; Johnson, E.W.; Siegel, A.M.; Steinberg, G.K.; Berg, M.J.; Scott, R.M.; Tedeschi, G.; Enevoldson, T.P.; Anson, J.; Rouleau, G.A.; Ogilvy, C.; Awad, I.A.; Lifton, R.P.; Gunel, M. Muta-tional analysis of 206 families with cavernous malformations. J. Neurosurg., 2003, 99(1), 38-43.
[http://dx.doi.org/10.3171/jns.2003.99.1.0038] [PMID: 12854741]
[61]
Ren, A.A.; Snellings, D.A.; Su, Y.S.; Hong, C.C.; Castro, M.; Tang, A.T.; Detter, M.R.; Hobson, N.; Girard, R.; Romanos, S.; Lightle, R.; Moore, T.; Shenkar, R.; Benavides, C.; Beaman, M.M.; Müller-Fielitz, H.; Chen, M.; Mericko, P.; Yang, J.; Sung, D.C.; Lawton, M.T.; Ruppert, J.M.; Schwaninger, M.; Körbelin, J.; Potente, M.; Awad, I.A.; Marchuk, D.A.; Kahn, M.L. PIK3CA and CCM mutations fuel cav-ernomas through a cancer-like mechanism. Nature, 2021, 594(7862), 271-276.
[http://dx.doi.org/10.1038/s41586-021-03562-8] [PMID: 33910229]
[62]
Zhou, Z.; Rawnsley, D.R.; Goddard, L.M.; Pan, W.; Cao, X.J.; Jakus, Z.; Zheng, H.; Yang, J.; Arthur, J.S.C.; Whitehead, K.J.; Li, D.; Zhou, B.; Garcia, B.A.; Zheng, X.; Kahn, M.L. The cerebral cavernous malformation pathway controls cardiac development via regulation of en-docardial MEKK3 signaling and KLF expression. Dev. Cell, 2015, 32(2), 168-180.
[http://dx.doi.org/10.1016/j.devcel.2014.12.009] [PMID: 25625206]
[63]
Detter, M.R.; Snellings, D.A.; Marchuk, D.A. Cerebral cavernous malformations develop through clonal expansion of mutant endothelial cells. Circ. Res., 2018, 123(10), 1143-1151.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313970] [PMID: 30359189]
[64]
Whitehead, K.J.; Chan, A.C.; Navankasattusas, S.; Koh, W.; London, N.R.; Ling, J.; Mayo, A.H.; Drakos, S.G.; Jones, C.A.; Zhu, W.; Mar-chuk, D.A.; Davis, G.E.; Li, D.Y. The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat. Med., 2009, 15(2), 177-184.
[http://dx.doi.org/10.1038/nm.1911] [PMID: 19151728]
[65]
Glading, A.J.; Ginsberg, M.H. Rap1 and its effector KRIT1/CCM1 regulate β-catenin signaling. Dis. Model. Mech., 2010, 3(1-2), 73-83.
[http://dx.doi.org/10.1242/dmm.003293] [PMID: 20007487]
[66]
Zhou, Z.; Tang, A.T.; Wong, W.Y.; Bamezai, S.; Goddard, L.M.; Shenkar, R.; Zhou, S.; Yang, J.; Wright, A.C.; Foley, M.; Arthur, J.S.C.; Whitehead, K.J.; Awad, I.A.; Li, D.Y.; Zheng, X.; Kahn, M.L. Cerebral cavernous malformations arise from endothelial gain of MEKK3–KLF2/4 signalling. Nature, 2016, 532(7597), 122-126.
[http://dx.doi.org/10.1038/nature17178] [PMID: 27027284]
[67]
Stockton, R.A.; Shenkar, R.; Awad, I.A.; Ginsberg, M.H. Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascu-lar integrity. J. Exp. Med., 2010, 207(4), 881-896.
[http://dx.doi.org/10.1084/jem.20091258] [PMID: 20308363]
[68]
Draheim, K.M.; Li, X.; Zhang, R.; Fisher, O.S.; Villari, G.; Boggon, T.J.; Calderwood, D.A. CCM2–CCM3 interaction stabilizes their pro-tein expression and permits endothelial network formation. J. Cell Biol., 2015, 208(7), 987-1001.
[http://dx.doi.org/10.1083/jcb.201407129] [PMID: 25825518]
[69]
Shenkar, R.; Shi, C.; Austin, C.; Moore, T.; Lightle, R.; Cao, Y.; Zhang, L.; Wu, M.; Zeineddine, H.A.; Girard, R.; McDonald, D.A.; Rorrer, A.; Gallione, C.; Pytel, P.; Liao, J.K.; Marchuk, D.A.; Awad, I.A. RhoA kinase inhibition with fasudil versus simvastatin in murine models of cerebral cavernous malformations. Stroke, 2017, 48(1), 187-194.
[http://dx.doi.org/10.1161/STROKEAHA.116.015013] [PMID: 27879448]
[70]
McDonald, D.A.; Shi, C.; Shenkar, R.; Stockton, R.A.; Liu, F.; Ginsberg, M.H.; Marchuk, D.A.; Awad, I.A. Fasudil decreases lesion bur-den in a murine model of cerebral cavernous malformation disease. Stroke, 2012, 43(2), 571-574.
[http://dx.doi.org/10.1161/STROKEAHA.111.625467] [PMID: 22034008]
[71]
Borikova, A.L.; Dibble, C.F.; Sciaky, N.; Welch, C.M.; Abell, A.N.; Bencharit, S.; Johnson, G.L. Rho kinase inhibition rescues the endo-thelial cell cerebral cavernous malformation phenotype. J. Biol. Chem., 2010, 285(16), 11760-11764.
[http://dx.doi.org/10.1074/jbc.C109.097220] [PMID: 20181950]
[72]
Maddaluno, L.; Rudini, N.; Cuttano, R.; Bravi, L.; Giampietro, C.; Corada, M.; Ferrarini, L.; Orsenigo, F.; Papa, E.; Boulday, G.; Tournier-Lasserve, E.; Chapon, F.; Richichi, C.; Retta, S.F.; Lampugnani, M.G.; Dejana, E. EndMT contributes to the onset and progression of cere-bral cavernous malformations. Nature, 2013, 498(7455), 492-496.
[http://dx.doi.org/10.1038/nature12207] [PMID: 23748444]
[73]
Petersen, T.A.; Morrison, L.A.; Schrader, R.M.; Hart, B.L. Familial versus sporadic cavernous malformations: Differences in developmen-tal venous anomaly association and lesion phenotype. AJNR Am. J. Neuroradiol., 2010, 31(2), 377-382.
[http://dx.doi.org/10.3174/ajnr.A1822] [PMID: 19833796]
[74]
Ucuncu, K.A.; Sengoz, M.; Peker, S. Gamma knife radiosurgery for hemorrhagic brainstem cavernomas. Turk Neurosurg., 2017, 29(1), 14-19.
[http://dx.doi.org/10.5137/1019-5149.JTN.21690-17.1] [PMID: 29372555]
[75]
Englot, D.J.; Han, S.J.; Lawton, M.T.; Chang, E.F. Predictors of seizure freedom in the surgical treatment of supratentorial cavernous mal-formations. J. Neurosurg., 2011, 115(6), 1169-1174.
[http://dx.doi.org/10.3171/2011.7.JNS11536] [PMID: 21819194]
[76]
Samanci, Y.; Ardor, G.D.; Peker, S. Management of pediatric cerebral cavernous malformations with gamma knife radiosurgery: A report of 46 cases. Childs Nerv. Syst., 2022, 38(5), 929-938.
[http://dx.doi.org/10.1007/s00381-022-05485-9]
[77]
Hongo, H.; Miyawaki, S.; Teranishi, Y.; Ishigami, D.; Ohara, K.; Sakai, Y.; Shimada, D.; Umekawa, M.; Koizumi, S.; Ono, H.; Nakatomi, H.; Saito, N. Genetics of brain arteriovenous malformations and cerebral cavernous malformations. J. Hum. Genet., 2023, 68(3), 157-167.
[http://dx.doi.org/10.1038/s10038-022-01063-8] [PMID: 35831630]

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