Letter by Filippidis et al Regarding Article, “Evaluating Strategies for the Treatment of Cerebral Cavernous Malformations”

Filippidis, Aristotelis S.; Fountas, Kostas N.; Kalani, M. Yashar S.; Zabramski, Joseph M.; Spetzler, Robert F.

doi:10.1161/strokeaha.110.606251

Cited by 4 publications

(1 citation statement)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treating patients with CCM with propranolol was first proposed in 2011 by Filippidis et al and in 2013 by Strahle et al who suggested it might be beneficial in some types of children intracranial haemangiomas [18,19]. This idea was first based on its spectacular efficacy in infantile skin capillary haemangiomas, an effect that was discovered by serendipity in 2008: two infants with severe haemangiomas were treated with propranolol for a cardiopathy and their malformations considerably decreased within a few days, until they became completely flat [20].…”

Section: Resultsmentioning

confidence: 99%

Could propranolol be beneficial in adult cerebral cavernous malformations?

et al. 2019

View full text Add to dashboard Cite

Surgery is the only therapeutic option for cerebral cavernous malformations (CCM) and is proposed, whenever possible, after haemorrhagic events, neurological symptoms, or epilepsy, radiosurgery being a controversial alternative in some cases. However, there is no treatment for non-accessible lesions, such as brainstem CCM, multiple CCM, or those located in functional areas. Propranolol, a non-selective beta-blocker used as first-line treatment for infantile haemangiomas, has proved spectacularly effective in a few cases of adult patients with CCM. We herein review the histological, in vitro data and clinical findings that support the idea of propranolol as a potential treatment for CCM. Since one retrospective study has not been conclusive, we support the idea that prospective trials are necessary.

show abstract

Section: Resultsmentioning

confidence: 99%

Could propranolol be beneficial in adult cerebral cavernous malformations?

et al. 2019

View full text Add to dashboard Cite

show abstract

Molecular Genetics of Familial Cerebral Cavernous Malformations

Dru

Eales

Martirosyan

et al. 2012

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Cerebral cavernous malformations (CCMs) are vascular lesions that afflict the central nervous system. The prevalence of CCMs in the general population is 0.1–0.5%, and the disease may present as a sporadic or familial form. The familial form of the disease shows a strong predilection for the Hispanic–American ethnic group. Current research suggests that the familial form of CCMs arises due to mutations that occur in one or more of three genes: CCM1 , CCM2 and CCM3 , which encode KRIT‐1 protein, malcavernin and programmed cell death 10, respectively. This article examines the known genetic insults to the CCM genes that may cause mutated, nonfunctioning protein products. Each has unique downstream intracellular effects that lead to CCM formation. Recommendations regarding genetic counselling for families with CCMs are presented. Key Concepts: Genetic Counselling, gross pathology and molecular genetics of CCM, differences in inheritance patterns between familial and sporadic CCM. CCMs are mulberry‐like vascular defects characterized by enlarged, leaky capillaries within the central nervous system. CCMs have a strong predilection for the Hispanic‐American ethnic group and may be present in patients as either a sporadic single lesion or an inherited multi‐lesion form. The most common symptoms for CCM patients with supratentorial vascular lesions are recurrent headaches and seizures whereas infratentorial lesions result in focal neurological defects and ataxia. The familial form of CCM disease is caused by mutations in one or more of the three genes: CCM1 , CCM2 and CCM3 whose protein products are relevant to endothelial proliferation regulation, intracellular osmoregulation and endothelial migration, respectively. K‐Rev interaction trapped 1, the protein product of CCM1 , is mutated in 56% of the familial CCM patients thus preventing its association with malcavernin and RAP‐1A/ICAP1 α leading to abnormal vascular morphogenesis and dysregulation of sprouting angiogenesis For the familial variant of CCMs, the strong genetic inheritance patterns suggest physicians should recommend patients for genetic screening for CCM1 , CCM2 and CCM3 mutations, as well as for patients with solitary lesions and a family history of the disease.

show abstract