Cerebral cavernous malformation [Neurosurgery Wiki]

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====== Cerebral cavernous malformation ======

//[[J.Sales-Llopis]]//

//Neurosurgery Service, [[General University Hospital Alicante]], [[Spain]].//

===== Latest Pubmed Related Articles =====

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1vqCZ1kRmpnqYW16Nyj8PwynclHVkPSHzMu8GNyCTT0yCzPYae/?limit=15&utm_campaign=pubmed-2&fc=20230412022105}}
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[[Cerebral]] [[cavernous malformation]]s (CCMs) are [[intracranial lesion]]s comprised of low [[flow]] and abnormally dilated capillary [[endothelial]] channels with increased permeability that predispose these vessels to episodes of [[thrombosis]] and focal [[hemorrhage]], resulting in [[seizure]]s and [[neurologic deficit]]s.


===== Molecular targets =====
 
There is a grave need for the identification of [[molecular targets]] for therapeutic treatment and [[biomarker]]s as risk predictors for [[hemorrhagic stroke prevention]]. Based on reported various perturbed angiogenic signaling cascades mediated by the CCM signaling complex (CSC), there have been many proposed candidate drugs, targeting potentially angiogenic-relevant signaling pathways dysregulated by loss of function of one of the CCM proteins, which might not be enough to correct the pathological phenotype, hemorrhagic CCMs
((Zhang J, Abou-Fadel JS. Calm the raging hormone - A new therapeutic strategy involving progesterone-signaling for hemorrhagic CCMs. Vessel Plus. 2021;5:48. Epub 2021 Jul 5. PMID: 35098046; PMCID: PMC8796995.))

===== Epidemiology =====

[[Cavernoma]]s comprise 8%-15% of intracranial vascular lesions, usually supratentorial in location and superficial. 
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Of 164 cerebral [[cavernous hemangioma]]s may be found in every age group including the neonatal period. The sex incidence is equal. In 126 cases (76.8%) the cavernomas were of supratentorial, in 34 cases (20.7%) of infratentorial site, and in 4 more cases (2.5%) there was multiple occurence of supratentorial and posterior fossa cavernous haemangiomas
((Voigt K, Yaşargil MG. Cerebral cavernous haemangiomas or cavernomas.
Incidence, pathology, localization, diagnosis, clinical features and treatment.
Review of the literature and report of an unusual case. Neurochirurgia (Stuttg). 
1976 Mar;19(2):59-68. PubMed PMID: 1264322.)).

see [[Cerebral cavernous malformation of the occipital lobe]].

25% of them occur in the [[pediatric age]] group
((Kosnik-Infinger L, Carroll C, Greiner H, Leach J, Mangano FT. Management of
cerebral cavernous malformations in the pediatric population: a literature review
and case illustrations. J Neurosurg Sci. 2015 Sep;59(3):283-94. Epub 2015 May 22.
Review. PubMed PMID: 25998208.
)).

see also [[Pediatric Cavernous Malformation]].

===== Classification =====

[[Cerebral cavernous malformation classification]].

===== Etiology =====

[[Cerebral cavernous malformation etiology]].

===== Pathogenesis =====

[[Cerebral cavernous malformation pathogenesis]]
===== Complications =====

see [[Intracranial hemorrhage from cerebral cavernous malformation]]


===== Clinical features =====


As an autosomal dominant disorder with incomplete penetrance, the majority of CCMs gene mutation carriers are largely asymptomatic but when symptoms occur, the disease has typically reached the stage of focal hemorrhage with irreversible brain damage, while the molecular "trigger" initiating the occurrence of CCM pathology remain elusive
((Zhang J, Abou-Fadel JS. Calm the raging hormone - A new therapeutic strategy involving progesterone-signaling for hemorrhagic CCMs. Vessel Plus. 2021;5:48. Epub 2021 Jul 5. PMID: 35098046; PMCID: PMC8796995.))
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Cerebral cavernous malformations (CMs) are a source of neurological morbidity from [[seizure]]s and [[focal neurological deficit]]s due to mass effect and [[hemorrhage]].


===== Diagnosis =====

[[Cerebral cavernous malformation diagnosis]].



===== Treatment =====
see [[Cerebral cavernous malformation treatment]].

===== Prognosis =====
[[Cerebral cavernous malformation prognosis]].

===== Research =====
Li et al. developed a model of CCM formation that closely reproduces key events in human CCM formation through inducible CCM loss-of-function and [[PIK3CA]] gain-of-function in mature mice. In the present study, they used this model to test the ability of [[rapamycin]], a clinically approved inhibitor of the PI3K effector mTORC1, to treat rapidly growing CCMs.

They show that both intraperitoneal and oral administration of rapamycin arrests CCM growth reduces perilesional iron deposition, and improves vascular perfusion within CCMs.

The findings further establish this adult CCM model as a valuable preclinical model and support clinical testing of [[rapamycin]] to treat rapidly growing human CCMs
((Li L, Ren AA, Gao S, Su YS, Yang J, Bockman J, Mericko-Ishizuka P, Griffin J, Shenkar R, Alcazar R, Moore T, Lightle R, DeBiasse D, Awad IA, Marchuk DA, Kahn ML, Burkhardt JK. mTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice. Stroke. 2023 Sep 25. doi: 10.1161/STROKEAHA.123.044108. Epub ahead of print. PMID: 37746705.)).

===== Case series =====

[[Cerebral cavernous malformation case series]]


===== Case reports =====

Tuleasca et al. present the pre-, per-, and [[postoperative]] course of an inferior parietal [[cavernous malformation]], located in [[eloquent area,]] in a 27-year-old right-handed Caucasian male, presenting with intralesional [[hemorrhage]] and [[epilepsy]]. Preoperative [[diffusion tensor imaging]] has shown the [[cavernous malformation]] at the interface between the [[arcuate fasciculus]] and the inferior fronto-occipital fasciculus. They describe the microsurgical [[approach]], combining preoperative [[diffusion tensor imaging]], [[neuronavigation]], awake microsurgical [[resection]], and [[intraoperative magnetic resonance imaging]].

Complete microsurgical [[en bloc resection]] has been performed and is feasible even in eloquent locations. Intraoperative magnetic resonance imaging was considered an important adjunct, particularly used in this case as the patient moved during the "[[awake]]" phase of the surgery and thus [[neuronavigation]] was not accurate anymore. [[Postoperative]] course was marked by a unique, [[generalized seizure]] without any adverse event. Immediate and 3 months postoperative magnetic resonance imaging confirmed the absence of any residue. Pre- and postoperative neuropsychological exams were unremarkable
((Tuleasca C, Peciu-Florianu I, Strachowski O, Derre B, Vannod-Michel Q, Reyns N. How to combine the use of intraoperative magnetic resonance imaging (MRI) and awake craniotomy for microsurgical resection of hemorrhagic cavernous malformation in eloquent area: a case report. J Med Case Rep. 2023 Apr 12;17(1):160. doi: 10.1186/s13256-023-03816-1. PMID: 37041613.))


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A patient who underwent subtotal resection of posterior fossa medulloblastoma with subsequent chemotherapy and radiotherapy at the age of 10 years. A new lesion in the region of the left foramen of Monro appeared 16 years later. Based on the imaging results, metastases or radiation-induced cavernoma was considered. The lesion had the same appearance on imaging as a rarely published intraventricular cavernoma of the foramen of Monro. Unlike the cavernoma of the foramen of Monro, this lesion was subependymal and intraforniceal. Using electromagnetic navigation and neuroendoscopy, the lesion was completely removed. Histopathological examination revealed a cavernous haemangioma.

This is a unique case of intraforniceal paraforaminal cavernoma that was successfully removed endoscopically using electromagnetic neuronavigation and without neurological sequelae.
((Liby P, Zamecnik J, Kyncl M, Zackova J, Tichy M. Electromagnetic
navigation-guided neuroendoscopic removal of radiation-induced intraforniceal
cavernoma as a late complication of medulloblastoma treatment. Childs Nerv Syst. 
2017 Jul 8. doi: 10.1007/s00381-017-3519-6. [Epub ahead of print] PubMed PMID:
28689346.
)).