脑海绵状畸形(CCM)是一个亚型of the vascular malformations found within the cerebral cortex. Although rare and usually discovered incidentally, these vascular abnormalities can predispose patients to spontaneous cerebral hemorrhage and subsequently lead to a myriad of neurological symptoms at presentation such as seizures and other focal neurological deficits. Although the symptoms and presentations of CCM have been adequately described in the adult population, disease characteristics and outcomes have not been extensively described in the pediatric population. Furthermore, the etiology of CCM—e.g., familial versus sporadic disease, as well as the risk factors for hemorrhage and neurological deficits and predictors of clinical and surgical outcomes—has not been adequately explored in the pediatric population. The current study attempts to classify and characterize differences in the clinical presentation, characteristics, and outcomes of CCMs between familial and sporadic cases within the pediatric population.
A retrospective review identified 131 pediatric patients with radiographically confirmed diagnosis of CCM. All pertinent demographic and clinical variables were collected. CCM lesions were characterized using T2-weighted and susceptibility-weighted angiography (SWAN) MRI. Statistical analysis was conducted using the t-test for continuous variables, whereas categorical variables were analyzed with the Fisher exact test or chi-square test. Multivariate analysis was performed using a Cox proportional hazards model with R version 4.2.0.
This retrospective study identified 131 pediatric CCM patients with a mean age of 8.4 years, and 54% (n = 71) were male. Twenty-seven percent (n = 35) were identified as cases with familial CCM, with the remainder classified as sporadic. The most common symptoms at presentation included generalized symptoms (headaches, nausea, and vomiting) or seizures, with a large proportion of patients also presenting as asymptomatic. No significant differences were observed in severity of symptoms between patients harboring different forms of the disease. Patients with familial CCM were noted to have a larger lesion size on average (5.26 cm3vs 1.6 cm3, p = 0.047). These patients also had a shorter progression-free follow-up interval, with 50% of patients showing progression by 888 days, compared with only 15% of sporadic CCM patients during the same period (p = 0.0019). Familial etiology of the disease and larger average lesion volume were independent, significant predictors of disease progression (p = 0.001, HR 3.29, 95% CI 1.65–6.54) and future hemorrhage (p = 0.023, HR 1.1, 95% CI 1.01–1.10), respectively.
Familial and sporadic CCMs tend to present with similar characteristics within the pediatric population. Patients with the familial form of the disease have an increased risk of progressive disease in terms of further hemorrhagic events.
INCLUDE WHEN CITINGPublished online July 21, 2023; DOI: 10.3171/2023.5.PEDS22397.
DisclosuresThe authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
PetersenTA,MorrisonLA,SchraderRM,HartBL.Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype.AJNR Am J Neuroradiol.2010;31(2):377–382.
CavalcantiDD,KalaniMY,MartirosyanNL,EalesJ,SpetzlerRF,PreulMC.Cerebral cavernous malformations: from genes to proteins to disease.J Neurosurg.2012;116(1):122–132.
SnellingsDA,HongCC,RenAA,et al.Cerebral cavernous malformation: from mechanism to therapy.Circ Res.2021;129(1):195–215.
WeiS,LiY,PolsterSP,WeberCR,AwadIA,ShenL.Cerebral cavernous malformation proteins in barrier maintenance and regulation.Int J Mol Sci.2020;21(2):675.
ZafarA,QuadriSA,FarooquiM,et al.Familial cerebral cavernous malformations.Stroke.2019;50(5):1294–1301.
SawarkarDP,JanmattiS,KumarR,et al.海绵使畸形ations of central nervous system in pediatric patients: our single-centered experience in 50 patients and review of literature.Childs Nerv Syst.2017;33(9):1525–1538.
SpieglerS,RathM,HoffjanS,et al.First large genomic inversion in familial cerebral cavernous malformation identified by whole genome sequencing.Neurogenetics.2018;19(1):55–59.
WangC,ZhaoM,WangJ,WangS,JiangZ,ZhaoJ.Frontal lobe cavernous malformations in pediatric patients: clinical features and surgical outcomes.J Child Neurol.2018;33(8):512–518.
FlemmingKD.Clinical management of cavernous malformations.Curr Cardiol Rep.2017;19(12):122.
ZabramskiJM,WascherTM,SpetzlerRF,et al.The natural history of familial cavernous malformations: results of an ongoing study.J Neurosurg.1994;80(3):422–432.
Vieceli Dalla SegaF,MastrocolaR,AquilaG,et al.KRIT1 deficiency promotes aortic endothelial dysfunction.Int J Mol Sci.2019;20(19):4930.
WangK,ZhouHJ,WangM.CCM3 and cerebral cavernous malformation disease.Stroke Vasc Neurol.2019;4(2):67–70.
Rosário MarquesI,AntunesF,FerreiraN,GrunhoM.Familial cerebral cavernous malformation: report of a novel KRIT1 mutation in a Portuguese family.Seizure.2017;53:72–74.
MespreuveM,VanhoenackerF,LemmerlingM.Familial multiple cavernous malformation syndrome: MR features in this uncommon but silent threat.J Belg Soc Radiol.2016;100(1):51.
Al-HolouWN,O’LynngerTM,PandeyAS,et al.Natural history and imaging prevalence of cavernous malformations in children and young adults.J Neurosurg Pediatr.2012;9(2):198–205.
MottoleseC,HermierM,StanH,et al.Central nervous system cavernomas in the pediatric age group.Neurosurg Rev.2001;24(2-3):55–73.
LeeJW,KimDS,ShimKW,et al.Management of intracranial cavernous malformation in pediatric patients.Childs Nerv Syst.2008;24(3):321–327.
AcciarriN,GalassiE,GiulioniM,et al.海绵使畸形ations of the central nervous system in the pediatric age group.Pediatr Neurosurg.2009;45(2):81–104.
HegdeAN,MohanS,LimCC.CNS cavernous haemangioma: "popcorn" in the brain and spinal cord.Clin Radiol.2012;67(4):380–388.
LiX,FisherOS,BoggonTJ.The cerebral cavernous malformations proteins.Oncotarget.2015;6(32):32279–32280.
D’AngeloR,AlafaciC,ScimoneC,et al.Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients.BioMed Res Int.2013;2013:459253.
HaasdijkRA,ChengC,Maat-KievitAJ,DuckersHJ.Cerebral cavernous malformations: from molecular pathogenesis to genetic counselling and clinical management.Eur J Hum Genet.2012;20(2):134–140.
LabaugeP,DenierC,BergamettiF,Tournier-LasserveE.Genetics of cavernous angiomas.Lancet Neurol.2007;6(3):237–244.
RiantF,CecillonM,Saugier-VeberP,Tournier-LasserveE.CCM molecular screening in a diagnosis context: novel unclassified variants leading to abnormal splicing and importance of large deletions.Neurogenetics.2013;14(2):133–141.
ShihYC,ChouCC,PengSJ,et al.Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.Epilepsia.2022;63(8):2056–2067.
GrossBA,DuR.Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis.J Neurosurg.2017;126(4):1079–1087.
PerriniP,LanzinoG.The association of venous developmental anomalies and cavernous malformations: pathophysiological, diagnostic, and surgical considerations.Neurosurg Focus.2006;21(1):e5.
AbdulraufSI,KaynarMY,AwadIA.A comparison of the clinical profile of cavernous malformations with and without associated venous malformations.开云体育app官方网站下载入口.1999;44(1):41–47.
All Time | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 242 | 242 | 242 |
Full Text Views | 37 | 37 | 37 |
PDF Downloads | 48 | 48 | 48 |
EPUB Downloads | 0 | 0 | 0 |