title: Correlation of the venous angioarchitecture of multiple cerebral cavernous malformations with familial or sporadic disease: a susceptibility-weighted imaging study with 7-Tesla MRI.
abstract: OBJECTIVE Multiple cerebral cavernous malformations (CCMs) are rare lesions that occur in sporadic or familial form. Depending on the disease form, the natural history and treatment of the lesions strongly vary. Molecular analysis of an underlying germline mutation (CCM1-3) is the most sensitive screening method to distinguish between sporadic and familial cases. However, based on the different pathomechanisms that are believed to be involved in either form, significant distinctions in the CCM-associated cerebral venous angioarchitecture should be detectable. This has not been systematically studied. METHODS A consecutive series of 28 patients with multiple CCMs (681 total) diagnosed on 1.5-T MRI underwent genetic screening for CCM1-3 mutations and high-resolution susceptibility-weighted imaging (SWI) of the cerebral venous angioarchitecture with 7-T MRI. Imaging data were analyzed to examine the CCM-associated venous angioarchitecture. Results were correlated with findings of molecular analysis for CCM1-3 mutations. RESULTS Two different SWI patterns (sporadic and familial) were found. The presence of associated developmental venous anomalies correlated with negative screening for germline mutations (11 sporadic) in all cases. All patients with confirmed familial disease showed normal underlying venous angioarchitecture. Additionally, a very unusual case of a probable somatic mutation is presented. CONCLUSIONS The SWI results of the venous angioarchitecture of multiple CCMs correlate with sporadic or familial disease. These results are consistent with the theory that venous anomalies are causative for the sporadic form of multiple CCMs.
authors.affiliation: Department of Neurosurgery.
authors.forename: Philipp
authors.initials: P
authors.lastname: Dammann
authors.affiliation: Department of Neurosurgery.
authors.forename: Karsten
authors.initials: K
authors.lastname: Wrede
authors.affiliation: Department of Neurosurgery.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery.|Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Matsushige
authors.affiliation: Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen.
authors.forename: Stefan
authors.initials: S
authors.lastname: Maderwald
authors.affiliation: Institute for Diagnostic and Interventional Radiology and Neuroradiology, and.|Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen.
authors.forename: Lale
authors.initials: L
authors.lastname: Umutlu
authors.affiliation: High Field and Hybrid MR Imaging, University Hospital Essen.|Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Quick
authors.affiliation: Center for and Department of Human Genetics, University of Regensburg.
authors.forename: Ute
authors.initials: U
authors.lastname: Hehr
authors.affiliation: Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rath
authors.affiliation: Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen.|Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; and.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ladd
authors.affiliation: Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald.
authors.forename: Ute
authors.initials: U
authors.lastname: Felbor
authors.affiliation: Department of Neurosurgery.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000075927:KRIT1 Protein / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins
keywords: CCM; CCM = cerebral cavernous malformation; CCM1–3; DVA = developmental venous anomaly; FA = flip angle; MLPA = multiplex ligation-dependent probe amplification; R = in-plane resolution; ST = slice thickness; SWI; SWI = susceptibility-weighted imaging; cerebral cavernous malformations; familial cavernomatosis; familial disease; high-field MRI; magnetic resonance imaging; susceptibility-weighted imaging; vascular disorders