title: Cerebral cavernous malformations with diffuse manifestation: A benign entity?
abstract: OBJECTIVE
  Cerebral cavernous malformations (CCMs) are a distinct cerebrovascular disease. A fraction of CCMs present as diffuse manifestations distributed over the cerebral hemispheres, cerebellum, and brainstem. The purpose of the present study was to explore the clinical picture of such CCMs.
  
  
  METHODS
  This study assessed the appearance of CCMs on magnetic resonance (MR) images, the presence of genetic mutations using the polymerase chain reaction method, and disease course over long-term follow-up in a total of 10 patients with diffuse CCMs.
  
  
  RESULTS
  The 10 patients were Japanese and comprised 5 males and 5 females with a mean age of 48.7years. Three of them presented with seizures, two with headache and intracerebral hemorrhage, two with numbness, and one with dizziness, while the remaining two were asymptomatic. Genetic analysis revealed CCM1 mutations in four patients, CCM2 mutations in three, and a CCM3 mutation in one. In a family with 2 CCM2 patients, the appearance of sustained diffuse CCMs on MR images significantly differed between the 2 patients despite the mutation being identical. During the mean follow-up period of 13.7years, none of the 10 patients showed evidence of neurological deterioration or symptomatic hemorrhage. The appearance of their CCMs on MRI did not show significant changes. Eight patients maintained normal neurological function.
  
  
  CONCLUSIONS
  CCMs with diffuse manifestation is a hereditary disease with satisfactory prognosis. Unrecognized genomic mutations may be involved in the genesis of these CCMs.
authors.affiliation: Department of Neurological Surgery, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan. Electronic address: shotaro@juntendo-urayasu.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Department of Neurological Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogino
authors.affiliation: Department of Neurological Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Miyajima
authors.affiliation: Department of Neurological Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Neurological Surgery, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Neurological Surgery, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan.
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Yasumoto
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging*; D002352:Carrier Proteins / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020786:Hemangioma, Cavernous, Central Nervous System / Q000000981:diagnostic imaging* / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; 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; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins
keywords: Cerebral cavernous malformations; Diffuse manifestation; Familial; Prognosis