Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non-familial disease

Eur J Neurol. 2022 May;29(5):1427-1434. doi: 10.1111/ene.15253. Epub 2022 Feb 3.


Background and purpose: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period.

Methods: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage.

Results: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases.

Conclusions: FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

Keywords: CCM; cavernous angioma; familial; multiple cerebral cavernous malformations; natural course; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / etiology
  • Hemangioma, Cavernous, Central Nervous System* / complications
  • Hemangioma, Cavernous, Central Nervous System* / diagnostic imaging
  • Hemangioma, Cavernous, Central Nervous System* / genetics
  • Humans
  • Magnetic Resonance Imaging

Supplementary concepts

  • Familial cerebral cavernous malformation