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Original research
Overview of cerebral cavernous malformations: comparison of treatment approaches
  1. Adela Bubenikova1,2,
  2. Petr Skalicky1,2,
  3. Vladimir Benes Jr2,
  4. Vladimir Benes Sr1,
  5. Ondrej Bradac1,2
  1. 1 Department of Neurosurgery and Neurooncology, Military University Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic
  2. 2 Department of Neurosurgery, Motol University Hospital, Second Faculty of Medicine, Charles University, Prague, Czech Republic
  1. Correspondence to Ondrej Bradac, Department of Neurosurgery and Neurooncology, Military University Hospital, Charles University First Faculty of Medicine, Prague 121 08, Czech Republic; ondrej.bradac{at}


Objectives The comparison of treatment efficacy for cerebral cavernous malformations (CCMs) has not yet been well researched.

Design PubMed, Cochrane Library, Science Direct, ISI Web of Science, Embase and additional sources were searched to identify cohort studies about the treatment of CCMs published between 1990 and 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed; the Newcastle-Ottawa Scale was used to assess the risk of bias and to evaluate limitations based on selection/outcome biases. The cumulative incidences with 95% CIs were calculated using the random effects model. The models of Poisson distribution were applied to evaluate risk factors of poorer treatment outcome by calculating rate ratios within 100 person-years with 95% CIs.

Results A total of 100 cohorts yielding 8994 patients treated for CCMs within 41 098 person-years of follow-up were analysed. The efficacy of ensuring the prevention of haemorrhage was 97% in surgical, 86% in radiosurgical and 77% in the conservative treatment. The lowest mortality (1%) was after radiosurgery, and the highest persistent morbidity (22%) was in natural history series. Deep-seated and brainstem CCMs were associated with higher bleeding rates. Lobar localisation was a protective factor in all analyses. Patients with history of previous haemorrhage were exposed to higher risk of rebleeding. Male gender was a protective factor associated with lower risk of post-treatment haemorrhage.

Conclusions Surgical resection of CCM is effective in ensuring the prevention of haemorrhage with acceptable morbidity and mortality, but conservative and radiosurgical management is a justified treatment alternative. Brainstem and deep-seated CCMs are predominantly associated with higher haemorrhage rates.

  • surgery
  • meta-analysis
  • systematic reviews

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Contributors AB, PS and OB had full access to all of the data in the meta-analysis and take responsibility for the integrity of the data. AB and PS screened titles and abstracts for eligible studies. Discrepancies were resolved on consensus meetings or by discussion with OB. AB and PS extracted data from the identified articles, and OB was a second reviewer. AB and OB performed the statistical analysis and take responsibility for the accuracy of the data analysis. All authors interpreted the data. AB drafted the manuscript, which was critically reviewed and revised for important intellectual content by all authors. OB accepts full responsibility for the work and the conduct of study, had access to the data, and controlled the decision to publish as a guarantor of the study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.