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Published on: September 4, 2017
Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data
Margaret A Horne1, Kelly D Flemming2, I-Chang Su3
1Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Insights
Predictors for symptomatic intracranial haemorrhage (ICH) in cerebral cavernous malformations (CCMs) were identified. Clinical presentation and brainstem location significantly increase ICH risk, aiding treatment decisions for CCM patients.
Area of Science:
- Neurology
- Neurosurgery
- Vascular Medicine
Background:
- Cerebral cavernous malformations (CCMs) are vascular anomalies that can lead to symptomatic intracranial haemorrhage (ICH).
- Previous risk estimates for ICH in CCM patients are imprecise, and predictors remain uncertain.
- Accurate risk assessment is crucial for guiding treatment decisions in CCM management.
Purpose of the Study:
- To provide precise estimates of the risk of symptomatic ICH in untreated patients with CCMs.
- To identify reliable predictors of ICH risk in individuals with CCMs.
- To inform clinical management strategies for CCM patients.
Main Methods:
- An individual patient data meta-analysis was conducted, pooling data from published cohorts of CCM patients aged 16 years or older.
- Systematic reviews of Ovid MEDLINE and Embase databases identified relevant studies up to April 30, 2015.
- Survival analysis and multivariable Cox regression models were used to estimate ICH risk and identify predictors.
Main Results:
- The 5-year risk of symptomatic ICH was estimated at 15.8% across 1620 patients from seven cohorts.
- Clinical presentation (ICH or focal neurological deficit) and brainstem location were significant independent predictors of ICH.
- Specific 5-year ICH risks varied significantly based on presentation and location, ranging from 3.8% to 30.8%.
Conclusions:
- The mode of clinical presentation and the location of CCMs are key independent predictors of ICH risk within five years.
- These findings offer valuable insights for clinicians in determining the optimal timing and necessity of CCM treatment.
- Precise risk stratification can improve patient outcomes and personalize management strategies for cerebral cavernous malformations.
Background:
Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis.
Methods:
We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis.
Findings:
Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7-17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2-9·7) and with brainstem CCM location versus other locations (4·4, 2·3-8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1-5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1-15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3-23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3-35·2) for 495 people with brainstem CCM presenting with ICH or FND.
Interpretation:
Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment.
Funding:
UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
