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Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study
Rustam Al-Shahi Salman1, Julie M Hall, Margaret A Horne
1Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. rustam.al-shahi@ed.ac.uk
Insights
The risk of recurrent bleeding or neurological deficits from cerebral cavernous malformations (CCMs) is higher than for a first event, particularly in women. These risks decrease over five years, aiding clinical management.
Area of Science:
- Neurology
- Vascular Malformations
- Epidemiology
Background:
- Cerebral cavernous malformations (CCMs) are vascular anomalies with a risk of bleeding and neurological deficits.
- Predictive factors for CCM-related events remain unclear.
Purpose of the Study:
- To quantify the risks of intracranial hemorrhage and focal neurological deficits in CCM patients.
- To investigate the influence of sex and CCM location on these risks.
Main Methods:
- Population-based study in Scotland (1999-2003) with validated CCM diagnoses.
- Prospective follow-up to identify outcome events and assess dependence.
- Primary outcome: composite of intracranial hemorrhage or focal neurological deficits related to CCM.
Main Results:
- The 5-year risk of recurrent events (42.4%) was significantly higher than first events (9.3%).
- Annual recurrence risk declined from 19.8% in year 1 to 5.0% in year 5.
- Recurrence risk was higher in women than men (p=0.01).
Conclusions:
- Recurrent CCM events pose a greater risk than initial events, with higher incidence in women.
- Risk of recurrence decreases over five years, informing clinical practice.
- Further research is needed to understand long-term risks and sex-based differences.
Background:
Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location.
Methods:
We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM.
Findings:
139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0-5·7 vs 29·5%, 4·1-55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1-15·4 vs 42·4%, 26·8-58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1-33·4) in year 1 to 5·0% (0·0-14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17).
Interpretation:
The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men.
Funding:
UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
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