Abstract
SummaryBackgroundCerebral 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.MethodsWe 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.Findings139 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).InterpretationThe 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.FundingUK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
Highlights
Cerebral cavernous malformations (CCMs) are common, occurring in one in about 600 neurologically asymptomatic people as evident on MRI scans and one in about 200 patients in hospital-based MRI or autopsy series.[1,2,3,4,5] Population-based annual CCM detection rates were 0·17 per 100 000 people in the USA from 1965 to 1992 compared with 0·56 (0·41–0·75) per 100 000 in Scotland from 1999 to 2000;6,7 this difference in detection rates might be partly explained by the increasing availability and use of brain MRI
Of CCMs diagnosed in adults on the basis of neurological symptoms, one quarter are identified owing to intracranial haemorrhage and another quarter are identified after a focal neurological deficit without radiographic evidence of recent haemorrhage;[13] the remainder of patients present with epileptic seizures.[14]
The symptoms leading to CCM diagnosis were incidental (n=66, 47%), epileptic seizure (n=35, 25%), intracranial haemorrhage (n=17, 12%), and focal neurological deficits (n=21, 15%)
Summary
Cerebral cavernous malformations (CCMs) are common, occurring in one in about 600 neurologically asymptomatic people as evident on MRI scans and one in about 200 patients in hospital-based MRI or autopsy series.[1,2,3,4,5] Population-based annual CCM detection rates were 0·17 (95% CI 0·00–0·34) per 100 000 people in the USA from 1965 to 1992 compared with 0·56 (0·41–0·75) per 100 000 in Scotland from 1999 to 2000;6,7 this difference in detection rates might be partly explained by the increasing availability and use of brain MRI. CCMs are prone to haemorrhage,[10] which results in distinctive diagnostic appearances on pathological examination and MRI.[10,11,12] Of CCMs diagnosed in adults on the basis of neurological symptoms, one quarter are identified owing to intracranial haemorrhage and another quarter are identified after a focal neurological deficit without radiographic evidence of recent haemorrhage;[13] the remainder of patients present with epileptic seizures.[14] Hospital-based case series have described the untreated clinical course of CCMs during mostly retrospective observation, with means of 1·9–5·2 years follow-up. Patients with brainstem CCM seem to have a higher risk of recurrent intracranial haemorrhage when indirectly compared with cohorts of patients with CCM in other brain regions (21·0–60·2%; figure 1),[15,20,22,24] internal comparisons within individual cohorts have not confirmed this finding.[17,21] Findings have not Lancet Neurol 2012; 11: 217–24
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