Clinical Course of Untreated Cerebral Cavernous Malformations

Kelly Flemming, M.D.
Teresa Christianson

Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH). However, diagnosis remains uncertain, partly due to small sample sizes and the infrequency of outcome events in previous studies. To accurately determine when and how to treat patients requires more precise estimation of clinical course, identification of prognostic factors, and derivation of prognostic models.

Robert Brown, Jr., M.D., M.P.H.
Robert Brown, Jr., M.D., M.P.H.

Mayo Clinic researchers, Kelly Flemming, M.D., Teresa Christianson, and Robert Brown, Jr., M.D., M.P.H., conducted a review to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. The review was published in The Lancet Neurology journal.

From a systematic review, researchers identified three prospective or retrospective hospital-based cohorts (Mayo Clinic, Rochester, MN; Toronto Western Hospital, Toronto; and Hôpital Lariboisière, Paris) and one prospective population-based cohort (Scotland) that could provide detailed data regarding clinical outcome between diagnosis and CCM treatment or last follow-up in adults with CCM.

The primary outcome of ICH within five years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent hemorrhage versus other modes of presentation and with brainstem CCM location versus other locations, 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% for 718 people with non-brainstem CCM presenting without ICH or FND, 8% for 80 people with brainstem CCM presenting without ICH or FND, 18·4% for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% for 495 people with brainstem CCM presenting with ICH or FND.

Based on these results, the mode of clinical presentation and CCM location are independently associated with ICH within five years of CCM diagnosis. These findings indicate that people with CCMs can be stratified into four groups to predict the 5-year risk of ICH. These risks can inform decisions about CCM treatment, by indirect comparison with estimates of the effects of treatment.



Kelley Luedke

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.