Predictors of Initial Presentation with Hemorrhage in Patients with Cavernous Malformations

Cavernous malformations (CMs) are low-flow vascular malformations of the central nervous system which are incidental or present with hemorrhage, seizures, or focal neurologic deficit (FND). Little is known about the time course of symptoms and the predictors of initial hemorrhagic presentation.

Beginning in 2015, consecutive patients with radiologically confirmed CMs were recruited and completed a structured interview and written survey at baseline. Medical records and magnetic resonance imaging studies were reviewed. Data collected included the following: comorbid conditions, select medication use, and location of CMs. Logistic-regression models determined predictors of initial presentation with hemorrhage.

Of 202 patients, 58.4% were women (average age at diagnosis, 43.7 ± 16.5 years). Of the patients, 37.1%, 6.5%, and 14.8% presented with hemorrhage, FND, and seizures, respectively. CM was an incidental finding in 40.6%. Most patients presenting with hemorrhage (66.7%) deteriorated over 2-30 days after symptom onset. Brainstem location correlated with a higher likelihood of initial presentation with hemorrhage. Aspirin use and nonsteroidal anti-inflammatory drug use were more common in patients with CMs who did not present with hemorrhage. The effect of estrogen and aspirin was stronger in the sporadic compared with the familial form of CMs. In women, estrogen use increased the likelihood of presenting with hemorrhage.

This prospective cohort study confirms brainstem location increases the likelihood of presenting with hemorrhage, but also supports a potential role of select medications on the initial clinical presentation of CMs. Further data from combined cohorts may aid in determining whether the influence of medications is different in familial versus sporadic form CMs.