Cerebral cavernous malformation

Introduction
Cerebral cavernous malformations (CCMs), often called "cavernomas" are found incidentally on 0.16% of MRI scans, making them the second most common vascular lesion seen after aneurysms (0.35%).

== Signs/Symptoms ==
 * Seizures
 * Stroke from associated hemorrhage
 * New focal deficits without evidence of hemorrhage

Diagnostic definitions

 * Definite CCM-related epilepsy: epilepsy in a patient with at least one CCM and with evidence of a seizure onset zone in the immediate vicinity of the CCM. Example
 * Probable CCM-related epilepsy: epilepsy in a patient with at least one CCM and with evidence that the epilepsy is focal and arises from the same hemisphere as the CCM but not necessarily in its immediate vicinity. At the same time, there is no evidence of other causes for the epilepsy
 * Cavernomas unrelated to epilepsy: epilepsy in a patient with at least one CCM with evidence that the CCM and the epilepsy are not causally related.

Diagnostic definition
Requires both:
 * Acute or subacute onset of headache, seizure, impaired consciousness, OR new/worsened focal neurological deficit referable to the location of the lesion
 * Radiological, pathological, surgical, or rarely only CSF evidence of recent hemorrhage

Risk factors
The best data available for this is a meta-analysis of 1,620 people from seven cohorts, which showed the following two risk factors: These combine together for the following prognostic model:
 * Hemorrhage as cause of initial diagnosis, HR 5.6 (95% CI 3.2-9.7)
 * Brainstem location of CCM, HR 4.4 (95% CI 2.3-8.6)

Use of antithrombotic therapy
Data is very limited. If there is a strong reason to give antithrombotics in a patient with a CCM that has never ruptured AND that is not in the brainstem, then it may be reasonable to administer one. There is very limited data for anticoagulation. In contrast to what one might expect, some studies suggest that the risk of CCM-related hemorrhage with the use of antithrombotic therapy may actually be lower than for those not on antithrombotics. Zuurbier et al. analyzed data from Scotland for 300 patients with CCM, 61 of whom used antithrombotic therapy after presentation and 239 of whom did not. They found a lower risk of hemorrhage during 15 years of follow-up in those on antithrombotic therapy (aHR 0.12 (95% CI 0.02-0.88), and found similar findings in a meta-analysis of other studies. However, there are some very significant problems with this study:
 * There were comparatively few patients with high-risk hemorrhage features of hemorrhage at initial presentation (total of 17% of the patients) or brainstem hemorrhage (11%)
 * Group imbalances: Among the patients with hemorrhage at initial presentation, only 5 (8% of the cohort) used antithrombotic therapy, while 47 (20% of the cohort) did not, p=0.035. Similarly, more patients with incidental diagnosis were using antithrombotic therapy (64%) than were not (38%), p=<0.0001.
 * The patients using antithrombotic therapy were sicker and older, and it is possible that they died prior to follow-up and were therefore not at risk to have further hemorrhage.
 * In exploratory analyses, results were no longer significant when restricted to brainstem hemorrhage, only those who presented initially with hemorrhage, or those who started antithrombotic therapy after initial presentation (as opposed to being placed on it beforehand). In fact, the 95% CI's crossed 1, meaning that there is a possibility that antithrombotic therapy increased the risk of hemorrhage.
 * Only 10 of 61 (16%) of patients on antithrombotic therapy were on anticoagulation, with the remainder on antiplatelet therapy only. So no conclusions can be made about anticoagulation.

Stereotactic radiosurgery
No randomized trial data is available, but data suggests that stereotactic radiosurgery is likely safe and may decrease the risk of future complications, especially in patients with brainstem cavernous malformations. A 2019 systematic review found no randomized trials evaluated stereotactic radiosurgery in patients with CCM, but analyzed 30 observational studies totaling 1,576 patients. The risk of hemorrhage after stereotactic radiosurgery was 2.40% per year (95% CI 2.05-2.80%), the risk of persistent focal neurological deficits was 0.71% per year (95% CI 0.53-0.96%), and the risk of death attributed to CCM or treatment was 0.18% per year (0.10-0.31%). The risk of hemorrhage seen after stereotactic radiosurgery is similar to the natural history of the disease untreated patients, (15.8% at 5 years, or an average of ~3% per year).

Specifically for patients with brainstem cavernous malformations, the natural history of the disorder in one large study was a 27.7% 5-year risk of hemorrhage (or approximately 5-6% per year). In contrast, after stereotactic radiosurgery in cohorts with ≥80% of patients having brainstem cavernous malformation, the 2019 systematic review included 303 patients (298 of whom had brainstem malformations) and suggested an annual risk of hemorrhage of 2.58%. Thus this treatment may be more useful in patients with brainstem cavernous malformations, where surgical risk is high but the risk of hemorrhage is also high.