Subclinical imaging changes in cerebral cavernous angiomas during prospective surveillance

Abstract

Objective: The purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease.

Methods: One hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board-approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed.

Results: There were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC.

Conclusions: Rates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.

Keywords: cerebral cavernous hemangioma; cerebrovascular disorders; intracranial hemorrhage; magnetic resonance imaging; natural history; vascular disorders.

FIG. 1.

Axial T1- (left-hand images) and T2- (right-hand images) weighted MR images showing a cerebellar CA lesion with the typical popcorn-like appearance at baseline (A) and after 1 year of follow-up (B) with demonstrated growth. The patient remained asymptomatic during this time period.

FIG. 2.

CONSORT diagram of included and excluded patients. Between September 2009 and February 2019, 327 patients with CAs, either solitary/sporadic or multifocal/familial, were screened. One hundred thirty-five patients were excluded from our study. One hundred ninety-two patients were included, of whom 144 did not have clinical or radiological changes during the follow-up period. There were 53 ACs in 34 patients, and 31 SHs in 24 patients. Some patients had both AC and SH events. In the diagram, n refers to the number of patients who were stable, or had AC or SH events.

FIG. 3.

Histogram including the number of cases during various epochs of prospective follow-up surveillance, and the number of cases with SH and AC logged during each epoch.