Outcome after surgical or conservative management of cerebral cavernous malformations

Abstract

Objective: There have been few comparative studies of microsurgical excision vs conservative management of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference.

Methods: We conducted a prospective, population-based study to identify and independently validate definite CCM diagnoses first made in 1999-2003 in Scottish adult residents. We used multiple sources of prospective follow-up to assess adults' dependence and to identify and independently validate outcome events. We used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances.

Results: Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p = 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurologic deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0).

Conclusions: CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients' lifetimes. Meanwhile, a randomized controlled trial appears justified.

Classification of evidence: This study provides Class III evidence that CCM excision worsens short-term disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits.

Figure 1. Progression to primary outcome, stratified by treatment group, during 5 years of prospective follow-up

Kaplan-Meier estimate of progression to primary outcome (at least 2 successive ratings of 2 or more on the Oxford Handicap Scale [OHS]), stratified by treatment group (red line = cerebral cavernous malformation [CCM] excision, black line = conservative management), during 5 years of prospective follow-up.

Figure 2. Progression to secondary outcome, stratified by treatment group, during 5 years of prospective follow-up

Kaplan-Meier estimate of progression to secondary outcome (symptomatic intracranial hemorrhage or new focal neurologic deficit [FND] definitely attributable to a cerebral cavernous malformation [CCM], possibly attributable to a CCM, or attributable to CCM treatment), stratified by treatment group (red line = CCM excision, black line = conservative management), during 5 years of prospective follow-up.

Figure 3. Postoperative adverse events in published studies of predominantly supratentorial or exclusively brainstem cerebral cavernous malformation

Meta-analysis of proportions of patients with postoperative adverse events (death within 30 days, symptomatic intracranial hemorrhage (ICH), or new or worsened focal neurologic deficit) in studies of predominantly supratentorial or exclusively brainstem cerebral cavernous malformation (CCM). CI = confidence interval.