Stereotactic Radiosurgery of Cavernous Malformations

Abstract

Stereotactic radiosurgery (SRS) has gained wider acceptance in the management of cerebral cavernous malformations (CCMs) over the last decades, although it remains controversial. The major concern is based on the lack of imaging evidence of cure, but controversies also arise from the different definition of hemorrhage, heterogeneous patient populations, poor definition of treatment protocols, and the lack of control groups. Critics in the past also stressed the high rate of adverse radiation effects (ARE) reported in early experimental papers, but this concern has recently faded with the increasing number of published papers from worldwide using modern treatment protocols reporting consequently low morbidity. However, long-term benefits of SRS to treat CCMs remain unclear, as the decrease of rebleed rate observed generally 2 years after SRS may be a reflection of natural history. Thus, we think that the key for proper interpretation of results is not only the application of modern treatment protocols, but the understanding of the natural history of CCMs. Based on our current understanding of natural history, hemispheric lesions appear to be more benign with lower annual bleed rate and risk of persisting disability, whereas those found in the thalamus, basal ganglia and brainstem typically have higher rebleed risk resulting in higher cumulative morbidity following subsequent hemorrhages. It seems also likely that the risk of rebleed—though decreases within the first years—remains higher than the baseline even 5 years after the first bleed and the long-term chance for hemorrhage free survival without treatment is low. The expanding number of available data from contemporary series of CCM SRS strongly supports the initial intuition that SRS is an effective treatment alternative for deep-seated CCMs with multiple hemorrhages reducing pre-treatment annual rebleed rates from about 30% pre-treatment to 1–2% within 2 years after treatment. Moreover, it appears to stabilize lesions after the first hemorrhage and the limitedly available data with sufficiently long follow-up time suggest that SRS is superior to natural history on bleeding prevention on the long term. Treatment alternative for the safe and effective microsurgery for symptomatic hemispheric lesions is not as warranted. However, for selected cases SRS can be offered confidently as similar results have been reported on smaller series, with a reduction of rebleed rates after a two-year latency period and with a good effect on seizure control comparable to surgical series. In modern SRS series the rate of persisting AREs is low (5–7%), resulting only in mild morbidity, similarly to additional morbidity caused by post-treatment hemorrhages that mostly occur during the initial 2 years after treatment. Admittedly, high quality evidence to define the relative roles of microsurgery, SRS and wait-and-see policy in the management of symptomatic CCMs is still missing. However, the increasing positive experience seems to overcome the initial resistance toward SRS as part of our armamentarium in the management of CCMs. Moreover, our recommendation for early SRS soon after presentation in neurologically intact or minimally disabled patients, especially harboring deep-seated CCMs due to their higher morbidity of both wait-and-see policy and microsurgery, seemed to gain broader acceptance more recently.