Surgical Management of Cavernous Malformations and Venous Anomalies

Natural History

Perhaps the most important aspect in the management of CCMs is an understanding of its natural history. Presenting scenarios include seizures, hemorrhage, headaches, focal neurologic deficits, and incidental findings on imaging studies. Lesions of the brainstem and spinal cord are more likely to present with neurologic deficit, while supratentorial lesions may be discovered simply due to headache or a new onset of seizure activity. Although a multitude of studies have aimed to define the natural history of CCMs, more specifically its annual risk of hemorrhage, there remains some uncertainty and large variations are reported across the literature. ^, This is likely due to the ambiguous definition of what constitutes a hemorrhage, as virtually all CCMs will radiographically exhibit some evidence of blood products. Some studies accept the presence of acute blood products within the caverns on imaging as evidence of a rupture event while others define rupture as a symptomatic hemorrhage with or without radiographic evidence of extranidal blood.

The largest mega-regression model estimates the annual risk of hemorrhage per person years of non-brainstem CCMs to be 0.3%–6.3% and brainstem CCMs to be 2.8%–32.3%. Risk of future hemorrhage is most strongly correlated to a prior hemorrhage event, but also includes lesion location in the brainstem, large size, and presence of an associated developmental venous anomaly (DVA). A symptomatic hemorrhage event increases the risk of subsequent hemorrhage within the first 2 years, with decreasing risk thereafter, a phenomenon coined “temporal clustering” as described by Barker et al. ^, Posthemorrhage full recovery is estimated to be 38.8% per-person-year (28.7%–48.8%). Posthemorrhage full recovery or minimal disability is estimated to be 79.5% per-person-year (74.3%–84.8%). Mortality following hemorrhage of CCMs occurs in 2.2% of cases. Age and familial variant versus sporadic variant (see Genetic Considerations below) were not found to be independent risk factors of hemorrhage. It is disputed as to whether symptomatic hemorrhages have a sex predilection, with some reports suggesting females are more at risk.

Although seizure activity is perhaps the most common presentation of a CCM, the lesion is not always documented to be the epileptic focus. CCMs do not include functional brain tissue, meaning the seizures are a result of mass effect, expanding hematoma, or presence of iron products after red blood cell breakdown following multiple microhemorrhages, scar formation, or encephalomalacia. ^{, ,} The risk of seizure after diagnosis of an asymptomatic CCM has been estimated between 1.5% and 4.3% per patient years. If the presenting symptoms include new onset seizure activity, the risk of subsequent seizure is estimated to be 5.5% per patient year. ^, There is no evidence that seizure activity increases the risk of CCM hemorrhage.

Epidemiology

Due to the growing availability of non-invasive imaging modalities, the prevalence of CCM is now realized to be much higher than previously postulated. Based on large postmortem and magnetic resonance imaging (MRI) surveillance studies, the incidence of CCM is now estimated at 0.15%–0.56% per 100,000 persons per year with a prevalence of 0.34–0.53. ^{, , ,} Although there is no obvious sex predilection, symptomatic males are noted to present in the second to third decade while females present between fourth and sixth decades. There is little evidence to suggest CCMs are likely to hemorrhage during pregnancy. CCMs are distributed throughout the central nervous system proportional to neural tissue, with the majority occurring in cerebral hemispheres followed by infratentorial and spinal cord.

CCMs are divided into sporadic or familial variants, with only an estimated 6% representing the familial form. The behavior between familial and sporadic CCM is similar, though familial subtypes are more likely to present with multiple lesions. The familial variant CCM is much more common in the Hispanic population, accounting for an estimated 50% of CCMs compared to 10%–20% of CCMs in non-Hispanics. ^,

Pathophysiology

CCMs are described as “mulberry-like” lesions characterized by endothelium-lined sinusoidal chambers lacking mature elements such as tight junctions, lamina, adventitia, or intervening neural tissue. The gross appearance of these lesions is due to sluggish blood flow leading to frequent thrombosis, recanalization, and calcifications ( Fig. 75.1 ). Classically, CCMs are not associated with mass effect and tend to displace surrounding brain tissue as opposed to invasion. Adjacent brain tissue is frequently associated with gliotic scar surrounded by macrophages and hemosiderin deposition as a result of frequent microhemorrhage. There is evidence of a disrupted blood-brain barrier with dysfunctional tight junctions allowing for abnormal volume of red blood cell traffic into the surrounding parenchyma, forming the hemosiderin observable on gross specimen and imaging.