CAVERNOUS MALFORMATIONS — Cavernous malformations (CMs) are also referred to as angiomas, cavernous hemangiomas, or cavernomas. They may occur sporadically or in a familial pattern. In these populations, de novo lesions have been demonstrated on serial MRIs. The de novo development of CMs after brain biopsy and after radiosurgery confirms the evolutionary nature of the lesions.

Three genes (CCM1, CCM2, and CCM3) responsible for familial cavernous malformations have been reported. Nearly all familial cases of cerebral cavernous malformation among Hispanic Americans have been linked to a founder mutation of CCM1 localized to 7q. Familial cases in white non-Hispanic families have been linked to CCM2 at 7p15-p13 and CCM3 at 3q25.2-q27 .

On gross examination, cavernous malformations have a characteristic "mulberry" appearance with engorged purplish clusters. They vary from 2 mm to several centimeters in diameter. Microscopic examination reveals that CMs are composed of dilated, thin walled capillaries with a simple endothelial lining and a thin, fibrous adventitia. Elastic fibers are not present in the vessel walls. There is typically no intervening brain tissue within the channels of the lesion.

The immediately surrounding tissue is usually gliotic and hemosiderin-laden due to previous hemorrhages. It contains dilated capillaries that may represent telangiectasias; this finding supports the integrative concept of capillary telangiectasias and cavernous malformations representing two ends of a spectrum in the development of cavernous malformations.

Developmental venous anomalies (DVAs) may be associated with CMs. In a series of 102 patients, DVAs associated with CMs were found in 23 percent; these occurred more often with lesions in the posterior fossa than the supratentorial compartment. A later series of 57 patients with CMs found associated DVAs in 25 percent, and atypical patterns of venous drainage associated with CMS were seen in an additional 35 percent. Inflammation, calcification and, rarely, ossification may be identified with CMs, usually in larger lesions.

The cerebrum is the most common location for CMs (70 to 90 percent). They have been reported throughout the supratentorial compartment, but most commonly are subcortical and predisposed to the rolandic and temporal areas. Posterior fossa lesions comprise approximately 25 percent of CMs in most large series, with the majority located in the pons and cerebellar hemispheres. There have been only 36 cases of spinal cord cavernous malformations reported in the literature.

Clinical presentation — CMs occur with equal frequency in males and females, with a mean age of 30 to 40, although women more commonly present with hemorrhage and neurologic deficits. CMs that are associated with DVAs or atypical venous drainage may be more likely to present with symptomatic hemorrhage than CMs that are not associated with venous anomalies. The presentation of CMs is specific to their location.

  bullet Supratentorial CMs commonly present with hemorrhage, seizures, and progressive neurologic deficits. Annual bleeding rates of 0.25 to 1.1 percent have been reported in several large series. Seizures and progressive neurologic deficits may be the result of mass effect and secondary compromise of the microcirculation, or of microhemorrhages with local hemosiderin deposition irritating cortical or subcortical tissue.

  bullet Infratentorial CMs commonly present with hemorrhage and progressive neurologic deficits. Lesions in the brainstem present with cranial neuropathies and long-tract signs that cause progressive neurologic decline due to the high volume of critical nuclei and fiber tracts in this area. Thus, the natural history of brainstem lesions is worse than that of lesions in other areas. The annual bleeding rate for brainstem lesions is 2 to 3 percent per year, with recurrent hemorrhage rates approaching 17 to 21 percent. Progressive neurologic decline is observed in 39 percent.

The natural history of asymptomatic lesions is significantly different from CMs presenting with clinical sequelae. A prospective study of 122 patients found that 50 percent were initially asymptomatic. At a mean follow up of 34 months, the hemorrhage rate in asymptomatic and symptomatic patients was 0.6 and 4.5 percent, respectively. This study did not find that gender or lesion location influence prognosis, although others suggest that female gender and infratentorial location are risk factors for subsequent neurologic disability. Lesion size and multiplicity do not appear to influence prognosis.

Diagnosis — Blood flow through CMs is minimal. Thus, they may not be seen on angiography and often are referred to as "angiographically occult." Other imaging modalities, particularly MRI, play a more important role in the diagnosis.

  Magnetic resonance imaging — MRI usually easily establishes the diagnosis of cavernous malformation. Characteristic findings on T-1 and T-2 weighted images include a "popcorn" pattern of variable image intensities consistent with evolving blood products. A dark hemosiderin ring, best seen on T2 or gradient echo sequences at the periphery of the lesion, is suggestive of remote hemorrhage. Lesions that mimic CMs on MRI include low grade gliomas, hemorrhagic metastases (particularly melanoma), and choriocarcinoma

Contrast enhanced images should be obtained once a CM is identified in order to delineate any potential associated DVAs. Contrast enhanced images often demonstrate DVAs since they are associated with normal flow. On the other hand, CMs may have only scattered enhancement that is variable and inconsequential. This is critical in surgical planning since the resection of DVAs may compromise normal cortical venous drainage patterns and lead to venous infarction.

  Computed tomography — CT usually demonstrates a nonspecific, irregular, hyperdense mass with variable degrees of calcification. A faint perilesional blush with contrast administration is a variable and nonspecific finding.

  Angiography — CMs demonstrate a capillary blush or early draining vein in approximately 10 percent of patients. These findings may be similar to the angiographic appearance of meningiomas. Digital subtraction angiography appears to be much more sensitive than MRI for detecting the presence of CM-associated atypical venous drainage.

Treatment — Asymptomatic CMs are observed, irrespective of location. Indications for surgical resection of accessible symptomatic cerebral and cerebellar lesions include progressive neurologic deficit, intractable epilepsy, and recurrent hemorrhage. One group reported excellent or good surgical outcomes in 97 percent of 65 patients with cerebral and cerebellar CMs at a mean follow-up of one year. A poor outcome was reported in 1.5 percent with an overall mortality of 1.5 percent. Patients with a long preoperative seizure history and poorer preoperative seizure control may need more extensive resection for seizure control than those with only a few seizures prior to surgery.

Patients with symptomatic CMs entirely surrounded by eloquent tissue (eg, rolandic cortex, brainstem, thalamus/basal ganglia) are usually observed despite the poor natural history associated with untreated brainstem and thalamic lesions.

Stereotactic radiosurgery is an alternative to conservative therapy in patients with such surgically inaccessible lesions. In one report, this technique was associated with a significant drop in the annualized hemorrhage rate from 17 to 5 percent after a two year post-treatment latency period. Improvement in seizure control also occurred. Other studies have also found a reduction in hemorrhage, especially two years or more after radiosurgery. Stereotactic radiosurgery has occasionally been associated with worsening of neurological deficits or other serious complications, and this observation has dissuaded many from using stereotactic radiosurgery until further data supports its use. The complications of stereotactic radiosurgery are discussed elsewhere.

Brainstem CMs often are treated due to their aggressive natural history when there is progressive neurologic deterioration, with or without recurrent hemorrhage, if the lesion lies near the pial surface or if a non-eloquent tissue corridor exists to the lesion. In one series of 23 patients with surgically treated brainstem CMs, 46 percent had transient neurologic deficits, 17 percent had new or worsened deficits, and 83 percent were significantly improved at a mean follow-up of 3.9 years. In a second retrospective analysis, no or only slight neurologic deficit was reported in 67 percent of 30 patients treated conservatively compared with 84 percent of 93 patients treated surgically. Microsurgical techniques are also being used with success in some centers

ARTERIOVENOUS MALFORMATIONS — Arteriovenous malformations (AVMs) are the most dangerous congenital vascular malformations. This topic is discussed separately.