Management of Cavernous Malformations

New information and technologies have improved the management of cavernous malformations (CMs). Cavernous malformations are well-circumscribed, multilobulated malformations made up of channels or caverns lined by a layer of endothelium. A subset of vascular malformations, they have a characteristic radiographic and pathologic appearance. Their pathogenesis is not completely understood, but the clinical presentation includes seizures of all types, hemorrhage, and acute or subacute focal deficits. CMs can occur anywhere in the brain — very often in the brainstem and, rarely, in the spinal cord.

There is a high incidence of asymptomatic CMs. They are often discovered as an incidental finding on MRI. Because the endothelial tight junctions are defective, all CMs, regardless of whether they are symptomatic, show evidence of microhemorrhages that occur over time.

Overt hemorrhage is less common but can have potentially devastating and life-threatening consequences. Overt hemorrhage is likely to recur in patients with a single CM-related hemorrhagic event.

Cardiovascular malformation location

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Improvements in Surgery

At Mayo Clinic, surgery is recommended if the CM is symptomatic and in an accessible location. If not, the CM is observed closely until intractable seizures, repeat hemorrhage, or worsening focal symptoms develop.

The definition of inaccessible location has changed. "Today," notes Giuseppe Lanzino, M.D., neurosurgeon at Mayo Clinic in Minnesota., "surgery can be done with a good degree of safety, even in areas traditionally considered inoperable such as the brainstem and thalamus."

Dr. Lanzino attributes improved safety to better microscopes and optics, more sophisticated understanding of the brainstem and its surgical anatomy, and better ability to monitor cranial nerve function intraoperatively. He also points to newer technology available at Mayo such as frameless stereotactic surgery, which has improved localization by providing real-time navigation during surgery.

Improved Detection through Advances in MRI

"Another major advance has been in MRI imaging, which has helped us understand and identify these lesions," adds Kelly D. Flemming, M.D., vascular neurologist with expertise in CMs at Mayo Clinic in Minnesota.

In the past decade, gradient echo imaging has helped identify CMs with greater precision (Figure 3). Most recent is susceptibility-weighted imaging, which can identify tiny CMs that conventional MRI sequencing would miss.

Mayo Clinic is fortunate to have these MRI tools, Dr. Flemming says. "Multiple CMs may be indicative of a genetic form of the condition. Also, in patients with CM-related seizures, susceptibility-weighted imaging can more precisely and accurately identify the symptom-causing CM, which, if small, may have been missed on traditional MRI."

Dr. Lanzino adds that at Mayo, epilepsy specialists are part of a multidisciplinary team that manages patients with a CM and seizures. They help localize the area of the brain from which the seizures arise — an area that may differ from the location of the CM. Dr. Lanzino notes, "At Mayo Clinic, we sometimes insert electrodes during surgery and from the information transmitted can arrive at the actual source of the seizures, which may or may not be the CM."

MRI scans of the brain with typical CM

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New Issues in Management and Risk Factors

In cases of a sporadic CM in which the CM has been removed, the chances of developing another lesion are rare. If the CM is removed surgically, the possibility of future CM hemorrhage is usually eliminated. Such is not the case with familial CMs.

Fig. 3. MRI scans of the brain with familial CM

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Familial CMs
A familial form of the disease often causes multiple lesions. The genetic predisposition is particularly prominent in the Hispanic American population. Approximately 50 percent of Hispanic Americans with a CM have a familial form, compared with 10 percent to 20 percent of white Americans with a CM.

The familial form is autosomal dominant, and 4 genes have been isolated, 3 of which can be clinically tested. Mayo offers genetic counseling as well as genetic screening for patients with a suspected familial CM.

Risk of Hemorrhage
The most common predictor of future hemorrhage is prior hemorrhage. There is debate about some other risk factors. Traditionally, pregnancy and medications like aspirin or warfarin, prescribed to prevent heart attack and stroke, have been considered risk factors for hemorrhage in patients with a CM.

Dr. Flemming hypothesizes that this assumption may not be the case in an investigation of the natural history of CM. Begun in 1989 and with 292 patients enrolled, the project is among the largest of its kind. When completed, it should help provide further guidelines for management of CM.