Specialty referral for cavernous malformation ensures timely care

Cavernous malformations (also called cerebral cavernous malformations, or CCMs) are abnormal clusters of capillaries that form as benign lesions in the brain or spinal cord. The lesions can alter the flow of blood, or may bleed, causing potentially serious complications including hemorrhagic stroke, seizures, paralysis, changes to hearing or vision, and even death.

While CCMs account for about 5 to 15 percent of all central nervous system vascular abnormalities, their actual prevalence is likely underestimated because of diagnostic challenges. The disorder—which is estimated to affect about 1 percent of the population—is often misdiagnosed as multiple sclerosis, meningioma, and metastatic brain tumors. Prompt and accurate diagnosis is critical for timely, sometimes lifesaving, treatment.

Penn Medicine is home to one of the country’s few dedicated centers for CCM care. Jan-Karl Burkhardt, MD, head of Penn Medicine’s division of Cerebrovascular Surgery and the CCM Center of Excellence, stresses that it’s never too early to involve an expert in cases of suspected or confirmed CCM.

“Because high-volume and specialized centers like ours see so many patients with cerebrovascular conditions on a daily basis, we can differentiate pretty quickly among conditions to determine which patient may need surgery and which one may not,” Dr. Burkhardt says.

If a patient does need surgery, Penn specialists have the expertise and tools to achieve excellent quality of life and surgical outcomes. “We are involved in new treatment approaches and are always up-to-date for possible involvement in clinical trials for non-surgical therapy other centers may not have heard about yet,” Dr. Burkhardt adds.

When is specialist referral for a cavernous malformation appropriate?

Because CCM is a rare diagnosis, neurologists or primary care providers may not see many patients with this disease, which can contribute to misdiagnoses and delays in care. Furthermore, decisions about whether and how to treat the condition can be nuanced and complex.

However, the cerebrovascular neurosurgeons at Penn Medicine can confirm the diagnosis with highly advanced imaging to prevent misdiagnosis and treatment delays.

“Whenever there’s potentially a diagnosis of any vascular malformation—send the patient to us directly,” Dr. Burkhardt says. “We’ll have a detailed look at it, help triage the patient in the right direction, and follow-up with the referring provider.”

Dr. Burkhardt and his team see patients at the Penn Medicine Cavernous Malformation Center, which has earned a Center of Excellence for CCM designation from the Alliance to Cure Cavernous Malformation. As one of only 12 institutions with this designation, the center meets stringent criteria to establish expertise and dedication to diagnosing and treating this condition:

• High volume of cases per year
• Multiple nationally renowned specialists
• Patient education and support programs
• Active research program in CCM to improve diagnosis and treatment
• High-resolution imaging with specific sequences for CCMs

The team also offers in-person and virtual second and third opinions.

Treatment of cavernous malformation: Surgical decision making

Depending upon the type, size, and location of the lesion, treatment for CCMs may involve observation or surgery (in rare cases stereotactic radiosurgery). A CCM specialist can help determine who should have surgical resection and who might be better served with medications to control symptoms, or observation, a more common approach.

Asymptomatic lesions may not require immediate surgery if they are stable in size. “But symptomatic lesions presenting with seizure or other neurological deficits may require surgery, as do symptomatic lesions in eloquent locations, such as in the brainstem,” Dr. Burkhardt adds. “My partners and I are well trained to resect these lesions safely.”

Dr. Burkhardt adds that surgery for CCM should always be done by a specialist with a great deal of surgical experience and expertise to ensure complete resection and the best possible outcomes. That surgeon and his team work closely with referring physicians to appropriately manage these complex conditions.

Minimally invasive options for resection

At Penn Medicine, the cerebrovascular neurosurgery team offers the full spectrum of skull base approaches or minimally invasive keyhole approaches—including sitting position or contralateral access strategies—to minimize the retraction of brain tissue and safely access eloquent lesions.

“We’re able to operate on every lesion, whether it’s simple or difficult or even if there are multiple lesions,” Dr. Burkhardt says. “We've seen basically everything there is to see, and with our routines and expertise, we can give the best possible surgical outcome.”

Sporadic versus familial cavernous malformations

Another factor in treatment decision-making for CCMs involves the distinction between sporadic (non-heritable) or familial-type lesions. About 20 percent of CCMs are caused by a genetic mutation in the CCM1, CCM2, or CCM3 gene. Therefore, patients suspected of CCM should have genetic testing and counseling.

“If we see more than one lesion, it’s very likely that this is a familial type, and then we recommend genetic testing,” Dr. Burkhardt explains.

In collaboration with the genetics department, the patient will be offered a blood test. If there is a mutation in one of the three genes implicated in this condition, screening for the rest of the family is recommended.

“Many patients I see for second opinions were never offered genetic services for CCMs because other centers don’t know that this exists or are not able to offer it,” Dr. Burkhardt says.

Information gleaned from genetic testing is essential to treatment decisions. In a sporadic solitary lesion, resection can offer a cure.

However, in cases of genetic mutation with multiple symptomatic lesions, less aggressive surgical treatment may be the best option. Surgery is reserved for symptomatic or recurrently symptomatic lesions.

The Penn Medicine cavernous malformations team

Care of a patient with a CCM extends far beyond the neurosurgeons at Penn Medicine. For the best possible outcomes, patients need a team dedicated to complex neurological conditions.

For example:

• Genetics specialists perform testing for CCM 1-3.
• Neurointensivists work in our intensive care units to monitor patients after surgery and maximize their recovery.
• Neurologists and epileptologists collaborate to assess baseline neurological status, rule out seizures, and help follow patients over time.
• Neuroradiologists perform MRI sequences as required to diagnose vascular malformations, including CCM. These images help to plan surgical intervention or compare images over time if a lesion is monitored.
• Neurorehabilitation specialists have advanced, specialized strategies to help patients maximize function after brain surgery.
• Pediatric neurologists and neurosurgeons are involved through a collaboration with Children’s Hospital of Philadelphia (CHOP), as many patients are diagnosed before adulthood. Transition of care to the team at Penn Medicine is coordinated once patients reach adulthood.

Research into cavernous malformations

Penn Medicine is one of a few leading centers for research in CCMs. Dr. Burkhardt and his research team, in close collaboration with Mark Kahn, MD, are exploring potential causes for lesion formation and disease progression. They use CCM-specific preclinical models (including mouse models) to investigate CCM mechanisms and new non-surgical treatment options with an eye toward future clinical trials.

Clinical consult and patient referral

To get a second opinion or consultation from a Penn Medicine expert in CCMs, call 877-937-7366, or submit a referral through our secure online referral form.