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Cerebral Cavernous Malformation and Hemorrhage

By Jack Hoch; Reviewed by Dr. Issam Awad


Although cerebral cavernous malformations (CCMs) have been diagnosed and researched for years, the mechanism by which these lesions hemorrhage remains poorly understood. While there are various theories regarding CCM hemorrhagic behavior, none have been unequivocally proven. Even so, the observed hemorrhage types deserve discussion.

Hemorrhage Types

Since CCMs are low pressure, low flow lesions, there is no clearly understood forcing mechanism which would result in a hemorrhage. Most of the bleeding can be divided into three groups:

  1. “Slow ooze”: blood slowly seeps through the cavern “walls” inside the CCM itself. Since the internal cavern walls are very weak, it doesn't take much for blood cells to penetrate them. Normally this does not result in noticeable symptoms, but over time, the lesion's shape or size can change. Almost all CCMs experience this type of oozing.
  2. Thrombosis: due to the stagnant nature of the blood in the CCM caverns, a thrombus (locally developed blockage/clot) can develop which can cause re-routing of the slow internal blood flow as well as growth inside the lesion. Much like 1) above, most times this is not clinically significant unless the lesion reaches a large enough size to impact surrounding brain tissue.
  3. Gross hemorrhage: blood escapes the confines of the lesion resulting in the deposit of blood products in normal brain tissue adjacent to the lesion. It is this hemorrhage type that is most commonly associated with overt clinical symptoms. Fortunately, the frequency of this hemorrhage type is lower than either 1) or 2). Symptoms primarily depend upon the exact hemorrhage location in the brain.

Clinical Significance of Hemorrhage and Potential Surgical Implications

For those patients experiencing overt hemorrhage, the sudden onset of disparate symptoms is both confusing and frightening. Many patients demand answers that are not yet available based upon past studies of the natural history of CCMs.

Receiving a CCM diagnosis upon experiencing symptoms is not a death sentence. The majority of lesions don't bleed and the ones that do normally don't explode like bombs. They may leak slowly, but this leakage can be enough to cause symptoms in the tight confines of the brain. There simply isn't enough room to accommodate foreign material such as excess blood. The result is compression or destruction of fragile nerve cells, resulting in the manifested symptoms.

The impact of a hemorrhage depends on its location in the brain. For example, the biggest problem faced by patients who have lesions in the temporal lobe is one of seizures. Hemosiderin, a type of aged blood product that can be deposited in adjacent brain tissue after an overt hemorrhage, is a known irritant. It is enough to cause seizures when found in this location.

Those harboring brainstem lesions normally suffer multiple and diverse symptoms (“focal neurological deficits”) ranging from double vision, nausea, balance problems, swallowing inability, and respiration difficultly among others.

Surgery is normally considered for those patients who have had more than one bleed in conjunction with worsening symptoms. Lesions such as these are normally considered “aggressive” and need to be removed, assuming the lesion is surgically accessible. While recovery from a hemorrhagic event normally occurs, many times a full recovery is not made. Each hemorrhage brings with it additional symptoms which may not resolve.

When considering surgery, pre-surgical patient condition is very important. The better the person's physical condition prior to surgery, the better the chances of a successful lesion removal and recovery. Neurosurgeons recommend scheduling surgery after varying periods post-bleed, if possible. This allows time for excess blood absorption, unmasking the lesion's boundary relative to healthy brain tissue; however, if surgery is contemplated, it should not be delayed so long after a bleed that the lesion begins to shrink, making extraction more difficult.

Hemorrhage and Pregnancy

It has not yet been determined whether there is an increased risk of cavernous malformation hemorrhage during pregnancy. Some researchers believe that increased estrogen during pregnancy causes changes in the walls of cavernous malformations in such a way that they are more likely to leak. However, there are no clear statistics from large scale studies on whether hemorrhages occur more frequently in pregnant women than in others with cavernous malformations. The vast majority of women complete a pregnancy without a hemorrhage or need for surgical removal of an angioma. However, pregnancy is a time of intense physiologic changes for mother and baby, and the consequences of hemorrhage or seizure may be more complicated than in the non-pregnant state. Any patient with neurovascular problems and/or epilepsy is urged to have their pregnancy overseen by a high risk obstetrician. Your obstetrician should work in close coordination with a neurologist or neurosurgeon that is familiar with your neurological history and who is knowledgeable about cavernous malformations and about epilepsy in pregnancy.

Preventative Measures and Other Considerations

So if you are diagnosed with a lesion, what precautions should you take? What should or shouldn't you do?

General consensus among neurosurgeons most familiar and experienced with CCMs is that patients harboring a lesion should:

  1. maintain blood pressure as low in the normal range as possible
  2. avoid blood thinning or anti-clot medications including aspirin, when possible. This is especially critical for patients whose lesions have demonstrated recent growth or hemorrhage. According to Dr. Issam Awad, chair of the Angioma Alliance scientific board, specific thinners to avoid include Coumadin and aspirin, but also common nonsteroidal antiinflammatory medications such as Advil, Motrin, and the newer Celebrex, Vioxx, etc. While many patients take these medications without problem, it is likely that hemorrhage risk is increased; this could be serious with Coumadin. Pros and cons should be discussed between your doctor and the neurospecialist watching the CCM. In contrast to the above medications, Tylenol (acetaminophen) is a common pain killer that does not cause bleeding tendency. This is recommended for CCM patients.
  3. stay away from roller coasters or any activity inducing strong gravitational force
  4. stay stress free. Of course, this is much easier said than done! Dr. Awad notes that stress can alter neurological symptoms after a stroke, and can account for fluctuations of symptoms. There is no known physiologic or hormonal basis for this. However, stress can increase blood pressure, which could be a problem in hypertensive patients with increased hemorrhage risk.

Patients with CCMs can:

  1. exercise moderately, but avoid strenuous activities such as heavy weightlifting that can cause acute spikes in blood pressure
  2. give birth vaginally (assuming the patient is female!) as long as the CCM is closely managed during the term of pregnancy
  3. fly in commercial aircraft with normal cabin pressures
  4. consume alcohol and caffeinated beverages in moderation

Dr. Awad notes that there has been some relation shown between diet pills, certain stimulants, and nasal decongestants containing phenylpropranolamine and intracranial hemorrhage in young patients, including possibly cases with CCM. These items have been taken off the shelves by the FDA, but it is possible that other excessive stimulants might cause bleeds.

He explains that stimulants may increase blood pressure in hypertensive patients and this could contribute to predisposition to hemorrhagic stroke. Extreme stimulants such as cocaine and other illicit drugs have been shown to cause brain hemorrhages among patients without prior history of high blood pressure, including cases pre-existing vascular malformations.


Because questions remain regarding the natural history of CCMs, the mechanism by which these lesions hemorrhage and the resultant consequences are not fully understood. The important consideration is that patients can lead long and healthy lives even after a hemorrhagic event. Should symptoms suddenly appear, don't delay in getting an MRI and consulting with a neurosurgeon that has extensive experience managing and treating CCMs. In this case, ignorance is not bliss!

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