Are there particular disorders that tend to affect the central nervous system?
AVMs would probably be the thing that I treat the most, and AVMs can occur everywhere in the body. They occur most frequently in the brain, so much of what I do day to day is treating brain AVMs with the neurosurgeons and the neurologists. In most cases, those tend not to go through the Vascular Anomalies Center because most of them are isolated brain AVMs. Sometimes they’re part of a broader complex, and the patient may have vascular anomalies elsewhere in the body, or they may have a tendency to develop them later on, or they may get referred to neurosurgery or to me through the Vascular Anomalies Center. Then there’s a set of AVMs and AVM-like conditions that partly involve the brain or involve the lining of the brain or the lining of the spine or the areas around it or the head and neck, and they can recruit brain vessels or not recruit brain vessels. Other vascular anomalies that we see outside the central nervous system (like venous malformations and lymphatic malformations) don’t really occur in the central nervous system in the same way. There may be analogues of them, but they’re quite different than they are in the rest of the body, so you don’t see a lymphatic malformation in the brain for example, or in the spinal cord.
Darren Orbach, MD, PhD
What are some of the broader complexes that involve CNS AVMs?
There are several conditions, some of which have been known about for a long time, others of which have been more recently discovered. One of the older ones is something called HHT which stands for hereditary hemorrhagic telangiectasia. That’s a condition that involves superficial-like vascular disorders of the skin and mucous membranes. It can involve the mucous membranes in the nose, so they often present with nosebleeds; the lining of the gut, so they often present with GI bleeds; and then they have brain AVMs. That one’s been known about for a long time, and those brain AVMs have some interesting characteristics that you don’t often see with isolated brain AVMs. This interaction between neuro and non-neuro is growing all the time, and one of the fun things about working in the Vascular Anomalies Center is that we’re increasingly identifying areas of intersection. For example, there is a gene that was isolated in the last few years called RASA1 and mutations in that gene had been found to cause a disorder called CM-AVM which stands for capillary malformation AVM. A capillary malformation is a skin stain, essentially; a very superficial vascular malformation. People who have this tend to have multiple capillary malformations with a family history of capillary malformations, and they can develop AVMs anywhere in their body, and it had been discovered that they can develop brain AVMs and do develop them at higher a frequency.
There are other conditions that are AVM-like conditions in the brain, like something called the vein of Galen malformation which has also now been associated with CM-AVM, and we found an association between spinal AVMs and CM-AVM and this RASA1 mutation, so that kind of interaction is happening a lot more.
Another more recently described condition is something called PHACES syndrome, which is an acronym that is a constellation of abnormalities in different parts of the body, but a major piece of it are arterial anomalies in the brain. The arterial supply to the brain can have very unusual branches, can have major vessels missing with supply provided by unusual pathways, and they too can develop brain aneurisms; they can develop something called moyamoya which is an isolated condition in the vascular supply to the brain where the large vessels start to close down. We’ve described, and now there is a recent paper describing that this is an accepted association, brain AVMs also in association with PHACES syndrome.
So I think that’s only going to become more and more true going forward, that a lot of things we used to think about as isolated problems of the brain and spine are actually part of a broader issue.
Darren Orbach, MD, PhD