Big Picture Updates on Guidelines, Trials and Biomarkers

Join us for an update with Dr. Issam A. Awad, cerebrovascular neurosurgeon at the University of Chicago and Emeritus Chair of the Alliance to Cure Scientific Advisory Board. In this webinar, Dr. Awad updates our community on our updated CCM clinical care consensus guidelines and findings from the Trial Readiness Project.

The audience brought so many great questions to the Q&A that we ran out of time. Dr. Awad was kind enough to answer some of the questions that weren't able to get to during the webinar, his responses are below.

Guidelines
Q. With the updates to diagnostic guidelines, would you anticipate more patients having their CCM detected much earlier (compared to when they typically show up at your clinic)?
A. Not necessarily more cases detected, but likely more accurate diagnosis. Not all black dots in the brain are CCMs, particularly in older patients or after radiation

Q. May I ask if there are any changes in HRT guidelines?
A. In progress, cannot tell what final guidelines are till everyone signs onto them.

Q. In your knowledge, how up-to-date are these practices and technologies to CCM Centers
outside of us? In Europe, for example.
A. The guidelines are our “how to” manual for CCM Centers for sure, and we hope all
physicians involved in the care of CCM patients can refer to them. CCM patients can make
sure doctors know about the guidelines and refer to them on the Alliance webpage
(Alliancetocure.org/ccmguidelines)

Trial Readiness/Natural History

Q. Is there evidence that rebleed risk drops dramatically after 3 years?
A. We only showed that rebleed risk is unchanged up to third year after a bleed. The TR
patients were not followed beyond that. Other natural history studies suggest some drop
after 3-5 years, but precise estimates for each year 3-5 and beyond are lacking

Q. What is the percentage of people who have CCM end up with spinal CCM resulting in
paralysis?
A. Less than 1% of patients with familial CCM develop paralysis from spinal CCMs

Q. What is the risk of recurrent cavernoma bleed in patients that need antithrombotics and
antiplatelet medications for cardiac disease or a pulmonary embolism?
A. Numbers are not known for cases with recent symptomatic hemorrhage, as these
medications are often stopped after a recent bleed. But we know that risk of bleeding is not increased in patients receiving these drugs, when there has not been any recent
symptomatic bleeds

Q. Are there any Vitamins or Minerals that, if taken at a higher dose than normal, can increase the risk of bleeding?
A. Excessive Vitamin E and fish oil can thin the blood. But it is not known what doses are risky in CCM.

Q. I learned new info that some people's guts have trouble with Sulfur, which can make histamine reactions worse. So, avoiding those foods with sulfur helps; I wonder if there is any relation for those sulfur-sensitive people with CCM?
A. No information about Sulfur in CCM

Biomarkers
Q. Can we have our doctors measure our inflammation? What are the tests for this?
A. Exact tests of inflammation, and levels that are relevant to CCM activity are being assessed. Not ready for testing by your doctor yet.

Q. What are the anayltes being looked at? circulating DNA or methylation, etc? There must be a threshold of amount of bleed to differentiate between leakage vs bleed? Also, for
prognostic - how does the temporal prediction work yet? SOOO COOL!!!!
A. Levels of some proteins, metabolites and microRNAs are definitely associated with recent bleeding and have great accuracy in predicting bleed or lesion growth. Stay tuned

Other Drugs
Q. Selective COX-2 inhibitors, like coxibs, were tested in mice to prevent lesion formation, and the results were great. Is there any perspective for human-testing these drugs?
A. Exact doses and safety in humans have not been assessed. Potential trials are being
discussed, with limited ability to test everything that worked in mice.

Miscellaneous
Q. We are in a situation with a regrowth with leaking of a previously surgically resected lesion. Is there any promising research for this situation?
A. All the trials to date have enrolled patients whose lesion was operated more than a year
earlier, and some lesion was left and rebled. Only cases whose symptomatic lesion has been completely resected with no recurrent