The editorial comment in the AJNR of Jan 09 by Jayaraman and Cloft is worthy of careful scrutiny, I believe. Although in my personal experience with Onyx and NBCA, final cure rates of brain AVMs from embolization alone are much lower than those published in the literature, the safety record of my patient population has been good, with one major exception. A patient in her 40′s, complaining of mild headache only, no previous bleed, ruptured a large AVM in the right frontal lobe some hours after an uneventful embolization with NBCA. The impact of this catastrophe on her life has been devastating. The question becomes, How many patients do I need to help in my career to offset the overall impact of this one calamity? I think that there is a reasonable body of doubt at this time from the observations of the ARUBA trial and other sources about how much we know concerning the natural history of unruptured AVMs and the complications we induce in doing what we think is the right thing. In the index paper by Panagiotopoulos et al. a significant complication rate of 7.3% is reported, i.e. permanent neurologic deficits. The authors are to be applauded for their honesty, but these realistic numbers are sufficiently high that they raise the question of whether these cases are worth the risk.
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THIS ARTICLE REFERENCES
Jayaraman M, Cloft HJ. Embolization of Brain Arteriovenous Malformations for Cure: Because We Could or Because We Should? AJNR Am J Neuroradiol 2009;30:107-08.
I do not want to be misinterpreted. The title of this blog is: EMBOLIZATION OF BRAIN ARTERIOVENOUS MALFORMATIONS FOR CURE. Therefore, what I said about IBCA and ONYX embolization of AVMs relates only to embolization aimed at complete cure. Otherwise, in my opinion pre-surgical and pre-radiosurgical embolization of AVMs is a valuable therapeutical alternative.
Guido Guglielmi
University of Rome
Italy
I think that IBCA or ONYX embolization of brain AVMs in an “uncontrollable”, “blind”, “let’s cross the finger”, “better to be lucky than good” procedure.
Much, much better an excellent vascular neurosurgeon!
Guido Guglielmi
University of Rome, Italy
In the early years of AVM glue embolizaiton, we worked to a hypothesis that maybe some complex AVMs could be completlely obliterated. Single pedicle small leasions were candidates, of course, also curable with excision. The few complex AVM cases that went on to complete obliteration days after a treatment had something in common – delayed outcome, and often low density or blood away from the nidus. It later made sense: to completely obliterate a mutli-pedicle complicated AVM, one needed to cause blockage of the main venous draiange, and the rest could clot. These were few and far between, without big bleeds ensuing.
This brings up the glue versus ONYX. Is Onyx more likely to get the venous outlet and thereby produce complete obliteration? What about the risk of bleeding with venous outflow occlusions? Are there features of AVM venous drainage that we don’t know, but predispose to safe complete embolization?
Rather than continuing the blind hope that a few of these cases will be completely obliterated, maybe there is place for vascular imaging study of the venous side of AVMs, seeking clues that predispose to this success. If the clues were known, maybe patients can be chosen for complete embolizaiton as an intention rather than luck.
The goal of brain AVM treatment is to protect the patient from a hemorrhagic event, neurological deficits and seizures and in the pediatric population to assure a normal psycho-motor development. Complete morphological cure of an AVM cannot always be achieved if these objectives are to be respected. This is particularly evident in children in whom a rapid anatomical (and not always clinical) cure has an elevated rate of morbidity and mortality, with some clinical consequences quantifiable only later in life. Partial targeted treatment is, in my opinion, an acceptable alternative in the management of high risk AVMs (particularly large ones and/or those in eloquent locations). Planning for an endovascular intervention involves a methodological analysis of the lesion and of the patient’s clinical conditions, setting up short and long term goals and a careful evaluation of the risks of the endovascular approach alone or combined, if necessary, with surgery and/or radiotherapy. Additionally, there are probably some operator dependent variants during the procedures, but like in other surgical specialties our results need to be comparable and even standardized in order to be believable. The results of an intervention should not be related to the “good luck” of the operator (like W. Jan Van Rooij previously states) but with a pre-established strategy and the percentage of complications and eventual patient outcome that we, the neuroradiology community, are willing to accept as ethical in our practices and training programs.
You could, of course, argue that the information that is available so far indicates that embolization carries considerably more risk and less efficacy than surgery or radiosurgery, and the literature would support that arguement. And if that is what you believe, then it would indeed be unethical for you to enroll patients into such a trial.
I’m just saying that some people already believe that embolization is a rational first line therapy to cure AVMs. If those people really believe that, then the burden of proof is on them and they should be encouraged to do a trial. If half of us believe one thing, and half of us believe the opposite, then perhaps this indicates that we do not know what the answer is. That is the sort of question that only a trial can answer.
And if they believe that embolization can be done with safety and efficacy similar to surgery or radiosurgery, then it is not unethical to randomize. Just because two physicians disagree about what is best for a patient does not mean that one of them has to be unethical. It just means that one or both should participate in a trial.
Some surgeons undoubtedly thought that ISAT was unethical, and therefore would never have participated. It would have been a tragedy if this trial had not been undertaken at all because a few physicians had such ethical concerns. As long as enough physicians agree that a trial asks a reasonable question that it is in the patients interest to answer, then a trial can happen. It is better that these physicians who disagree with you do a trial and prove or disprove safety and efficacy rather than they just adopt a new practice without proof.
This is how we can move past “think tank” medicine and into evidence based medicine.
My last reply was slightly truncated. What I meant to say was that until we have literature documenting >90% cure rates for embo with similar complication rates to surgery or SRS, it would be unethical to randomize.
While I obviously agree that attempting cure in most circumstances is associated with higher risk, I do feel that embolization is a useful part of treating AVMs. We routinely embolize medium to large AVMs in preparation for radiosurgery or surgery. Small AVMs (90% cure rates with embolization for small to medium AVMs with similar complication rates to surgery or radiosurgery, it would be unethical to randomize.
Why not a trial of embolization vs. surgery or embolization vs. radiosurgery?
If there are physicians who believe embolization might be the way to go, why don’t they start a randomized trial to prove safety and efficacy?
After having embolized over 300 AVMs, I have become modest for all the reasons that Cloft and Morris mention. Complete cure by embolization is mostly not an achievement but just good luck at the cost of a high risk of post embolization hemorrhage when the veins are occluded or occlude later on by thrombosis because of slow flow. If a small nidal remnant remains, a hemorrhage is almost certain. Our strategy in AVM treatment is to restrict embolization as much as possible in favour of Y-knife and surgery. Embolization has by far the highest complication rate of the three modalities. Of 50-70 AVMs treated annually, embolization is performed in 5-10.
AVMs should only be treated in institutions with all three treatment modalities. Indication and choice of modality in consensus with neurosurgeons and radiosurgeons.
So: do not embolize an AVM unless it is absolutely necessary. Other treatments are much safer!