Sunday, 17 July 2011

MS Controversy: Inflating Veins, Deflating Symptoms

BACKGROUND: Multiple sclerosis, also referred to as MS, is an autoimmune disease that affects the brain and spinal cord. Inflammation damages the nerves, causing impulses to be stopped or slowed. The cause of MS is unknown, and there is no cure. MS is more common in individuals of northern European descent, and women are more than twice as likely to develop MS as men. The condition usually affects people between the ages of 20 and 50 years, and the average age of onset is approximately 34 years.
(SOURCE: National Institute of Neurological Disorders and Stroke, NINDS Multiple Sclerosis Information Page)
SIGNS AND SYMPTOMS: Most people experience their first symptoms of MS between 20 and 40 years of age. Initial symptoms often include blurred or double vision, red-green color distortion, or blindness in one eye. Many MS patients experience muscle weakness in their extremities and difficulty with coordination and balance. The symptoms may be severe enough to impair walking and standing and can produce partial or complete paralysis. MS patients also typically experience numbness, prickling, or "pins and needles" sensations, and pain. Hearing loss, speech impediments, tremors, and dizziness are other frequent complaints. Nearly half of all MS patients experience cognitive impairments such as difficulties with concentration, attention, memory, and poor judgment, but such symptoms are usually mild and are frequently overlooked.
(SOURCE: National Institute of Neurological Disorders and Stroke, NINDS Multiple Sclerosis Information Page)
TREATMENT: There are several treatment options for multiple sclerosis. They range from oral medications to injections. One newer and somewhat controversial treatment option is known as venoplasty for chronic cerebrospinal venous insufficiency or CCSVI. CCSVI treatment is a non-operative, minimally invasive intervention. It is typically performed as part of a catheter-based endovascular procedure. CCSVI treatment requires either balloon angioplasty and/or stent placement to open or clear obstructions from the veins that drain the brain and spinal cord. Treatment risks include post-procedural bruising, infection and short-term (1-2 hours) post-procedure dizziness or headache.
The procedure was coined by Italian vascular surgeon, Paolo Zamboni, whose wife has MS. Zamboni theorized blood flow might be impaired by iron deposits clustered near the jugular veins. Almost all the patients Zamboni tested with Doppler ultrasound had veins in the neck that were narrowed, twisted or blocked. In 2009, Zamboni published results of a study after trying the balloon procedure on a small group, including his wife and finding that most had fewer MS attacks and improved quality of life. Patients reported abandoning their wheelchairs, being able to think more clearly and having better vision.
MOFFITT CANCER CENTER: Bulent Arslan, M.D., from Moffitt Cancer Center performs the venoplasty procedure. "The reason we started performing this specific procedure at Moffitt is because a patient contacted me personally after checking the Society of Interventional Radiology website and found out that I am an interventional radiologist with experience and interest in vein treatment. I agreed to provide this service to her and once she had a very good outcome, she referred more patients. As patients had good outcomes, we continued performing the procedure. Although the mission of Moffitt Cancer Center is obviously to help prevent and cure cancer, the center is not opposed to helping other patients in need if the physicians have time and ability to treat them."
Bulent Arslan, MD, an Associate Professor of Radiology at the University of South Florida and Associate Member at Moffitt Cancer Center & Research Institute, Interventional Radiology & Endovascular Therapy, talks about a controversial new treatment for patients with multiples sclerosis.
Can you quickly discuss how the idea of performing venograms for patients with MS came to be here at your clinic?
Dr. Bulent Arslan: The whole thing started through an e-mail from a patient who found my name on Society of International Radiology (SIR) website. All information regarding interventional radiologists who are members of SIR can be obtained via this site. One of my interests is endovascular treatment of vascular disease. We treat arteries and veins using catheters, wires, balloons and stents. The patient asked me if I was familiar with angioplasty procedure for treatment of CCSVI (chronic cerebrospinal venous insufficiency) and if I would be interested in performing it on her. I responded that, “I haven’t heard of the procedure other than just here and there. I haven’t performed this procedure on anybody yet, and I don’t know if it would benefit her in particular.” She then started sending me literature that had been published – myriad retrospective studies – and asked me if I would perform the procedure. I was a little reluctant. She said, “I live in Tampa. If you would do this for me, I would stay here otherwise I will have to travel to Bulgaria or some other place, which might not be safe for her. We then agreed on it. I told her that I could do the venogram, and if there is a significant blockage (you are not supposed to have a blockage in your veins), we could treat it although I am not promising anything because ultimately we are not sure that this is what it is. That is how it started. Subsequent to that, another patient contacted me who knew her, and then we scheduled and performed the procedure. She then had a dramatic improvement in her symptoms.
Was there anything that you saw that warranted this procedure?
Dr. Bulent Arslan: The ultrasound study that we performed demonstrated that the flow wasn’t as it was supposed to be. That is the initial test we perform – a noninvasive and nonharmful test that can be performed on anybody devoid of any risk. It tells us how the blood is flowing through the jugular veins. We observed abnormal flow in her ultrasound, which justified the venogram, a minimally invasive procedure to look at the veins in more detailed way. Once the venogram was performed, we saw a tightening on both of the jugular veins, which is not supposed to be there. People don’t know the prolifics yet, but bottom-line . . . if you have a vein or artery that has a blockage significant enough that there is a visual presentation, it should not be there and resulting in symptoms, this ultimately justifies correction.
What’s the connection to MS?
Dr. Bulent Arslan: The connection to MS is not fully understood. There is a theory that because of the blockage in the veins, there is a higher pressure in the intracranial veins, which results in either the exposure of the brain to toxic materials and/or micro-hemorrhages. That theory is not yet proven, but they suggest that MS could be result of these. The other theories are that this could just be a manifestation of MS. Regardless, there is one thing for sure, the venous abnormalities are much more common in MS patients. Even though the whole thing has not been proven yet with a prospective randomized trial, just seeing the level of stenosis in MS patients with the venograms that is being implemented in myriad centers, there is definitely a correlation.
What did you do for her with this procedure?
Dr. Bulent Arslan: We basically went in through the groin vein. We use a very small needle so that I can get into the vein and through that vein we can advance all the catheters and wires under the x-ray guidance to the veins we are interested in evaluating. We brought the catheter to her jugular vein, and place the catheter tip slightly above the jugular vein within the cerebral venous sinuses. At that position dye is injected into the venous system. Dye essentially replaces blood, and it shows us the shape of the veins as well as the flow patterns. If there is a reflux, which should not be happening, we are able to observe it via following the dye applied under X-Ray. The venous flow should be towards the heart, plus if there is an anatomical narrowing that we can identify, we will call our attention to that. That shows us where it should be treated and justifies the treatment. We put a balloon where the blockage is located and dilate that blockage with the balloon, and put our catheter back up and check it to see whether there was an improvement or not. We do that until we get enough improvement in the vein so that blood flow is not restricted. We did that on two of her jugular veins and achieved excellent results. According to our nurses, she started having symptomatic improvements (improved grip strength) on the table, which I didn’t believe at the time. Afterwards, her arm strength got quite a bit better and she started walking after her recovery period, which she was not able to do before.
Are you convinced that this is a procedure that works for MS patients or is the jury still out?
Dr. Bulent Arslan: The jury is still out. I’m sure that it helps certain patients significantly. It took me about five cases to truly believe in the benefit of it. With something totally new as this procedure you need time as well as evidence. We still need a randomized trial to make sure that there is no question on anybody’s mind. The fifth patient was the worst patient that I had ever treated. He came in, in a wheelchair, his arms and legs were contracted. His movements were very, very limited. He couldn’t even turn his head. He couldn’t clear his throat. He could not speak. He was legally blind. It was almost like a coma situation. We had to do his venogram from the left side because we could not straighten his right knee. We did this procedure, and he had the worst blockages until then. One side was approximately 99 percent blocked, and incessantly neurologists will ask, “Well, what about the gradient in the vein?” To prove a blockage to be real or not, you have to show that the blood pressure in the vein above the blockage as well as below the blockage has a significant difference. In him, it was a 18-millimeter mercury, which is very rare for the veins. You should have zero to tree pressure difference in the veins. So for him, 18-millimeter mercury pressure difference in the veins above and below the blockages on both sides, was very dramatic. You can never see that in a normal person. Period! We treated one of his sides with the balloon. The other side was completely blocked. It wouldn’t open up with the balloon, so I had to put a stent in, which I don’t like to do but in his case it had to be done because there was literally nothing to lose. He was supposed to come for his 4-week follow–up. He didn’t, so I was worried that he did not have any improvements. He showed up another 4-weeks later. He was able to move his arms. He is started to see. His vision went from 20/200 to 20/30. On his initial visit, his wife had to translate everything that he said because I was unable to understand him. But during the follow up visit he had this whole conversation with me with a very clear voice. He was still in a wheelchair, but he was able to eat, able to move his arms with contractures improved. He used to have 3-4 severe headache episodes everyday, which he did not have any since the day of the procedure. After that case, I had no question in my mind regarding the efficacy of this procedure. In due course, it is going to take a lot of convincing to show people the validity of this procedure if they haven’t witnessed it’s benefits firsthand as I have with these patients.
Why is this so controversial?
Dr. Bulent Arslan: People don’t know about it. Some neurologists refuse to see the patients who are considering this procedure (follow-up with the patients), and in medicine, rightfully, you need concrete evidence before you promote something. I’m all for that. I completely agree with that. All we have right now is what these patients see themselves, and I am the only one who is seeing this transformation. It’s not evidence. It’s just what you are experiencing. Assumption of this CCSVI-MS theory is correct also implies that all of those people over the years managing MS happened to miss this, which is not easy to accept unless the evidence is concrete. There is something called placebo effect in medicine. If a patient believes hard enough that they are going to improve as a result of a procedure or medicine, they will experience certain improvements. However, placebo can only go so far. These improvements will not be regaining sight for someone who was once blind. You cannot really do that no matter how hard you want it to happen. You are going to hear, “Oh . . I feel better. My fatigue is gone.” Those could be placebo. That can happen. In my experience, there are certain symptoms that are improving that are really not going to be impacted by the placebo effect. To prove that these results are not due to the placebo effect, we need to enlist 200 patients where 100 of them will not have the treatment and the other 100 will actually have the procedure. Patients will not know if they actually had the angioplasty or not and then a neurologist will examine them in an effort to determine if there is a difference between those two groups, which will hopefully happen soon.
Obviously this is not a cure. What is it?
Dr. Bulent Arslan: It is a treatment. It is used to relieve patients of their symptoms. It makes a huge impact on patient’s lifestyle, and we do a lot more for a lot less improvement in other fields for these patients. If you talk to these patients, it’s kind of a new life for them. Just being able to eat, not having to have a diaper – something as little as that has such an effect on these individuals. We take for granted what a lot of MS patients are unable to do. Any little improvement that you can give to them is a vast improvement in their eyes.
Do you think that this may become a standard of care?
Dr. Bulent Arslan: Yes, I think so. It may take a while. It could take anywhere from three to five years, but I think that this is going to become a common thing when the prospective randomized trials are done. Right now, the patients that are getting this treatment are only a minute fraction of all of the MS patients. There is a vast population of MS patients that are out there that are completely unaware of this treatment. Once the trials have concluded, if they support a benefit to MS patients, then it will become the standard of care. One thing about this treatment is that it is not a permanent solution or cure. Anytime that you angioplasty a vein or an artery, it will come back . . . it’s just a matter of time. They will need to repeat treatment. It is sort of a maintenance therapy in essence, similar to that of the drugs that you take all your life. Instead of everyday, it will be something that needs to be done again every six months or three years (depending on the patient and depending on the blockage).