ISNVD 2016-moving forward

[Cece]

https://twitter.com/ccsviaustralia

 1:45 -2:05 PM - Ivo Petrov, MD, PhD – “Clinical outcomes of neurovenous angioplasty by a cardiologist”

Petrov's clinic has treated over 1300 patients with CCSVI with coexisting diagnoses of MS, migraine, ALS or Parkinsons. Mean EDSS before the procedure was 6.7 which went down to 5.2 after the procedure (!). Functional improvement happened in 62%. Any patient who deteriorated clinically after the procedure was in fact found to have vein restenosis. Restenosis occurred in 50%, which seems high, but at least it didn't occur in the other 50%.

Dr. Petrov says that CCSVI is a real vascular pathology. Endovascular treatment of CCSVI is safe. Successful treatment results in immediate improvements in perfusion. Dr. Petrov is a cardiologist who has treated CCSVI for five years now.

Very encouraging.

[Cece]

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8:40 - 9:00 - Marcello Mancini, MD, “Evaluation of cerebral hemodynamics with microbubble-enhanced ultrasound imaging and magnetic resonance imaging in MS patients”

This sounds more interesting than I'd anticipated. Microbubbbles turned out to be a contrast agent with gas used in ultrasound or MRI imaging. It can be used to evaluate how long the blood takes to circulate, particularly through the brain, and blood flow changes within the brain. It can be used to measure jugular reflux. Dr. Mancini found reflux in 22% of patients with MS. "Delay of transit time" or how long it takes the blood to exit the jugulars was up to three times higher in people with reflux.

And he found a correlation between EDSS disability and a lower washout rate (or how long it took the blood to exit the brain) in people with MS. Washout rate was 54% in healthy controls and 19% in people with MS (not entirely sure what that means). Total inflow arterial reduction in MS also correlated with EDSS disability. But what is causing the reduction in arterial inflow? Is it the slowed washout rate that also slows the inflow?

[Cece]

9:50 – 10:05 AM. Platform talk #9 Laura Pelizzari "A semi-automatic Method for Anatomical Measures of the Internal Jugular Veins.

Pelizzari emphasized the importance, which has been neglected by some CCSVI researchers, of measuring the cross sectional area of the entire internal jugular vein. Significant differences can occur across cervical levels, meaning the top of the vein may be wider or less wide than the bottom of the vein or the middle of the vein and the only way to be accurate is to measure the vein at all points.

[Cece]

 10:20 – 10:40 AM – Clive Beggs, PhD, “Retrospective overview of CSF and neurodegeneration work undertaken by members of ISNVD.” 

Clive Beggs, who is brilliant, says that the key finding of the 2009 Zamboni CCSVI study was the presence of cerebrospinal fluid flow in the caudal direction in the aqueduct of Sylvius in the MS patient. I am assuming that caudal (headward?) is the wrong direction for the CSF to be flowing. I am also assuming that the aqueduct of Sylvius is something I should be able to find on a picture of a brain if I'm as into CCSVI as I am, but is it where the IJVs merge with the venous sinuses and then the venous sinuses merge with each other, working backwards from the IJV? If Clive Beggs says this is the key finding from Zamboni's study, it probably is. He also said that the 2012 Zivadiov study showed that the aqueductal pulse (again, the aqueduct of Sylvius) is greater in the CSF of MS patients than in healthy controls. As jugular flow is impeded, there is a modest rise in pressure in the venous sinuses, lower bulk flow and increased amplitude. There is a very close correlation between intracranial venous and cerebrospinal fluid volumetric signals. Stored venous blood is expelled when the aqueductal cerebrospinal flow reverses. I wish I was there to hear him explain this more fully, because I do not understand that last part or the aqueductal CSF in general. Back to science class for me.

[Cece]

 11:00 – 11:20 AM – Norman R. Relkin, MD “Reversal of periventricular white matter intensities in iNPH.”

Dr. Relkin says that low dose acetazolamide (Diamox) reverses periventricular white matter hyperintensities in idiopathic normal pressure hydrocephalus by as much as 34%. So why is this not an MS treatment, when we too have periventricular white matter lesions?

[Cece]

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2:25 – 2:45 PM - Hector Ferral, MD – “Clinical outcomes of a Dutch treatment registry”

I am confused because Dr. Ferral is in Chicago, so was he also involved in the Dutch registry, or was he involved with doing the statistical analysis of the Dutch registry? Anyway, the registry had 751 treatments. A registry as has been discussed here before is a study that tracks data going forward but does not set up the design as a randomized study would and is therefore of less scientific weight, but still of interest. In the registry, 88% of the patients received angioplasty. Of those, 45% reported significant improvement and 15% reported mild improvement (It's not stated but does that mean 60% reported no improvement? I wonder about the techniques used in the angioplasty with that high of a no improvement, was the stenosis effectively found and removed?). The most improved symptoms were reported to be fatigue, cognitive fatigue, temperature sensitivity, bladder or bowel function and quality of life.

[Cece]

2:45 - 3:05 PM – Salvatore JA Sclafani, MD, FSIR – “Reasons for failure in neurovenous interventions” 

Dr. Sclafani is up next! He is looking at disappointments after the procedure such as patients who experience no improvement, or improvements that then go away, or worsening or complications. Some of the reasons for such disappointments are failed diagnosis, incomplete treatment and no treatment follow-up. A reason could be an incomplete assessment; doctors must check all veins that can impact cerebrospinal fluid flow. There are overlooked abnormalities, all of which we've talked about in his thread: valvular stenosis, webs, septa, hypoplasia, thickening valves, and renal vein entrapment. (I have always liked his focus on this; I have always thought that every MS patient deserves a thorough and precise diagnosis and treatment of all the abnormalities that affect blood flow, not just the typical thickened valves low in the jugulars but everything else as well, so that each individual patient gets the best outcome that they can achieve and nothing that could help is left undone or unexamined.)

Some of the problems that can arise are the inability to catheterize (I don't think that is typical on a first attempt but later if a vein has been damaged by the first angioplasty then it can be extremely hard to get past the clots or damage in order to retreat); another problem is hypoplasia, for which he does not have a solution; another problem is a recanalized occlusion, for which a stent might work. (My opinion on all three of these problems is that these are what arise after a bad angioplasty, and so the way to treat these problems is to have them never arise in the first place, and so the first angioplasty needs to be done expertly and precisely and safely, and the best way for that to happen is for the doctor to be experienced and IVUS to be used and a standardization of techniques such as how large to inflate the balloon or how long to inflate it needs to be established.)

Now we're on to Dr. Petrov, who is talking about stem cells and regenerative medicine.

[Cece]

4:05 -4:20 PM - Helen Kavnoudias “Randomised, double-blinded, controlled (with sham) study of percutaneous transluminal angioplasty for extracranial vein stenoses in patients with multiple sclerosis”

The internet ate my post about the Australia study. Sigh. The big points were that the study was double-blind and randomized, which is the gold standard for a trial. There was a trend toward significance in EDSS disability improvement (p=.08)(it would need to be p=.05 to be significant so the probability of the EDSS improvement happening by chance was 8% instead of 5% so only 3% too high) and the study would need to be increased to a larger scale to have a chance at reaching significance. The study seems well designed, particularly in that it was planned ahead of time what to do if restenosis occurs, which was to have a second procedure in which the restenosis would be treated. Since balloon angioplasty is not 100% durable, this would seem to be a necessary protocol of any study. A drug was used -- midazolam -- to prevent patients from remembering the procedure so they did not know if they were in the treated or control group. Back when we were debating the ethics of a sham procedure, it was thought that the possibility of side effects from the sham (or in this case from the midazolam) might make it unethical to design the trial that way, so it is interesting that they were able to go ahead with this. Maybe midazolam does not have much risks or side effects? Also interesting was that no placebo effect was seen in the sham group! No placebo effect at all.

I would like to see the Australian researchers get the funding needed to continue this study. There were some exciting results so far, particularly with the EDSS improvements.

[Cece]

5:40 - 6 PM – Eleuterio Toro - “Progress towards a global circulation mathematical model, incorporating detailed CSF and lymphatics dynamics.”

C'mon, I'm excited about this one, and no tweets? CCSVI Australia is the only source of ISNVD info as it's happening. https://twitter.com/ccsviaustralia I'm excited for this one because the mathematical models give logical underpinnings to CCSVI theory. There are mathematical models that are well accepted for a stenosis would affect the heart, for example, and having those mathematical models for how our jugular stenoses affect cerebrospinal blood flow should increase acceptance of this as an abnormal state and not a variation of normal.

[CureOrBust]

4:05 -4:20 PM - Helen Kavnoudias “Randomised, double-blinded, controlled (with sham) study of percutaneous transluminal angioplasty for extracranial vein stenoses in patients with multiple sclerosis”

The big points were that the study was double-blind and randomized, which is the gold standard for a trial.

I was treated by the team in Melbourne years ago, I remember discussing the trial with the Dr when it was still in the concept / ideas stage. They were always planning on a crossover design, but originally, they were spit-balling the idea of having the Dr's making great exclamations of how bad the veins were before they ballooned them, and how much improved they were after; ie try to push for a placebo effect. And the crossover (ie the placebo arm also got the treatment X months later) was to hopefully help resolve the issue/ethics of non-treatment. They obviously could not get over the risk of the sham procedure itself.

A drug was used -- midazolam -- to prevent patients from remembering the procedure so they did not know if they were in the treated or control group. Back when we were debating the ethics of a sham procedure, it was thought that the possibility of side effects from the sham (or in this case from the midazolam) might make it unethical to design the trial that way, so it is interesting that they were able to go ahead with this. Maybe midazolam does not have much risks or side effects?

As I said, I had treatment (ie way before the trial) by this team. That was my second treatment. In the first treatment, I only had a local at the entry point. It was fairly early in all this, so the Dr was very cautious and did not balloon much and obviously did not balloon hard. When he was about to blow up the balloon, he said I would feel a little pressure. I felt absolutely nothing. At second treatment (by the Melbourne team) before the procedure, the Dr took me through it, and said that I would receive a local at the entry, and was almost apologetic in telling me that at the Hospital it would be performed at REQUIRED by policy that I be give "something" (Cant remember what exactly) that would at least make me "forget the procedure". During the procedure, I pretty much felt nothing except at the last second or two when the balloon was blown up, the pain just started to build, but luckily the balloon was released before it became unbearable. As you can see, I think I actually remember the procedure. When the Dr checked on me in recovery, the number of sites they said they ballooned matched with my memory of the procedure. Does anyone know if midazolam causes a blackout / memory gap or possible fake memories? I am sure I remembered the whole procedure as if I was conscious; well, now its more than cloudy due to the years.

[CureOrBust]

2:45 - 3:05 PM – Salvatore JA Sclafani, MD, FSIR – “Reasons for failure in neurovenous interventions” 

Dr. Sclafani is up next! He is looking at disappointments after the procedure such as patients who experience no improvement, or improvements that then go away, or worsening or complications. Some of the reasons for such disappointments are failed diagnosis, incomplete treatment and no treatment follow-up.

Do you now if he is covering patients that simply do not respond? eg Someone who was treated by himself (ie IVUS etc) , later in his experience?

[Cece]

Do you now if he is covering patients that simply do not respond? eg Someone who was treated by himself (ie IVUS etc) , later in his experience?

I don't know, but that is without doubt a disappointment, and it would fit the topic.

[Cece]

 10:20 – 10:40 AM – Clive Beggs, PhD, “Retrospective overview of CSF and neurodegeneration work undertaken by members of ISNVD.” 

Clive Beggs, who is brilliant, says that the key finding of the 2009 Zamboni CCSVI study was the presence of cerebrospinal fluid flow in the caudal direction in the aqueduct of Sylvius in the MS patient. I am assuming that caudal (headward?) is the wrong direction for the CSF to be flowing. I am also assuming that the aqueduct of Sylvius is something I should be able to find on a picture of a brain if I'm as into CCSVI as I am, but is it where the IJVs merge with the venous sinuses and then the venous sinuses merge with each other, working backwards from the IJV? If Clive Beggs says this is the key finding from Zamboni's study, it probably is. He also said that the 2012 Zivadiov study showed that the aqueductal pulse (again, the aqueduct of Sylvius) is greater in the CSF of MS patients than in healthy controls. As jugular flow is impeded, there is a modest rise in pressure in the venous sinuses, lower bulk flow and increased amplitude. There is a very close correlation between intracranial venous and cerebrospinal fluid volumetric signals. Stored venous blood is expelled when the aqueductal cerebrospinal flow reverses. I wish I was there to hear him explain this more fully, because I do not understand that last part or the aqueductal CSF in general. Back to science class for me.

Science class has a reading assignment: a newly published article from Dr. Beggs et al on internal jugular vein cross-sectional area and cerebrospinal fluid pulsatility in the aqueduct of Sylvius.

In conclusion, our study provides evidence of a biomechanical link in healthy individuals between the cerebral venous outflow and the motion of the CSF pulse in the AoS, which is independent of age, BMI and cardiovascular risk factors. In healthy individuals, increased IJV-CSA at the lower cervical levels, indicative of raised IJV pressure, is linked with increased CSF pulsatility in the AoS. However, this relationship appears to be profoundly altered in MS patients, particularly on the left hand side, suggesting the presence of physiological changes associated with the cerebral venous drainage system.

http://journals.plos.org/plosone/articl ... ne.0153960