reperfusion injury in CCSVI/MS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

reperfusion injury in CCSVI/MS

Postby Cece » Thu Jun 09, 2011 9:55 am

We have not talked much about reperfusion injury but it must be a part of the cycle with MS. Here's the wikipedia on it:
Reperfusion injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.

Presumably in CCSVI, it is low-grade oxgyen deprivation, not total ischemia, although there would also seem to be trigger events where oxygen levels are stressed (perhaps childbirth, perhaps time spent at high altitudes).

I also think about my own procedure and the dramatic brightening of colors afterwards. The assumption is that the brightening was due to a restoration of normal brain oxygen levels.

So are we at risk of reperfusion injury, either in the normal course of our MS/CCSVI or immediately after the procedure, if the degree of oxygen deprivation was relatively severe?

We have known a few patients who have gotten worse immediately after what seemed to be a successful procedure in terms of no clotting and the blood flowing properly. We haven't had a good answer for that. It's only been a few cases.
The damage of reperfusion injury is due in part to the inflammatory response of damaged tissues. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage.[1] The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. Leukocytes may also build up in small capillaries, obstructing them and leading to more ischemia.

Reperfusion injury may be the name for what we've been experiencing all along, when we talk about the white blood cells attacking. Steroids or DMDs would be effective against this. It can be an excessive reaction to the injury, so that as much or more damage is done by the white blood cells' attack as it was by the initial oxygen-deprivation injury.

Cheer has been saying all along that MS may be more comparable to a series of ischaemic events.

As for if reperfusion injury might occur (particularly in more easily inflamed brains?) as an immediate result of CCSVI treatment, I don't know. Hypothermia and hydrogen sulfide are the only things listed in wikipedia as protective against reperfusion injury. Presumably most of us have low grade chronic issues rather than acute, but we also have areas of CNS damage that might be particularly vulnerable to another insult.
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Postby Merlyn » Thu Jun 09, 2011 3:02 pm

But none of this is unique to MS... same thing occurs in autism, cerebral palsy and a few other conditions.



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Postby 1eye » Mon Jun 13, 2011 1:05 pm

All I saw there was a link to "Google Docs". Don't use it, myself.
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Postby MegansMom » Thu Jun 16, 2011 4:44 am

This might explain my daughter's course right after her venoplasty.

Symptoms pre-angioplasty: fatigue, headache, intermittent difficulties processing thoughts, impaired short term memory, slight blurry vision, recent ( a month prior- lasted 24 hrs) Right sided facial weakness with numbness and loss of sensation, slightly impaired balance, fleeting intermittent electrical sensations down both arms to fingers, numb anterior thighs.

Post venoplasty: all of the above stopped, fatigue ended immediately,as did headaches, vision improved, memory and thought processing ( thinking) improved and continued to improve over months, balance improved immediately, no more electrical sensations left with venoplasty, numbness of thighs got smaller and smaller over weeks/ months and disappeared. No reoccurrence of facial weakness.

New symptoms that came post venoplasty: Expressive aphasia ( going to say the "wrong" word, this got less and less over 3 months and then stopped. Numb pinkies...pinky fingers bilaterally ( they have normal function but feel numb) , this remains her residual reminder.

We never knew why she would get rid of all of her previous symptoms but acquire new ones. I thought maybe the new oxygen level caused a previously injured area inflammation, because it got less and less frequent and then finally left. This may explain the cause.

She is now approaching the 9 month mark and doing great!
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My 35 yo daughter is newly dx 8/19/10 (had 12 symptoms)
Dx with Type A CCSVI- 1 IJV & double "candy wrapper" appearance of her Azygos
Venoplasty done Sept 21, 2010
Doing extremely well-
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Postby Cece » Thu Jun 16, 2011 7:07 am

MegansMom wrote:New symptoms that came post venoplasty: Expressive aphasia ( going to say the "wrong" word, this got less and less over 3 months and then stopped. Numb pinkies...pinky fingers bilaterally ( they have normal function but feel numb) , this remains her residual reminder.

I've been trying to compile a list of what could cause this (new persistent symptoms immediately post-venoplasty). It hasn't happened to many people but certainly we've had a handful of reports. Some have reported new numbness immediately post-procedure. One person reported difficulty walking immediately postprocedure (that did not resolve, at least six months later). One person reported severe headache immediately postprocedure, that persisted. And here is your daughter's report of new numbness and expressive aphasia postprocedure. I did not have any new symptoms postprocedure, thankfully. (My own expressive aphasia is a giveaway that I am tired; it comes on then.)

My list of theories:
* reperfusion injury
* damage done by the travel and stress of procedure
* in cases of severe blockage, ballooning the other side blocks the blood flow causing possible damage
* MS relapse, coincidental timing
* damage by toxins from Herxheimer's response if co-morbidity of Lyme or other infection (if patient feels flu-like symptoms, as has been reported by some)
* immediate restenosis worse than it was to begin with
* reaction to the contrast used in the procedure or any medications given
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Postby MegansMom » Thu Jun 16, 2011 8:05 am

Incidentally, her expressive aphasia ( which was 3 months in duration, basically getting less and less frequent over 3 months) could be brought on by : stress, caffiene or smoking !
It correlated with a vasoconstriction sort of trigger.

If indeed it was inflammatory in nature that would make sense, as it might have eventually healed if the environment was conducive for healing, ie adequate oxygen, glucose, WBCs, etc. I likened it to a live wire (axon) with it's insulation frayed(demyelination) that need to grow new insulation (remyelination) over time.

She worked hard on quitting smoking, exercising and eating well. It all seemed to help.

Exercise seems to really be key to triggering production of microparticles that seem to help rehabilitation of the damaged areas and the symptoms such damage might have caused. NO production is greatly improved with normal sheer stress, oxygen and glucose levels.

I wish they could test the Endothelin1 levels of pwCCSVI pre and post venoplasty as this my be key in causing more vasoconstriction than in a normal person. Does the high rate of E1 drop after PTA? does it cause restenosis?

So many things to study....
Last edited by MegansMom on Fri Jun 17, 2011 8:31 am, edited 1 time in total.
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My 35 yo daughter is newly dx 8/19/10 (had 12 symptoms)
Dx with Type A CCSVI- 1 IJV & double "candy wrapper" appearance of her Azygos
Venoplasty done Sept 21, 2010
Doing extremely well-
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Postby 1eye » Thu Jun 16, 2011 8:16 am

I don't want to concern you at all: I think the progress is fantastic. It's just that I have had a numb pinkie since 1989. It was my first symptom that never completely went away. I blame it on a bad sleeping posture with pressure on my neck. Of course hindsight 20:20. Anyway it sounds very familiar. Numb but fully functional. Kind of like frozen by a dentist. I have other areas now but that one's still with me. Be good to your neck. Take deep breaths. Try to sing. Don't slouch.

Just a thought: maybe there's some nerve that came into contact with something during the procedure -- mine's only one of my pinkies. Maybe she had both sides ballooned?
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Re: reperfusion injury in CCSVI/MS

Postby Cece » Tue Nov 13, 2012 9:07 am

http://news.pall.com/article_display.cf ... le_id=4421
Controlled reperfusion COBRA technique. It reduces leukocytes in the blood, making reperfusion injury less likely.

research on pigs: http://www.ncbi.nlm.nih.gov/pubmed/14688696
Conditioned blood reperfusion markedly enhances neurologic recovery after prolonged cerebral ischemia.
Last edited by Cece on Wed Mar 27, 2013 11:35 am, edited 1 time in total.
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Re: reperfusion injury in CCSVI/MS

Postby Cece » Wed Mar 27, 2013 11:30 am

From Dr. Zivadinov, discussing the PREMiSe study results at the AAN neurology conference:
"When you reopened those veins in the neck, I think something happened in reperfusing the brain and re-exacerbating disease activity. The message of this is clear. The majority of patients who are relapsing-remitting should not undergo this treatment," he said in an interview.

http://www.clinicalpsychiatrynews.com/n ... 50d27.html

Dr. Zivadinov suggests that reperfusion injury may be occurring when the veins are opened. This doesn't mean that veins shouldn't be opened; it means that the reperfusion injury needs to be addressed too. Also reperfusion injury might be a one-time thing, while benefits from the procedure might be ongoing. This sheds a different light on the PREMiSe results.
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Re: reperfusion injury in CCSVI/MS

Postby cheerleader » Wed Mar 27, 2013 12:23 pm

Cece--
this may or may not be true (believe me, I'm a reperfusion believer, but I think that's a problem BEFORE CCSVI is treated, not after.) https://www.facebook.com/notes/ccsvi-in ... 0894457211

The results of the cine/spinal fluid study are VERY different than the Premise study, and both had participation of BNAC. There were less relapses and lesions in the immediate treated group in the CSF study.
I have the full paper.

These were relapsing-remitting patients, a group of 15. 8 were treated immediately, 7 were treated six months later.

The immediate treatment group of 8 had only one relapse and a few lesions on MRI. The delayed treatment group (delayed by six months) of 7 had four relapses and many lesions on MRI. In that study, the researchers posit that in the six months between the immediate studied group and the delayed group, there was further damage, due to less venous drainage. That the immediate treated group had better venous flow, better CSF flow and less disease activity. This shows that treatment muted the immune reaction.

It's very very concerning that these 2 BNAC studies have such different results.
And that one was presented at AAN, and one was published in a vascular journal.

One HUGE question I have---Dr. Galeotti treated the patients in the delayed/immediate CSF study, and Dr. Siddiqui treated in the Premise trial. Could lack of experience in treating CCSVI be affecting patient outcome???

Here is the abstract for the CSF study----it is a very different result than Premise. BNAC needs to answer for this. Zivadinov cannot be positing these things in public without explaining the CSF study. Buy the paper, if you want to learn more...this is a big deal.
http://www.jvir.org/article/S1051-0443( ... 9/abstract

To any who donate to BNAC---you must ask, why are these 2 studies showing such vastly different in results??
And why is only one being publicized??
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Re: reperfusion injury in CCSVI/MS

Postby Cece » Wed Mar 27, 2013 1:33 pm

cheerleader wrote:The results of the cine/spinal fluid study are VERY different than the Premise study, and both had participation of BNAC. There were less relapses and lesions in the immediate treated group in the CSF study.
I have the full paper.

It makes the brain spin.
Much better results in that study, and yes the difference in treating doctors may well be what made the difference.
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Re: reperfusion injury in CCSVI/MS

Postby MrSuccess » Wed Mar 27, 2013 9:46 pm

I don't know how to work that quote thingy ...... and have no desire to learn how , so I'll have to go 'old school ' and reprint this :

" It's very very concerning that these 2 BNAC studies have such different results. And that one was presented at ANN, and one was published in a vascular journal "

Well , there you have it. Same Organization . Same researchers. Different opinions.

Think that point is lost on the Neurological World ? :razz:

A long held goal of the CCSVI movement .... is to have CCSVI get some ink in their journals


Mission ..... Accomplished .


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