tysabri's effect on cerebral blood flow

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

tysabri's effect on cerebral blood flow

Postby Cece » Mon Jan 31, 2011 9:58 am

Eur Neurol. 2010;64(2):124-8. Epub 2010 Jul 22.

Natalizumab and regulation of cerebral blood flow: results from an observational study.
Reinhard M, Rosengarten B, Kirchhoff L, Hetzel A, Rauer S.

Department of Neurology, University of Freiburg, Freiburg, Germany. matthias.reinhard @ uniklinik-freiburg.de

Abstract
BACKGROUND: Natalizumab inhibits adherence of leukocytes to the cerebral endothelium. Since leukocytes play a role in regulating vascular tone, natalizumab may also affect cerebral vasoregulation. The aim of this observational study was to investigate whether neurovascular coupling and cerebral autoregulation are altered following routine clinical infusion of natalizumab in patients with relapsing-remitting multiple sclerosis.

METHODS: In 18 patients receiving regular infusion of 300 mg natalizumab, neurovascular coupling to visual stimulation and dynamic cerebral autoregulation (phase and gain of 0.1-Hz oscillations) were measured by transcranial Doppler ultrasound (before, and 2 h and 2 days after the infusion). A repeated examination 28 days after infusion served as a control situation.

RESULTS: Neurovascular coupling was altered 2 h and 2 days after infusion with an overshooting initial hemodynamic response. After 28 days, neurovascular coupling was similar to values before the infusion. Dynamic cerebral autoregulation, cerebral blood flow velocity and pulsatility index in the middle and posterior cerebral artery were unaltered.

CONCLUSION: Natalizumab infusion is associated with a temporarily increased initial hyperemia to functional activation. Such a hyperreactivity suggests an increased bioavailability of nitric oxide during functional activation.

http://www.ncbi.nlm.nih.gov/pubmed/20664205

"A temporarily increased initial hyperemia to functional activation" means better blood flow to a region of the brain, if I am understanding this correctly. Tysabri's main mechanism-of-action is through locking up the leukocytes but this short-term improvement in blood flow should help a brain suffering from poor blood flow, as a secondary mechanism, perhaps?
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Postby pairOdime » Mon Jan 31, 2011 10:15 am

If many of the benefits are due to cerebral vasodialation & increased NO availability, there are much less toxic substances that can perform the same task. I wonder how many of the MS drugs are actually working as vasodialators to some degree? Again, there are much less toxic substances that provide improved blood flow. The endothelial health program, supplements, androgrens, etc...
It's a paradigm shift
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Postby 1eye » Mon Jan 31, 2011 12:38 pm

Maybe I have anger issues. I get EXTREMELY angry when I see stuff like:

"The aim of this observational study was to investigate whether neurovascular coupling and cerebral autoregulation are altered following routine clinical infusion of natalizumab in patients with relapsing-remitting multiple sclerosis. "

What makes me see red is the pseudo-scientific use of the term relapsing-remitting. It is a way of limiting the liability of health insurance companies to a subset of 'MS' patients, so that the rest (so-called Secondary and Primary Progressive) may be entirely abandoned, as being too difficult and/or too far gone and/or too old to treat. Without any scruples, people who are not seen by their physicians as being obedient or cooperative enough can also be conveniently reclassified. It is a very easy thing, to get rid of those seen as troublemakers, or in any way unpleasant, and the schedule for their periodic appointments becomes annual or less. "Diagnose and Adios" becomes simply "Adios".

The next thing that happens after this reclassification into the actuarial 'high-claimer' category, is that car insurance and drivers license are taken away, and caregivers are told not to allow the person any use of stoves, knives, etc. "for their own good". No wonder there is a high suicide rate. These people are being erased! Has anyone not heard the story of someone burning themselves out of numbness? How many people actually are ever that numb? You want complete security? Coffin-nails work.

Of course, Tysabri is expensive, and only worthwhile submitting to usury for, if it is going to do some good. I think one of the reasons some people are so scared of MS being traced to CCSVI is that the only possible reason for this inhuman and I think illegal treatment of the infirm, and legitimately insured, is the old excuse that "we don't know what causes it". Once we cannot rationalize using this argument, a lot of unpleasant things have to be faced, and a lot of people will be justifiably angry, instead of sad and depressed. Faces are going to turn red on both sides of the neurology fence, but for different reasons.

Is there any particular reason, if the real problem is congenital, for the continuing stupidity of this caste system?
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Postby eric593 » Mon Jan 31, 2011 1:54 pm

1eye wrote:Maybe I have anger issues. I get EXTREMELY angry when I see stuff like:

"The aim of this observational study was to investigate whether neurovascular coupling and cerebral autoregulation are altered following routine clinical infusion of natalizumab in patients with relapsing-remitting multiple sclerosis. "

What makes me see red is the pseudo-scientific use of the term relapsing-remitting. It is a way of limiting the liability of health insurance companies to a subset of 'MS' patients, so that the rest (so-called Secondary and Primary Progressive) may be entirely abandoned, as being too difficult and/or too far gone and/or too old to treat. Without any scruples, people who are not seen by their physicians as being obedient or cooperative enough can also be conveniently reclassified. It is a very easy thing, to get rid of those seen as troublemakers, or in any way unpleasant, and the schedule for their periodic appointments becomes annual or less. "Diagnose and Adios" becomes simply "Adios".

The next thing that happens after this reclassification into the actuarial 'high-claimer' category, is that car insurance and drivers license are taken away, and caregivers are told not to allow the person any use of stoves, knives, etc. "for their own good". No wonder there is a high suicide rate. These people are being erased! Has anyone not heard the story of someone burning themselves out of numbness? How many people actually are ever that numb? You want complete security? Coffin-nails work.

Of course, Tysabri is expensive, and only worthwhile submitting to usury for, if it is going to do some good. I think one of the reasons some people are so scared of MS being traced to CCSVI is that the only possible reason for this inhuman and I think illegal treatment of the infirm, and legitimately insured, is the old excuse that "we don't know what causes it". Once we cannot rationalize using this argument, a lot of unpleasant things have to be faced, and a lot of people will be justifiably angry, instead of sad and depressed. Faces are going to turn red on both sides of the neurology fence, but for different reasons.

Is there any particular reason, if the real problem is congenital, for the continuing stupidity of this caste system?


I believe Tysabri has only been found to be effective in those with RRMS. So when doing an observational study on its effects on existing Tysabri users, the only group of Tysabri users that should be found are those with RRMS since that's the only group the treatment has been indicated to have any benefit for.
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Postby frodo » Mon Jan 31, 2011 5:11 pm

1eye wrote:What makes me see red is the pseudo-scientific use of the term relapsing-remitting.


Hey, what about the pseudo-scientific use of the word MS? What is MS? a clinical condition? the conjunction of several attacks? the presence of scars in the brain? the presence of gadolinium enhanced spots in a MRI? Any of these things would define a different set of patients, but nobody cares to agree in a definition. MS is in fact a "very unscientific disease".
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Postby Cece » Mon Jan 31, 2011 5:39 pm

I see it as them not having any answers for the PP and SP patients but pushing ahead with the pseudoscientific autoimmune theory because it kinda sorta works a little for awhile in RR patients. But we don't need kinda sorta answers when CCSVI provides real answers.
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Postby blossom » Mon Jan 31, 2011 6:47 pm

1eye, i am in agreement with so much of what and how you say things. this putting us into catagories with symptoms i have always refused to acknowledge that us that have been put into their bushel baskets of rrms, spms, ppms or whatever the hell they choose to call it are all one and the same named ms. has to be different causes and different cures per say. or else why do so many respond so different to treatments whether it is mainstream med, diet, bee sting, chiro. etc. and even ccsvi. but if you think about it, most of these things that help has to do with blood flow..........now, the old research that dr.zambonni looked into and started the ccsvi treatment was not something that had not been looked at yrs. ago in one way or another but was "conveniently put under the shelf". with things like the doppler, mri's and modern technology to test better and the internet spread the word. ccsvi was born.

i cannot believe that the drug co.'s and modern med. was that naive or stupid that they were not aware that if the blood flow was corrected it could help or possibly cure many that had symptoms they named ms. sooo what was the logical money makeing thing for them to do?? well, if they got the plumbing part fixed and drugs couldn't be a life time moneymaker for them the best thing for the greedy suckers to come up would be drugs that had a positive effect on the blood flow to and from the brain somewhat that would maybe give some a little relief for awhile--but then that would damage the body otherwise and then they could sell you more drugs. and, yes, there is the old nervous system trick. no doubt, it is involved, but look at dr. haacke's research on how the slow blood from the brain leaves iron deposits that effects our nervous system. on and on.

and yes, 1eye, the more age a older person gets on them the more without them coming out and saying it--the more you are wrote off. as i am in my "golden yrs." i experience that. as if it wasn't tough enough dealing with all the hippocracy when i was a little younger---now i gotta fight the fight that i'm not senile or sorta passed over like day old bread.

and, guess what, the last neuro. i was to-even though i had him test me like i'd never been diagnosed and nothing jived that my diag. was very questionable---his words were to me---well, you got something wrong---my response to him was---No SHIT!! But, guess what he suggested-----TAYSABRI. i said no thanks, i don't think so. he said, well you gotta try something. yeah right. i'm gonna try a drug that might make me worse than senile and they are not even sure what the hell is going on with me "after 20 yrs"--oh yeah, they decided to call it ms.

this neuro. would not even listen about ccsvi--but he wanted me to try tysabri--what's tysabri run a yr?? and those other expensive worthless drugs??

no, i don't think the drug co's are that naive and stupid about blood flow effecting ms and i'm sure a lot of other diseases too someway or another.

and i'm not that senile or naive to buy into it. and, the drug co.'s aren't that naive or stupid--you can take that to the bank!!
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Postby 1eye » Mon Jan 31, 2011 7:49 pm

eric593 wrote:I believe Tysabri has only been found to be effective in those with RRMS. So when doing an observational study on its effects on existing Tysabri users, the only group of Tysabri users that should be found are those with RRMS since that's the only group the treatment has been indicated to have any benefit for.


They do a lot of testing on those people with those "phenotypes" to prove that, did they? Know any of those test subjects? Why would they risk a PML death in a person who's not the right caste? I know one of those early subjects, and she's on FTY-720 now. They only had tested it on "RRMS" when the PML started happening. Doubt if you could get a doctor to prescribe it, if he/she didn't want to, even if you were "RRMS". Especially in Canada on our so-called "universal" system. Maybe if you were willing to pay cash in the US. I'm sure the vendor would come up with a script for you.

Traditional so-called DMDs are in the hands of self-appointed gatekeepers who don't want to lose that role. They do it to limit the liabilities of insurers, and. are well rewarded. I've had my fun, you can have your thread back :D
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Postby Cece » Mon Jan 31, 2011 8:02 pm

1eye, no, keep going, I was feeling complacent and now I am getting my fire up! ;)

It doesn't make sense to me to classify MS as an autoimmune disease when there's primary progressive MS, which does not respond to the DMDs. If primary progressive were autoimmune, wouldn't the DMDs work? And if they don't work, then the house of cards falls, in my opinion, especially after CCSVI can be found in every last neck.
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Postby blossom » Mon Jan 31, 2011 11:29 pm

the symptoms that i have that they choose to call ms--from day 1 has been referred to as "ppms". yet, the neuro. wanted me to try tysabri. i know "he really did care about me" -uhhuh- ??????/???/??/?
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Postby 1eye » Tue Feb 01, 2011 10:33 am

Cece wrote:1eye, no, keep going, I was feeling complacent and now I am getting my fire up! ;)

It doesn't make sense to me to classify MS as an autoimmune disease when there's primary progressive MS, which does not respond to the DMDs. If primary progressive were autoimmune, wouldn't the DMDs work? And if they don't work, then the house of cards falls, in my opinion, especially after CCSVI can be found in every last neck.


I think it is falling. That's the thing about those houses. Once they start. they fall fast. It ain't like a row of dominoes.

Some of the people who post here are awfully good at getting fires burning. But then I think things are very tinder-dry right now, and maybe easily sparked. Once they start, who knows what may happen? I feel like I'm in a vortex of metaphoric kaleidoscopy.
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Re: ccsvi

Postby 1eye » Tue Feb 01, 2011 10:37 am

blossom wrote:the symptoms that i have that they choose to call ms--from day 1 has been referred to as "ppms". yet, the neuro. wanted me to try tysabri. i know "he really did care about me" -uhhuh- ??????/???/??/?


To be fair, those stats won't tell you how the individual patient will react. We learned that from people like Dr. Mengele.
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