Inflammation

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

Inflammation

Postby mrhodes40 » Mon May 04, 2009 1:42 pm

Inflammation is a big deal for the brain: it cannot tolerate it at all well.

One of the issues we have been hit with is how can MS be venous if inflammation suppression via revimmune metheylprednisolone etc helps people with MS.

I have offered that MS is an inflammatory disease and that is how we can account for the conundrum: the venous damage happens then the immune system responds to heal the damage and THAT causes damage of its own: inflammation itself hurts the brain.

I'd like to discuss research related to that line of thought here.

from CLiCK HERE

Thrombolysis heralded a new era of acute intervention for ischemic stroke, accompanied by an increasing need for comprehensive acute critical care support. There remains the prospect of novel cerebral protection strategies. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade, both in the CNS and in the periphery. Closely linked events are induction of a classic acute phase protein response, activation of the hypothalamic-pituitary-adrenal axis (HPAA) and sympathetic nervous system (SNS), and rise in body temperature, all of which appear to importantly influence the outcome. Thrombolysis aside, various therapeutic strategies have been trialed without success recently, primarily directed at influencing neuronal activity and survival directly. Inflammation itself offers an attractive target, mainly because of its potential to exacerbate the spread of damage to the ischemic penumbra. A promising novel therapeutic approach is the interleukin-1 receptor antagonist (IL-1ra), which limits the action of the cytokine IL-1, a pivotal mediator in the pathophysiology of acute neurodegeneration. We discuss inflammation and its mediators in acute ischemic stroke, the systemic stress, and acute phase protein responses to acute ischemic stroke, how inflammation is relevant in deteriorating ischemic stroke, the impact of physiological variables, and both current and emerging interventions for acute ischemic stroke.



This paper essentially says that in a stroke the inflammation itself expands the damage and makes it worse. They are going to try limiting the damage by stopping interleukin -1 with a drug.

This is very similar to the tysabri approach which blocks adhesion molecules and prevents inflammatory cells from going into the brain.

CLICK HERE

. These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS. Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury. In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Peripheral infection and inflammatory processes are likely to be important in this respect. Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair. Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects. Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets. New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems. Considerable opportunities therefore exist for the development of novel therapies. It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms. Newer approaches have included antimicrobial and antileukocyte strategies. One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist


Again part of the damage is caused by inflammation and they are considering making some drugs similar to the ones we use in MS to help the situation.

Note I bolded the deal on "head injury". The mechanical damage caused by the CCSVI could be considered a type of head injury.

FOUND HERE
Ischemic stroke is the most frequent cause of persistent neurologic disability in modern Western societies. Albeit it is still not clear whether inflammation is merely an epiphenomenon or rather has a disease-promoting function, accumulating evidence implicates inflammation in many forms of acute neurodegenerative disorders including ischemia. The immune cell influx during a neuropathological event is thought to be elicited by glial cells, especially microglia.This article reviews the cellular and molecular pathways involved in stroke-induced inflammatory response in the CNS. We focused on how CNS innate immune cells including microglia and macrophages play integral roles in receiving and propagating inflammatory signals, and how activated microglia secrete a wide range of factors. We present the relevance of the expression of adhesion molecules after ischemia including selectin, immunoglobulin superfamily, integrins, and the role of inflammatory mediators such as cytokines, chemokines and matrix metalloproteinases. Further, we explore the role of transcription factors in inflammation, and the function of immunomodulation and innate and adaptive immunity in brain ischemia, focusing on immunosupression therapies for acute stroke. Although several approaches for anti-inflammatory treatment have proven effective in animal models, clinical trials of immune system modulation therapy after stroke have not yet proved successful. There is still much to be done in order to translate interesting findings into therapies, but undoubtedly studying the cellular and molecular pathways may not only improve our understanding of inflammatory mechanism but also serve as a basis for designing effective therapies.


Again they are using immunosuppression for stroke to limit the damage after the stroke.

No one argues that a stroke is "autoimmune", yet the same types of drugs that help MS also help stroke victims reduce the level of damage.

The fact is that damage in the brain is always accompanied by damaging inflammtion. This is true in spinal cord injury too: inflammation causes some of the damage and strategies that limit it will help limit the secondary damage to the area after the SCI has occurred.

I will add that much earlier in the big thread we explored the research related to inflammation in venous ulcer, the prototypical model for the CCSVI caused MS lesion. Just like in stroke, much of the damage in a venous ulcer comes from inflammation secondary to the venous insufficiency.

Thus we see why it is not true that "if (insert any immune suppressive drug here) helps, that proves MS has to be autoimmune."

If MS lesions are caused by CCSVI then inflammation is going to be part of the process and it is going to be damaging to the tissue. And just like in stroke, suppression will help limit it somewhat. But the cure is to take away the cause of the injury, not just to take away the inflammation.

Ok we can talk about it if we like! Add some other papers to develop this!
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Postby cheerleader » Mon May 04, 2009 2:40 pm

This is a terrific topic, Marie...and one that Jeff and I touched on with Dr. Dake. He said that the slow down in perfusion (blood supply in and out of the brain) created by Jeff's blocked jugulars, leads to edema (swelling) and cell death in the brain (due to hypoxia or lack of oxygen) and that this begins an inflammation cascade. Since this blood is slow to get out of the head, it forms a vicious cycle. There is no need for autoimmunity in this picture. Slowed perfusion and inflammation is all you need to get MS. Without autoimmunity.

Here's a paper which talks about how the slow down of blood in the brain changes microcirculation, perfusion and leads to a break down of the blood brain barrier and MS...new MRI technology is allowing us to see what happens BEFORE lesion formation...and it starts with perfusion and inflammation.
We had it on the BIG monster thread, but it's worth including here:
Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a longitudinal perfusion MRI study
http://brain.oxfordjournals.org/cgi/con ... /127/1/111
The reduced blood supply in such lesions accounts for a higher probability of permanent tissue destruction, which might be an explanation for the observation that ring-enhancing lesions account for a more destructive disease course (Morgen et al., 2001).

Taken together, our data on cerebral blood perfusion measurements during lesion formation in multiple sclerosis patients with relapsing–remitting disease course indicate that elevation of perfusion is an early event in the development of a plaque. Improving the resolution of this technique might not only give new insight into the pathomechanisms in multiple sclerosis, but also lead to a more sensitive measurement of disease activity and treatment effects (Miller, 1996; McFarland et al., 2002).


CCSVI explains slowed perfusion in MS-
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby mrhodes40 » Mon May 04, 2009 2:48 pm

had it on the BIG monster thread, but it's worth including

We should mine the thread and tease it into subjects a little now that we can it seems to me. the data is "lost" and hard to find as it is now

I'm glad you did that one it is a good paper!
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Postby mrhodes40 » Mon May 04, 2009 2:55 pm

I just want to point out that the bit you posted mentions the 'elevation of perfusion' is the first event before a plaque develops....that means it gets congested; EXACTLY like the CCSVI model says it does.
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Postby sou » Mon May 04, 2009 3:25 pm

Hi.

Let me speak like an electrician for a while. I found that perfusion (F) is given by following the formula:

F = (Pa - Pv)/R

Pa = pressure of artery
Pv = pressure of vein
R = "resistance" capilaries pose to blood when crossing them

It resembles the Ohm's law for electrical currents.

The formula says it all: If, for any reason, Pv increases, it will result in a decrease in perfusion. R in the nervous system is usually constant.

What is crossing my mind is that Pv affects perfusion more when R is small. The younger the person, the smaller the value of R, the higher the effect of higher venous pressure to perfusion. R increases as the vessel walls harden with time.

These thoughts may be completely wrong, since I have no idea what are the real values for R. However, could this contribute to the reduction of inflammatory activity of MS with age, and sometimes reduction in progression rate?

10.5 hours to MRV!!!

sou
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."
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Postby mrhodes40 » Mon May 04, 2009 4:12 pm

Sou, oh my we are lucky you are here to share your thoughts. What an interesting idea.

Plus the MS lesions harden the area , the early work with Charcot he talks about how hard the lesions are to the touch they are hard lumps in the brain tissue. Then think that they are ALWAYS adjacent to veins.

Now in cirrhosis of the liver the liver scars up and gets hard and the blood can't get through because the area is hard and the vessels can't flex like they need to.

Taking these together we can guess that as the patient gets older the "r" value would be impacted automatically.

Good thought, glad you posted it!
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Postby cheerleader » Tue May 05, 2009 7:26 pm

sou wrote:Hi.

Let me speak like an electrician for a while. I found that perfusion (F) is given by following the formula:
F = (Pa - Pv)/R
Pa = pressure of artery
Pv = pressure of vein
R = "resistance" capilaries pose to blood when crossing them
The younger the person, the smaller the value of R, the higher the effect of higher venous pressure to perfusion. R increases as the vessel walls harden with time.


sou, this is an interesting model...and you and Marie are right, the older the body gets, the more the venous structure hardens, and the slower the return of blood to the heart. I think this is why RRMS eventually flips over into progressive MS after a period of 20 years or so. The brain (and less so, the spine) have opportunities to recover from demyelination in a younger body, with more flexible veins and less perfusion. It becomes a vicious cycle as the body ages. Jeff is 45.

What Dake showed me on MRV was how inflexible and "tough" Jeff veins looked. If left unstented, I truly think Jeff was close to flipping into progressive. Zamboni showed that Jeff's type of blockage (C) flipped to SPMS sooner than other forms.
Finally, the conversion to SP course was consistently observed in type A, B, C patterns (95%), but proportionally higher in patients with both the IJVs blocked (56% of type C)


Jeff's brain was rewiring like crazy to keep working, but his cervical spine had no other place to go to rewire. The dual jugular assault was too much.

And as for primary progressive MS folks, the damage can happen at a younger age, and much more quickly, because the spine is less able to recover:

We also observed that the PP course was related to a CCSVI pattern significantly different as compared to RR and SP, suggesting that the location of venous obstruction plays a key role in determining the clinical course.
For instance, PP course, characterized by a slowly progressive syndrome with spastic paraparesis and MRI demonstration of MS plaques in the spinal cord, 20,30-32 was significantly associated to obstruction at several levels of the azygous vein and of the lumbar plexuses (type D pattern, Fig. 3, Table III). In this situation venous blood of the spinal cord can be drained only in an upward direction, and is shunted toward the venous plexuses inside the spine (Fig. 3, 4), contributing to explain the correlation between type D and spinal cord involvement in PP patients.



I truly hope that some PPMS patients may be able to get MRVs and stent surgery. There's been a fire lit under me, and I want to get the word out.
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby skydog » Tue May 05, 2009 8:27 pm

Words out !!! I am doing all I can to get in line for testing and treatment if needed. The big hurdle for me is the insurance thing. Will they accept me uninsured ? Limited in funds, but would spend my last dime if this would help me. Already talked to my mom about a road trip to test the waters. She was a graduate at Stanford and has many friends in the area. Thank you cheer for giving me hope. And a big thanks to Jeff for bravely forging ahead with this treatment. Peace and Health Mark
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Postby cheerleader » Wed May 06, 2009 6:12 am

skydog wrote:Words out !!! I am doing all I can to get in line for testing and treatment if needed. The big hurdle for me is the insurance thing. Will they accept me uninsured ? Limited in funds, but would spend my last dime if this would help me. Already talked to my mom about a road trip to test the waters. She was a graduate at Stanford and has many friends in the area. Thank you cheer for giving me hope. And a big thanks to Jeff for bravely forging ahead with this treatment. Peace and Health Mark

Mark, I have no idea if lack of insurance will preclude you. It's worth a call to find out. I'm wishing you all the best,
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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby mrhodes40 » Wed May 06, 2009 6:37 am

Mark, my insurance is balking, but I have medicare too and they said it may cover it---I already have dopplers showing a problem though so I have "proof" of an issue.

On to the topic:inflammation


and you and Marie are right, the older the body gets, the more the venous structure hardens, and the slower the return of blood to the heart.


The Ornish diet has people keep fat just as low as Swank. The ornish diet has been shown to reduce atherosclerosis (hardening of the arteries) and inflammation.

Similar to the Swank diet in content, it is hard to do to be so very good at not eating any meat etc. and keeping fat so very low.

But if you look at the artery angle it fits in with this new model very well and accounts for the success of tht approach.
marie
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Postby peekaboo » Wed May 06, 2009 7:28 am

cheer wrote:


I truly hope that some PPMS patients may be able to get MRVs and stent surgery. There's been a fire lit under me, and I want to get the word out


I'm that PPMS person cheer & once any results happen I will go to war w/you...I used to be in marketing/Pub Rel. I know a few tricks...
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Postby cheerleader » Wed May 06, 2009 7:36 am

peekaboo wrote:I'm that PPMS person cheer & once any results happen I will go to war w/you...I used to be in marketing/Pub Rel. I know a few tricks...

I didn't know that fact about you, Peek. I really hope there will be some answers for you, and we all look forward to utilizing your PR know-how.
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Husband dx RRMS 3/07
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http://ccsviinms.blogspot.com
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Postby skydog » Wed May 06, 2009 7:43 am

Hey thanks you guys for the support. I am looking into Insurance from all angles. One year out before medicare kicks in. Do not want to wait that long, so if its out of pocket so be it. Just finished listening to Dr. Michel Dake's podcast. What a great speaker. You can tell by his voice he is a very passionate and authentic person. He is sure to bring great strides in our health quests. On the inflammation issues my two cents worth ( Garlic.... ) the best blood thinner, antibiotic plant I can grow here in the Pacific northwest. Peace Mark
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Postby cheerleader » Sun Feb 07, 2010 10:54 am

BUMP
a classic Marie
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby zinamaria » Mon Feb 08, 2010 11:03 am

Hello to all,

I am still so new to all this so I need to ask (sorry for my ignorance) what 'BUMP' means...because I just got on this thread, (can I still add to it? i hope so) and had not read this thread before, so many good threads to go through, but this one caught my eye because of what Marie and Cheer say about inflammation and its relation to CCSVI.
This makes so much sense! What struck me was the 'age' factor that Cheer mentioned, and so I just wanted to throw in my 2cents, and say that I am 48 with RR and hope it does not go into progressive etc (about 12 yrs now).

I practice yoga daily because yoga, specifically, unlike other forms of 'exercise' keeps things stretched and helps circulation as well, and I was just thinking about the neck veins.
In the yoga I do, which is not so traditional, we do not strain the neck, in fact we work at letting the neck totally relax, and then I also do 'neck' stretching daily, and I am hoping this will keep the jugulars, and circulation going...yoga, even in a wheelchair, which I am not, can be done, arms and neck, twists in the torso etc...
Anyhow I would think this 'creating' space internally, which is what yoga's aim is, would help to keep even veins flexible. I tend to think they can and are exercised when I am in a practice.
Any thoughts on this?

Oh ya, and garlic, I'm with you there! But then my peers have commented on my breath and even body odor, I eat so much of it! Oh well....


Peace,
Zina
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