CCSVI and CCVBP

[uprightdoc]

...
Dr F I think the key point we are all hovering around is whether the breach of the BBB is the 'main' reason that 'MS' occurs...


...There needs to be reason to give the dx that isn't challenged and that is why I asked others such as Franz Schelling is the finding of Dawsons Fingers or periventricular lesions the deciding factor.

As Ed pointed out to me the MRI findings of lesions, white spots, hyperintensities are indications of inflammation and not de-myelination so we need a focus point for the 'real' dx of 'MS'. Too many of us have ongoing progression that is related to the disability that is accumulating rather than than the core action that causes 'MS', imo.

I don't think that breach of the BBB is the major cause of MS. It is my opinion that the lesions of MS are a sign of what caused or continues to cause the problem, not the cause of the problem. Although sometimes they do, in most cases the signs, symptoms and lesion locations don't necessarily correlate.

It's hard to disagree with Dr. Schelling on anything related to MS. He should be one of the experts that helps rewrite the definition and diagnostic criteria for MS. While I agree with Dr. Schelling that Dawson's Fingers and periventricular lesions are a deciding factor for classic MS, the problem is that those criteria exclude many patients who have no visible lesions in the brain but have lesions in the cervical cord. These patients typically have greater progression and disability issues. One of the problems is, we still don't have the technology to see all the lesions and pathology so some cases with cervical lesions may have them in the brain but we just don't see them.

Hyperintesity signals aren't necessarily a sign of inflammation. They can also be a sign of edema or they can be a sign of scar tissue due to demyelination or degeneration of the nerve. It takes different scanning techniques and a discerning neurologist to make the determination. Some are too close to tell. On the other hand, it's hard to imagine a case of chronic edema that wouldn't be associated inflammation due to the accumulation of anaerobic and metabolic wastes resulting in immune reactions.

[Squeakycat]

Lesions are due to different causes and each cause affects permeability differently. For example, inflammation, edema and scar tissue affect permeability of the BBB in different ways that increase or decrease permeability. As you mentioned, trauma can also damage the BBB due to tension and shear stresses. Enlargement of the ventricles (ventriculomegaly) stretches the BBB which can increase its permeability. Increased permeability, however, isn't necessarily associated with an increase in signs, symptoms or pathology.

Doc,
Speculating here, but are relapses not periods in which there is a break in the BBB and a highly active immune response?

There is a high level of some kind of activity which manifests itself clinically as a relapse.

And aren't the signs/symptoms of MS likely a function of just which nerves are damaged, what areas of the brain are being subject to hypoxia, and if there are "stealth pathogens" involved, where they are located?

Those are question, not contentions. :>)

[uprightdoc]

Ed,
You have some good well thought out points. I will read them tomorrow.

Breach of the BBB is just one theory and obviously malfunction of the endothelium anywhere can be destructive to local tissues. The problem is that the leaky brain theory has too many holes in it that don't explain the signs, symptoms or progression.

Have you considered the affect of sluggish blood and CSF circulation and consequence of stagnation and the accumlation of metabolic wastes? How about the effect to the glutamate cascasde? I suspect that chronic ischemia can initiate ischemic cascades. What about the affect of pressure such as glaucoma. Can turbulent CSF flow and abnormal hydraluics similary damage the brain?

[Squeakycat]

I do agree that the calcitriol protocol proposal is fairly benign and should be studied. I suspect it is probably works primarily as an anti-inflammatory agent. Nearly all MS patients have inflammation so it can't hurt to try.

Doc,

Whew! Glad my ignorance of all this didn't lead you to think Hayes might not be on to something. :>)

Vitamin D is much more than an anti-inflammatory. It controls the cell replacement cycle. It activates the local, adaptive immune response to infection or injury. And as such, it seems as though it is a critical factor in MS as all the studies of it environmentally, epidemiologically, genetically and clinically have shown.

To the extent that what Hayes has found in EAE mice is true in humans with MS, then a key to stopping it is to bypass the problem of the conversion of D3 to calcitriol by administering a single dose high enough to be available in the brain and spinal cord which brings the immune response under control and appears to reset the conversion process so that it works and remission can be maintained with D3 alone.

I want to be very clear that if this works in humans, it is not a silver bullet. Something is causing breachs in the BBB and that still needs to be fixed. And to the extent that it works, there is still a need for a healthy diet, exercise, no smoking and all the other things like this that contribute to good health. As much as it appears to be a key factor in EAE and possibly MS, it would be naive to think it is the only factor.

[Squeakycat]

The problem is that the leaky brain theory has too many holes in it that don't explain the signs, symptoms or progression.

Doc,
". . . the leaky brain theory has too many holes in it . . ."

Pun intended? :>)

[Squeakycat]

Breach of the BBB is just one theory and obviously malfunction of the endothelium anywhere can be destructive to local tissues. The problem is that the leaky brain theory has too many holes in it that don't explain the signs, symptoms or progression.

Have you considered the affect of sluggish blood and CSF circulation and consequence of stagnation and the accumlation of metabolic wastes? How about the effect to the glutamate cascade? I suspect that chronic ischemia can initiate ischemic cascades. What about the affect of pressure such as glaucoma. Can turbulent CSF flow and abnormal hydraluics similary damage the brain?

Doc,
Starting at the end of your list of factors. I fully accept that turbulent blood flow can damage the BBB, but I'm not sure that is what you are saying.

Similarly, local hypertension has to be a factor at least in terms of the ventricles in permeability of the BBB.

Hypoxia and concomitant poor removal of metabolic waste as a result of impaired circulation would certainly be factors.

Everything, including the glutamate cascade that flows from the ischemic cascade is likely involved in some way.

The only thing I actually know about any of this is that it very complex, intimately entwined, and beyond mortal comprehension, at least by this mortal. :>)

You've brought up the subject of signs and symptoms that aren't explained by a breach of the BBB. Can you give me an example of this? If you are referring to things like MS fatigue, I certainly agree. That seems far more likely to be the result of impaired circulation than damage to nerves and is clearly a major part of MS and something that responds on the table to CCSVI venoplasty indicating to me that it is likely not caused by injury to nerves which would necessarily take much longer to heal.

Can the signs and symptoms be broken down between those that result from damage to nerves such as paralysis, paresthesia, lack of control of things like swallowing, bowels and bladder, and those that result from something else including things that logically would happen if blood flow is impaired in some way?

Calcitriol + D3 would not address things other than nerve damage and the active, overly pro-inflammatory immune response. It isn't going to improve blood or CSF circulation. These things still have to be treated as the prime cause of MS.

[Squeakycat]

I don't think that breach of the BBB is the major cause of MS.

Doc,
Not arguing with you on this as much as trying to understand what you are saying.

In your previous message, you pointed to things such as poor circulation, imperfect removal of metabolic waste, hypoxia and so on as things that cause signs and symptoms associated with MS. That makes perfect sense to me.

This begs two questions:

• ** If you only had some or all of these things without demyelination, would that be MS?
  ** Or are you suggesting that these things could be a cause of demyelination even if there was no breach of the BBB?

My earlier contention that MS is characterized by a breach in the BBB which causes demyelination was not meant to exclude other co-factors that cause problems for pwMS, but to suggest that these are the two basic factors in the disease which could (does) have many other co-factors.

Again, not contesting what you are saying as much as trying to understand it in the context of MS.

[NZer1]

The test that will help push this knowledge further will also be calcitriol in serum (blood level) versus calcitriol in CSF and if that shows to be lower in the CSF it will be an indication of immune activity and that may have shut down Vit D to calcitriol conversion and the halt of immune cell apoptosis therefore a cascade will continue.

Tests have been done to compare the Vit D in serum and CSF but that has missed the learning opportunity about the conversion to calcitriol and purpose of calcitriol when the immune system is activated.

;)
Nigel
ps thanks for humouring me Ed, my bugs are smiling !

[uprightdoc]

...
Any model is imperfect, but we can't study disease in humans and terminate their lives to examine brain tissue so we need animal models as a starting point.

There are a number of obvious reasons that things we learn in models won't work in humans. I think the biggest of these is that lab mice are very homogeneous genetically compared to the far greater variation in humans.

In the case of the Hayes study, the relevant genes exist in humans and mice and there are similar levels of the same immune components found in both.

Who says that genes in mice are relavent to study MS in humans? While the genes may be relevant for studying similar autoimmune reactions to EAE in mice and humans they are not necessarily genes possibly related to the cause of MS. For example, I suspect that genes related to structure, such as the design of the cranial vault, craniocervical junction and spine, as well as the design of the circulatory routes of the brain play a role in MS. In this regard, mice don't stand upright and walk around on two legs. They aren't even remotely similar to humans from a structural standpoint. As it is, humans show a great deal of variability in prevalence of MS according to race, gender and geographic location. Despite genetic similarity for autoimmune funcitons, MS affects females far more than males. It also affects Europeans far more than Asian or African races, as well as people living in more northern lattitudes. Thus, I don't see how EAE or mice with experimentally induced disruption of the blood brain barrier serve as good models for studying the cause of MS in humans.

[NZer1]

So, Dr F apart from your views on mice does any of the rest of the details Ed has put forward regarding the calcitriol deficiency in the CSF link with your theory for MS and de-generative disease?

You have spoken about cascades in the past and the lack of calcitriol to induce apoptosis seems to me to fit with the cascade pattern?


Nigel

[uprightdoc]

... You've brought up the subject of signs and symptoms that aren't explained by a breach of the BBB. Can you give me an example of this? If you are referring to things like MS fatigue, I certainly agree...

According to the leaky blood brain barrier therory, lesions are a sign of breach or disruption of the blood brain and CSF barrier. In this regard, the classic lesions of MS are typically supratentorial (above the posterior fossa), periventricular and perivenular (Dawson's fingers). Many MS signs and symptoms, however, are often from infratorial structures (within the posterior fossa) such as the brainstem and cerebellum. The only lesions that I have found that clearly correlate with the signs and symptoms is optic neuritis and lesions in the optic nerve. It hard to explain arm and leg weakness according to classic lesions. Moreover, many patients have no lesions or obvious signs of disruption of the blood brain barrier. Some patients without lesions have more progressive conditons and greater disability.

Aside from optic neurtitis, do you know of any cases where the lesions correlate with the signs and symptoms?

[Robnl]

Hi Doc (and all),

Yesterday is visited the chiro with the Cox 7 and 8 table.
My impressin is good, he saw almost all the issues that you see, he started with an easy & gentle treatment....
He will send me a report by mail with i will post here so you an judge it and maybe can give some advice. He is willing to cooperate with you concerning the treatment.

A good step forward i think

Rgds,

Robert

[uprightdoc]

... In your previous message, you pointed to things such as poor circulation, imperfect removal of metabolic waste, hypoxia and so on as things that cause signs and symptoms associated with MS. That makes perfect sense to me.

This begs two questions:

• ** If you only had some or all of these things without demyelination, would that be MS?
  ** Or are you suggesting that these things could be a cause of demyelination even if there was no breach of the BBB?

My earlier contention that MS is characterized by a breach in the BBB which causes demyelination was not meant to exclude other co-factors that cause problems for pwMS, but to suggest that these are the two basic factors in the disease which could (does) have many other co-factors...

If you had signs of poor circulation, imperfect removal of waste and hypoxia causing progression and remissions and exacerbations of optic neuritis, arm and leg weakness and sensory loss etc., without signs of demyelination, most neurologists would diagnose the patient as having probable MS. The problem is that we don't have the technology yet to see all the potential lesions or early signs of demyelination or nerve degeneration.

It is my contention that lesions are often a sign of what caused the problem. Dr. Schelling's theory regarding violent venous blood and CSF reflux (backjets) makes sense as a cause for the location of the supratentorial, periventricular and perivenular lesions.

[uprightdoc]

So, Dr F apart from your views on mice does any of the rest of the details Ed has put forward regarding the calcitriol deficiency in the CSF link with your theory for MS and de-generative disease?

You have spoken about cascades in the past and the lack of calcitriol to induce apoptosis seems to me to fit with the cascade pattern?

I don't see how calcitriol deficiency in CSF is related to my theory regarding the cause of neurodegenerative diseases. It does however, make a great deal of sense as a potential therapy in light of the glutamate cascade, as well as inflammation and their role in neurodegenerative processes. Among other things, excess calcium associated with the glutamate cascade leads to the formation of destructive enzymes. Calcitriol may help to restore proper calcium physiology and mitigate its potentially destructive effects.

[uprightdoc]

... Yesterday is visited the chiro with the Cox 7 and 8 table.
My impressin is good, he saw almost all the issues that you see, he started with an easy & gentle treatment....
He will send me a report by mail with i will post here so you an judge it and maybe can give some advice. He is willing to cooperate with you concerning the treatment.

A good step forward i think

It's a very good step forward. The doctor has the right attitude. He should progress slowly at first and watch for signs of adverse reactions. He can also test your quadricep and hamstring muscles with seated knee raises and front leg kicks. Hamstrings are very strong even in weak people so it is best to test them while your are lying down pulling your heel to your buttocks. I like to further isolate the hamstrings to semimembranous, semitendinosis and biceps femoris tests. It would also be helpful to test toe and heel raising while standing to test foot strength. It's even better to test foot strength while you are lying down to better isolate the different muscles.