Cerebral circulation time in MS is double that of normals

[cheerleader]

Full paper in pdf form.

Blinded study. Cerebral circulation and hypoxia in MS is not correlated with EDSS, disability, lesions or inflammation. It appears to precede all of this---

http://www.plosone.org/article/fetchObj ... tation=PDF

as Dr. Zamboni tweeted---now we need to understand how the venous system might be impacting this slowed cerebral blood flow in MS.


cheer

[1eye]

Full paper in pdf form.

Blinded study. Cerebral circulation and hypoxia in MS is not correlated with EDSS, disability, lesions or inflammation. It appears to precede all of this---

http://www.plosone.org/article/fetchObj ... tation=PDF

as Dr. Zamboni tweeted---now we need to understand how the venous system might be impacting this slowed cerebral blood flow in MS.


cheer

Thank you for this watershed study.

I think a couple of people have shown in studies that MSers have high fluid resistance. The answer is obviously CCSVI. However progressive cases have very few mitochondria, capable of burning O2 correctly, left in their blood. One answer might be to decrease the vascular resistance (stenoses) and then completely replace the blood. If it contained invisible EBV cells, they will be thrown out too.

Then the brain-retraining will have a chance to persist.
Hyperbaric oxygen can also help speed recovery.

[CureOrBust]

If it contained invisible EBV cells, they will be thrown out too.

I would hazard a guess that most "problematic" EBV would be in the brain cells themselves (or spinal fluid maybe?), otherwise this method would also assist other viral infections such as AIDS & Ebola

Hyperbaric oxygen can also help speed recovery

DO you have a link for these studies?

[1eye]

If it contained invisible EBV cells, they will be thrown out too.

I would hazard a guess that most "problematic" EBV would be in the brain cells themselves (or spinal fluid maybe?), otherwise this method would also assist other viral infections such as AIDS & Ebola

Hyperbaric oxygen can also help speed recovery

DO you have a link for these studies?

About the mitochondria:

Pathological mechanisms in progressive multiple sclerosis
Mahad, Don H et al.
The Lancet Neurology , Volume 14 , Issue 2 , 183 – 193

About the EBV: (edited by me to make complete)

Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy
Michael P Pender, Scott R Burrows
Clin Trans Immunol 3: e27; doi:10.1038/cti.2014.25

EBV DNA has been detected in the CSF or cell pellets isolated from the CSF in only small proportions (0–12.5% and 18.2%, respectively) of MS patients, with no significant differences between MS patients and controls.99, 100, 102, 104, 115 Even in patients with a demonstrated high level of EBV infection in B cells and plasma cells within brain tissue, the frequency of detection of EBV DNA in the CSF was low (12.5%).115 The use of single-cell reverse transcription-PCR for EBER1 on individually sorted B cells and plasma cells from the CSF has yielded conflicting results, with one study detecting no EBV-infected cells116 and another study finding an increased frequency of EBV-infected B cells in the CSF of patients with MS compared with patients with non-inflammatory neurological diseases.111

This is the guy who supposedly has had some success with progressive MS.

I am just guessing about the blood replacement. I guess I just had that impression: it likes to hide in b cells. If they expand clonally to fight infection, maybe the EBV piggybacks on that. So every infection could make you worse.

I don’t know what all has been tried on Ebola or AIDS.

The UK has hyperbaric oxygen centres on the National Health plan for pwMS, so I’m told.

[Cece]

In conclusion, the absence of a correlation between lesion volume and CCT confirms that hemodynamic alteration is not related to parenchymal lesion and other MS-linked clinical features, but rather, is a pathognomonic feature of disease.

Pathognomonic!

pa·thog·no·mon·ic
pəˌTHäɡnəˈmänik,ˌpaTHəɡnə-/
(of a sign or symptom) specifically characteristic or indicative of a particular disease or condition.
https://www.google.com/webhp?sourceid=c ... hognomonic

Hemodynamic alteration is present at the start of the disease. Hemodynamic alteration is nearly universal among people with MS. If these two statements are true, then hemodynamic alteration is grossly understudied in MS.

Here's a citation from the paper:

In addition, Color-coded quantitative DSA has been used to evaluate CCT in patients
with steno-occlusive arterial disease before and after endovascular treatment [32].

Lin CJ, Hung SC, Guo WY, Chang FC, Luo CB, et al. (2012) Monitoring peri-therapeutic cerebral circulation
time: a feasibility study using color-coded quantitative DSA in patients with steno-occlusive arterial
disease. AJNM Am J Neuroradiol 33:1685–1690. doi: 10.3174/ajnr.A3049

It seems it would be possible to measure CCT in patients before and after endovacular CCSVI treatment. If CCT is "pathognomonic" in MS and if it can be shown to be improved after jugular angioplasty, that would be some good evidence in favor of treatment.

[cheerleader]

Absolutely, Cece!!! REALLY great points. This slowed cerebral circulation appears to be a hallmark of ALL stages of MS. It is pathognomic.

Jeff had his venous return measured after venoplasty treatment, and his blood flow out was doubled through his jugular veins and repaired stenotic dural sinus. But, as you mention above, this complete picture of cerebral circulation could be tested in patients treated for CCSVI and used as a new biomarker, just as it is in those who have their stenotic carotid arteries treated with angioplasty.

The endothelium can heal, if it has proper laminar flow, nutrition, oxygenation--and then it can do its job. Maintain the BBB so that it can fight infections, keep the immune system intact and in its place. Keep out viruses, bacteria and plasmic particles which lead to iron deposition. We've been treating the invading cells--but not fixing the leaking dam, or the hypoxic situation which leads to this breakdown. PML and other side effects have been the result. A mechanistic repair might allow the body to heal.
exciting times,
cheer

[Sharon]

Cure or Bust: look at the research by Dr Philip James on hyperbaric and MS -- better yet read his book "Oxygen and the Brain".

I have had amazing improvement in cerebral perfusion with HBO treatment. I have the pre and post SPECT scans to validate. I did not start treatment though until I was satisfied I had good arterial/venous flow and csf.

Sharon

[1eye]

This paper defines a condition which should be addressed, and should be treated by doctors. If it is a fundamental ubiquitous feature of MS, as constantly present as lesions or axonal loss, it should be common knowledge, whether or not it correlates with myelin loss, disability, cognition, loss of dexterity, or any of the commonly used metrics of MS. It should be investigated until its detailed nature is as known to the best of the abilities of current science. I, as a lone anecdote, have known about the disease since 1966. It has always been described to me as a myelin problem. Now that we know it is also a circulation problem doctors should treat it, and it should be covered by medical insurance. It should be on the curricula of general medicine classes. Reproduce the experiment until you are blue, if you want, but treat the sick. Doing nothing does harm. Stop doing it.

Yours Truly,
Not A Doctor

[vesta]

Just as harmful - even criminal - is to continue "drug" research subjecting MSers to repeated MRI scans with gadolinium dye in hopes of finding some easy cure while ignoring the circulation issue. That research is stressful and entirely misguided.

[1eye]

So is this virtual hypoxia (oxygen present, but not useable by normal metabolism) present still after venoplasty? My guess is it will be, because the mitochondria and/or B cells are still under EBV's flag. My guess is that's why we progress: the iron leak is enough to disable us, but not kill us outright. The mitochondria get worse with every new leak in the BBB, until not enough respiration or metabolism are possible.

The endogenous retrovirus MSRV might be at work here. Does anybody know where it was detected? Lesions, black hole sites, the BBB? White matter? Grey? Blood and everywhere it goes? How do MSRV and EVB get along together?

I cannot see a link between any of this and the too-much nitrogen oxide piece. But I am Not A Doctor.

Anyway, we have more to find out...

[CureOrBust]

In relation to HBO, making a general statement, most rigorous published papers have not found a significant benefit, and hence its not part of the standard treatment by a neurologist. But unlike CCSVI, it is simpler to "get right" and has been around for many years. Since around 1970?

Double blinded placebo controlled trial of 80 patients (full paper available)
http://www.bmj.com/content/bmj/292/6517/367.full.pdf

Abstract
Eighty four patients with multiple sclerosis were treated in monoplace chambers with either hyperbaric oxygen at 2 atmospheres nabsolute or placebo. Comprehensive double blind assessment was carried out before, immediately after, and one month after treatment. There was no clinically important or significant benefit in any of the four major criteria of outcome-namely, them patient's subjective opinion, the examiner's opinion, the score on the Kurtzke disability status scale, or the time taken to walk 50 m. Out of 40 other clinical variables assessed, two (the sensory scale and timed writing with the left hand) showed a significant improvement without any subjective clinical correlate or change in any of seven other tests of left hand function. No group of symptoms was perceived by the patients as having improved more after treatment with hyperbaric oxygen than placebo. It is concluded that there is no basis for recommending hyperbaric oxygen in the treatment of multiple sclerosis.

Double-blinded, placebo controlled 11 patients
http://archive.rubicon-foundation.org/x ... sequence=1
"No statistically significant differences"


Small 19 patients
http://jnnp.bmj.com/content/48/6/497.full.pdf+html

Abstract

The effects of hyperbaric oxygen at a pressure of two atmospheres absolute were studied in a group of patients with chronic progressive multiple sclerosis. A slight but statistically insignificant shortening of the visual evoked potential latencies was seen after treatment with hyperbaric oxygen as compared with placebo treatment. The treatment did not appreciably halt the progression of the disease and deferioration occurred more often among the patients in the treatment group than in the control group.

And for balance sake, the one I did find to have positive results. It derived that the difference was because of length of treatment; ie 1year in this trial. I also think the 5 days a week is more than the others. And I do nt know how they consider the exact same treatment as a "booster" as compared to the initial treatment?
http://dspace.rubicon-foundation.org:80 ... sequence=1

So if we were to take this positive study as a way forward, if you do 5 days per week for less than 6 months and notice improvements, they should be questioned.

I am not against HBO, and plan to try it myself, However, I think we need to be honest as to the scientifically proven results.

When doing any research, I would really recommend google scholar (and unselect patents) over a plain web search.
https://scholar.google.com

[vesta]

I have found that swimming boosts blood flow through the brain and gives me the feeling that I have been "oxygenated". Any congested feeling in my head feels cleared up. And recently I've been using a contraption that gets my legs going like a stationary bike and have been pleasantly surprised to find that this works almost as well as swimming. (Plus, I can do it during the winter.) O.K., that's anecdotal, but why not try it? Cheerleader referred to a video prepared by Matt Embry, Ashton Embry's son,
http://www.mshope.com (Matt Embry's video)
which gives a classical "recipe" for MS Healing. His CCSVI relief lasted 3 months and then the vein closed again, but he has found that brisk exercise keeps the blood flowing. (That is my experience). He is a good looking hunk in great shape which isn't my case, but if I had known about the blood circulation aspect of MS I wouldn't have the déficits I now have. So everyone can get "oxygen" therapy by MOVING.

http://www.mscureenigmas.net/

[1eye]

In relation to HBO, making a general statement, most rigorous published papers have not found a significant benefit, and hence its not part of the standard treatment by a neurologist. But unlike CCSVI, it is simpler to "get right" and has been around for many years. Since around 1970?

I would suggest that this is not a question of whether the average MS patient benefits, coompared with no-HBO pwMS. You could proceed further with that alone, from the premise that CCT is influenced by neck vein stenosis, and then test first whether the best 1 or combined tests was at all different with the patients standing up vs lying down.

But what I would be interested in is whether there was any difference in various outcome measures (inlucing CCT, as Cece pointed out), say in the first year, in different cohorts of different ages, in people specifically recently treated, with the CCSVI procedure for MS, with lying-down-HBO, compared to age (group or exact) matched pwMS , who were treated in the same way by the same doctors for CCSVI recently, without HBO. You would have to find co-operating HBO facilities and the same CCSVI physician (who uses IVUS), so you would also have had to get their co-operation.

Of course it would be blinded as much as possible.

Because those requirements would likely be too restrictive, probably that would be impossible to do any time soon. Unfortunately the number of subjects willing to do it would be few, it is probably a pipe-dream unless some angel-type funding happens.

In the meantime it will just have to go on the list, with moderate exercise, swimming if you can, weight training and aerobic, and the new diet you prefer, of things that might improve your chances. There is even more new evidence http://news.yale.edu/2015/02/16/anti-in ... g-revealed, and a drug being tested in Ireland, based on an endogenous protein that slows or halts the MS inflammation, as well as bountiful anecdotal cases, that shows a change in diet is probably going to be necessary to get optimum results. The one cheerleader recommends can be found on http://www.ccsvi.org. Or just google diet for endothelial health. If I had the $ I would do the HBO, based on the anecdotes. But that's just me. Where $ doesn't get in the way, most people weigh what they know and their guts.

In fact I would collect as much survey-type evidence as possible, on all pwMS who are in control groups, including diet and exercise, whenever I ran a trial to test an MS treatment. It is not usually collected, that I know of.

Many controversies can be successfully resolved that way, if a clinical trial gets this kind of information as a general rule. That would be my idea of the scientific role of the MS Society; not just the usual, but also compiling information, and making recommendations to investigating doctors, on the kinds of things which need surveying, current controversies, etc. They are in a good position to collect data long term. That might shed a lot of light.

Anyway, BHO helps healing. This is a question of whether it helps CCSVI patients heal from the procedure. If I had the bucks, I would use it after any procedure whose outcome is uncertain. Uncertainty is certain with this one, isn't it?

[Sharon]

I might be able to answer a few of the queries about HBOT. From my personal perspective, I chose to look at HBO as a way to heal damaged tissue and not as a therapy for MS. At my age (71), I have reached a threshold where the deck is kind of stacked against me -- not only because of the MS but now, even more so, because of the age factor. Last year I began looking at all the information I had garnered since going to Stanford for my CCSVI procedure in June 2009 and how it related to me personally - i.e. brain perfusion, traumatic brain injury (concussion), EBV, mitochondria, cerebrospinal fluid, cranio-cervical anomolies, food allergies including calcium, to name just a few. There were some things that I could not change (for instance a malformed clivus bone which jets my cerebrospinal fluid into my spinal cord which just happens to be the location of my largest MS lesion). I knew I could work on diminishing the chronic damage -- the acute damage, the sclerosis, was something I probably could not change. (I believe that we sometimes forget “sclerosis” is healing; unfortunately, it happens to destroy function.

Fast forward, after a lot of research and meeting with some of the pioneers in the field of HBO, I decided to proceed. To measure efficacy of the treatment, I had a triple head SPECT scan prior to starting treatment. Based on my scan, the MS, and my age, Dr. William Maxfield, http://www.hyperbaric-care.com/hyperbaric_maxfield.htm prescribed 40 consecutive treatments at 2.0 ATA - 15 min./dive...60 min. 100% oxygen @ 2.0 ATA...15 min/surface. I was treated six days a week until completing the 40 dives. (note: in some instances, you can dive two times a day -- I chose not to). During the last 20 treatments I was also doing physical therapy. I waited one month (there is a residual improvement after stopping treatment of HBO); and then I had my post SPECT scan. Brain tissue which was "idling" (not dead -- it was alive but not able to metabolize energy) and brain tissue which was over active showed improvement. The SPECT report preHBO stated a “markedly abnormal brain scan involving both hemispheres, greater on the right then the left, and also involving the basal ganglia areas”. The SPECT report postHBO stated a “moderate abnormality in both the cerebral hemispheres with a patchy-type of localization.” I am currently proceeding with maintenance treatments 2 dives per month. I will have a followup SPECT scan after completing six months maintenance.

This is one view of many images taken during the SPECT scan. The top view is the pre-scan; bottom post. The tan and red color is optimal metabolic activity (i.e. perfusion). The yellow, green and blue is diminished activity. Note the increase in the tan and red on the bottom image.

My improvements are unique to me – I hesitate to mention because I do not want anyone to assume they would have similar improvements. I believe because we all have different starting points whether it be with exercise, diet, medication, AGE, we are going to respond differently. One improvement that everyone receives is an 800% increase in their own stem cells. For me, 800% (because of my age) would be a lessor quantity than a 25 yr old, and it is much less than those receiving stem cell infusions. For now, I am satisfied with the 800% increase, and I know that if I decide to do stem cell treatment I now have an oxygenated healthy environment for the stem cells to survive. (stem cells die without oxygen).

One more point, I did not concentrate on looking at the HBOT research for MS, I looked at my known pathologies and the HBO research that related to them.

The largest long term study by Perrins and James Long-term hyperbaric oxygenation retards progression in multiple sclerosis patients
http://www.msntc.org.uk/downloads/Perri ... 1_2005.pdf

Interesting debate related to above linked study (reminiscent of what we are seeing in the current CCSVI controversy)
http://dspace.rubicon-foundation.org/xm ... sequence=1

I hope this personal perspective is of interest to those looking at HBO.
Sharon

[vesta]

Thank you for your wonderfully detailed report and links.