Dr. Frohman and Normal Pressure Hydrocephalus

[cheerleader]

Dr. Eliot Frohman, professor of neurology at Southwestern University- was a moderator and participant in the CCSVI convocation. He consistently had cogent and insightful questions and comments during the day. One of his points has stayed with me, and prompted me to do some more research on cerebrospinal fluid. Dr. Frohman commented that CCSVI was reminding him of his shunting treatment of normal pressure hydrocephalus ...mainly in the fact that the third ventricle was being enlarged in both MS and NPH- Here's his comment-

I have seen this happen in “normal pressure hydrocephalus- (NPH) Where there is a loss of gait, cognitive and bladder issues and the lesions disappear because the expanded ventricle swallows the lesion. I have shunted the brains of NPH patients, and they showed remarkable improvements. Again, the enlargement of the third ventricle precedes the changes.

Here's NPH-

The brain and spinal cord are surrounded by a clear fluid called cerebrospinal fluid (CSF). This fluid is produced and stored in cavities in the brain called ventricles. It circulates around the brain, moving from ventricle to ventricle. The purposes of the fluid are to cushion and protect the brain and spinal cord, to supply them with nutrients, and to remove some of their waste products. Any excess fluid drains away from the brain and is absorbed by other tissues.

Hydrocephalus is a condition in which there is too much CSF in the ventricles. This occurs when the natural system for draining and absorbing extra CSF does not work right. The ventricles enlarge to accommodate the extra fluid and then press on different parts of the brain, causing a number of different symptoms. Hydrocephalus has many different causes. Some people are born with the condition, while others develop it during their lives.

Normal pressure hydrocephalus (NPH) is a type of hydrocephalus that occurs in adults, usually older adults. The average age of people with NPH is older than 60 years. NPH is different than other types of hydrocephalus in that it develops slowly over time. The drainage of CSF is blocked gradually, and the excess fluid builds up slowly. The slow enlargement of the ventricles means that the fluid pressure in the brain may not be as high as in other types of hydrocephalus. However, the enlarged ventricles still press on the brain and can cause symptoms. (The term "normal pressure" is somewhat misleading.)

We know that hydrocephalus can occur due to jugular stenosis or blockage. This is well documented in Crouzon's and jugular foramen stenosis....but the hydrocephalus is REALLY apparent. In normal pressure hydrocephalus, it takes longer to cause damage, because it is a slower process. So...I took it from here to look in to why some more progressive folks might be having restenosis after stenting...PERHAPS the CSF excess pressure is not relieved enough by merely opening the jugulars, restenosis can form. I have sent the following research to Dr. Dake-
http://www.ajnr.org/cgi/content/full/28/4/656

By definition, in secondary intracranial hypertension (SIH), there is an underlying medical condition, whereas in IIH, the cause is not known. In many cases of SIH, an increased cerebral venous pressure raises the intracranial pressure as in dural venous fistulas, venous sinus thrombosis, or venous sinus compression.1 However, in almost all patients with IIH (and also in our patients), neuroimaging shows narrowing of the transverse sinuses,2,3,5–7 not reflecting acute thrombosis. The important question is whether those venous abnormalities are cause or consequence of increased intracranial pressure. In the former situation, fixed stenoses (for example postthrombotic fibrotic changes) could obstruct the venous outflow, increase intracranial venous pressure proximal to the stenosis, and lead to increased CSF pressure as a result of a reduction in CSF absorption via the arachnoid granulations. In this setting, a pressure gradient across the stenosis should be measured and reconstruction of the venous lumen with endovascular stents would be effective in lowering elevated CSF pressure. This procedure was successfully used several times4,6 but seems not to be efficient in all patients.6 In the latter (ie, venous abnormalities as a consequence of intracranial pressure), elevated intracranial CSF pressure could lead to a secondary narrowing of the sinus lumen by compression, which can be reversed by lumbar puncture or shunt surgery procedures.5,7,8 In fixed stenoses (the 1st model), therapeutic reduction of CSF pressure should have no effect on sinus diameter.

If you're still following me here...this is the thought....maybe in most individuals (like my Jeff), it is the stenosis causing the CSF level changes, and resolving the stenosis takes care of it....BUT maybe in some folks, like our dear skydog....it is the CSF levels causing the stenosis, and relieving the stenosis in one place only creates restenosis somewhere else, because the CSF issue is not resolved.

We'll see what Dr. D says on this, or if my thinking is wrong. THIS IS WHY WE NEED NEUROS WORKING WITH VASCULAR DOCS TOGETHER...
cheer

[LR1234]

Maybe the anwser in those cases would be to reguarly drain the CSF fluid or something??? would that work?

[fernando]

I've posted something somewhat related in this thread:

http://www.thisisms.com/ftopict-8100.html

An excerpt:

How blood flow influences cerebrospinal fluid flow can be gauged from something called "cranial compliance", a measure of the elasticity of the brain's vascular system. "The cranium is a bony cavity of fixed volume, with the brain taking up most of the space," says Robin Kennett, a neurophysiologist from the Oxford Radcliffe Hospitals in the UK. "Every time the heart beats and sends blood into the cranium, something else has to come out to prevent the pressure rising to levels that would damage the brain." So, as fresh blood flows into the brain's blood vessels, cerebrospinal fluid flows out into the space around the spinal cord through a hole in the base of the skull called the foramen magnum.

[fernando]

http://www.beckleyfoundation.org/science/projects1.html

Investigating Cerebral Circulation as the Physiological
Underpinning of Consciousness

A collaboration between the Beckley Foundation and the Sechenov Institute of Evolutionary Physiology and Biochemistry,
St. Petersburg, led by Prof. Yuri Moskalenko,
Amanda Feilding and Peter Halvorson

One of the projects we are most excited about at the Beckley Foundation is our collaboration with Prof. Yuri Moskalenko investigating cranial compliance. Cranial compliance is a measure of the functioning of the cranial system as a whole: the skull, the brain tissue, and all the liquids that flow through and around this complex system. Cranial compliance is determined by the interaction of all these components, and the results of our investigation so far have shown that a better understanding of these interactions is of crucial importance for healthier brains and improved cognitive functioning throughout the whole of one's life.

The Cranial System and Cranial Compliance

The circulation of blood in the brain differs from that of the other organs because the brain is encased within a nearly-rigid container, the cranium. The situation is further complicated by a second fluid system in the brain, the cerebrospinal fluid (CSF) system, which circulates in its own compartments and interacts with the blood system. These systems are interdependent such that changes in the volume, pressure and movements of one system should lead to concomitant changes in the other, consistent with the laws of fluid dynamics. The study of brain circulation has therefore evolved into the study of the bio-mechanical principles of how fluids move through soft tubes inside a closed container under pressure. There are many different configurations by which the two fluid volumes interact, and learning more about these reveals vital new information about brain circulation and its implications for health.

The concept of brain circulation from this systemic point of view, as a complex biological system, has been given the name cranial compliance or CC. Understanding CC is relevant to medical professionals as well as for each and every one of us. Changes in the elasticity of this complex system over the life span have been shown to have a direct impact on cerebral health and cognitive functioning, as our most recently completed research clearly demonstrates. To know and to manage cranial compliance is as important for the good health of the brain as knowing and managing one's blood pressure is for the heart. The good news is that our research indicates that early, proactive management of cranial compliance may counteract the diminution in brain functions considered to be an inevitable part of normal ageing.

The importance of good cerebral circulation and our intuitive understanding of this is highlighted by the long history we humans have of devising practices that improve our cerebral circulation. The benefits of yogic breathing exercises to cranial compliance, for example, indicate an appreciation that inspiration and expiration (i.e. respiratory pressure changes) are one of the driving forces of brain circulation. Indeed, the respiratory system can be considered as a third fluid system in terms of the effects it has on blood and CSF movements. Altering the extent and rhythm of breathing influences the quality and quantity of fluid movements around the brain.

As described above, to really understand cranial compliance and cerebral circulation you have to consider the brain and the cranial system as a holistic whole. The complex cranial structures that influence brain circulation are:-

1) the skull and it's membranes; 2) the vessels and their blood content; 3) the brain tissue; and 4) the cerebrospinal fluid system within all of its various compartments and convolutions. The CSF system cushions the brain and is, most importantly, responsible for the cleansing of the tissue, like a special lymphatic system just for the brain that can remove waste products too large to pass back into the blood stream.

[radeck]

Thank you for the information, cheer. To be honest I wasn't aware of the possibility of re-stenoses after stenting, only after ballooning. Are such re-stenoses usually above or below the old stenoses, or are they at the stented location itself?

[cheerleader]

Ok...
We've had one patient treated by Dr. Dake who had new stenosis show up in different areas than were stented...I'm merely wondering if there is a correlation to his CSF. This has nothing to do with progressive MS or azygos involvement (he didn't have any) I'm just putting the CSF issue out there. Jeff's the furthest stent-o-teer out at 4 months and he had a balloon procedure at 2 months, to get rid of a thickening at the base of his left stent- but no restenosis. We just don't know what the future holds at this point. So far, all other patients (aside from skydog and Jeff) seen at their 2 months have been OK.
Dr. Zamboni had a 47% restenosis in the jugulars at 18 months in the same area, with just ballooning.
Would like to get back to the research I posted regarding CSF as a creator of stenosis...any thoughts?
cheer

[mrhodes40]

Well that is interesting material!! Normal pressure hydrocephalus can leave people with dementia if they do not get the shunt effectively in place in a timely manner. It is a terrible problem, I knew someone with that issue and a failed shunt.

What they mean about the stenosis being secondary is that the enlarged ventricles themselves are pressing on the veins up in the sinus which is near and in that situation the patients are not recovering just with a stent in the veins...in such a case a shunt and a stent would be required....or a possibly lumbar puncture, the reason is that as soon as you did it some of the pressured fluid would come out and the sinus would decompress, they mention you could test for this secondary situation that way.

But I thought I understood Mark's new stenosis is low down in the jugs not in the sinus If all secondary stenoses end up in the sinus that may be at issue but so far has anyone had a sinus stenosis after the fact?

I think I remember one person had one in the first place, isn't that interesting to think about, a stenosis that increases venous pressure... but also results in intracranial pressure on the sinus after the fact as well? A double whammy! Wow, what a neat thing we can get treatment

There is a fly in the ointment though: MSers do not have intracranial hypertension if we did, that would be noted in all of us when we got our testing. A lumbar puncture would show it. Normal pressure hydrocephalus is a little different in that it is not a high pressure deal, even though it presses on tissue, it is a mild press. The similarities between the CCSVI and NPH have to do with the low pressure situation....but still pressure.

I am not sure that even though stenosis of the sinus can happen in the SIH situation you can extrapolate and say that it also can do that in NPH.....

But you know what?? Reading this gets me to thinking, they've been dinking around putting hardware in people's heads for a long time really. And the confirmation of the venous issues being at fault is really sort of gut wrenching to read.............

once again I am feeling a sadness this has taken so very long. I had been kind of sanguine about it, you know? Thinking sort of that they didn't have the technology etc etc. But when you think about NPH you realize this kind of treatment has been available for a long time actually, all it needed was for MS was for someone to recognize it and start acting on that.
marie

[cheerleader]

But I thought I understood Mark's new stenosis is low down in the jugs not in the sinus If all secondary stenoses end up in the sinus that may be at issue but so far has anyone had a sinus stenosis after the fact?

I think I remember one person had one in the first place, isn't that interesting to think about, a stenosis that increases venous pressure... but also results in intracranial pressure on the sinus after the fact as well? A double whammy! Wow, what a neat thing we can get treatment

There is a fly in the ointment though: MSers do not have intracranial hypertension if we did, that would be noted in all of us when we got our testing. A lumbar puncture would show it. Normal pressure hydrocephalus is a little different in that it is not a high pressure deal, even though it presses on tissue, it is a mild press. The similarities between the CCSVI and NPH have to do with the low pressure situation....but still pressure.

I am not sure that even though stenosis of the sinus can happen in the SIH situation you can extrapolate and say that it also can do that in NPH.....
marie

Thanks for the clarification, Marie. I had wondered if something as "insignificant" as NPH would even show up as a pressure change for MSers when lumbar punctures were done, since it's not true intracranial hypertension, but a slow increase created by CCSVI. You're right...Mark's restenosis was further down in the lower jugs- and this study doesn't fit. I don't think anyone else has shown any restenosis, so this CSF involvement as primary to stenosis doesn't seem to apply.

And you're also right...it was eye-opening to me to hear Dr. Frohman talk about NPH and his success in shunting it, and to hear all the docs talk about how we haven't a clue about the lymphatic system, venous system and the impact on the brain....I felt the same way as you...shouldn't we be further along!!?? Why hasn't this been investigated?

Cerebrospinal fluid and the lymphatic system are also part of CCSVI...as more and more studies are completed, we'll get the full picture and learn how a slowing and build up of all of these fluid systems impact the brain.
cheer

[skydog]

Bingo! This is all seeming far too familiar with how I feel that in my particular case this has all come about. Just a brief rundown 1. in my early childhood periodic mild heat stroke even when well hydrated. Why? 2. several times in the past 30 yrs I can remember a feeling of fluid sloshing in my head. 3. from high school until the last couple of years nearly constant swollen glands in my neck and arm pits. I might have ended the gland issues with the ABX treatment two years ago but NPH may remain the issue. Allot to think about and mostly beyond my comprehension right now but my gut level feeling is we are right on track here in my case. Thank you Cheer for starting these thoughts. You have once again put the right people together with the right puzzle pieces. I can now picture full recovery... Peace, Mark

[bestadmom]

Hi Mark,

I've followed your surgery and post op and 2 month follow-up and am baffled and disappointed that your recovery isn't as cut and dry as we all would have hoped for.

I hope you get the answers to your on going problems and can easily fix them.

Michelle

[skydog]

Marie, Just some random thoughts about my case that I would like to pass by you and others here. I know that after reading so many other cases and what I have experienced that and I will quote Dr. Dake here I am the Odd Duck! So with that said here is my ramble. As I posted earlier most of my adult life I have had these swollen lymph glands in my neck and right arm pit that were small and sometimes tender but always present. Now they are nearly impossible to locate and never tender like they were in the past. Might have cured this issue with some tooth extractions and a coarse of ABX lyme protocol. Could having a long standing localized low grade infection in my sinus or root canal have played a big part in creating a slow build up and periodic flares of excess cerebrospinal fluid that gave me the sloshing brain feeling? Remember were talking on and off for thirty years. Now with periodic pressure buildups or can I loosely call it NPH? And is it possible that my brain is actually pressing down on the pig tailed jugulars causing a crimp. Thus CFS buildup being a possible cause of stenosis. Also Dr. Dake and I talked briefly on the possibility that just the weight of the brain sagging down on the jugs at the sigmoid sinus area could be a factor in my case. Now is it possible that faulty valves in the veins above and or below cause the new stenosis? I keep thinking about the collapsed fire hose analogy here. Just visualize a cheap garden hose on a hot day running at low pressure and volume down a slope. Twist or move it even slightly and it will kink and flatten out in any weak areas down stream even while still under some low pressure and flow. Could the jugular vein be weak enough just to collapse like this. I am trying to tie all this together with the lymphatic system and inflammation being the origin. Low grade infection, more lymphatic fluid, over reacting ventricals, increased CSF. I know you dismissed this earlier but its not clear in my foggy head why. This may repeat some of my earlier post but would like to see this investigated further. This odd Duck is feeling the blues a bit lately. My heat intolerance is off the charts when the ambient temp gets over 65 degrees I am dunking my hot head in a sink full of cold water just to keep moving not to mention all the other symtoms that have come roaring back to haunt me daily. Peace, Mark

[mrhodes40]

Ok Here's the deal: According to Dr Frohman and his presentation at Bologna, MS may have some similarities to normal pressure hydrocephalus because he notes that NPH has a venous issue that stops CSF resorbtion, and CCSVI has similar venous issues, so we MSers may have some NPH type stuff too.

NPH is a misnomer, there is some increased pressure in the CSF, but small compared to regular hydrocephalus.

Cheer got interested in the idea of intracranial pressure based on this insight wondering if it may have something to do with the restenosis and found a paper on idiopathic intracranial hypertension, which is a HIGH pressure situation.. That paper postulated this situation:

blocked venous drainage means that the fluid in the ventricles is not reabsorbed like it should be....THEREFORE in some people the ventricles are pressing on the sinus.........THEREFORE if you just use a stent to open the veins in that person, it is not enough because the sinus is still pinched....so you can test it out by doing a lumbar puncture to see if that allows the pressure to drop enough that the sinus opens up. If it does then you do a shunt and a stent; the shunt will alleviate the extra CSF and the stent will open the vein so the resorbtion can take place as it should.

Cheer wondered if the IIH situation with regards to the pinching of the sinus might explain restenosis in MSers who have been treated.

I offered probably not because
1. the restenosis is not occuring in the sinus.
2. NPH is NOT the same as IIH, IIH causes noticeable pressure issues with the CSF and if an MSer had that kind of pressure then had a lumbar puncture the neuro would notice it. They would also notice papilledema when they peer into your eyes and vision problems would be different than MS (frequently blindness)

So even if MS has some similarities with NPH, it is not likely to be a type of IIH.

So restenosis in the bottom of the neck is not going to be caused by excess pressure in the CSF, nor is it likely to be caused by congestion of the parenchyma. If you decided to put forth a theory that the venous congestion made the brain parenchyma kind of of swollen and tight, and that this was somehow pressing on veins, the vein affected would have to be inside the skull where that dynamic could take effect.

Such a thing may be at issue (40% fewer veins?) but I am just glad Dr Frohman is already following this angle of CSF as a secondary issue to the jug or other stenosis.............

I mean maybe PPMS patients have a secondary NPH going on... if so maybe some will not respond as well to stents, but that is borrowing trouble. All of this is speculative and we are way ahead of the horse

[radeck]

Marie, this may have been brought up before, but I think for many people stumbling upon this thread it will be an obvious question so maybe anybody has knowledge to discuss this here: Taking skydog's garden hose analogy, there's obviously another way to constrict the garden hose besides external pressure, which is internal pressure reduction. As you mention the 40% less veins found in (average) MS brains, there's an obvious interpretation of the constriction constriction downstream...

Putting it the other way around, it is more difficult for external pressure to constrict a hose that is under high internal pressure. In particular if it's in the neck, why would that external pressure change for good at some point in somebody's live? It seems to me here the only physically possible explanation is low internal pressure, that probably also caused the initial stenosis upstream.

Now for stenosis that are close enough to the CSF for there to be an interaction, have there been measurements of blood pressure upstream from the stenosis, in comparison to CSF pressure? If such measurements can be done, that would immediately explain what's going on. If the CSF pressure is higher, it may the reason for the stenosis, and opening the stenosis with a balloon may not last very long. If the pressure is lower in the CSF, the stenosis must have another reason, and opening it is most promising.

[mrhodes40]

In particular if it's in the neck, why would that external pressure change for good at some point in somebody's live?

Dr Zamboni was in Sardinia looking at children with venous malformations, which included jugular stenosis. These children did not have MS but 20 years later when they checked back 90% of them did, so the stenosis did not happen suddenly in their lives, it was there a long time before MS developed. MS lesions develop slowly.

Venous malformations are common and they are just the way some people are made.

Lew's one jugular had an inverted valve in it so the blood flow was blocked from the head rather than being blocked if it came as reflux!! Blocked so it could not go OUT!

My jugulars are pressed shut not because they collapsed but because the tissue on the outside is just too tight, like my sister had crowded crooked teeth and mine are naturally straight. We do not need to come up with some explantion of how something pressed on hers in order to understand it, she was just made that way same way my neck was made with too little room, or Lew was made with an inverted valve.

The cenaculum presentations were in accordance that these are looking congenital.

It is not making sense to me that collapsed veins are the explanation for stenosis... are you saying they are collapsed not stenosed... or that the collapse causes stenosis ...or that the stenosis makes veins collapse downstream from the stenosis itself?

[cheerleader]

radeck-
Marie's right on all of this...
99% of the people seen have some sort of congenital malformation....Jeff's and Marie's jugs were compressed from tight space in the jaw, Mel had two left jugs, Lew had two left jugs, Cat had a cyst....each of these venous malformations is congenital. No need for any internal pressure issues, the veins were malformed. Once they were opened, the blood flow returned.

I was making a supposition in Mark's (skydog) case...he is our only restenosis-er, and listening to Dr. Elliot Frohman in Bologna got me thinking about CSF.
I found a study regarding re-stenosis and made a suppostion, but it was TOO big a leap, because it does not correlate with Mark's profile. There may be a congenital issue in Mark that's been missed-

Or perhaps, we will find in a small segment of cases, that there are internal pressure issues dealing with CSF....but it is too early. I know Dr. Dake is working hard to figure out Mark's case. He is the flow master, and I have the utmost confidence in his ability to comprehend all of this-
cheer