Dr. Frohman and Normal Pressure Hydrocephalus

[1eye]

Not as bad as Heisenberg,

Don't remember the details, but that if you successfully measure the velocity of an electron, you can't ever find out it's position, and vice versa. The thing that is very common in many systems is that measurement changes the system, sometime so much so that the measurement itself is invalidated or made impossible.

[cheerleader]

A new paper on the correlation of NPH and MS.

Here is a case of a young woman dx with MS. She is treated with interferon for 8 yrs., continues to progress. Her doctors note signs of possible hydrocephalus on her MRI, and decide to measure her saggital sinus venous pressure, and note that it's elevated. After further testing it is decided she has NPH. A shunt is surgically place, CSF is diverted and her symptoms of incontinence, gait problems and headaches are gone.
http://www.springerlink.com/content/n03021j816641500/

Hydrocephalus can look like brain atrophy on MRI--and can be easily dismissed as simply atrophy due to MS by doctors. Thankfully for this patient, her doctors went another step and noted the slow CSF and venous flow, elevated pressure, congestion and treated her.

This woman had white matter lesions and an MS diagnosis, but her symptoms were caused by NPH. At 28, she was far too young to get an NPH diagnosis. Lucky for her, her doctors looked outside the box. What if her earlier MS diagnosis was only the first sign of venous congestion , increased intracranial pressure and slowed cerebral flow?

BNAC is noting the pwCCSVI have slowed CSF flow, and venoplasty improves this. It is a measurable improvement BNAC found in their CCSVI clinical trial. Everyone with CCSVI had slowed CSF levels. Everyone had improvements with venoplasty.
http://registration.akm.ch/einsicht.php ... KEN_ID=900

I really can't believe it's been three years since Dr. Frohman made his comment in Bologna, and he has not explored this connection any further...I feel like it's becoming clearer--with the FONAR testing and improved CSF flow at BNAC. When will the neurologists who understand NPH step up to the plate and LEAD this research. Dr. Frohman....it's time!
cheer

[MarkW]

A new paper on the correlation of NPH and MS.
Here is a case of a young woman dx with MS. She is treated with interferon for 8 yrs., continues to progress. Her doctors note signs of possible hydrocephalus on her MRI, and decide to measure her saggital sinus venous pressure, and note that it's elevated. After further testing it is decided she has NPH. A shunt is surgically place, CSF is diverted and her symptoms of incontinence, gait problems and headaches are gone.
http://www.springerlink.com/content/n03021j816641500/

Hello Cheerleader/Joan,
Again I ask that we are scientific in postings. Just because Neuros engage in poor science, CCSVI advocates should not do the same. A report of one patient is not a report of correlation. This report simply indicates pwMS should be diagnosed for CCSVI syndrome. If stenoses are found they should be treated.

BNAC is noting the pwCCSVI have slowed CSF flow, and venoplasty improves this. It is a measurable improvement BNAC found in their CCSVI clinical trial. Everyone with CCSVI had slowed CSF levels. Everyone had improvements with venoplasty.
http://registration.akm.ch/einsicht.php ... KEN_ID=900

The BNAC trial shows pwCCSVI show improvements in CSF flow if pwCCSVI are treated with venoplasty, that's all. I need to read the whole paper to comment further as I am unsure if a complete examination of possible stenoses was undertaken in the BNAC study.

I realise I am being pendantic but CCSVI advocates need to be more accurate than MS Neuros.
Kind regards,
MarkW

[cheerleader]

Mark--this is a thread I started in 2009 to discuss the implications of CCSVI on cerebral spinal fluid levels and clearance. If you are not interested, please don't bother reading this thread. I think it's interesting, and it's part of the discovery process. So do the researchers who discovered CCSVI.


Dr. Zamboni began this exploration of altered CSF flow.

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics.
Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R.
Source
Vascular Diseases Center, University of Ferrera, and Bellaria Neurosciences, Ferrara and Bologna, Italy. zmp@unife.it
Abstract
Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.

http://www.ncbi.nlm.nih.gov/pubmed/20018140


Dr. Zivadinov is continuing the exploration:

Thursday, October 11, 2012, 15:30 - 17:00
Cine cerebrospinal fluid imaging changes in patients with multiple sclerosis after venous angioplasty. A 1-year follow-up study

R. Zivadinov, C. Magnano, R. Galeotti, C. Schirda, B. Weinstock-Guttman, E. Menegatti, J. Hagemeier, A.M. Malagoni, D. Hojnacki, C. Kennedy, I. Bartolomei, C. Beggs, F. Salvi, P. Zamboni (Buffalo, US; Ferrara, IT; Bologna, IT; Bradford, UK)
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). Percutaneous transluminal angioplasty (PTA) of duplex-detected lesions (in the internal jugular and/or azygos veins) was previously applied in a pilot study of 15 MS patients to preliminarily assess whether PTA reduced MS disease activity, when used in addition to standard medical treatment. The higher percent brain volume change decrease over the first 6 months (-1.27%) in the immediate treatment group (ITG) suggested a more pronounced pseudoatrophy effect compared with the delayed treatment group (DTG) (-0.57%), possibly because of a potential anti-inflammatory effect of PTA or alternatively, due to a decrease in brain volume or improvement in cerebrospinal fluid (CSF) flow because of better venous drainage following angioplasty.
Objectives: To investigate changes in cine cerebrospinal fluid (CSF) pulsatile flow and velocity measures in patients with relapsing-remitting (RR) MS who underwent venous angioplasty.
Methods: This was a prospective cohort study, that included 15 patients with RRMS and duplex-detected CCSVI. Eight patients had PTA in addition to medical therapy (ITG) immediately following baseline assessments, while 7 had delayed treatment with PTA after 6 months of medical therapy alone (DTG). CSF pulsatile flow and velocity measures were quantified over 32 phases of the cardiac cycle, using a semi-automated method. These outcomes were compared between ITG and DTG at baseline, 6 and 12 months of the study.
Results: At baseline, there were no significant differences between ITG and DTG in CSF pulsatile flow (p=0.474) or velocity (p=0.714) measures. However at month 6, significant improvement in CSF pulsatile flow (p<0.001) and velocity (p=0.013) was detected in the ITG compared to DTG. This difference persisted at month 12 of the study for CSF pulsatile flow (p=0.001) and velocity (p=0.021) between the two groups. Within-group changes showed significant improvement in CSF pulsatile flow over 12 months in both ITG (p=0.033) and DTG (p=0.024). No significant within-group changes were found for velocity in both treatment arms.
Conclusions: This study shows that in MS patients with CCSVI, PTA treatment has a beneficial effect on CSF flow and velocity measures. This improvement could be due to better venous drainage following angioplasty.

http://registration.akm.ch/einsicht.php ... KEN_ID=900


Dr. Fabrizio Salvi has talked about normal pressure hydrocephalus in CCSVI in a presentation:


Considering NPH and cerebrospinal fluid dynamics is important. I'm just writing about one aspect on this thread, for other laypeople. There are threads on CCSVI and chiropractic, jaw alignment, supplements, jugular vein reconstruction, high iron. This one is on CSF. I'm kind of tired of you telling me what's important. It's more than pedantic, it's very patronizing.
cheer

[Cece]

Here is a case of a young woman dx with MS. She is treated with interferon for 8 yrs., continues to progress. Her doctors note signs of possible hydrocephalus on her MRI, and decide to measure her saggital sinus venous pressure, and note that it's elevated. After further testing it is decided she has NPH. A shunt is surgically place, CSF is diverted and her symptoms of incontinence, gait problems and headaches are gone.
http://www.springerlink.com/content/n03021j816641500/

At first I thought this was a case study of a patient who was misdiagnosed MS but actually had hydrocephalus, but no, the patient had both conditions. Odds are the patient also has the third untreated condition of CCSVI, since it is highly associated with MS. I wonder if treating the CCSVI would have normalized the hydrocephalus without the need for a shunt.

[MarkW]

Hello Cheerleader/Joan,
I hoped you would read the words I actually wrote "I ask that we are scientific in postings". You posted "A new paper on the correlation of NPH and MS". This not demonstrated in the paper because one report of one patient is not a report of correlation. Lay people on this site read your postings as gospel. I only ask that you are scientific in your postings.
You are taking the theories published in research papers and posting them as established scientific facts. This is a disservice to the researchers who could get misquoted. The actual conclusions said "This study shows that in MS patients with CCSVI, PTA treatment has a beneficial effect on CSF flow and velocity measures. This improvement could be due to better venous drainage following angioplasty. (my highlights)
Joan you wrote "I'm kind of tired of you telling me what's important." I am not telling you what is important for CCSVI syndrome. To be clear there is insufficient evidence to state why venoplasty works for pwCCSVI. Please post on the evidence of NPH and MS, as evidence not established fact.
Let's leave the poor science to MS Neuros.
Kind regards,
Mark

[Rogan]

Hello Cheerleader/Joan,
To be clear there is insufficient evidence to state why venoplasty works for pwCCSVI.

You really believe what you wrote MarkW?


Cheerleader has been on this since the beginning.

Thank you Cheerleader.

Please show her common Internet courtesy, and please extend her some respect for spreading these "scientific ideas". There are hundreds of links on this site that explain how venoplasty improves cranial circulation. Some of the most recent have to do with Dr. Haacke actually measuring the increased blood flow post venoplasty. This post on NPH and Dr. Eliot Frohman, professor of neurology at Southwestern University, from 2009 is fascinating and very scientific. Shunting of the brain to provide relief is fascinating and I would imagine involved a great deal of science to pull off.

Take your anger out on NICE not Cheerleader. It is not Cheerleader's fault that the English can't think through this logically, that of course proper blood flow to the brain helps pwCCSVI. They are more hung up on the science and less focused on common sense. I am sorry to take a dig on your health care system but it sounds so stuffy, and at times your posts somehow reflect that holier than thou atmosphere.

Be nice to Cheerleader

[cheerleader]

Thanks, Rogan. Mark felt I was saying this is a proven correlation....but if you read my post on the anecdotal case of the woman with MS and NPH, you see lots of "what ifs" and "discovery process". I thought that one case was interesting, that's all. And I'm so glad that Dr. Haacke started measuring cranial circulation and oxygenation after we had a discussion with the Hubbards on what might be measurable, tangible benefits of venoplasty. (I knew Jeff's results would be called placebo.) And CSF measurements may well be coming from Dr. Haacke in the future. He's really the friend of pwMS, and his work is laying the foundation as we move forward. He is an incredible scientist.

My rant was more about the fact that Dr. Frohman understood what CCSVI might be doing to MS brains back in '09, since he has been studying the results of NPH, and knew all about how the increased size of the third ventricle was common in MS and NPH---but this phenomena is called "brain atrophy" on MRI, once an MS diagnosis is made. And frankly, it ticks me off that he isn't working with vascular doctors to understand this. I mean, if you were he, wouldn't you be intrigued??

What Cece brings up is key...would that woman's NPH have improved if she had been treated for CCSVI with venoplasty, and not shunted? The recent BNAC study shows that venoplasty alone, without surgical shunting, provided better clearance of CSF and a change in flow velocity in ALL who were treated. Now, here's the kicker.....there MAY BE a correlation here with Alzheimer's, Parkinson's, dementia and other diseases of neurodegeneration---these are all diseases where slowed cerebral bloodflow (hypoperfusion) and slowed CSF clearance harm brain tissue. Shunting CSF works for some, but not all of these patients. And I know of one study going on that is looking at this correlation and learning exciting things.

I am not a scientist, I am not a spokeperson for pwMS. I just care about this research for personal reasons. My Dad had undiagnosed NPH, and died way before his time, because his gait was shuffling, he was becoming confused, he fell, hit his head, bled in the brain and never pulled out of it. My husband lost his peripheral vision as a kid, from drusen and increased pressure on his optic disc, and he developed MS decades later. The way I look at it, I'm doing this for my kid, because his deck is loaded.

Mark's a good guy, an outspoken advocate for CCSVI treatment. He has a tough time in the UK where Lemtrada/Coles/Compston reign. I'm lucky to live in the wild west. But we're all on the same team.
cheer

[Cece]

I am indebted to Cheer for her role in digging into CCSVI back in 2008 and 2009, and her tireless advocacy since then. Because of what I learned here, I pursued CCSVI and I got treated and I am grateful as all get out.

MarkW brings his educated background in pharmacy and his focus on advocating de-stenosis without getting overly caught up in theories. Valuable contributions.

If the issue is over the phrasing of "A new paper on the correlation of NPH and MS," it could be said that it was a new paper on a case study that fit into a theory of a correlation between NPS and MS. Most of us who are not pedantic might not notice that distinction in phrasing.

[MarkW]

Hello Cheerleader/Joan,
To be clear there is insufficient evidence to state why venoplasty works for pwCCSVI.

You really believe what you wrote MarkW?

Hello Rogan,
I absolutely believe that "there is insufficient evidence to state why venoplasty works". There are a few plausible theories but insufficient evidence to say that one is dominant over the others. If you want to argue this me, I can do this.
For the record I was one of the people in the UK who convinced NICE to allow 'percutaneous venoplasty for pwMS'. The current situation in the UK allows freedom to IRs/VSs to conduct venoplasty in a trial, even in an open trial. Are there many countries in the world officially allowing this?

MarkW's focus on advocating de-stenosis without getting overly caught up in theories....... Most of us who are not pedantic might not notice that distinction in phrasing.

The real issue Cece is that many of the theories do not consider the whole of MS. This allows MS Neuros to ridicule the CCSVI theories with respect to MS. The long established practice of the pharmaceutical industry is to promote a 'cure' without understanding how or why it works. That is why I focus on advocating de-stenosis without getting overly caught up in theories, it is an established and very successful marketing method.
Joan the bad news for you is that I judge your posts to a higher standard than a lay person's posts. MS Neuros are searching for weaknesses in the CCSVI syndrome argument, please give nothing away. I hope that my input will help protect you from them, by focussing your words. Most CCSVI researchers act as if good research will win quickly. In contrast I see a very hard turf war is being waged by the MS Neuros, the lawsuit against Prof Dake is an example.
Yes we are on the same side. I remain a critical friend.
Kind regards,
MarkW

[Rogan]

Thanks MarkW, and thanks for your efforts to provide better healthcare in England.

Sorry, I misspoke. It sounds like NICE is more open minded than the controlling Canadian system.

You don't believe the MRI's and images that show the dye moving through the previously clogged veins that have been liberated by PTA? Or does that not represent "sufficient evidence "? Do you further doubt that venoplasty works for varicose veins or treatment of the liver disease Budd Chiari?

I'm not a doctor so I am way out of my league, but hasn't venoplasty been a long accepted tool to treat clogged veins?

I must be missing something behind your logic? Sorry.

[cheerleader]

The problem with using "destenosis" as a rallying cry is that neurologists do not think jugular veins are important. They see no reason to mess with veins. They believe collateral circulation is sufficient for the brain, and ligating jugular veins is not deleterious to brain health The venous circulation of the brain is under-researched and far from understood. It is only through perfusion studies we can establish the essential nature of jugular veins. Dr. B.B. Lee explained this to me at length in Bologna. Venous circulation is one of the most under-researched, misunderstood subjects in medicine....yet veins are more important than arteries, since they clear toxins and metabolites from tissue and return deoxygenated blood back to the heart.

So....back to normal pressure hydrocephalus and links to CCSVI and MS research, which is what this thread is all about. Showing the essential nature of venous return from the brain with objective science is important.
cheer

[cheerleader]

FONAR upright MRI is providing further evidence of flow obstructions in people with MS when they are seated. Here is the full paper on cervical trauma, cerebrospinal fluid blockage and genesis of multiple sclerosis by Dr. Damadian, inventor of the MRI----well worth reading the 33 pages:

http://www.fonar.com/pdf/PCP41_damadian.pdf

[cheerleader]

Thanks to Happydance for sending along a paper which looks at Cerebrospinal Fluid markers in chronic adult hydrocephalus.
http://www.fluidsbarrierscns.com/content/3/1/11

Hydrocephalus and MS share many markers in CSF, including

MBP-

• Myelin Basic Protein
Myelin Basic Protein (MBP) is a known indicator of brain damage and in particular of demyelination [8,49]. It is known that in hydrocephalus there is demyelination of the periventricular white matter and so MBP appears as an attractive marker to study the degree of this pathological process. Sutton et al. measured the levels of this protein in the CSF of hydrocephalic patients with different aetiologies and proposed that active hydrocephalus produces significant periventricular demyelination, probably as the result of mechanical stretching [34]. Interestingly, the degree of ventriculomegaly was positively correlated with the levels of MBP. The findings become more interesting since we know from the studies of Whitaker et al., that cerebral atrophy is not associated with elevated MBP values [50]. Later, Longatti et al. in 1993 examined the levels of MBP pre- and postoperatively. In their study of 17 patients with hydrocephalus who underwent surgical CSF diversion they observed that the levels of MBP decreased following the shunt operation, suggesting that MBP is an index of brain damage and its levels could be used as an indication for shunting [51]. They have not however correlated the levels with shunting outcomes. However, high levels of MBP before shunting may be explained by the pooling of molecules in stagnant CSF, which then decrease after flow is restored by shunting. In another study of 57 patients with NPH, the levels of MBP did not differ significantly between patients with NPH, vascular dementia, AD, and controls [41]. However, the levels of MBP were higher than controls.

Tau Protein

Tau protein, a microtubule-associated protein has been found to be elevated in the CSF of patients suffering from Alzheimer's disease [15], as well as in patients with Lewy body dementia, corticobasal degeneration [61], and Creutzfeldt-Jakob disease [62] indicating that it is a marker of neuronal degeneration.

Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis
http://msj.sagepub.com/content/11/3/261.abstract

• Sulfatide

Sulfatide is a glycosphingolipid component of myelin and it has been recently understood by experiments in sulfatide-null mice, to be essential for the maintenance of CNS myelin and axon structure [71]. In an early study, the role of sulfatide was studied in patients with communicating hydrocephalus [33]. The preoperative CSF sulfatide levels were found to be higher in the NPH group with cerebrovascular aetiology, when compared with the rest of the NPH patients. The authors postulated the presence of irreversible ischemic white matter lesions in the hydrocephalic group with cerebrovascular disease. Since the sulfatide levels were normal in most of the NPH patients, they considered that demyelination plays a minor role in the pathogenesis of NPH.

Don't want to be accused of drawing any conclusions....but, like Happydance, I do see a possible correlation with degredation of white matter, stagnant CSF and neuronal degredation. And certainly more circumstantial evidence which needs to be reviewed.

cheer

[cheerleader]

Retrograde jugular flow associated with idiopathic normal pressure hydrocephalus.
http://www.ncbi.nlm.nih.gov/pubmed/18570299

To clarify the relation between the drainage pathway of cerebrospinal fluid and the development of idiopathic normal pressure hydrocephalus (iNPH), we examined flow patterns of internal jugular veins in 20 patients with iNPH and 13 control patients using air-contrast ultrasound venography during the Valsalva maneuver. The iNPH group had a significantly greater frequency of retrograde jugular venous flow (19/20, 95%) than the control group (3/13, 23%) (chi(2) test, p < 0.001). Our results suggest that retrograde jugular venous flow may be associated with the development of iNPH; therefore, the analysis of retrograde jugular venous flow could be a useful element in the diagnosis of iNPH.

yes, this is with Valsalva, where true CCSVI is without Valsalva----but still an interesting correlation.
cheer