BNAC research : A Tale of Two Studies

March 27, 2013 at 2:43pm

There have been two venoplasty studies undertaken by the University of Buffalo and recently released/publicized.  I thought it might be good to compare them, side by side.  Because the conclusions and results are worlds apart, and there needs to be an explanation.

Dr. Robert Zivadinov is the lead investigator in both studies.

PREMiSe Study Phase #1  Cine/CSF Study  

Published in the Journal of Vascular Radiology March 2013

No publicity  

Discussed at International Society for Neurovascular Disease Conference

http://www.ncbi.nlm.nih.gov/pubmed/23523158

PREMiSe Study Phase #2

Poster/Publicity at American Academy of Neurology  March 2013

Press conferences, videos, lots of news coverage all over the world.

http://www.buffalo.edu/news/releases/2013/03/021.html

Both are Venoplasty studies in mainly RRMS patients.  

PREMiSe study phase 1--Dr. Robert Galleotti, treating IR 

has worked with Dr. Zamboni for many years, has treated hundreds of CCSVI patients

an expert in venoplasty for CCSVI.  Venous drainage is improved >75%

"Improved venous parenchyma drainage"  Lower number of lesions on MRI for treated patients, less relapses.  

More studies are warranted!  PTA is good for the brain.

PREMiSe study phase 2-- Dr. Adnan Siddiqui, treating IR, relatively new to CCSVI venoplasty
Venous drainage is NOT improved to marker of >75%.  In fact, it is only improved to 50%!  (meaning treatment was a failure!!!)

 Headlines read, Liberation Therapy may make MS worse!

Nine patients treated, showed 19 new lesions on MRI.  PTA is bad.

 "more sizable changes in venous outflow [were] associated with increased disease activity primarily noted on MRI,"  Dr. Zivadinov and his colleagues concluded.

How are we to know what to believe? 

Is venoplasty helpful or harmful?  Is this about experience in the treating IR?  

Is this about how research is framed for the different audiences of vascular vs. neurological conferences?  

If phase 2 of PREMiSe did not reach a restoration of <75% venous flow, as it was supposed to....is this trial a failure?  

Because one study shows the venoplasty for CCSVI reduces lesions, relapses and improves CSF and venous drainage when flow is restored to <75%.

while the other study shows the exact opposite.

Which is the truth?

Does anyone want to answer this?

Joan

Cerebrospinal Fluid (CSF) and CCSVI

   March 14, 2013

Researchers at BNAC discover that venoplasty increases the rate of flow of CSF in the brains of those treated with for CCSVI.  CSF flow continues to improve a year after treatment.  

http://www.ncbi.nlm.nih.gov/pubmed/23523158

CSF and CCSVI will be the focus of an upcoming roundtable discussion, hosted by CCSVI Alliance in New Orleans this coming April.

http://events.r20.constantcontact.com/register/event?oeidk=a07e760jpn3867c9dc5&llr=pflw7ieab

Most of us are familiar with cerebrospinal fluid as it is used in the diagnosis of MS.  A lumbar puncture (or spinal tap) removes some of this liquid from the spine.  If there are specific markers in the fluid, called oligoclonal banding, it is a sign that myelin is degrading in the central nervous system, and indicative of MS.

CSF is vitally important to brain health. We've know that CSF is part of the equation in blood flow in CCSVI.  In fact, Dr. Zamboni noted that the severity of CCSVI was related to altered CSF flow in this study: 

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

Most of the published CCSVI research is focused on measuring blood flow.  But the brain and spine are unique in the body, in that CSF factors into blood volume in the central nervous system.

I first wrote about CSF on the forum This is MS in 2009--because I'd returned from Bologna and heard a neurologist discuss how he found parallels in CCSVI venoplasty and shunting for normal pressure hydrocephalus (NPH). 

 http://ccsviinms.blogspot.com/2012/11/normal-pressure-hydrocephalus-once.html#more

I wanted to explore this topic, because we are going to hear more about the importance of CSF flow in the coming months.  There are some very exciting developments happening right now in CCSVI research, and they involve CSF flow. 

Cerebrospinal Fluid has four very important functions for the brain.

1. Supports the brain.  The weight of the brain is suspended in cerebral spinal fluid.

2. Protects the brain.  By providing a cushioning space around tissue

3. Cleanses the brain.  Rinses metabolic waste through the blood brain barrier and out through venous bloodflow.

4. Maintains perfusion level of the brain. CSF is self-regulating, and lessens volume when there is a problem with perfusion.   When CSF levels increase, perfusion (cerebral blood flow) of the brain decreases. 

Vascular Headache and MS

This is from an AAN presentation made in 2010, Migraine More Common in Women with MS-

http://www.aan.com/PressRoom/Home/PressRelease/803

The study involved 116,678 women who were part of the Nurses’ Health Study II. Of these women, 18,000 had been diagnosed with migraine at the start of the study. The women were followed every two years for 16 years. During the study, 375 women were diagnosed with MS. Of those, 82 had reported at the beginning of the study that they had been diagnosed by a doctor with migraine.

The study found that women with a migraine diagnosis at the beginning of the study were 47 percent more likely to develop MS than women without a diagnosis. The results were the same regardless of age, where they lived, Scandinavian ancestry, vitamin D levels, smoking status and body mass index.

The research represents the first large scale study of its kind to explore the relationship between migraine and MS.

A medical blogger with MS writes about the research.

According to the migraine/multiple sclerosis (MS) study, women with migraine headaches may be nearly 50 percent more likely to develop multiple sclerosis (MS) than those without them.

This announcement seems to clarify and affirm what countless female multiple sclerosis (MS) patients have known from personal experience, but without medical confirmation, for decades.

Traditionally, physicians have been somewhat reticent to confirm any possible link between migraine headaches and the demyelinating neurological disease known as multiple sclerosis (MS). Migraines, after all, are classified as vascular headaches, rather than a neurological condition.

"Vascular or migraine type headaches have even been reported as the first symptom of MS," the National Multiple Sclerosis Society has said.

http://voices.yahoo.com/neurologists-link-migraines-multiple-sclerosis-5490331.html

Here is a meta-analysis from 2012, which looked at 1,864 MS patients and 261,563 normals.

We found a significant association between migraine and MS (OR = 2.60, 95% CI 1.12–6.04)

MS patients are more than twice as likely to report migraine as controls. Care providers should be alerted to ask MS patients about migraine in order to treat it and potentially improve quality of life. Future work should further investigate the temporal relationship of this association and relationship to the clinical characteristics of MS.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045295

In 1952 Compston and McAlpine found that 2% of MS sufferers experienced migraine within 3 months of MS onset.

Q J Med. 1952 Apr;21(82):135-67. Some aspects of the natural history of disseminated sclerosis.

McALPINE D, COMPSTON N.

Here is one curious young neurologist, who, in 1989, took the research from the 1950s and noted that vascular headache was a presenting symptom of MS.  (He is now one of the most vocal detractors against CCSVI, calling it a hoax.)

Dr. Mark Freedman's abstract--

Vascular headache of migraine-type may be a presenting symptom of multiple sclerosis (MS), a condition usually not considered in the differential diagnosis of a severe headache accompanied by neurological signs. We reviewed records of 1,113 patients with MS seen from 1967-1987 and found 44 cases whose initial attack or subsequent exacerbations were heralded by a migraine-type headache. Twenty-seven patients had no prior history of migraine, and of these, 12 presented simultaneously with their first headache and MS attack. Twenty-three patients had symptoms of a posterior fossa mass lesion. The significance of these results and possible pathogenesis is discussed.

http://www.ncbi.nlm.nih.gov/pubmed/2924210

+++++++++++++++++++++++++++++

Migraine is a known vascular condition.  The pain of migraine comes from the abnormal functioning of the brain's blood vessels.  Migraine is also associated with white matter lesions in the brain.  And yes, MS researchers have been "reticent" to comment on this very direct link of the vasculature and MS.

There is a vascular connection to MS.  Neurologists and MS researchers know it.  What they choose to do with this information is another matter.

Joan