Exciting New MS Treatment!

NEWS RELEASE

A new MS drug appears to alter fluid dynamics and repair the blood brain barrier!
In fact, 63% of the patients treated with Perfuza (toxicmuzab) had no new or enhancing MS lesions at 12 months! In light of recent discoveries of the brain's lymphatic vessels and the connection to venous flow, we are thrilled to be able to offer MS patients a drug treatment which may be addressing CNS fluid dynamics.

Here's more on the impressive results of Perfuza from a recent publication in JAMA---

We found a reduction in the mean number of new brain lesions (corresponding to more lesion- free patients) in the toxicumab group compared with the placebo group at 6 to 12 months. The delayed and positive effect on the magnetic resonance biomarker suggests that toxicumab could affect the dynamic of the blood-brain barrier.

Gadolinium enhancement is a marker of damage to the blood-brain barrier, whose time course depends on lymphatic drainage18 and hence on venous drainage from the skull.19 Previous studies have reported that venous pressure is lowered3 and cerebrospinal fluid dynamics is improved20 after taking toxicmuzab, thereby favoring the drainage of cerebro spinal fluid into the dural veins, which depends on a pressure gradient between the subarachnoid spaces and dural veins.21,22

Another study23 reported that white matter lesion load was inversely correlated with reduced cerebrospinal fluid dynamics, as measured by MRI. In addition, flow improvement through the internal jugular veins owing to toxicmuzab has been reported to improve brain perfusion in patients with RRMS.21 It has also been reported that the development of a new MS plaque was preceded by sustained MRI-detected hypoperfusion before the plaque was identified on MRI.24,25

link

Incredible, right???  Finally.  A drug which can potentially affect the blood brain barrier!
Perfuza (toxicmuzab) may be the greatest money-making MS drug in history.
Projections are now at 2-3 billion for 2018 alone.


Only kidding.

The paper I'm quoting from, verbatim, is the recent JAMA review of angioplasty for CCSVI from the Brave Dreams clinical trial. 

Just replace my made up block buster drug Perfuza (toxicmuzab) with angioplasty to restore venous flow.   And then, write a conclusion and snarky editorial that says that we should not pursue this treatment any further, and that CCSVI research is over.

Even though the conclusion of the paper says that over half of patients saw benefit in cerebral blood flow from CCSVI treatment.

The editorial which goes along with this publication is actually incorrect.  The author of the editorial, Dr. Ari Green***, claims that there was absolutely no benefit in those treated for CCSVI, that there was no reduction in new lesions.  Here, read the editorial for yourselves, and read the paper again, and tell me---isn't this incorrect?
https://jamanetwork.com/journals/jamaneurology/fullarticle/2664000

***Dr. Green has received personal compensation for activities with Inception Sciences, Mylan Pharma, Medimmune, and Bionure. Dr. Green has received personal compensation for serving on the board of Inception Sciences. Dr. Green holds stock and/or stock options in Inception Sciences. Dr. Green has received research support from Inception Sciences, Biogen, and Novartis.  link
Dr. Green's Inception Sciences Company owns the patent for an antihistamine-like molecule thought to remyelinate neurons. I wrote about the absurd hype regarding a 1.3% improvement in visual acuity here:  link

To recap---this published paper from the neurologists of the Brave Dreams trial just proved, conclusively-
1. CCSVI is a real condition in people with MS.
2. There are a variety of venous malformations.  There were patients with closed jugular valves, refluxing blood flow, and hypoperfusion.
3. Venoplasty was able to restore normal flow in 54% of the patients.  Not all malformations can be treated with PTA alone.
4.  63% of treated patients had no new MS lesions on MRI at 12 months.
Doesn't this count for something?  At least additional study?

What is real news? What is fake news?
Is this simply spin or is it something darker?

If a room full of neurologists look at the results from CCSVI venoplasty and conclude 
"The delayed effect of venous PTA 6 months after the procedure on the magnetic resonance biomarker suggests a possibility that PTA may produce benefit for a subgroup of patients with MS. This should be further analyzed and investigated." 

yet still write a conclusion and editorial suggesting CCSVI research be stopped--- what is reality?

Please, tell me.  Honestly, I'm flummoxed.

More ahead.
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. 

Normal Pressure Hydrocephalus---the once "controversial" discovery of Dr. Salomon Hakim

November 25, 2012 at 1:59pm

Those of us interested in moving CCSVI diagnosis and treatment forward can always learn from history.

In the 1960s, a neurosurgeon in Bogota, Columbia made the controversial claim that he could reverse neurodegeneration by surgically diverting an excess of cerebrospinal fluid (CSF) by placing a shunt in his patients.

Professor Salomon Hakim first published his thesis in 1964 and then published 6 case reports of "normal pressure hydrocephalus" in The New England Journal of Medicine and the Journal of the Neurological Sciences in 1965. Hakim rose to the forefront of academic medicine as he described a newfound ability to reverse symptoms of “neurodegeneration” that had long been considered irreversible.

link

It is important to understand that today, 60 years after Hakim's discovery, treating normal pressure hydrocephalus is an accepted practice, even though diagnosing NPH is an inexact science.  There were never any double blinded clinical trials for this surgery.  Hakim claimed he could reverse gait impairment, cognitive problems and urinary incontinence by diverting CSF flow.  And the proof was in his patients' recovery.  No one cries "placebo effect!" after a patient recovers mobility, cognition or bladder control once treated for NPH.

Here is a first hand account of the changes in brain function and recovery, written by a woman treated for NPH.  Her story was published in the New York Times.

link

I first learned about NPH from Dr. Elliot Frohman in Bologna, Italy--at the first CCSVI conference in September 2009.  It was Dr. Frohman, an MS specialist and neurologist, who commented that CCSVI treatment reminded him of the success he had seen after treating his patients for NPH. Here is what Dr. Frohman said about venoplasty for CCSVI.  I wrote it down in my notes, because his comment literally stunned me.

 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.

So, what's NPH?  And what might it have to do with CCSVI?

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 (literally water on the brain) 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. 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.)

And cerebrospinal fluid is affected by venous return.  Open jugular veins are essential for CSF clearance.  link

The less blood flowing through the brain back to the heart, the more CSF can build up and reabsorption is hindered.  For those who want to learn more about this connection, I highly suggest reading Dr. Michael Flanagan's book and blog, The Downside of Upright Posture.

Venoplasty for CCSVI changes cerebrospinal fluid flow rates.  

The reseachers at BNAC noted that even 12 months after venoplasty, the patients treated for CCSVI had a faster rate of CSF flow going through their brains.  

link

My husband had a profound relief of fatigue, cognitive fog, heat intolerance, spasms and sleep apnea after being treated for CCSVI in May 2009. These improvements still continue, now 3 and a half years later.  His third ventricle is now normal on MRI, he has no gray matter atrophy.  

Dr. Frohman and his neurological community would have you believe that Jeff's benefits from CCSVI venoplasty are placebo, while the patients they have treated for NPH benefits are real.  Why this cognitive dissonance?  

Only more research, publications like the BNAC paper on cerebrospinal fluid changes after venoplasty, and more pressure from patients and caregivers will provide answers.

Joan