Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of CCSVI and cerebral hypoperfusion. This blog is informative only--all medical decisions should be discussed with your own physicians.The posts are searchable---simply type in your topic of interest in the search box at the top left.Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the immune paradigm of MS, and continues the 20 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.To learn how this journey began, read my first post from August, 2009. Be well! Joan
Monday, December 31, 2012
December 31, 2012 at 9:33am
What's old is new.
2013 is the 150th anniversary of Eduard Rindfleisch's publication describing MS as a vascular disease.
Rindfleisch, a German pathologist, studied post-mortem brain samples from people with MS. He noted that inside all of the lesions he could clearly see an enlarged blood vessel. He believed the inflammatory response seen in the MS brain was created by hypereremia, or engorgement, due to blocked blood flow.
It's now 2013. 150 years is a long time. Too long.
Here is what Rindfleisch noticed in the MS brain in 1863.
If one looks carefully at freshly altered parts of the white matter ...one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood...All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation.
Rindfleisch E. - "Histologisches detail zu der grauen degeneration von gehirn und ruckenmark". Archives of Pathological Anatomy and Physiology. 1863;26:474–483.
Unbelievably, in 2012 researchers begin to look at the cerebral veins of people with MS while they are alive, using MRI venograms. And they notice what Rindfleisch saw---engorged penetrating veins in active, or newly-formed lesions.
They conclude that the cerebral veins in people with MS are not normal----149 years after Rindfleisch said this.
Here is a timeline which outlines the history of the study of MS as a vascular disease.
When you read this timeline, notice how the researchers asserting the vascular connection used actual autopsied brain tissue from people with MS. These are not manufactured mouse models of MS. Notice how many times the words perivenous, veins, blood and fibrinogen are mentioned, thoughout the decades of research.
An inflammatory process is activated whenever there is a break in the blood brain barrier in humans. The idea that MS is created by a rogue immune system-- crossing the blood brain barrier and attacking myelin-- is STILL only a theory. The break in the blood brain barrier precedes demyelination in MS. Why does this happen?
Dr. Zamboni showed how extracranial venous malformations could lead to cerebral hypoperfusion. A process that would lead to a hypoperfusion/reperfusion injury to the brain.
A process that would explain what Rindfleisch noted 150 years ago and researchers see today. And despite what some neurologists are claiming, Dr. Zamboni's theory has not been disproven by their research. Because they are not looking at collateral circulation, hypoperfusion and mean transit time.
When MS specialists claim that "we've investigated the vascular connection to MS, and there's nothing there" they are usually referring to Dr. Tracy Putnam's research and trials of newly discovered blood thinners in people with MS. This happened in the 1940s, when Dr. Putnam was modeling MS lesions by blocking the venous sinus of dogs. Dr. Putnam was just beginning to understand the implications of blocked venous flow on the brain, when Thomas Rivers created the EAE model of MS. People wanted a cure for MS, and looked to the creators of the polio vaccine for the answers. Vascular research was abandoned. For those interested in more of this history, here is the story of TJ Putnam.
The following paper was published by researchers at the Royal Free Hospital of Medicine in London. It is available online, in toto, for free. The reason it is important is that researchers examined actual autopsied brains from people with acute MS, and studied the lesions on an immunohistochemical level. This paper was published in 1994.
Immunohistochemical study of vascular injury in acute multiple sclerosis.
AIMS--To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.
METHODS--Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen.
RESULTS--Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.
CONCLUSION--It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.
Why is there so much reticence by MS researchers to truly collaborate wih vascular doctors, to understand Dr. Zamboni's discovery of truncular venous malformations in the extracranial veins of pwMS?
Cleveland Clinic/Case Western studied post mortem jugular veins from pwMS and found the presence of a novel venous valve that had not been described in anatomy textbooks. Just as Dr. Zamboni said, pwMS have truncular venous malformations. Yet there has been no more investigation into this phenomena. Why not?
It is now four years since the first group of patients and caregivers began discussing Dr. Zamboni's research on This is MS. And so far, only BNAC has collaborated with Dr. Zamboni to study his doppler protocol. Millions of MS Society dollars are spent on a variety of diagnostics--without looking at the deep cerebral veins, with utilization of valsalva manuever, without consulting phlebologists on the nature of truncular venous malformations. All of the wasted time and money, in an attempt to quell vascular research, and assert the dominance of immunomodulating drugs.
Let's celebrate 2013 as the 150th anniversary of Rindfleisch's observation.
We call for collaboration. It's time.
Happy New Year!!
Monday, December 10, 2012
MS and the Orkney Islands--the BIG picture
December 10, 2012 at 6:57pm
New research shows that the world's highest MS rates are found on Scotland's Orkney Islands. Researchers are tying this to the environmental factor of sunshine, latitude and vitamin D levels and potential genetic markers, but there's much more to this story. Because the Orkney Islands population have some serious health issues. It's not just MS.
Here's more on the MS rates on the Orkney Islands which was announced today:
The Orkney islands in Scotland have the highest incidence of multiple sclerosis in the world, a new study has shown, lending weight to the theory that the absence of strong sunlight may be a factor.
The north of Scotland has been known for some time to have a high prevalence of MS, but the first study of its kind in 40 years has found that the rates in the Orkney Islands, Aberdeen and Shetland are not only very high but have increased since the 1980s.
The prevalence of the condition in Orkney is far higher than has been recorded anywhere else. One woman in 170 in the islands suffers from the degenerative disease – it is more common in women than in men. Shetland has a rate of 295 per 100,000 and the city of Aberdeen has 229 cases per 100,000. The highest reported rates worldwide were previously 350 per 100,000 in Alberta and Nova Scotia in Canada.
Dr Jim Wilson, of the University of Edinburgh's centre for population health sciences and one of the authors of the study published in the Journal of Neurology, Neurosurgery and Psychiatry, said the answer was at least partly genetic. "Our study shows that Orkney has the highest prevalence rate of MS recorded worldwide.
The figures will also be welcomed by those who believe the high prevalence of MS in northern climes is linked to an absence of strong sunlight, which is needed to make vitamin D in the body. Some scientists and campaigners have lobbied public health authorities for mass dosing of vitamin D in Scotland.
Dr Wilson said this was an ongoing topic of research. "We have 2,300 people in Orkney who are having their vitamin D measured. We will certainly get the answer," he said. "It is probably important but it is not the only factor."
What this press announcement fails to mention is that this MS study is just one part of several major studies being undertaken on the Orkney Islands. And Dr. Jim WIlson has been involved in these other studies, as well. The results have shown high rates in cardiovascular disease, diabetes, stroke and other cardiovascular issues for Orkney inhabitants. Here is some information from 2004 and the ORCADES study.
Tuesday, December 4, 2012
Fibrinogen---found In ALL neurodegenerative diseases, not just MS
December 4, 2012 at 9:29am
The "news" this week was that fibrinogen, an essential clotting protein, crosses over the blood brain barrier in the mouse model of MS and initiates the disease process by destroying nerve cells.
Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation
But this isn't news. Researchers have been studying this process in neurodegenerative disease for a decade. Because this process happens when the blood brain barrier breaks down.
The overall findings from study of Alzheimer's Disease brain tissue and in vivo in Abeta(1-42) and Abeta(1-42) plus fibrinogen stimulated rat hippocampus suggest microglial responses to promote increased extravasation of blood protein as a critical component in amplifying inflammatory reactivity and causing neuronal damage in inflamed AD brain.
Fibrinogen is a pleiotropic blood protein that regulates coagulation, inflammation and tissue repair. Fibrinogen extravasates in the nervous system after injury or disease associated with vascular damage or blood-brain barrier (BBB) disruption. Fibrinogen is not merely a marker of BBB disruption, but plays a causative role in neurologic disease as a potent inducer of inflammation and an inhibitor of neurite outgrowth. Fibrinogen mediates functions in the nervous system as a ligand for cell-specific receptors. In microglia, fibrinogen mediates activation of Akt and Rho via the CD11b/CD18 integrin receptor, while in neurons fibrinogen induces phosphorylation of epidermal growth factor (EGF) receptor via the alphavbeta3 integrin. Pharmacologic targeting of the interactions of fibrinogen with its nervous system receptors could provide novel strategies for therapeutic intervention in neuroinflammatory and neurodegenerative diseases.
Why the race for researchers to understand fibrinogen?
Because pharma wants to monetize a way to block it.
That's right....researchers are not studying WHY fibrinogen is breaking through the blood brain barrier. No one is looking at causation.
Everyone is studying this to find a pharmacological means of stopping fibrinogen.
But, what if there is an underlying mechanism which begins fibrinogen activation in all neurodegenerative disease?
Wouldn't that be something to study? Wouldn't that be causation, and lead to potential answers in disease aetiology?
Tuesday, November 27, 2012
Nov. 27, 2012 10:17 AM
NIH researchers find that fibrinogen appears to be "the trigger" which begins neurodegeneration in MS.
Researchers are honing in on fibrinogen as a mediator in vascular disease, and they are also finding a link in MS.
Fibrinogen is always present in the blood. The normal range is 200 - 400 milligrams per deciliter (mg/dL).
Fibrinogen is a protein which is made in our livers. It's the signaling protein for fibrin, which allows our blood to clot. When people develop venous ulcers on their legs, due to chronic venous insufficiency, it's fibrinogen that leaks from the veins and creates a build up of fibrin, depleting the tissue of oxygen and allowing those hallmark ulcers to form. This is called a "fibrin cuff." It's fibrinogen which initiates the coagulation cascade and causes our blood to thicken, as a response to low oxygen levels.
Dr. Zamboni was the first to suggest that MS lesions looked a lot like venous ulcers because of the fibrin cuffs found in both sites of injury.
And researchers have noted that fibin deposition comes FIRST, before demyelination.
Here is some recent research on this connection:
Compromised vasculature in the nervous tissue is a pathogenic manifestation apparent in traumatic injuries, such as spinal cord, optic nerve, and sciatic nerve injury, as well as in central nervous system (CNS) diseases with autoimmune characteristics, such as multiple sclerosis (MS) (7).
Blood-brain barrier (BBB) disruption precedes clinical symptoms in MS patients (8), and fibrin is deposited in the lesions (9, 10), apparently before cerebral tissue injury and demyelination (11). Fibrin deposition also coincides with areas of demyelination (12), as well as with areas of axonal damage.
Sunday, November 25, 2012
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.
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.
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.
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.
Sunday, November 18, 2012
Seasonal Affective Disorder (SAD) and MS
November 18, 2012 at 9:54am
The days are shorter. Sunlight is hard to find. We bundle up against the cold. We also put on the extra winter pounds, sleep more and move less. For those who live in the northern latitudes, the shorter days of winter are a reality. And this can affect our mood and general health. As we exercise less, our blood flow slows down. We feel more fatigued, more hopeless. The risk of cardiovascular disease increases.
There is a syndrome doctors know about---called "seasonal affective disorder" or SAD. It is very prevelant in northern latitudes. Most of the association is with mood, or levels of depression. But it is also linked to cardiovascular disease.
What connection does this have with MS?
MS is a disease linked to northern latitudes, lack of vitamin D and lack of ultraviolet rays. And with the link to CCSVI, we are learning more about the vascular risk.
For 68 years latitude has been identified as an important risk factor in the occurrence of multiple sclerosis (MS), but not satisfactory explanation has been offered for this relationship. Epidemiological studies of MS, however, have failed to take into account the degree of change in the amount of ambient light over the course of the year, a variable which is closely related to photoperiod and latitude. Seasonal affective disorder (SAD), another illness for which latitude is a risk factor, appears to be related to the decrease in ambient light during the winter months, and offers some relevant insights into the geographical distribution of risk for developing MS.
There is a very strong correlation between UV rays, photorelaxation and cardiovascular disease.
Here's a small sampling on this research.
Dr. Furchgott and the Discovery of Photorelaxation
I've been reading up on the effect of UV rays on the body, and I came back to the research of Nobel prize winning researcher, Dr. Robert F. Furchgott. He passed away in 2009, and his university keeps his web page online. Dr. Furchgott was a professor at SUNY Downstate in Brooklyn, NY---the same place where Dr. Sal Sclafani recently retired and where the first CCSVI conference was held in the US! Here's Dr. Furchgott's page--
Dr. Furchgott discovered the process of photorelaxation over 40 years ago. What he noted in the lab was that exposure to UV rays changed the endothelium, encouraging nitric oxide production and vasodilation of arteries.
Tuesday, November 13, 2012
Nicoletta Mantovani-- A Woman Reborn
November 13, 2012 at 8:47am
Today, there are over 50 publications reporting on this story, which is important news in Italy. I've translated one more link, from Ferrara, where Dr. Zamboni's trial is beginning. Please note that the reporter states that Dr. Zamboni is going up against powerful opponents--namely the pharmaceutical industry and neurologists in their employ. Miss Mantovani and Dr. Zamboni and all of us around the world are requesting clinical trials for his procedure. Independent research, without corporate interest. Joan
Zamboni Method, Nicoletta Mantovani is reborn from multiple sclerosis
The weekly People Pavarotti's widow says her relief from this illness is thanks to the care created by the Professor from Ferrara. But his clinical trial Brave Dreams, operating for just a short time, is already receiving criticism from some medical journals
by Marco Zavagli | Ferrara | 13 November 2012
A woman reborn. Reborn from the disease, multiple sclerosis. Thanks to the care of Dr. Zamboni. She has always believed and experimented in care for MS, with which she has struggled for years.
She is the honorary president of CCSVI in MS society, a non-profit organization and she is also sick. A president who has been known to be such. Nicoletta Mantovani, the widow of Luciano Pavarotti has been able to get in line and wait her turn. She did not "run away" abroad, as they must do in Canada, where the angioplasty intervention for obstructed neck veins is now on the agenda. She was patient like everyone else. Without utilizing the benefits that the money and fame could provide.
And today, as she confided in an interview published in People, she is "a woman reborn."
Tuesday, October 9, 2012
Annette Funicello and CCSVI
October 9, 2012 at 9:01am
This week, we've had a very black and white demonstration of the issues behind the manufactured "CCSVI controversy" and why there is no movement in the research of this vascular condition.
On the one hand, we saw Annette Funicello's lack of venous flow, as reported by Dr. Donald Ponec in San Diego, CA. Standing on camera with CTV reporter, Avis Favaro, and the images of Annette's jugular veins, Dr. Ponec discusses her case. In 2011, before treatment, Annette had only 30% flow through her right jugular vein and absolutely NO FLOW through her left jugular vein. Beyond that, the blood was refluxing on the left side of her brain, traveling through her brain and over to the right side in order to exit. No one, including Dr. Ponec, has any idea how long this flow pattern was occurring in Annette's brain, nor how a disturbed blood flow pattern like this could potentially harm her brain. All we know is that this is not normal, and slowed perfusion harms brain tissue.
Annette Funicello had CCSVI.
After venoplasty treatment and a restoration of normal flow through both jugular veins, her husband Glen sees color return to her face. She can now swallow on her own, her breathing is less labored. And we can only imagine what might have been if this brilliant woman had been diagnosed and treated in the beginning stages of her disease.
Was this story of America's sweetheart covered in the American press?
No. Not even one word.
How ironic that this story has to be told in the Canadian press.
Friday, September 21, 2012
September 21, 2012 at 9:07am
We've just learned that one target of BG-12/Tecfidera, the new oral super drug /furniture fungicide, and Nrf2 activator from Biogen, is oxidative stress. This drug uses the Nrf2 pathway to combat oxidative stress.
What is oxidative stress, and how does it impact multiple sclerosis?
I first started reading about oxidative stress when I began researching the Endothelial Health program to help my husband Jeff. I did this because his blood and body showed signs of oxidative stress. The following info is from the program.
Our bodies constantly react with oxygen as we breathe and as our cells produce energy. However, our use of oxygen is a double-edged sword: we need oxygen to survive, but as a consequence of using oxygen, highly reactive molecules, known as “free radicals,” are produced.
Free radicals are atoms or molecules with electrons which have lost their partner electron, often as a result of our respiratory or metabolic process, or from outside influences. Free radicals can disrupt the balance of nitric oxide, damage the endothelium and leave it overly permeable, allowing toxins to pass into our tissues9.
In most instances, our body has an adequate supply of antioxidants obtained from food to neutralize these free radicals, but if the body is depleted, or if there are too many coexistent factors, injury to the endothelium and a change in the balance of NO may occur.
People with MS have lower levels of antioxidants in their blood. It's a scientific fact, pwMS have serious oxidative stress.
Oxidative stress in patients with multiple sclerosis.
We have investigated the oxidative stress in the blood (plasma, erythrocytes and lymphocytes) of 28 patients affected with multiple sclerosis (MS) and of 30 healthy age matched controls, by performing a multiparameter analysis of non-enzymatic and enzymatic antioxidants--
In conclusion, the blood of patients with MS shows the signs of a significant oxidative stress. The possibility of counteracting it by antioxidant administration plus an appropriate diet, might represent a promising way of inhibiting the progression of the disease.
Oxidative stress in multiple sclerosis
Accumulating data indicate that oxidative stress (OS) plays a major role in the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS), leading to OS, generated in excess primarily by macrophages, have been implicated as mediators of demyelization and axonal damage in MS. ROS cause damage to main cellular components such as lipids, proteins and nucleic acids (e.g., RNA, DNA), resulting in cell death by necrosis or apoptosis. In addition, weakened cellular antioxidant defense systems in the central nervous system (CNS) in MS, and its vulnerability to ROS effects may augmented damage. Thus, treatment with antioxidants might theoretically prevent propagation of tissue damage and improve both survival and neurological outcome. Central nervous system is particularly susceptible to ROS-induced damage due to the high oxygen demands of the brain and low concentration of endogenous antioxidants.
There are many more published papers on MS and oxidative stress, and all of the end with something to the effect of ---gosh, we really should have more studies done on how antioxidants help keep pwMS healthy!
But no one does these studies, because there is NO MONEY TO BE MADE!!
You can simply go and eat more fresh fruits and vegetables, take some antioxidant supplements, vitamin D, stop smoking and drinking, exercise and take care of yourself.
This is what I explained to Jeff when our family started doing the Endothelial Health Program together. Dr. Terry Wahls, Dr. George Perlmutter and Dr. George Jelinek would tell you to do the same.
Now---how does oxidative stress fit into the CCSVI scenario?
Oxidative stress is actually found in all neurodegenerative disease---Alzheimer's, Parkinsons, MS and dementia. These diseases share two things that contribute to oxidative stress:
1. Iron deposition in brain tissue
2. Hypoperfusion, or slowed blood flow through the brain.
So, we can see that pharma is figuring out there's more to MS treatment. They've seen the papers on CCSVI research, hypoperfusion, oxidative stress and gray matter atrophy. But they will never tell you that in those words, because the want to keep selling you Tysabri, chemotherapies and other immune ablating drugs. They will, however, figure out a way to sell you a pill that addresses oxidative stress.
And you can bet your bottom dollar they are working on a drug to increase cerebral perfusion.
That's why we have to share this information, and help each other and those newly diagnosed with MS.
Because there is hope, but there will be no miracle pill.
Sunday, September 9, 2012
September 9, 2012 at 8:53am
It's important to work with your doctor and go through all of the differential diagnoses before accepting an MS diagnosis as final--especially before beginning a disease modifying treatment. For a list of 100 other diseases and medical situations which can be mistaken for MS, please see this publication:
It is apparent that diagnosing MS is not an exact science, but more akin to a process of elimination.
In the three years since I began writing about MS research, I've heard from readers originally diagnosed with MS, who were later told it was actually Celiac disease, low vitamin B12 levels, migraine, Lyme disease, ischemic disease, Hughes Syndrome, TIAs, co-infection with Cpn and other illnesses.
Please note, I do not question my husband's MS diagnosis. I question the characterization of his disease process as autoimmune. According to the McDonald criteria, he has MS. He has lesions disseminated in time and space, and had banding in his CSF.
But what is MS? Isn't is simply a diagnosis made by looking at symptoms, not aetiology?
Was Jeff's disease diagnosis related to his venous malformations and slowed collateral blood flow?
Here’s more on “undiagnosing MS” from a paper published in Neurology journal last year, authored by three neurologists. I purchased the paper to learn more, so I could share this information with you. It is entitled,
“Undiagnosing” multiple sclerosis: The challenge of misdiagnosis in MS
Three academic neurologists sent out a questionnaire to other academic neurologists in the US---they utilized names and e-mails from the Consortium of MS Centers registry and via google.
242 individual neurologists and 122 survey were completed--which resulted in a response rate of 50.4%
These neurologists were asked:
“Have you ever evaluated a patient who carried a diagnosis of MS (given by another provider) for longer than a year who, after your neurologic exam and review of lab data, you strongly felt did NOT in fact have MS?”
Nearly all respondents (95.1%) had evaluated such a patient in the past.
Over one-third (34.4%) reported seeing 6 or more misdiagnosed patients in the last year, including 20 (17.2%) respondents who had seen 10 or more such patients.
Saturday, September 1, 2012
Safety and Efficacy of Venoplasty for CCSVI-PUBLISHED RESEARCH
September 1, 2012 at 8:28am
Here is the list of published research on venoplasty for CCSVI. As the stack of publications grows, it is my hope that the media and medical establishment will refer to these studies, and the correct medical terms. This is no longer "controversial liberation therapy"
This is venoplasty, or endovascular treatment, for CCSVI.
Clinical Improvement after Extracranial Venoplasty in Multiple Sclerosis
Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients with multiple sclerosis.
Catheter venography and endovascular treatment of chronic cerebrospinal venous insufficiency.
Reported outcomes after the endovascular treatment of chronic cerebrospinal venous insufficiency.
Safety of outpatient endovascular treatment of the internal jugular and azygos veins for chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis: A retrospective analysis
Safety profile of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.
Endovascular treatment for chronic cerebrospinal venous insufficiency
The Hemodynamic Impact of Balloon Angioplasty in Multiple Sclerosis Patients with Chronic Cerebrospinal Venous Insufficiency
Evolution in quality of life and epidemiological impact after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis.
Venous angioplasty in multiple sclerosis: neurological outcome at two years in a cohort of relapsing-remitting patients
Endovascular treatment of patients with chronic cerebrospinal venous insufficiency and multiple sclerosis.
Venous angioplasty in patients with multiple sclerosis: results of a pilot study.
Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe?
For all the published research on CCSVI, please visit (and support) CCSVI Alliance
Saturday, June 30, 2012
June 30, 2012 at 10:34am
There is a new paper from the neurological division of UBC on the natural improvements and disease course that occur in pwMS who are NOT treated with disease modifying drugs. This data uses measurements from patients' birth, rather than MS onset. Researchers call these patients who never received disease modifying drugs "treatment naive"--and there are not many of these folks around to study anymore, so this paper is very important.
Here is what the study showed, from a recent presentation by lead investigator Professor Helen Tremlett:
The natural history of MS and implications for clinical practice
Professor Helen Tremlett, University of British Columbia Hospital, Vancouver, opened the conference with an overview of long-term natural history studies of MS in British Columbia. Data from this large cohort suggested progression of MS is slower than previously thought, which has implications for designing clinical trials and determining the long-term effectiveness of disease modifying therapies (DMTs).
Data demonstrated that by measuring time to outcomes from birth rather than from onset of MS men and women have similar disease outcomes (time to reach EDSS 6); an older age at onset is favourable; relapses do not affect long-term disability outcomes and early relapses only impact progression over the short-term. Whilst young patients with MS may gain long-term benefit from treatment with DMTs, older people may find limited benefit. Interestingly, MS relapse rates naturally decrease over time and a five year relapse-free period was common (occurring in 77% of people with relapsing remitting MS) independent of drug therapy.
Please note, this is all new info, and goes against common and current thought about MS disease progression--
Men and women have similar disease outcomes.
Older age at onset is favorable
Relapses do not affect long term diability
It's common to go 5 years without a relapse.
Relapse rates decrease over time, and older people will find limited benefit in DMTs.
Monday, June 25, 2012
June 25, 2012 at 1:47pm
I wanted to put together the research I've compiled for the cause of multiple sclerosis as a disease of primary neurodegeneration due to hypoperfusion with secondary reperfusion injuries. I felt it was important to document this research. I also want your input and thoughts.
The reason why MS relapses and remits during the onset of the disease has been difficult to understand, and impossible to replicate in animal models of MS. EAE, the current model for MS, is not like MS. EAE is more akin to ADEM, in that it does not relapse and remit. It's a constant immune reaction. I believe stroke and cardiovascular researchers, like Dr. John Cooke at Stanford, will be better able to create animal models of MS using perfusion--or blood flow. Immunology departments have had 60 years to model MS, and they still don't have it right.
Most of us know the word hypoperfusion---meaning the slowed or less than normal blood flow we see in the MS brain. It was a published theory of Dr. Bernhard Juurlink which first prompted my exploration into hypoperfusion and MS. I read his 1998 hypothesis paper in 2007, after Jeff returned from a trip to high altitude with dozens of lesions and an MS diagnosis.
Most of us know the word hypoperfusion---meaning the slowed or less than normal blood flow we see in the MS brain. It was a published theory of Dr. Bernhard Juurlink which first prompted my exploration into hypoperfusion and MS. I read his 1998 hypothesis paper in 2007, after Jeff returned from a trip to high altitude with dozens of lesions and an MS diagnosis.
Dr. Dake mentioned in a presentation at ISNVD how hyperperfusion (otherwise known as reperfusion injury) occurs BEFORE an MS lesion forms. He referenced this paper, which discusses how this perfusion change happens before the break in the blood brain barrier, before the immune system entry, before demyelination. The very first step is a change in perfusion. I wanted to know--why?
I believe reperfusion injury explains the relapsing remitting course of early MS and ties together Dr. Zamboni's research into CCSVI, collateral circulation and hypoperfusion in the MS brain. There will be an explanation as to how this theory functions in progressive MS at the end of this note.
Friday, June 22, 2012
June 22, 2012 at 12:04pm
For those who haven't had a chance to read about the history of the beginnings of the MS Society and the founding neurologist, Dr. Tracy J Putnam---here's a bit of background on the vascular history of MS.
The very latest research into multiple sclerosis is discovering what Dr. Putnam hypothesized. MS is created by a response from the vascular system to injury.
New research, published this month, continues Putnam's thesis, at the cellular level.
Something is signaling the vascular cells in the brain.
Here's how it works.
Astrocytes are beautiful, star-shaped cells that live in the central nervous system. ( I love the fact that our smallest cells look like the largest bodies in our solar system. There's wonderful symmetry in creation.)
Astrocytes are the most abundant cell in the human brain. One of the most important things astrocytes do is support the endothelial cells in our brain, and maintain the very important blood brain barrier. The blood brain barrier should have tight junctions, that don't allow blood particles into brain or spinal tissue. (For those new to the idea of the endothelium, please check out the Endothelial Health program I made for Jeff. It will explain how MS and our blood supply are connected.)
Researchers have recently noted that when the brain is subject to hypoxia, or low levels of oxygen, the blood brain barrier becomes open, or "permeable." This allows infiltration of blood cells and the immune system, which create damage to the brain. Please notice that if the blood brain barrier was not open, T and B cells would not have entry. The immune system isn't just going into the brain, uninvited and without cause. The gate is wide open.
Blood brain barrier (BBB) permeability is an early and prominent feature of inflammatory CNS conditions, including MS (13), viral encephalitis (14), and traumatic and hypoxic/ischemic injury (15). BBB disruption correlates with neurologic exacerbation, and MS patients with contrast-enhancing plaques are more likely to have irreversible pathology (13, 16). BBB breakdown leads to edema, metabolic imbalance, excitotoxicity, and ingress of factors that potentiate inflammation and inhibit repair (17–20) and facilitates infiltration of T and B lymphocytes, macrophages, and neutrophils (21). In diseases such as MS, current options to restrict relapse severity are limited, and patients may benefit from more selective agents (22).
What is going on? What signals the astrocytes to open the gate? Researchers are looking specifically at VEGF--vascular endothelial growth factor.
Studies have identified astrocytes as regulators of BBB induction and maintenance (9–11) and have implicated astrogliosis, particularly induced by IL-1, as a driver of both BBB breakdown and repair (10, 12, 48). The mediators producing the effects of reactive astrocytes are incompletely characterized, and our data revealed VEGF-A as an important astrocyte-derived inducer of BBB disruption and pathology in vivo. Although VEGF-A–induced vascular permeability has previously been implicated in pathogenesis of disorders, including myocardial infarction, CNS hypoxia/reperfusion injury, and tumor growth and metastasis (49), and we and others have previously speculated on its role in BBB breakdown (12, 26), this study is the first to our knowledge to show the significance of astrocyte-derived VEGF-A in lesion pathogenesis and generation of clinical deficit in models of CNS inflammatory disease.
This is the first study that has noted the importance of astrocyte derived VEGF in the formation of lesions and brain damage in a model of MS.
Please note the other diseases that have VEGF created "vascular permeability"--hypoxia and myocardial infarction--are vascular diseases. VEGF-a is activated in situations where there is low oxygen, and the organ begins to suffer the effects of low O2.
So, what is VEGF and why does it matter in MS?
Vascular endothelial growth factor (VEGF) is a chemical signal produced by cells that stimulates the growth of new blood vessels, called "angiogenesis." This is part of a system which restores the oxygen supply to tissues when blood circulation is inadequate.
VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, and new vessels (collateral circulation) to bypass blocked vessels.
Here is a rather pejorative look at the vascular connection, written in a condescending tone by a group of German Neurologists--
Vascular pathology in multiple sclerosis: mind boosting or myth busting?
The idea of MS being a vascular disease is not new. In the 1930s T.J. Putnam proposed venous obstruction as the primary alteration in MS . Given the venotopic localization of MS plaques, this hypothesis has been discussed on and off ever since. In 2007 an Italian group headed by P. Zamboni added new fuel to the fire by demonstrating that venous blood flow alterations can be found at a high frequency in MS patients .
While the concept of CCSVI has gained much attention in the field of MS research and in particular among MS patients, there is increasing evidence that the relation of venous changes to the pathophysiology of MS may not be as simple as initially described. Most importantly, new MR imaging techniques add to the notion of vascular changes in MS, yet again raise doubts whether these alterations are cause or rather consequence of the disease process.
(At the end of the article, the authors state they have nothing to disclose, yet all of them have participated in many MS drug trials. Drugs which are based on the EAE immune model of MS- Dr. Linker has received personal compensation for activities with Bayer Health Care, BiogenIdec, Merck Serono, Novartis and TEVA Pharma. Dr. Linker has received research support from BiogenIdec, Novartis and TEVA Pharma.)
Why is it only neurologists who believe some "mystery mechanism" disease process is behind VEGF activation, blood brain barrier disruption and inflammation---when we have other models of vascular disease in vivo, such as stroke, which illustrate how hypoxic injury creates this scenario?
If MS specialists want to continue to pretend there is no vascular involvement in MS, and that MS is a disease of a mysterious and crazed immune system, they can keep saying it-- and creating, testing and selling the drugs. But the truth is, all of the research continues to point to the importance of the endothelium and the vascular response of the body to injury of the brain.
What's causing the injury? Slowed flow through the brain, hypoperfusion, low O2 and glucose levels from collateral venous return? Makes sense to me. More to come.