Hope in China-- a new clinical trial

Over the past couple of years, I have been following a group of Chinese researchers from the Beijing Institute for Brain Disorders.   This group is using stents to repair slowed jugular venous flow, reduce collateral veins, improve intracranial hypertension and cerebral perfusion in a variety of patients.

My interest in this area comes from the fact that my husband was treated this same way in 2009.  His benefits from jugular stenting continue, as he has had no new white matter lesions.  He sleeps soundly, dreams, and wakes refreshed.  He had a huge reduction in headache.  His visual loss has ceased.  His fatigue has been reduced.  His gray matter atrophy has been reversed.  He has had no MS progression in eleven years.
Here is the publication on his treatment at Stanford
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164629/

The Beijing Institute for Brain Disorders was founded in 2012, in the hopes of using new technologies to prevent and repair neurological disorders.  The group of neurosurgeons have published  that jugular venous stenting is a safe and effective procedure, which is helping a variety of patients with neurological disorders.

They have seen intracranial hypertension, headache, visual disturbances, and tinnitus improved in 15 patients who had stents implanted in their jugular veins.
https://www.ncbi.nlm.nih.gov/pubmed/29114973

Because of their preliminary study, this group is now undertaking a randomized clinical trial in Beijng with 60 participants, utilizing stents in jugular veins of patients with jugular vein stenosis.  link to clinical trial

Here is what they will be looking at over the course of one year.  (Please notice how the secondary outcome measures are similar to measures used in Multiple Sclerosis clinical trials--and similar to my own husband's benefits from treatment.)

            ++++++++++++++++++++++++++++++++++++++++++
Primary Outcome Measures  
Correction of internal jugular vein stenosis (IJVS) and abnormal collateral veins 
[Time Frame: baseline, 1, 6 and 12 months ]
The status of internal jugular vein blood flow and collateral veins will be evaluated by imaging modalities, mainly including: Jugular Vein Doppler Ultrasound, Magnetic Resonance Venography (MRV), Computed Tomography Venography (CTV) and Digital Subtraction Angiography (DSA)

Secondary Outcome Measures  :
The evaluation of cerebral spinal fluid (CSF) pressure 
[Time Frame: baseline, immediately post-stenting, within 1 month ]
CSF pressure will be assessed by lumbar puncture

The evaluation of headache 
[Time Frame: baseline, within 1, 6 and 12 months ]
The intensity of headache will be assessed with the Headache Impact Test-6 (HIT-6  The evaluation of tinnitus [ Time Frame: baseline, within 1, 6 and 12 months ]
The severity of tinnitus will be assessed by the Tinnitus Handicap Inventory Questionnaire (THIQ)

The evaluation of the severity of papilledema and other ophthalmological conditions 
[ Time Frame: baseline, within 1, 6 and 12 months ]
The severity of papilledema will be assessed based on Frisén papilledema grade (FPG) criteria; the assessment of other ophthalmological conditions including visual acuity, visual field, and fundus etc. will be based on visual acuity chart, visual fields picture, and optical coherence tomography (OCT) etc.

Changes in cerebral white matter (WM) 
[ Time Frame: baseline, within 12 months ]
The characteristics of WM will be evaluated by Magnetic Resonance Imaging (MRI).

The evaluation of cognitive function [ Time Frame: baseline, within 12 months ]
Cognitive function will be assessed with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and/or the Modified Telephone Interview for Cognitive Status (TICS-M).

The evaluation of mental status [ Time Frame: baseline, within 12 months ]
Mental status will be assessed with the Hospital Anxiety and Depression Scale (HADS). The HADS score ranges between 0 and 21 for either anxiety or depression. A cut-off point of 8/21 is indicated for anxiety or depression.

The evaluation of sleeping status [ Time Frame: baseline, within 12 months ]
Sleeping status will be assessed with the Pittsburgh Sleep Quality Index (PSQI) and/or the Athens Insomnia Scale (AIS). The PSQI score provides an overall score ranging from 0 to 21, where a cut-off score of ≤5 denotes a healthier sleep quality. The AIS score provides an overall score ranging from 0 to 24, where a cut-off score of <6 denotes a healthier sleep quality.

The extent of disability or dependence in the daily activities 
[ Time Frame: baseline, within 12 months ]
The extent of disability will be assessed by the modified Rankin Scale (mRS). (Score 0-no symptoms; score 1-no significant disability; score 2-slight disability; score 3-moderate disability; score 4-moderately severe disability; score 5-severe disability; score 6-dead.)

                             +++++++++++++++++++++++++++++++++++++++++
Finally, here is a brand new published review from this same group, 
"Understanding jugular venous outflow disturbance."
link

I have read the full paper, and am confidant that this research group knows what they are doing, what they are looking for, and what the stakes are.  By removing Multiple Sclerosis from the equation, they will be able to proceed, without the interference of pharmaceutical interest--which has daunted the study of CCSVI.

Thanks to the Beijing Institute for Brain Disorders for taking on this very important study.

Joan

The brain contains 400 miles of blood vessels....

A year after Jeff was diagnosed with Multiple Sclerosis, I wrote several university researchers regarding MS as a vascular disease of endothelial dysfunction.  One of these researchers was at my alma mater, the University of Rochester.  I had first read about his work in our alumni newsletters, and later on pub med. link

Berislav Zlokovic was initially inspired to understand the blood brain barrier's role in neurodegeneration after losing a dear friend to ALS.

"The vascular system is crucial to health -- it's how oxygen and other nutrients are delivered to cells, and how toxins are removed," said Zlokovic, who is professor of Neurosurgery and Neurology and director of the Center for Neurodegenerative and Vascular Brain Disorders. "Any damage to the vascular system is a serious threat to the organism. It's clear now that the vascular system is certainly involved in the development of ALS."

Zlokovic first began doing research on the disease in 2004, when a former classmate from medical school who had been diagnosed with ALS and was looking for new treatments contacted him. By the time his friend died two years later, Zlokovic was well underway in studies investigating the possible role of the vascular system. link

He has been one of the premiere researchers looking at how the vasculature is implicated in the breakdown of tight junctions in all diseases of neurodegeneration.  I wrote to him about Dr. Swank's prior research on capillary fragility, and how I thought it made sense when observing the petechial bleeding on my husband's legs, his enhancing MS lesions on MRI, and the possibilty that the cause of both was systemic endothelial dysfunction.
(Swank RL. Subcutaneous hemorrhages in multiple sclerosis. Neurology. 1958; 8: 497-498.)

Dr. Zlokovic did not reply to my intial inquiry, but we did eventually connect after his presentation at the ISNVD as the keynote speaker, 2011 in Bologna.  He soon left the U of R for the University of Southern California's Keck School of Medicine.

I was thrilled to see that his lab has recently received $25 million in grants to study how leaky blood vessels in the brain contribute to Alzheimer's Disease.  link

Berislav Zlokovic, MD, PhD, a pioneer of the theory that fixing the brain’s leaky blood vessels will prevent Alzheimer’s disease, has received four grants totaling up to $24.9 million over five years.

The funding allows Zlokovic, director of the Zilkha Neurogenetic Institute, to attack from different fronts the blood-brain barrier, a gatekeeper that prevents toxic substances from entering the brain.

“The brain contains 400 miles of blood vessels that can stretch from Los Angeles to San Francisco,” said Zlokovic, chair and professor of physiology and biophysics at the Keck School of Medicine of USC. “If there is a leak along this vascular tube and the pothole is, for example, near the hippocampus — the center of learning and memory — that can contribute to the development of dementia and Alzheimer’s disease. We can delay the onset or slow the progression of Alzheimer’s if we are able to fix leaky capillaries when they first start, some 10 to 15 years before Alzheimer’s symptoms even surface.”

But at the same time, I'm deeply saddened by the realization that we are still in this same place----sixty years after Dr. Swank first noted leaky capillaries and petechial rashes in people with MS and successfully treated this issue in many patients with diet and exercise. link   Thirty years after Dr. Franz Schelling discovered the venous connection to MS and inspired Dr. Paolo Zamboni to look at jugular reflux in people with MS.  link  It sometimes feels like an endless cycle of discovery and amnesia, as researchers uncover, and then willfully bury or forget the vascular connection to diseases of neurodegeneration.

“The blood-brain barrier’s leaks allow many blood-derived toxic products, cells and pathogens to enter the brain and directly damage brain circuits involved in memory and learning,” Zlokovic said. “Additionally, bad proteins that normally are ejected from the brain, such as beta-amyloid, have to struggle against the flow of traffic. This situation can eventually lead to ‘a second hit’: Beta-amyloids and tau tangles remain in the brain and cause damage that become evident years later.”

The research will determine the structure of the perivascular space, how cerebral brain fluid reacts to changes in brain equilibrium and blood-brain barrier leakage. The ultimate goal is to identify therapeutic targets for the treatment of small vessel disease of the brain, which may contribute to cognitive impairment.

I honestly hope Dr. Zlokovic and his team find new therapeutic targets.  They sure have a bunch of money to do so.  However, researchers might do well to also look at mechanistic issues behind these leaky blood vessels.  Venous hypertension and CCSVI were contributing to the breakdown of my husband's blood brain barrier.   Venoplasty to repair his jugular veins resulted in disease reversal for him--with no new lesions and a reversal of gray matter atrophy.   The spots on his legs, and the spots in his brain were connected.  Diet and exercise have continued this virtuous cycle of healthy cerebral perfusion, shear stress, and endothelial cell health. 

Don't wait for this ongoing research loop to end with some new blockbuster drug.  There are things you can do today, to help heal your endothelial cells and limit the breakdown of capillaries.
Promise.   link


Joan

Vascular factors affect MS disease progression

I know, I know.  You'd think it would be obvious by now that the heart and brain are connected, and that vascular health has an impact on MS disease process.   But in the 10+ years I've been following MS research, it seems as though researchers are continually surprised when they learn that cardiovascular comorbidities have an impact on MS progression.

There are two new research papers from Canadian MS specialists, published in the AAN journal Neurology, which have found a connection between blood flow and MS progression.  I am thankful to know that Dr. Helen Tremlett's team continues to look at this connectivity--- but frustrated by the lack of recommendations being made by MS Societies and MS specialists regarding lifestyle interventions like nutrition and exercise.  There is still a huge disconnect.

The first paper found that people with hyperlipidemia (which is an abnormally high content of fats in the blood---measured by LDL cholesterol numbers)  and migraine had an increased MS relapse rate.  
Link to "Comorbidity increases the risk of relapse in MS"

The second paper also looks at cardiovascular comorbidities, like ischemic heart disease and found a link in disease progression and disability.  link to "Effects of physical comorbidities on disability progression in MS"

The Centre for Brain Heath in Canada has recently published an article on this research, in which Dr. Tremlett says---

"Our findings suggest that if you could alter the trajectory of a comorbidity, you may be able to improve outcomes in MS.”
link

And how do patients reduce heart disease, lower their LDL cholesterol, improve vascular comorbidities?   Well, no surprise here.  Researchers don't want to say, they would like funding for more research.

“This suggests that we may need to take a more holistic approach to managing MS and related comorbidities,” says Dr. Zhang. “Effective treatment for each comorbidity may reduce disability risk. We need more research to identify the most appropriate treatment approach for each comorbidity in MS.”

Information for the disability progression study came from health administrative data across Canada, with nearly 30 years of anonymized clinical records providing detailed insight into the relationship between comorbidities present before and after MS symptom onset and disability progression over time.

Dr. Roy Swank published on ALL of this in the 1950s.  And he was routinely mocked by MS neurologists who felt that MS was an autoimmune disease which could not be altered by diet and lifestyle.  But they were wrong.   link

Don't let another 60 years go by.  Take control of your life, your own health today.  Eat a heart healthy, colorful diet full of plants, move as much as you can, get UV rays, decrease stress and increase laughter.  Get good sleep, don't smoke, stay involved in community and learning.  Because science shows that these things can make a difference in your MS disease process.  link

The heart brain connection is real.

Joan

New research on cholesterol clearance and MS

Long-time readers of this blog will remember a variety of posts on fats, lipids, cholesterol and inflammation in multiple sclerosis.  It was Dr. Roy Swank's research on ingestion of animal fats and the changes to the vascular system which first interested me in this connection.  Once again, what is old in MS research is new.

Research published this week from the Technical University of Munich explores how the degredation of myelin leaves a destructive cholesterol residue in the brain, which increases an inflammatory response and blocks myelin regeneration.  It appears that with age, the process of transporting cholesterol out of the brain becomes less efficient.  (Important to state that this research was done on a mouse model of MS.)

"Myelin contains a very high amount of cholesterol," explains Prof. Simons. "When myelin is destroyed, the cholesterol released has to be removed from the tissue." This is performed by microglia and macrophages, also referred to as phagocytes. They take up the damaged myelin, digest it and transport the non-digestible remainder, such as cholesterol, out of the cell by transport molecules. However, if too much cholesterol accumulates in the cell, cholesterol can forms needle-shaped crystals, which cause damage the cell. Using a mouse model, Simons and his team showed the devastating impact of the crystalline cholesterol: It activates the so-called inflammasome in phagocytes, which results in the release of inflammatory mediators, attracting even more immune cells. "Very similar problems occur in arteriosclerosis, however not in the brain tissue, but in blood vessels," says Simons.
link

Although cholesterol synthesis in the brain is considered a different process than cholesterol synthesis in the rest of the body, lower plasma levels of HDL cholesterol have been found to be related to MS.  Cardiovascular researchers have been looking at this fact, in relation to the heart brain connection.  

HDL plasma levels have also been associated with other neurodegenerative diseases such as multiple sclerosis (MS).74 Patients in the acute phase MS have been reported to have lower HDL-C levels compared with those in the remission phase, and they show a higher probability of developing acute inflammatory lesions (assessed by MRI).74–768 Moreover, HDL inhibits cytokine-induced expression of adhesion molecules in endothelial cells.72
link

Why are HDL levels important?  Because HDL, also known as "good cholesterol", contains the transport protein ApoA1---needed to take cholesterol out of the blood and tissue.

Here's more research on low levels of ApoA1 found to be linked to MS severity.  The lower HDL
ApoA1 plasma levels, the more severe the disease. 

ApoA1 was reduced by approximately 25% in patients with relapsing-remitting MS, 50% in those with secondary progressive MS, and 75% in patients with primary progressive MS, the most severe form of the disease. link

Here's a whole blog post from 2013 on "Good" cholesterol and your brain
link

While we wait for researchers to create their cholesterol transport block buster MS drug, or to repurpose things like statins (please, don't go there, so many side effects!)---there are things pwMS can do today, to encourage this process in their own bodies, by increasing your HDL levels with lifestyle.

1. Don't smoke.  Quitting smoking will increase good cholesterol by 10%

2. Lose weight.  Extra weight depletes HDL.

3. Exercise.  Within 2 months of regular exercise, you can increase your HDL by 5%

4. Choose healthier fats for your diet. Avoid transfats and saturated animal fats.  Choose omega 3s and monosaturated fats found in nuts, olive oil, and fish

5. Add fiber to your diet--lots of fresh fruits and vegetables, legumes and oats

6. Limit alcohol consumption.

link

7. Check your vitamin D, magnesium, calcium and zinc levels--make sure they are in balance.
link

Keep an eye on the latest MS research.  

It continues to affirm the heart-brain connection, and the importance of living a vascularly healthy life.

Be well,

Joan