Brain Drain

2015 is a watershed year for our understanding of brain drainage.  A lymphatic system for the central nervous system has been discovered.  For two centuries it was thought none existed, its absence the second pillar of the blood-brain barrier.  Now, a full-fledged lymphatic network it has been identified microscopically, hidden in the walls of the dural meninges of the venous sinuses that drain blood from the brain into the internal jugular veins.   The research also demonstrated the transport through these lymphatic vessels of white cells, including T-cells, and CSF immune macromolecules.  In 2015 another brain drainage system was also discovered.  Coined the glymph system it permits the drainage of the interstitial fluid that surrounds brain cells to flow out between the astrocyte foot pads surrounding CNS capillaries and venules.

Neuro-immunology will change, having failed for half a century to document auto-immunity or in fact any direct attack by the immune system on healthy myelin.  The discovery of a brain lymphatic drainage system opens a new front on the advances in understanding brain perfusion and venous drainage.  Do these newly discovered systems function normally in multiple sclerosis?

Few internal jugular venoplasties are performed for MS currently, primarily because of the high re-stenosis rate, 30-50% of patients have a return of their pre-venoplasty symptoms and ultrasound shows the vein obstructed again.  We are waiting for better methods to keep the veins open.  But why venoplasty helps so many patients is still an open question.  Does the discovery of the brain’s lymphatic system, which drains into the internal jugular veins, provide us clues?  Previously it was theorized that venous hypertension resulted from the jugular narrowing, or that sluggish flow in the venules allowed red cells and iron to cross the blood-brain barrier inciting inflammation.  Now we can ask if Paolo Zamboni’s theory of chronic cerebrospinal venous insufficiency is associated with a lymphatic insufficiency as well.  We can expect soon to know what cells and proteins are passing through these lymphatics and how they affect the oligodendrocytes that make myelin, and how lymphatic flow relates to venous flow.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14432.html

http://jem.rupress.org/content/early/2015/06/09/jem.20142290.abstract

ISNVD FEB 9,2014

ISNVD Feb 9,2014
Day 2
Nitric Oxide and Vascular Hypothesis in MS
Dr Yulin Ge
Diffuse Inflammatory activities
NO
inhibit mitochondria aerobic respiration and neurovascular coupling tiring out leas to decrease of oxygen consumption
leading to hypoxia
 leading to hypo-perfusion  an d to neuronal/axonal dysfunction and neurodegeneration

apoptotic cell death of oligodendrocytes at later stages of lesion development
measuring NO effects using MRI
effects on oxygen metabolism
effects on oxygen delivery
Facts of oxygen metabolism in brain
brain uses 20% of total oxygen
oxygen delivery..
oxygen consumption in MS is decreased
oxygen metabolic abnormalities in MS measured with TRUST MRI
why is there is less oxygen consumption in MS
it's not only atrophy but it's because of the mitochondria has high levels of NO
BOLD...
CO2 like NO is a  potent vasodilator and can cause increase of CBF
compared to controls MS showed significantly decreased CVR
The CVR defect inMS...impaired vasculaar regulation of blood flow supply or defective neurocoupling mechanism may affect effective oxygen delivery
decreased CMRO2 in MS and decreased CVR inMS
recent accumulating evidence of mitochondrial of/NO hypotheses in neuronal axonal tissure damage
both O2 delivery and O2 uptake impairment can lead to chronic hypoxic condition
NO is not the only mechanism that is responsible to neurodegeneration
the increase in NO may be from the endothelium or microglia( as a result of infection) but either is due to inflammation

Perfusion imaging in stroke
Its current clinical status and its role in treating patients
Dr Larry Latour

there is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke
what is a mini stroke and being treated with tPA?
15 minutes makes a difference in the treatment of an acute ischemic stroke. It is safe to reat even if it's a mimic of a stroke...as the treatment can prevent a stroke




Hemodynamic impairment in MS...Imaging techniques and perspectives
Yulin Ge
vascular hypotheses has been around for numerous years
pathology in MS...vascular
perivascular inflammation...Dawson's finger...new lesions start around abnormal vessels
first imaging sign of lesion formation
 BBB breakdown and increased permeability
with effective anti inflammatory drugs
first sign is prominent perivenular space using 7T MRI
perfusion MRI
detect abnormality before lesion
increased perfusion in NAWN just before lesion formation
venous dilation in initial inflammatory stage... priminet venules companied with increased perfusion
enhancing lesion with increased perfuion
new or recurred lesion activity that are not seen on conventional MRI
the is hemodynamic impairment in MS
fibrin deposition, small venous thrombosis, intimal hyperplasia
there are lesions with different type of perfusion patterns
significantly reduction of perfusion in deep GM in MS
vascular component is critical in neurological disease
MS patients with cardiovascular problems have increased MS problems




SPECT and PECT perfusion changes after CCSVI restoration
Paolo Zamboni

diffuse hypo-perfusion in MS is a FACT. It cant be explained with autoimmunity but CCSVI is a valuable hypothesis
hypo-perfusion precedes plaque formation approx 2 weeks earlier
chronic plaques were more prevalent in WM regions with lower relative perfusion.  can ccsvi be a strong contributor to hypoperfusion. may outflow restoration restore brain perfusion
the data support a role of ccsvi in cerebral hemodynamic changes, such as a decreases of CBV and CBF regardless of diagnosis of MS
theres is a relationship between brain perfusion and jugular flow
flow reduction in and significant flow increase in collaterals
the collateral veins drain blood respect to ED inflow to the head
are the collateral veins filled by premature intra extra cranial anastomosis?
hypo-perfusion may be consequence of  blood shunting through meningeal arteries
pilot study with 5 ccsvi cases...not only MS
used PET scan.
3 patients who improved with venoplasty ...one of them had Huntington disease had improvement of perfusion
pilot study 2 using SPECT using open angioplasty
8 ccsvi cases
vast majority of patients improved flow
PET and spect both reliably detect change in perfusion in ccsvi
spect demonstrate hypoperfusion in ccsvi
the procedure seems to cause significant improvement


The rest of the morning session was devoted to traumatic brain injury:

Abstract...cerebral hemodynamic changes in mild traumatic brain injury at the acute stage

Abstract...altered IJV hemodynamics and impaired cerebral auto-regulation in patients with panic disorder
PD patients have decreased IJV lumen

Traumatic brain injury and vascular consequences
state of the art understanding the fundamental physiology of TBI...from research to treatment

Dr Ramon Diaz Arrastia
single most common cause of death and permanent disability in young people under 45
10%-15% of pts with TBI have micro blood vessel injuries
there is also diffuse meningeal injury
 chronic mild tB of retired professional boxers
cerebral blood flow is normal but the reactivity of the blood vessels is impaired
Treatment:
Sildenafil,erythropoietin, statins, G-CSF, VEGF, pioglitazone, exercise , enriched endothelia progenitor cells, from cord blood or bone marrow, low level laser light therapy, Infrared can penetrate the skull.
It has anti inflammatory properties and promotes angiogenesis and releases NO
people who have had TBI in early life have an increased risk of dementia in later life.


Typical vascular lesions of TBI and their evolution
Dr Gunjan Parikh
brain micro vascular tree
the first thing hit is the dura and cortex
prospective study of acute TBI in the ED with blood on clinical CT or on MR
256 subjects had indications of hemorrhage
all were considered mild TBI



The clinical spectrum and natural history of TBI Sequelae
Dr Karen Tung

role of perfusion and SWI in TBI
how TBI and how it relates to the micro vasculature of the brain
neurovascular unit NVU
TBI damages the vessel wall or causes impaired perfusion and cause tissue ischemia
BBB dysfunction results in edema and may affect protein clearance and accelerate brain aging or disease pathology


State of the Art...the role of imaging and venous abnormalities in TBI
Dr Zhifeng Kou

Abstract...Hemorrhagic lesions based on venous and arterial damage and its clinical correlation in Traumatic Brain Injury
Hardik Doshi


Abstract...Thalamic Shape and Cognitive performance in amnesic mild cognitive impairment
Hyun-kook Lim

It is my understanding that the ISNVD will provide summaries of each of the presentations in a few weeks.

ISNVD Feb 8,2014

ISNVD Feb 8, 2014
Session I. A multi-Modality Approach to Extra Cranial Venous Disease
Dr Zivadinov session chairperson
1. The Current Status of Ultra sound Imaging for the Screening of CCSVI...Dr Marcello Mancini...Univ. Naples
ccsvi can be non invasively diagnosed by combined transcranial and extracranial echo doppler
CCSVI more frequent in MS than in normal controls
Italian study 1800 subjects
the assessment of CCSVI was highly operator dependent... the echo color doppler is an ideal tool for assessing cerebral venous return

What is the Normal Jugular Vein Valve Function?....Dr Erica Menegatti
using echo doppler they were able to see the motility of the IJV valve leaflets in healthy volunteers
findings 50% showed absent valve on 1 side
in healthy subjects in IJV leaflets are always mobile and open in up right position
62% of HC with valve absence at least of one side suggests a progressive loss of motility.


Prevalence of Extracranial Venous Narrowing on Catheter Venography in pwMS
Dr.Lindsay Machan
CCSVI more prevalent in pwMS?
BC Saskatchewan study...published in Lancet
evaluate the frequency of venous stenosis in pwMS vs controls, and siblings of MS patients.
ultrasound trained in Ferrara and used the Zamboni criteria
the subjects were blinded
the venography protocol was developed with Gary Siskin, MD and an SIR discussion group
standardized upright and supine venography measures
no significant differences in each group but MS patients felt moderately better.
Dr Zamboni challenged this study!!!!

Identifying CCSVI with Cervical Plethysmography
Paolo Zamboni
measured in normal controls
hydrostatic gradient in cerebral venous outflow
upright there is negative hydrostatic pressure
zero hydrostatic pressure in supine
posture shows restricted venous outflow in ccsvi vs normal when the system is stressed through change in position
the system fills up quicker because the outlet pathways are restricted in CCSVI


Diagnostic Contributions of Catheter Venography for Screening of CCSVI
Dr Hector Ferral
limitations of catheter venography is radiation exposure contrast media and may miss subtle issues.
review the Venographic protocols of CCSVI
reviewed 8 papers.
R femoral vein is the easiest access
power injection most popular
Delayed emptying is an important criteria...greater than 6 sec is severe
patients with severe stenosis had emptying between 6 and 27 sec
proposal:
r femoral vein( Dr Zamboni said in PPMS the L entrance is better)
catheter straight multi-perforated
contrast depends on IVUS availability
injection...Power injector
position of pt is supine
multimodal approach is important

What Additional information Can Intravascular ultrasound Provide?
Adnan Siddiqui
looked at azygos and IJV
blinded evaluations
IVUS  is the best evaluation tool and was compared to catheter venography

Molecular Markers of Abnormal CNS Hemodynamics
Dr. Steven Alexander PhD
endothelial cells are important they create the bBB
abnormal pressure patterns.. links to neurodegenerative disease.Vascular stress is related to neurodegenerative disease. intra abdominal hypertension disturbs BBB
endothelial cells under shear or stress release micro-particles can affect distant gene expression
APP is associated with neurovascular disease and is a precursor to amyloid
oscillating shear causes increased APP which is released into the brain.
altered pressure can rapidly and reversibly modulate BBB
Different shear patterns alter brain endothelial transcription factors
Some transcription factors and microRNA's between cells as a novel form of distant site epigenetic modification
APP is released by brain endothelial cells and is packaged into micro-particles
Differential transfer of APP laden micro-particles may contribute to several forms of neurovascular degeneration

State of the Art1: Why we need a multi-modality diagnostic approach for CCSVI
MR, catheter venography, ultra sound, and IVUS all have positive aspects.
PREMISE study used a multi-modality approach
ISNVD has a position statement for the screening for diagnosis of CCSVI
Two abstracts were presented:
Abstract 1: Extracranial brain draining veins in a mouse: Assessment by high resolution ultrasound and MR angiography of the neck
Brain drains from the external jugular in the mouse and in humans it is IJV's

Abstract 2:  Inverse relationship between IJV narrowing and increased brain volumes in healthy individuals
IJV narrowing has been implicated in CNS pathologies
Similarly brain volume reduction...atrophy...has also been linked to CNS pathologies
However, IJV narrowing and atrophy have never previously been linked
Assessment of the relationship between IJV CSA and atrophy in healthy individuals
the hypothesis is increased narrowing...stenosis...would correlate with increased atrophy...reduced brain volume
Secondary outcome is assessment of age effects and cervical location on these potential associations
IJV narrowing was not associated with brain atrophy...mechanism unknown
Dr Ziv Haskal Moderator
Designing an endovascular trial...What elements are essential and why CCSVI trials might differ from Disease Modifying trials
Dr Kottil W. Rammohan...Neurologist Univ. Miami(director of MS center)
what is the short term effect of the procedure
Long term benefits....as a stand alone or adjunct to a disease modifying treatment (DMT)
any trial has to be blinded
no trials have been done that meets the test of Cochran Review .
Essential elements of all clinical trials.
evidence, population, intervention. comparison, outcome , time (EPICOT)
Defining CCSVI is the biggest problem
Should use ambulation as an evaluation tool
"having an open label trial is unconscionable"


State of the Art :Current results of safety and efficacy of CCSVI therapy in MS patients
Gary Siskin (Dr Dake presented)
studies have demonstrated very low adverse events with venoplasty. It is a very safe procedure
Efficacy
improvement in a majority of patients but not all. Patients with severe delayed flow did not do as well as those with moderately delayed flow
EDSS at one month and one year significantly improved
cutting balloons are safe for those patients who had failed venoplasties.



Procedural Endpoints.  How to Best measure Meaningful Flow Impairment, Inter and Post Procedural Therapy
Hector Ferral
 IVUS Driven Intervention..provides accurate information of vascular pathology shows, webs, valves, dissection, intramural problems.
Optimizing Pure Venographic Therapy :  there is no validated approach

Intervention Studies in 2014
The Time is Ripe for Primary and Replicative Therapy Trials in MS
Ziv Haskal
science is not linear, often not in types of therapeutics
what happened in MS and CCSVI?
the venoplasty is less dangerous than present treatment (DND's)
it's time for more research

Therapy Trials Need to Wait. The Landscape has changes
Dr Kottil W. Rammohan
Are we ready to do a randomized controlled trial? Dr Zamboni's trial was replicated by Dr Troulbasse and could not reproduce the same results in Vancouver.
Dr Hubbard and challenges Dr Rammohan and says MS has not been proven to be immune modulated.

Abstract 3...A report of 4 cases of anterior cranial fossa dural arteriovenous fistula: surgical consideration and technique using intraoperative indocyamine green angiography.
Kuhyun Yang,MD


Abstract 4...Classification of venous outflow in the extracranial vessels in a large cohort of MS patients.
Sean Sethi...with Dr Haacke's research group
4th study  showing abnormal flow in the IJV
used MRi and assessed the the IJV
MS subjects wer classified as stenotic or non stenotic
did flow quantification at c2/c3 and c5/6
61% of the MS were stenotic

CCSVI and Parkinson's
Mark Haacke
In MS patients, iron deposition occurs in both the basal ganglia and midbrain similar to what is seen in idiopathic Parkinson's Disease.
23 PD patients and 23 Normal Controls
there are abnormal structural and flow findings in PD patients.

Etiologies of jugular venous abnormalities in transient monocular blindness
Dr Chun-Yu Cheng
sudden painless transient visual loss
there is venous outflow resistance in the IJV
IJV stenosis is found in in transient monocular blindness

Age Related White Matter Changes, Alzheimer's Disease and Jugular Venous Reflux
Dr Clive Beggs
Pilot study and IJV reflux.
JVR is associated with age related white matter changes, particularly in posterior brain regions.
12 pts with AD 17 healthy controls 24 mild cognitive impairment
dirty appearing white matter is a region of intermediate signal intensity between that of T2 lesions which may develop into lesions later on.
AD patients had significantly reduction of dirty white matter, and increased lesion formation

JVR and brain atrophy
increased brain volume in grey and white matter...
venous blood pooling is a possiblity

Cerebral venous drainage impairment in idiopathic intracranial hypertension
Dr Noam Alperin
venous drainage in supine and upright postures
in the upright posture, venous drainage shifts from the jugular to secondary veins and is significantly less pulsatile

Headache and venous abnormalities
Dr Wei-Ta Chen
vein related cerebrovascular disorders with headache
cerebral venoos thrombosis
vasculitis
arteriovenous malformation
dural arteriovenous fistula
carotid cavernous fistula
Headache disorders with venous abnormalities
idiopathic intracranial hypertension
spontaneous intracranial hypotension
migraine.
IIH is not benign...they may lose vision
treatment IIH
endovascular stenting is one tx option
spontaneous intracranial hypotension=
orthostatic headache, neck tightness, subjective hearing symptoms
evidence of CSF leakage on imaging
TX of SIH:
bed rest, hydration, epidural blood patch
Migraine
unilateral, throbbing,associated symptoms are nausea, photophobia and phonophobia, duration 4-72 hrs
aura...visual, sensory, aphasia,motor
if you compress bilat IJV it can make migraine worse.
IJV volume increases during attack
decreased in IJV compliance in migraine
venous hypertension occurs during a migraine



venous abnormalities involve in high altitude associated neurological disorders
Dr Mark Wilson
what happens when you are gradually exposed to increased altitude?
can get a headache, mountain sickness or
high altitude cerebral edema
those with HA's had large  venous sinuses
being in space is not good for your eyes due to venous hypertension

Cerebral venous drainage impairment and cerebral small vessel disorders
Dr Han-Hwa Hu
CVDI linked to small artery disease
association with impaired cerebral auto-regulation
association with lacuna stroke
association with white matter diseases

There were a couple of presentations that followed but because of my "brain overload" I decided to take a break.
Will post again tomorrow!

ISNVD 2014 Keynote

ISNVD 2/14 Conference
Day I
Meeting and greeting so many remarkable people is such an inspiration. The energy in the room has been palpable. I think there will be a lot of excellent science presented at this conference if the keynote address is any indication.
I'm posting this as the notes I took at the presentation. I apologize for abbreviations, poor sentence structure etc but I wanted to share ASAP.
Keynote speaker...Dr. Paula Grammas PhD

The Role of Blood Vessels and Inflammation in the Pathogenesis of Neurological Disorders.
Texas Alzheimer's research and care Consortium...Director

brain endothelial cells
bbb function
synthetic/metabolic capabilities...brain has more vasculature than any other part of the body

the tight junctions of the bbb are very important
the brain endothelial cells are very important metabolically
endothelial cells actively regulates the neruonal micro environment
neurpathological and neuroimaging studies indicate that 1/3 AD cases are complicated by vascular problems

AD and CVD...inflammation, oxidative stress and apoE4 expression common to both AD and CVD...
endothelial cells are widely recognized as key players in development of neurologic disease
brain endothelium produces toxins in brain in AD
blood vessels in AD...?
NO can be toxic to neurons in high doses.  NO is made by endothelial cells and in small amts. is fine. in AD these cells become abnormal
AD vessels an over expression of iNOS and is usually not present in endothelial cells. this iNOS is very toxic in large amounts....caused by stress and inflammation
micro vessels in AD are inflamed
something is making the endothelial cells make inflammatory proteins
Thrombin is an inflammatory protein and is found in the AD brain in the micro vessels and CSF...inflammation in the vessels has been found in AD
vascular activation and angiogenesis have been documented in the AD brain
no new blood vessels in the AD brain...what does that mean?
vascular activation as a target for AD therapeutics
animal studies are being done now...
animals have been given a Pfizer drug (Sunitinib)  causing angiogenesis have improved the animals cognitive abilities
in vitro Sunitinib improves the function of the endothelium
possible trigger for vascular activation is hypoxia
a key mediator in both angiogenesis and hypoxia is Thrombin
 Thrombin inhibitors improve the function of the mice
"what's good for the heart is good for the brain"
While waiting for the cure of AD take care of any causes of inflammation (ie Diabetes) with diet and exercise.
Hypoxia stimulates the endothelial cells to create a host of inflammatory messengers designed to cause angiogenesis (creation of new blood vessels). So why is there hypoxia? Is the hypoxia chronic or intermittent? These are some questions that need to be answered!
Looking forward to the first full day of learning!

The Gut Brain Connection

Gut Brain Connection

Hippocrates said “All diseases begin in the gut”!

Our western culture’s love of processed foods, the use of antibiotics in our dairy and meats and GMOs have led to a destruction of our friendly gut flora. Pain relievers, such as aspirin and NSAIDS, and steroids also damage the gut flora. Birth control pills, sleeping pills, GERD medications and numerous other drugs cause problems within the GI tract.

Eating a diet filled with too much simple carbohydrates, sugars and processed foods increases the fungi that live in our gut flora. If the fungi and “bad bacteria” outnumber the beneficial bacteria we are prone to develop disease.

 According to Natasha Campbell-McBride MD, neurologist and author of The Gut and Psychology Syndrome, there are dietary measures for restoring a healthy gut.  She recommends taking a probiotic supplement and a diet that includes food sourced probiotics from fermented foods and water and milk kefirs.

Eating fermented foods on a regular basis is the most effective way to heal a “leaky gut”, a condition that exists because of a weakened and often inflamed, permeable intestinal membrane, which allows undigested food particles to enter the blood stream.

The science is there, we are what we eat and we can heal ourselves with the help of fermented foods.

September FDA Update

We had expected to receive a response from the FDA the day after Labor Day but did not. David called  the FDA on September 3rd and spoke to one of the reviewers who was very friendly. She said we were down to minor issues and sent the document to us.  This latest deficiency notice focused on the frequency of adverse events noted in the literature and, once again, said they recommended but do not require a sham control group. Once again, we explained that patients had to pay for this treatment themselves and were certainly not going to pay for a sham treatment.  David called the agency again to ask why they keep asking the same question each month and the reviewer he spoke to said they understood that we couldn't provide a control arm but "we're required by congress" to mention study design considerations in all correspondence.

Of course a double blind placebo controlled trial  is the only way to prove once and for all if venoplasty helps MS patients but this is a very difficult and expensive study to do.  We sympathize with Dr Siskin that he had difficulty recruiting subjects who might only get a sham procedure.

 Our philosophy with the Registry is to continue collecting data and improving venoplasty technique under the auspices of the FDA to keep up the momentum until such a double blind placebo controlled study can be done.

Here is a very brief summary of where we stand with the FDA:

 It's not funded, patients or their insurance must pay for the procedure.  There are ultrasounds before and at 1 week and 1, 6 and 12 months.  The FDA is also allowing only one brand of stent under clearly constrained circumstances, and requiring that patients have an EDSS score before and at 12 months.  Otherwise it's pretty straightforward quality-of-life and adverse event form completions.  Approximately 100 people have expressed interest in participating and a group of very experienced interventional radiologists around the country are waiting to begin ( we're not posting their names yet until they have a chance to review the final FDA requirements).

Decrease your inflammation

Inflammation Information 

The evidence seems incontrovertible that low grade inflammation weakens the brain endothelium and promotes neurodegeneration. For a thorough review see Dr David Perlmutter’s article:

The Role of Inflammation in Neurodegenerative Disorders: Integrative Approaches to Challenging Neurological Disorders

 http://www.worldhealth.net/pdf/bookstore/aamt_vol7_30_perlmutter.pdf

Dhttp://drperlmutter.com

An anti-inflammatory diet and lifestyle change (stress reduction, exercise, gluten free/Paleo diet) are critical for endothelial health. Anti-inflammatory foods help to keep the immune system in balance and not over-inflame when stimulated. To effectively decrease inflammation it is essential to  completely avoid man-made foods, sugars, gluten and food allergens.

 Anti-inflammatory foods include, but are not limited to coconut products, berries, and non-denatured, whey protein from grass-fed cows and goats. Anti-inflammatory herbs such as turmeric, ginger, boswellia, cinnamon, rosemary, & oregano among others should be used as much as possible.

Naturally fermented foods such as red cabbage sauerkraut, kimchi, & coconut kefir are excellent foods for restoring healthy gut bacteria.which is essential in decreasing inflammation.  Additionally, a high quality probiotic supplement with 50+ billion microorganisms should be consumed regularly.

http://www.naturalnews.com/038915_inflammation_foods_healing.html

A balanced immune response in the body is also dependent upon healthy vitamin D levels. Vitamin D helps the body recognize between foreign and self proteins. This reduces inflammation and auto-immune reactions.Healthy Vitamin D3 levels should be between 60-100 ng/ml. Be sure to get tested and supplement if necessary.

The Hubbard Foundation believes that people should be tested for low grade inflammation. These are some tests you might consider:

Vitamin D…25(OH)D

http://www.vrp.com/single-vitamins/vitamin-d3-deficiency-linked-to-a-surprising-number-of-health-concerns

Oxidized LDL

http://cholesterol.about.com/od/lipoproteins/f/oxidizedldl.htm

High sensitivity C-reactive Protein

http://www.nlm.nih.gov/medlineplus/ency/article/003356.htm

Homocysteine

Here’s some more information:

http://drbenkim.com/articles-homocysteine.html

To help decrease inflammation we recommend the use of Tumeric (curcumin is the main anti-inflammatory component of Tumeric).

http://www.ncbi.nlm.nih.gov/pubmed/12676044

You can make a delicious tea which you can drink hot or cold throughout the day:

Add the juice of a lemon or lime to a cup of hot water. Add a few slices of fresh ginger, a sprinkle of turmeric and cayenne with a little bit of Stevia ….if you like your tea sweet.

In addition, you can add some supplements such as:

Nrf2 activator

Omega 3

Neprinol (systemic enzymes which help to thin the blood by removing fibrin)

Astaxanthin

We also recommend eating lots of dark colorful vegetables, grass fed beef, free range chicken and eggs. Ridding your diet of simple carbs like rice, pasta, bread and sugars you can reduce inflammation.

We  believe being under the care of an integrative medicine, functional medicine or naturopathic doctor can be of great benefit.

To find a naturopath near you go to:

www.acam.org

Here are some links for more information:

http://www.naturalnews.com/038915_inflammation_foods_healing.html

http://www.greenmedinfo.com/blog/are-mental-disorders-result-neuroinflammation

http://www.collective-evolution.com/2013/05/30/new-study-shows-cannabinoids-improve-efficiency-of-mitochondria-and-remove-damaged-brain-cells/#_

http://www.greenmedinfo.com/article/stevia-anti-inflammatory-and-immunomodulatory

Responses to comments on our June Newsletter

As most of you know we have been negotiating with the FDA since their warning letter in May 2012 to get their approval to continue our Registry which had already enrolled over 400 MS patients receiving venoplasty.  In their most recent request for revisions they have asked that we add EDSS scores before and one year after the treatment.  We agree that this is an additional burden and that EDSS scores are incomplete and inaccurate. However, we have no choice and, at least ,in the United States these neurology evaluations should be covered by insurance.  We are aware that most insurance is presently not covering the venoplasty itself and patients will have to pay for this themselves.  We have approximately 6 IRs that have been waiting to begin doing the procedure again when we get approval. They are listed on our web site where you can also let us know if you might be planning to participate. www.hubbardfoundation.org/participating-irs

Dimethyl Fumerate update

This week's Neurology Today published a story on PML in patients taking dimethyl fumarate.  There have been a total of 4 patients in Europe.  Each of the patients had severe and prolonged lymphocytopenia - low lymphocyte counts in their blood.  All of them recovered after being taken off fumarates.  Severe lympocytopenia occurs in 3% of patients taking fumarates.  One of the patients had also been treated with methotrexate, another with steroids.  Robert Fox MD interviewed for this story thought that either infection or a significantly altered immune system might be the culprit rather than the fumarate itself.  The cause of lymphocytopenia is not yet known, especially since the mechanism of action of fumarates is suppression of oxidative stress, not immunosuppression per se.

Dr Hubbard has been communicating with David Perlmutter,MD http://www.DrPerlmutter.com/ regarding the dosage of Nrf2 activators with those with neurodegenerative disease. Dr. Hubbard is concerned that only one or two tablets per day of the supplemental forms of fumarate derivatives is too low a dose for MS patients.Both Drs Hubbard and Perlmutter are  suggesting patients push the dose to three or four tablets per day, or even to the point of getting some flushing or nausea (common with Tecfidera) and then backing off a until they feel better and that would be the working dose.

Dr Perlmutter also suggested that instead of increasing the Nrf2 activator (Protandim or Xymogen Nrf2 activator) patients may add more Turmeric and Sulforaphane along with the product.

When you are making any changes to your medications or supplements you should always consult with your trusted medical professional.

Brain Healthy Decadence

Cacao Hazelnut Brain Bliss

Nearly all of the ingredients in this decadent spread are beneficial for brain function. Check out the notes below for more information!

*2cups Hazelnut Butter

1/3 cup cacao

1/3 cup coconut oil

20-30 drops Hazelnut Stevia (if you only have plain liquid Stevia that should be fine)

pinch of salt

Place all ingredients in a food processor and blend.

Enjoy as a fruit dip, spread or the way I like it….by the spoonful!

Hazelnut butter

1lb raw hazelnuts.

Preheat oven to 350°

Roast for 10-15 min on a sheet pan.

When cool, place in food processor with a pinch of salt. Blend until smooth.

Benefits of Hazelnuts:

 Hazelnuts are rich in vitamin B6 which is necessary for nervous system function. In addition,B6 is necessary for the creation of myelin, the insulating sheath of the nerve that increases the speed and efficiency of electrical impulses, allowing the nervous system to operate optimally. What's more, vitamin B6 is instrumental in the synthesis of the neurotransmitters serotonin,

melatonin, and epinephrine.

Benefits of Coconut Oil:

There are numerous benefits of coconut oil (too many to explain here).

“There's another substance that can feed your brain and prevent brain atrophy. It may even restore and renew neuron and nerve function in your brain after damage has set in.

Ketones are what your body produces when it converts fat (as opposed to glucose) into energy. And a primary source of ketone bodies are the medium chain triglycerides (MCT) found in coconut oil!

http://www.healthdiaries.com/eatthis/8-health-benefits-of-hazelnuts.html

Coconut oil contains about 66 percent MCTs.”

http://www.naturepacific.com/contents/en-us/d227_virgin-coconut-oil-brain-food-prevent-Alzheimers.html

Benefits of Cacao:

“Flavanols may act on the brain structure and function directly by protecting neurons from injury, improving metabolism and their interaction with the molecular structure responsible for memory researchers said. Indirectly, flavanols may help by improving brain blood flow.”

http://www.sciencedaily.com/releases/2012/08/120813173205.htm