Welcome! This blog contains research, information on lifestyle, nutrition, dietary supplements 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 15 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, January 11, 2016

Thalamic Atrophy and MS progression

Why does MS progress?  What allows the disease to erode physical and mental abilities?  This is the big question for researchers and patients alike.  In the 1940s, it was assumed that the visible scars upon autopsy, the white matter lesions showing demyelination, were the cause of MS progression.  And the EAE mouse model of MS was created. MS was an autoimmune disease in which the myelin sheath was destroyed.  link

As MRI technology developed, the efficacy of disease modifying MS drug treatments was determined by the lack of new white matter lesions.   White matter lesions were considered the "bio marker" of MS disease progression.  And a twenty billion dollar a year business was created.  The narrative goes something like this:  MS is an autoimmune disease.  The immune system target is myelin.  The immune system is destroying myelin and must be stopped!  White matter lesions cause disability.  This was the finely crafted explanation of MS treatment, which continues today.

But it's not completely true.

We've known for quite a while that MS is not truly an autoimmune disease---any more than stroke is an autoimmune disease.   The immune system does the same thing when there is a break in the blood brain barrier in stroke and there is a similar antigenic response to myelin.

In MS,  myelin destruction appears to be secondary to death of neurons

and the main correlate to disease progression is loss of gray matter, not white matter lesions.

That's why someone with MS, like my husband Jeff, could present with over 20 white matter lesions, a dozen enhancing, and still be able to jog and bike, with a <1 EDSS.   It's also why progression in MS continues after the immune system stops "attacking" myelin during the RRMS phase.   People with progressive MS may no longer have new white matter lesions, but the disease certainly doesn't stop.   It's also why people with primary progressive MS don't have many white matter lesions.

As Dr. Philip James says, "Scars are a sign of healing."  Multiple Sclerosis means many scars, and these scars are a sign of an immune system attempting to repair the damage done during the break in the blood brain barrier.  And stopping demyelination does not stop MS progression.

Immunomudulating MS drugs may affect white matter lesions, but they do not prevent gray matter atrophy.

The assessment of brain volume changes on serial magnetic resonance imaging (MRI) scans can provide an objective measure of the neurodegenerative component of multiple sclerosis (MS) pathology. Results from placebo-controlled and crossover clinical trials indicate that immunomodulating (e.g. recombinant interferon-beta [IFNbeta]-1a [Rebif] and IFNbeta-1b [Betaferon] and glatiramer acetate [Copaxone]) and immunosuppressive (e.g. cladribine and alemtuzumab) treatments for relapsing-remitting (RR) and secondary progressive MS lack substantial efficacy in preventing the development of brain atrophy, despite the marked effects of these treatments on clinical and MRI outcomes of disease activity.

The striking differences in EDSS development at one year follow-up, combined with the high subcortical atrophy rates in EDA patients compared to controls, support the use of NEDA as an outcome measure in MS. The high subcortical atrophy rates in the EDA patients, combined with the high proportion of patients treated with first line DMTs in this patient group, underlines the need for treatment strategies targeting GM atrophy in early RRMS, especially in patients with evidence of disease activity.

The thalamus might be, thus, an ideal region of interest to test the effectiveness of new neuroprotective MS drugs. Especially, we will address underlying pathological mechanisms operant during thalamus degeneration in MS, such as trans-neuronal or Wallerian degeneration. Furthermore, we aim at giving an overview about different paraclinical methods used to estimate the extent of thalamic pathology in MS patients, and we discuss their limitations. Finally, thalamus involvement in different MS animal models will be described, and their relevance for the design of preclinical trials elaborated.

As you can see, MS drug companies know gray matter atrophy is a real problem in disease progression, which is why they are paying researchers to look at thalamic atrophy in MS, and see how their newest drugs are doing in maintaining gray matter.   Check out BNAC's recent grants----Teva, Biogen and Novartis all want to know if their drugs are stopping gray matter atrophy.  This is not coincidence.   http://www.bnac.net/?page_id=359
Dr. Zivadinov has been publishing on thalamic atrophy and MS progression for a few years now.

So, what's the thalamus?  Where is it, and what does it do?
Your thalamus is a vital brain structure, which resides deep within the brain as gray matter--called "gray" because of its color.  Gray matter is neurons and glial cells. and lacking the white matter color created by myelin.  The thalamus is responsible for relaying information to the rest of your brain.  It receives sensory input: the auditory, visual, smell and touch messages, and directs those messages to the rest of the brain.  If the thalamus is damaged or loses neurons (what we call "atrophy),  vision problems, sleep problems, balance and walking problems would result.  Just like what we see with MS progression.

The walls of the third ventricle are formed by the thalamus, so when there is shrinking and a loss of gray matter--the third ventricle expands and gets wider, as it fills with more cerebrospinal fluid.  Your brain, like all nature, abhors a vacuum.  CSF fills in the gaps.

Here are some MRI examples of how the thalamus shrinks, and the third ventricle (the black area in the center/top of the brain) expands--  from left to right--normal brain, RRMS, and right is progressive MS

Want to find out how your own brain is doing?  Ask the MRI techs to look at your gray matter.  Specifically your thalamus and width of the third ventricle.  They can go back and compare your past MRIs, too.  That's how we found out that Jeff's gray matter atrophy had reversed, and his gray matter now looks normal, nine years since MS diagnosis and almost 7 years since treatment for CCSVI.  The width of his third ventricle is completely normal.  No sign of any gray matter loss.

Here's more on MRI technology and measuring the thalamus.  Note that the researchers mention how "ventricular enlargement" can give an indication of gray matter loss.
Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy with the extent of unspecific, global brain atrophy, represented by ventricular enlargement.

The notion that clinically relevant MS pathology is restricted to focal WM lesions has been overwhelmingly negated by an expanding body of neuropathologic data implicating significant cortical myelin, neuro-axonal, and synaptic loss,, in both early and late stages of the disease. Pathology afflicting the deep GM structures, in particular the thalamus, is frequently observed in MS, but less well studied.

I would suggest that understanding how CSF, (g)lymph and blood are all drained through the deep gray matter structures of the brain via the venous sinus and paravenous pathways is vitally important.

Maintaining gray matter should be the target for all MS treatments.

Last November, we learned that Vitamin D levels are correlated to gray matter health in MS.

Here are all my blog posts on maintaining gray matter.  I've been writing about this for awhile, and am truly shocked that this topic is not being discussed by MS specialists, who are still hyperfocused on white matter lesions.

Hope this helps you understand your own brain, and gives you some questions to ask the MRI techs and your neurologist.
Keep learning---it will maintain those neurons, and keep your gray matter going strong!



  1. Such excellent information. I wonder if a pineal cyst is important? It was remarked as "incidental" in my case.
    Thank you again, Joan... you are forging the way.

    1. you're welcome, Sheryl! Hmmm...small pineal cysts are not uncommon and show up on 10% of MRIs, but yeah, it's all about CSF flow.

  2. Any theories as to why Jeff's gray matter atrophy reversed and why his gray matter now looks normal? That's pretty darn awesome!

    1. Oh, duh! I just read it--he had CCSVI.

  3. Hi Karen---the theory is that the venoplasty and stenting of his stenotic jugular veins and stenotic transverse sinus allowed for better venous flow and perfusion. Blood, cerebrospinal fluid and lymph go through those veins---so improving drainage has helped his brain heal. Jeff also follows the Endothelial Health Program---which optimizes many factors known to maintain gray matter health. Hope the info helps! http://ccsvi.org/index.php/helping-myself/endothelial-health

  4. Thank you so much Joan; love your articles it always gives me the feeling of light at end of tunnel.

  5. Thank you always from me here in UK .

  6. So much great info Joan-thank you. Wondering about any way to re-establish venous drainage following thrombosis of a stent placed in the right IJV. The left IJV (albeit small) is still flowing post angioplasty.

    1. So sorry to read about your thrombosis, Karen. It's a real problem with stents, and is why anticoagulation therapy with blood thinners is essential aftercare. It's also why patients need regular followup care from their IRs. Your IR would know your best options--if there might be a procedure to open the occluded stent. I'm not a doctor, I just compile the research. The body does form collateral venous drainage--your blood is most likely going through the one good IJV and your vertebral veins. Do all you can to stay active and keep blood flowing. Here's the aftercare program I put together with the doctors. Hope it might help! http://ccsvi.org/index.php/helping-myself/ccsvi-treatment-aftercare