Cortical atrophy evident even at early stages of MS
A number of pathology and imaging studies have recently highlighted the effect of MS on cortical gray matter, showing that the cortex is also subject to damage (in some cases extensive) and suggesting that different disease mechanisms are occurring in white vs. gray matter. A new study adds to this evidence by finding cortical tissue loss in people even in very early stages of MS compared with healthy controls. In this study, 115 patients at the MS Center in Padova, Italy were given MRIs, as were 40 control subjects. The images were analyzed for cortical thickness, brain atrophy, and lesion load. The MS subjects were classified as CIS (clinically isolated syndrome, or one attack with no MRI evidence of dissemination in space); p-MS (possible MS, or one attack with MRI evidence of dissemination in space); and RRMS and SPMS. The CIS and p-MS subjects were scanned within 6 months of their first symptom.
Results showed that all MS groups except for the CIS group exhibited significant cortical thinning compared with the controls. All cortical regions appeared to be affected, however, some regions were more greatly affected than others. Also, comparison of regional thickness with symptoms showed some correlations -- for instance, visual impairment was correlated with visual cortex thinning, and motor function impairment was correlated with motor cortex thinning. Only very modest correlations were seen between cortical thickness and brain lesion load (with no such correlation seen in p-MS cases) and no correlation was found between cortical thickness and white matter atrophy, supporting the hypothesis that cortical loss is not a side effect of white matter lesion development but happens independently.
The authors suspect that their failure to detect cortical thinning in CIS cases was a result of low numbers (only 10 subjects) and the fact that some of these subjects were not going to develop MS. They are extending their study for two years to further examine the dynamics of cortical loss in MS.
Cortical atrophy
Hollie,
Does this mean we are further than ever from understanding this disease? It started off as an auto-immune disease where inflammations caused damage to myelin. Now we are looking at a neuro-degenerative disease - more akin to MND/Parkinsons. Surely someone can work out what's causing the extensive damage! (not you the MS "experts")
I wouldn't say we are
I wouldn't say we are further than ever from understanding the disease. I would say that the information being revealed about the disease indicates that it's more complicated than we would all like it to be. But even if new data contradicts what we thought we previously knew, it's better to have found that out than to continue acting on a belief that isn't true. Our challenge is to figure out how to navigate this tangled web of information to understand what is really happening in MS.
cortical atrophy
I agree, The only thing these MS "experts" are expert at is asking for more money!
Isn't it time they start providing some answers to basic questions. How long do you think it will be before they have their hand out?
Atrophy
I posted the first comment but totally agree with the second poster. I'm sick and tired of hearing bad news about MS - it's now a disease of grey matter in addition to white matter, it's a diffuse disease throughout the CNS not just a focal disease based on lesions etc etc. The "experts" are great at telling us that it is much worse than first thought, but totally useless at identifing what is causing the damage. First we had the anti-inflammatory drugs (the interferons and copaxone) and we were told that they slow the disease down / or modify it - now it seems that there isn't much evidence that they do much at all. More and more drugs are added to the pipeline but how can the companies develop them when they don't know what the real problem is? Neuro-protection has been talked about for years but nothing ever makes it to market. I'm a great admirer of the work of ACP, but I'd be interested in Art's view of the progress made by the experts since ACP was created some seven years ago. In my next life I'll be an MS researcher as you've got a job for life.
Progress to date (in my opinion)
Sorry for the delay in replying - been out of the office and
away from email.
A lot has changed since the summer of 2001 when we launched ACP. Not counting Rebif and Novantrone (rebrandning of existing drugs) we have Tysabri on the market (yes, it has some warts, but looks promising). FTY720 is looking promising for the first oral drug. But again, this is directed at inflammation.
I'd say the most important work done to date has been that done by the pathologists and imaging folks. Imaging is important because the brain is difficult to inspect in living humans. New modalities are being developed that allow us to see more and better.
The pathologists have really called into question the central dogma of MS - that it is an autoimmune disease of the white matter. It is now uncertain if the inflammatory response is the primary insult - so treatments that only address inflammation may not be the best way to deal with the disease. Neurons are being damaged in both the white and gray matter - without inflammation present. The concepts of neuroprotection and neural repair are now commonly discussed and are being persued by pharma.
So I would say very little has been *done* (meaning we have a direct benefit available to those with MS), but we've seen a lot to convince us to take some new directions. There's been a big stall on the investigation front since Betaseron and Avonex showed you could make a billion dollars with an anti-inflammatory drug.
We need to know the causes of this disease. I just don't see any other way we can confidently state we are doing something about it. Anything else is just hoping for luck and miracles. Not a strategy I'm willing to bet on. That's why I started ACP.
***
Art Mellor, Accelerated Cure Project for MS, art-msnews -at- acceleratedcure.com
drug yardsticks and atrophy
It disturbs me to hear that the main effect of MS -- disability -- is possibly not even related to the main yardstick that people have been using as a standard by which to measure new MS drugs -- lesion load. What bothers me even more is that people still believe in the actuarial distinctions drawn between different courses of MS.
Yes, OK, lesions are the most visible effect and are what gave MS its name. But since it is also characterized (possibly from the beginning) by atrophy, which will lead to disability if it does not somehow slow down or stop, can we stop treating some people as if they have a different disease?
If it is true that the medicines that treat "RR"MS stop working in "SP"MS, can anyone tell me why?
Do any existing medications slow atrophy? Slowing atrophy sounds like a good indicator of treatment success too.
-Chris Sullivan
Chris, There was one small
Chris,
There was one small study of antibioitcs by Siiram and Stratton at Vanderbilt that showed significantly slower atrophy in the treated group. Of course, this was a much overlooked fact because lesion load, as you state, is always the yardstick.
Chris, When was the report
Chris,
When was the report done for antibiotic research by the Vanderbilt scientists?
Journal of Neurological
Journal of Neurological Science 2005 Jul 15;234(1-2):87-91
cortical thinning
I was not making any distinction between atrophy of white and grey matter (cortical thinning). If they are not directly related, that might explain why people without new lesions still have progressing EDSS scores. Which kind of atrophy did the people at Vanderbilt study? Did they make a distinction?
-Chris Sullivan
I believe they used The
I believe they used The Brain Parenchymal Fraction, defined as the ratio of Brain Parenchymal Volume to the total volume within the Brain surface contour, this is used to measure Whole Brain Atrophy that had occurred. So it doesn't look like they made a distinction.
Atrophy, progress, etc.
Hi.
Granted, it can be frustrating and discouraging to learn that things keep changing all the time. But, even the "experts" have to learn as well. I help with research on neuronal precursor cells (brain stem cells). And the doctor I work with told me that there are two different types of researchers--ones that do it purely for their own enjoyment of research, and don't care where it leads, and those that sincerely care about it leading to therapies and cures for helping people--and that we need them BOTH. With each new discovery, there is more information to process and new avenues that weren't able to be observed before that point. So, there really are very few "experts" that just want to get fat paychecks just for getting to play around with test tubes. Now THAT assumption is really unfair. Multiple sclerosis is an extremely complicated disease, with many different aspects that have to come together in certain ways, or MS wouldn't develop in the first place. So, MS is a disease that affects both white and grey matter, it is a disease that is neurodegenerative--both in the brain and CNS, it is also an autoimmune disease and it has many different etiologies (ways it began/developed) just like each person has a different set of fingerprints. At each point in the history of MS research, scientists used the best knowledge they possessed at the time to devise ways of helping those afflicted. Nothing is ever perfect, and any remark that refers to the amount of years spent researching a disease "should have yielded results by now" is ridiculous because it shows an arrogance about not really understanding the nature of scientific research. It isn't perfect, and the answers are hardly ever definitive. Just look at any other research--like about cholesterol. The levels of certain types, to be considered healthy, keep changing constantly . . . even though we need a certain amount in our diet to process the food we eat for energy.
So, try not to be too hard on the researchers. Although a certain amount of skepticism is important as well. We could all do our part in this too, as well as making the research more potent and move along faster, by keeping journals of our symptoms and daily life.
Just think about it.
Be encouraged. It's not an autoimmune disease!
I truely believe MS is NOT an autoimmune disease. The immune system is respondng correctly to a well armored and tenacious "infection", Nanobacterium sanguineum. It is in some peoples blood and takes years to decades to manifest itself in various parts of our bodies. Two years ago I tried a new and untested approach. I felt that Nanobacterium sanguineum (NB)played a role in MS. I tested high positive. An MRI established a baseline lesion record then I treated for NB for one year followed by a second MRI. There was no change in my lesion load where there had been increasing numbers before. My symptoms became absent and remains so. I continue to supress NB and remain MS "free". Treatment is cheep with no untward side effects. I take no other medications.
I refer you to the book "The Calcium Bomb: The Nanobacteria Link to Heart Diease & Cancer" by Douglas Mulhall & Katja Hansen ISBN 1-59411-101-4. Also check out http://www.nanobaclabs.com/ . Over two years ago I became aware of Nanobacterium saguineum (NB) now refered to as Calcifying Nano-particles (CNP). After reading the book I felt there is a conection to my MS. I contacted Nanobac labs to learn that no one with MS had been treated. I tested high positive and began a year long treatment with a baseline MRI and year end MRI to compare. The side effects were nominal and comparable to treatment of other dieases involving NB. The MRI studies indicated no advancement of my lesions. In fact they were "identical". My MS symtoms stemming from an imbalanced endocrine system were arrested. All of my other symptoms have steadily improved. I remain exacerbation free. I take no other medications. I continue to supress NB and feel better than normal. A friend with MS has begun this treatment a few months ago with more dramatic results than mine. She is more advanced than I. The treatment involves taking a suppository of 1200 mg EDTA (disodium calcium), 500 mg tetracycline HCI, and suppliments to support the treatment and tissue cell and blood vessal health. The suppliments contain vitamins C, Niacin, B-6, Folate and coenzyme Q-10. Also EDTA, L-lysine, L-arginine, L-ornithine, bromilain, trypin, grape seed extract, hawthorn berry and papain are in this suppliment. The cost is about $10 a day for the initial treatment and a few dollars a day for maintenance. I take these all before bed. To date there has not been any scientific study on the conection between NB and MS. I believe that MS is NOT an autoimmune disease. Rather, I believe that the immune system is performing correctly, trying to remove NB which it cannot. Sustained inflamation gives the appearance of a myelin attack. The body is removing myelin to expose new unNBdamaged calcium channels in order to maintain regulation of the sodium potassium pump and thus electrical signal in the nerve, relapse and remission. Finally, enough myelin has been removed that the signal becomes too inefficient and you have progession. Also many of our symptoms are not due to our lesions. A poorly functioning edocrine system, due to NB, is producing imbalances which present as MS symptoms. I could go on. Is there a scientific reference to a conection? Not yet. Cures or treatments begin with some knowledge, obsevation, recognition or even an "AHA". I suggest that we test a small but significant group of MSers for the presence of NB. If the results show that it exceeds significantly above the 15%, or so, average in the general population then a blind study would be in order, and so on. Unfortunately, or not, there is not a patent readily here. The meds are off the shelf so money to study this is lacking. NASA is studying NB in kidney stones. Heart diease and cancer are being studied too. Lets put MS in the mix. If I am wrong, ok. If I am right or partly right, it's only good. It's not hard to find out. Remember stomach ulcers? Too much acid, right?. No, it took ten years for that Australian Dr to be heard and now stomach ulcers are treated by antibiotics.
Do you have MS? If so, I think this makes some sense to you.
I am targeting NB.
"...Why do we calcify when our blood calcium level is normal? NB seem to be the only known pathogens to grow a calcified shell when calcium is not plentiful and acidity is neutral. Kajander and his colleagues found that they suck calcium from their surroundings, then combine it with other chemicals and compounds, such as cholesterol or lipids, to secrete biofilm. Ciftcioglu (now on contract with NASA) found that this solidifies into apatite, a calcium compound armor. The capacity to generate such a shell under regular blood-like conditions seems unique to NB. The ability to do that when low and moderate concentrations of calcium are present may explain why we calcify when our calcium blood levels are balanced...Once NB are encased in their shell (of calcium phosphate) they go semidormant... The shells are hard to strip off. It resists heat, radiation, and drugs." (pg 61 Mulhall).
I have experimented with diet for a number of years and the bottom line is that a diet that alkalizes the body controled or reduced my MS symptoms. That means NO SUGAR, learn to like millet and green leafy veges. You heard it all before. But high acid forming foods are avoided, low acid forming foods are subtituted with alkali forming foods when possible and high alkali forming foods are sought out. Before I started the NB treatment I supplimented minerals along with enzymes, vitamins, probiotics, (focused on antioxidants). Calcium needs to be balanced with magnesium in a ratio of 1 to 2 taken with cod liver oil, lemon flavor tastes fine. I was very low in rubidium and supplimented it too. There were the regular minerals we are familiar with but they are too many to discuss here. Now I take a mineral program designed to compliment this thereapy. Also DRINK PLENTY OF WATER (8-10 glasses a day).
EDTA (ethylenediaminetetraacetic acid) is given to patients suffering from heavy metal toxicity. If you have lead poisoning they give you IV EDTA. EDTA is bound atomically with a lighter weight metal for ingestion, in this case disodium calcium. When it encounters a heavier metal it releases the calcium and binds with the heavier. The idea is that EDTA will bind with the calcium phoshate shells, break the armor down and allow the tetracycline to kill the NB inside. EDTA is approved by the FDA as a food additive.
" The treatment has been administered at home once a day by the patient in three parts (a suppository, an antibiotic, and a neutraceutical... # The suppository contained a base with the calcium dissolving and removing agent EDTA. # The capsule contained tetracycline hydrochloride.. an antibiotic that is effective against NB. # The neutraceutical contained enzymes and amino acids systems to disolve fibroid deposits and soft plaque. It also sustained levels of disodium calcium EDTA.."( pg 94 Mulhall) and a blend of suppliments mentioned earlier above.
This all seems a bit from left field but if you try to learn what is known about NB you will find that other ailments you may have make sense. MS has gone from my consciousness. What have we to loose by being open to something new? Ask a neurologist what causes MS and what will they tell you? ... Understand your MS from what you feel and therfore know. As Christopher above says, "do your part in this too". Our learning is daily. I am suggesting a cause, test and treatment. I have tested this on myself and the result has been remarkable. Some others are working through it and we are very excited.
What do you think about this?