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Joined: Mar 26, 2005 Posts: 595 Location: Northamptonshire, England.
Posted: Thu Mar 08, 2007 12:20 pm Post subject: Normal-appearing brain isn't normal
Newer imaging techniques reveal that normal-appearing grey and white matter actually do have abnormalities in MS brains, although I'm not sure exactly what those 'abnormalities' signify...
Joined: Sep 12, 2006 Posts: 901 Location: Dayton, Ohio USA
Posted: Thu Mar 08, 2007 7:18 pm Post subject:
Whoa, I had to read that three times. That's very interesting; thanks Dom. The first thing I thought was 'who cares'? But then I thought that this may be one more piece of the puzzle. They are getting a better "microscope" with this new technology. Studying something they hadn't seen before could lead to all kinds of new directions. This is really exciting when you think about it.
Joined: Mar 09, 2007 Posts: 17 Location: New England
Posted: Fri Mar 09, 2007 6:45 pm Post subject:
Keep in mind I'm a newbie and not as well educated on this as I should be... (a lot of times when trying to understand this disease I make "common sense leaps"... however, I find out more and more that this disease often defies logic)
If we are assuming that normal-appearing grey and white matter are infact often abnormal in MS patients, does this mean that there is a large possibility that A LOT of folks with chronic MS-like symptoms are being misdiagnosed? (with or without Obands in spinal tap) Is it possible for them to have no focal white matter lesions and still have the abnormal grey and white matter?
I hoped it would feel like some kind of miraculous recovery when, after 6 months of treatment I went from 27 "active" white brain lesions to only 5 of the larger ones. And yet... I still felt as sick as I did when I had 27. I don't understand this disease yet... YET! _________________ "Some women aren't meant to be tamed... we are meant to run free until we find someone just as wild to run with"
Joined: May 04, 2006 Posts: 3456 Location: Mid-Michigan
Posted: Fri Mar 09, 2007 7:07 pm Post subject:
ClancyPavillion wrote:
If we are assuming that normal-appearing grey and white matter are infact often abnormal in MS patients, does this mean that there is a large possibility that A LOT of folks with chronic MS-like symptoms are being misdiagnosed? (with or without Obands in spinal tap) Is it possible for them to have no focal white matter lesions and still have the abnormal grey and white matter?
I think it's safe to say that all of these questions and many more can be suspected but never known until something specific and unique to ms is discovered which allows doctors to unquestionably discern who has ms and when ms starts.
Obviously time of diagnosis has little or no relationship to when the disease process actually started. Was it there when you were in high school? Was it there when you were in your mother's womb? Who and how many people around you has a version of ms so mild that they might never know?
No way of knowing until we can put a finger on something specific which defines "ms".
Bob _________________ Wife diagnosed with RRMS in Feb. 2006.
Joined: Mar 09, 2007 Posts: 17 Location: New England
Posted: Fri Mar 09, 2007 11:25 pm Post subject:
Very true, bob... I appreciate the perspective. _________________ "Some women aren't meant to be tamed... we are meant to run free until we find someone just as wild to run with"
Dom,
thanks for another interesting link. Actually, a couple of years ago a "sticker thread" was started on a Finnish forum where people can post interesting studies on development of imaging techniques and recent findings. I found these studies there that - more or less - support the information you posted:
"In early RRMS, grey matter MTR abnormality is apparent. The correlation with mild clinical impairment (in this essentially non-disabled cohort) suggests that NAGM MTR could be a clinically relevant surrogate marker in therapeutic trials."
"The results of this study, combined with those of others, suggest that widespread axonal dysfunction is associated with fatigue in MS. Increased recruitment of cortical areas and pathways in response to brain injury may be responsible for the patient's sense that the effort required to perform actions is disproportionately high."
"These observations suggest that progressive normal-appearing gray matter damage might yet be an additional factor leading to the accumulation of disability in progressive MS."
"Statistical mapping analysis of brain MTR data provides valuable information on the relationship between the location of brain tissue damage and its functional impact in patients with MS, even in the earliest stage of the disease."
"We conclude that lesional and non-lesional MTR values can be significantly less pronounced in benign multiple sclerosis than in a cohort of RR patients at their earliest disease stages, suggesting that brain tissue damage is milder in benign multiple sclerosis than in early RR disease."
"Brain grey matter and white matter is abnormal in both early RR and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy appears clinically relevant in PPMS treatment trials."
"MS normal-appearing white matter containing very little perilesional tissue is characterized by increased glial cell numbers without evidence of axonal dysfunction."
"The volume of lesions visible at MRI only correlates moderately with clinical disability measurements. This may be due to disease activity outside the visible lesions."
As a layman I'd suggest that almost all permanent disability could be caused by axonal degeneration and gray matter abnormalities. Maybe disability caused by demyelination could be reverseable even after a relative long period of time.
-finn _________________ "You get to an age where what you might be gives way to what you have been. You weren't Einstein. You weren't anything. That's a bad moment."
Joined: Mar 26, 2005 Posts: 595 Location: Northamptonshire, England.
Posted: Sat Mar 10, 2007 9:11 am Post subject:
Wow! That's a lot of information and comment -- all good!
Loobie,
Yes, more powerful techniques can lead to really exciting breakthroughs -- I suppose you could look at it two ways: either proving that we'd been barking up the wrong tree for decades, or that something unexpected could turn up with a surprisingly simple "cure".
ClancyP,
"Common Sense leaps" are, in my opinion, extremely valuable. Perhaps they are something which we, as amateurs with a broad overview but an intense personal interests, can provide that the experts cannot. Maybe most of those leaps would be dismissed as laughable by researchers, but one day perhaps...
Bob,
The presence of lesions and their number is looking less and less secure as a measure of MS severity. Sometimes, post-mortems have been carried out on people of advanced years who have died of natural causes, and lesions have been found. Sometimes they say that "This person had MS but never knew it", and sometimes, as in this forum, we have heard that up to 95 per cent of "normal" people have lesions, so they are not even necessarily proof of MS. You're right: we need an absolute, definitive, incontrovertible test for MS, then some of the confusion and contradictory evidence might clear up.
Finn,
I hope that the researchers in the link I posted have acknowledged, in the full text, the Finnish findings that you posted, and that they have been working to validate and confirm the results. Otherwise it would seem that they have wasted time and money duplicating the tests and coming to the same conclusions!
I hope that the researchers in the link I posted have acknowledged, in the full text, the Finnish findings that you posted, and that they have been working to validate and confirm the results. Otherwise it would seem that they have wasted time and money duplicating the tests and coming to the same conclusions!
Yeah, I hope so too :-) Seriously, there might still be some kind of learning (and validating) process going on with the new imaging techniques such as MTR. In any case, it is good to remember that it was only less than three years ago when first "gray matter studies" were published. And science is slow...
-finn _________________ "You get to an age where what you might be gives way to what you have been. You weren't Einstein. You weren't anything. That's a bad moment."
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