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Multiple Sclerosis Damage Also Found In "Normal" Brain Tissue
Main Category: Multiple Sclerosis News
Article Date: 31 Aug 2006 - 18:00pm (PDT)



The effects of multiple sclerosis (MS) extend beyond visibly affected areas into large portions of the brain that outwardly appear normal, according to a study appearing in the September issue of Radiology.

"This disease process in the normal-appearing brain tissue affects the brain globally and has substantial clinical impact," said the study's lead author, Hugo Vrenken, Ph.D., from the Multiple Sclerosis Center at VU University Medical Center in Amsterdam, The Netherlands.

MS is a chronic, autoimmune disease characterized by the destruction of myelin, the protective layers that surround nerve cells. It can affect numerous body functions, and symptoms may include visual and speech impairment, memory loss, depression, muscle weakness, loss of coordination, numbness or pain, bowel and bladder problems and sexual dysfunction.

MS affects approximately 400,000 people in the United States and as many as 2.5 million worldwide, mostly women between the ages of 20 and 50, according to the National Multiple Sclerosis Society.

"The areas of demyelination, or lesions, in patients with MS can be visualized with magnetic resonance imaging (MRI). However, the volume of lesions visible at MRI only correlates moderately with clinical disability measurements," Dr. Vrenken said. "This may be due to disease activity outside the visible lesions."

To gain a better understanding of the effects of MS on the whole brain, Dr. Vrenken and colleagues studied T1 changes in normal-appearing white and gray brain matter in patients with MS.

T1 is a measurement of proton relaxation after exposure to a magnetic field and a radiofrequency (RF) pulse. Due to this RF pulse, protons in the body first reach an excited state and then relax back to a state of equilibrium by funneling the excess energy to the surrounding tissues. T1 refers to the time required for protons to relax to the equilibrium state in this particular manner.

The researchers investigated T1 changes in 67 patients with MS and 24 healthy control volunteers. T1 graphs of normal appearing white and gray matter were significantly different for patients with MS than for controls. Moreover, these graphs differed among patients with MS based on the type of disease: secondary progressive (SP), relapsing-remitting (RR) or primary progressive (PP). The results were most pronounced in patients with SP disease, where at least 31 percent of normal-appearing white matter and 20 percent of cortical normal-appearing gray matter were affected. In RR disease, 16 percent of normal-appearing white matter and 9 percent of cortical normal-appearing gray matter were affected. In PP disease, the normal-appearing white and gray matter affected were 11 percent and 8 percent, respectively. These changes were found throughout the brain, including areas remote from localized lesions that are typically associated with MS.

"These findings demonstrate that in MS, disease processes outside MR-visible lesions are not limited to a few sites but act throughout the brain and affect large fractions of normal-appearing white and gray matter," Dr. Vrenken said. The researchers also explored correlations between the areas of the brain being analyzed in the patients with MS and the level of atrophy or clinical disability present.

"The results suggest that the damage to normal-appearing brain tissue plays a larger role in the progression of atrophy and clinical disability than do the visible lesions," Dr. Vrenken said.

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Journal attribution required.

Radiology is a monthly scientific journal devoted to clinical radiology and allied sciences. The journal is edited by Anthony V. Proto, M.D., School of Medicine, Virginia Commonwealth University, Richmond, Va. Radiology is owned and published by the Radiological Society of North America, Inc. (RSNA.org/radiologyjnl)

The Radiological Society of North America (RSNA) is an association of more than 38,000 radiologists, radiation oncologists, medical physicists and related scientists committed to promoting excellence in radiology through education and by fostering research, with the ultimate goal of improving patient care. The Society is based in Oak Brook, Ill. (RSNA.org - http://rsna.org/)

"Whole-Brain T1 Mapping in Multiple Sclerosis: Global Changes of Normal-appearing Gray and White Matter." Collaborating with Dr. Vrenken on this paper were Jeroen J. G. Geurts, M.Sc., Ph.D., Dirk L. Knol, Ph.D., L. Noor van Dijk, M.D., Vincenzo Dattola, M.D., Bas Jasperse, M.D., Ronald A. van Schijndel, M.Sc., Chris H. Polman, M.D., Ph.D., Jonas A. Castelijns, M.D., Ph.D., Frederik Barkhof, M.D., Ph.D., and Petra J. W. Pouwels, Ph.D.

Contact: Heather Babiar
Radiological Society of North America

Since 5% of MS patients don't show lesions, I have often wondered how many of us in limboland at BT, including UNDXdCraig fall into that category. How do they dx MS if there are no lesions? If your article and this one and the many others about atrophy and disability are true, then maybe some limbolanders fall into that category. I was very surprised when the MS clinic didn't discharge me in spite of 3 MRI's that didn't show lesions. The clinical signs are present, my neuro elected not to do a LP. While I hate limboland, if they could dx MS based on corpus callosum and brain atrophy, maybe Craig and I would have an answer. Whatever this is, it certainly isn't getting better. At least they can treat the symptoms, which gives one a quality of life. Thank goodness for the MS clinic, I went from 10% quality of life to 90% most days.



'Invisible' Brain Changes May Be Key to MS Progression
29/08/2006 9:40:00 PM


TUESDAY, Aug. 29 (HealthDay News) - New research suggests that subtle, undetected changes in brain tissue affect disease progression for people with multiple sclerosis.

"We showed that these changes affect brain tissue throughout the brain, and that changes are greater for patients with secondary progressive MS than for those with the preceding phase, relapsing remitting MS," explained lead researcher Hugo Vrenken, of the VU University Medical Center in Amsterdam, The Netherlands.

His team published its findings in the September issue of Radiology.

MS is an incurable inflammatory disease of the central nervous system marked by muscle weakness, numbness and loss of coordination. Disease severity can range from the relatively benign to cases involving serious disability and death. Many experts consider MS an autoimmune disease, in which the body attacks its own tissues, especially the protective myelin sheath surrounding nerves. About 400,000 people in the United States are diagnosed with MS, according to the National Multiple Sclerosis Society.

In MS patients, standard MRI imaging sometimes reveals brain lesions or plaques that may reflect disease-linked changes in mental or physical function.

Currently, doctors use these images to help diagnose MS. However, an abnormal MRI doesn't always mean MS, and normal results don't necessarily rule out the disease.

In fact, a small proportion of MS patients, about 5 percent, have MRI results that don't reveal any lesions (or plaques) in the brain, according to the National Multiple Sclerosis Society.

What clinicians don't see on a standard MRI - but research scientists can see, using more advanced technology - are other, subtle changes that are also potentially related to disease course and disability.

Measuring these changes that fall "under the radar" could give doctors a better understanding of the disease, allowing them to offer patients a more clear-cut prognosis, the researchers said.

Using advanced MRI technology called "T1 mapping," the Dutch team compared the brain tissue of 67 patients with MS and 24 healthy controls. The researchers focused on changes in areas not showing up as MS lesions (or plaques) on standard MRI images.

T1 imaging showed changes occurring in MS in large parts of brain tissue that would otherwise go undetected. According to the findings, depending on the stage of the disease, these changes may occur in 10 percent to 30 percent of brain tissues not showing any visible damage on standard MRI.

Changes were more pronounced in patients with more advanced, secondary progressive MS than those with the less advanced form of the illness, called relapsing remitting MS, Vrenken said.

"This demonstrates that patients who are further along in the disease do not only develop more visible lesions, but that also the brain tissue not showing visible lesions becomes more affected," he added.

The observed brain changes were more strongly associated with clinical disability than were lesions visible on standard MRI. "This suggests that the changes, though possibly subtle, may be responsible for part of the patients' disability," Vrenken said.

"The tricky part of MS is the variability in progression of disease," noted Dr. Patricia A. O'Looney, director of biomedical research programs at the National Multiple Sclerosis Society.

MRI has been a boon to MS diagnosis since the early 1990s, allowing for earlier detection, in conjunction with other assessment tools. "It has also allowed doctors to look at the disease more objectively, by allowing them to see the damage in the brain, not just rely on whether patients feel well or bad," says O'Looney.

However, "What's missing in both research and clinical care now is a (long-term) predictor of disability," added O'Looney.

Some people can remain fully functional for 20 years before symptoms worsen, while other MS patients deteriorate quickly. Right now, what science can't tell doctors and patients at the time of diagnosis is if, when, or how fast the disease will progress.

So, any method that could predict prognosis based on brain tissue changes would be of great help to doctors, O'Looney said.

"The ultimate hope for MS patients is to stop the neuro-degeneration that happens and causes disability," said O'Looney. Right now, though, science is still unraveling just how the disease manages to do its damage.




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