Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gray Matter Damage in the Brain of MS Patients Linked to Cognitive, Physical Deficits, New UB Research Finds

22.10.2003


Results further implicate iron deposits in brain in MS impairments



The mental impairment and problems with walking experienced by patients with multiple sclerosis (MS) are linked to damage in the brain’s gray matter, with MRI findings suggesting the damage is due to toxic deposits of iron, researchers from the University at Buffalo have shown for the first time.
Previous breakthrough work by the team had linked deep gray matter iron deposits to the disease course of MS, brain atrophy and overall disability, but not to cognition or ambulation. Results of these latest studies were presented today (Oct. 21, 2003) at the annual meeting of the American Neurological Association in San Francisco.

The researchers, affiliated with the Buffalo Neuroimaging Analysis Center (BNAC) and Jacobs Neurological Institute, use specialized, computer-assisted magnetic resonance imaging (MRI) technology to focus on hypointensity, or unnatural darkness, of gray matter structures as seen on so-called T2-weighted images. This condition is referred to as T2 hypointensity. Using this approach, they were able to show that structures in the brain’s deep gray matter of MS patients contained T2 hypointensity compared with normal individuals, suggesting higher-than-normal levels of iron deposits, and confirmed the relationship of T2 hypointensity to MS symptoms.



"Traditionally, we thought MS was strictly a ’white matter disease,’ involving the brain’s neural pathways that allow various gray-matter structures to communicate with each other," said Rohit Bakshi, M.D., UB associate professor of neurology, first author on the new studies and founding director of the BNAC. "Through our computerized imaging analysis capabilities, we were able to visualize gray matter structures deep in the brain of MS patients and found some to be atrophied.

"We also found MRI evidence of abnormally high levels of iron," he said. "Moreover, these changes weren’t associated with the amount of white-matter damage, so this was all new information. If we’re going to treat this disease, we have to know where the damage is."

The finding concerning gray matter atrophy resulted from the researchers’ work with a brain structure called the caudate nucleus, which is an important nerve center for controlling movement and cognitive processing. Other laboratories have studied the role of the caudate nucleus in Alzheimer’s disease and Huntington’s disease, but the BNAC is the only center studying it in MS patients using state-of-the-art MRI techniques.

The current studies take the BNAC’s previous research to the next level, in an effort to determine the role of excess iron in specific MS disabilities. Bakshi and colleagues tested walking ability and cognitive impairment respectively in two groups of MS patients that underwent the specialized MRI brain scans to assess T2 hypointensity of the gray matter structures thought to be involved in these conditions.

The ambulatory study involved 41 MS patients who completed a timed 25-foot walk, a standard measure of physical dysfunction. These times were compared with T2 hypointensity in the gray matter, as well as brain atrophy and additional anatomical brain changes known to occur in MS. Results showed that T2 hypointensity was the only brain change directly associated with impaired walking ability, and the strongest association with walking ability pointed to the brain structure known as the dentate nucleus. This structure exists deep in the cerebellum, the brain region responsible for coordination and smooth movement of the limbs.

The study of cognitive impairment involved 28 MS patients who took tests measuring learning, speed of information processing and working memory. Test results were compiled into an attention/memory composite, which was compared with the same measures of brain change used in the ambulation assessment. T2 hypointensity in the brain’s deep gray matter structures was the only measure that predicted cognitive impairment in these patients, results showed.

"We suspect that MS patients have defective blood-brain barriers, the cell layer that prevents potentially toxic substances from entering the brain," Bakshi said. "Excessive iron entering the brain may damage the deep gray matter structures through generation of free radicals and lipid peroxidation, as well as inflammation, all of which would destroy neurons. We have tissue samples from two autopsied brains showing high iron levels in these gray matter structures in patients with MS compared to controls."

Bakshi said the other possibility is that high levels of iron are a result of the neurodegenerative process that occurs in MS. "When brain cells are destroyed, in aging for example, iron levels increase in the brain. High levels of iron also are seen in Alzheimer’s and Parkinson-related diseases. There is still a debate about cause-effect of iron in all of these conditions.

"We do think, however, that hypointensity in the deep gray matter is a strong predictor of disability, progression of the disease and subsequent brain atrophy in MS," he said. "If future longitudinal studies support these findings, it may be possible to design a new treatment to prevent iron build-up, which could prove beneficial to MS patients. However, we must have further studies to draw definitive conclusions," stated Bakshi.

Additional researchers on the studies were Christopher Tjoa, a first-year UB medical student; Ralph Benedict, Ph.D., UB neuropsychologist and associate professor of neurology; Andrew Fabiano, third-year UB medical student; Jitendra Sharma, M.D., a graduate student at Roswell Park Cancer Institute; Robert Bermel, fourth-year UB medical student; Frederick E. Munschauer, M.D., professor and chair of the UB Department of Neurology, and Bianca Weinstock-Guttman, M.D., assistant professor of neurology.

The studies were funded by grants from the National Institutes of Health, National Science Foundation and the National Multiple Sclerosis Society, and by an Alpha Omega Alpha medical school research fellowship and an American Academy of Neurology Student Interest in Neurology Summer Scholarship.

Lois Baker | University at Buffalo
Further information:
http://www.buffalo.edu/news/fast-execute.cgi/article-page.html?article=64280009

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>