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 Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

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: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>