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 GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

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: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>