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cheerleader wrote: Dr. Haacke has found a correlation between iron deposition, hypoxic death and the amount of disability and progression.
cheer

E. M. Haacke1, M. Makki2, Y. Ge3, M. Maheshwari1, J. Garbern4, O. Khan5, J. Hu1, M. Selvan1, and L. Zahid1
1
Radiology, Wayne State University, Detroit, Mi, United States, 2Radiology and Neurology, Wayne State University, Detroit, Mi, United States,
3
Radiology, New York University, New York, NY, United States, 4Molecular Medicine and Genetics, Wayne State University, Detroit, Mi,
United States, 5Neurology, Wayne State University, Detroit, Mi, United States

Introduction: MRI has been used routinely to diagnose and monitor multiple sclerosis spatially and temporarily. Although T2WI
is highly sensitive in the detection of hyperintensitises in white matter, these studies are not specific to the status of the disease.
Recently, a number of studies have suggested that there is iron deposition in dentate nucleus, cortex and adjacent subcortical white matter, brain stem, basal ganglia and thalamus. These results showed that hypointensities of T2WI highly related to brain atrophy, disease course and physical disability. For example, nonheme iron deposition has been reported to shorten T2 relaxation time in the basal ganglia [1] as well as in lesions [2] in the cortical and subcortical regions [3] of the brain in multiple sclerosis (MS) patients. These studies were based on conventional or fast-spin-echo T2W imaging, which is not sufficient for detecting a subtle iron component that may be associated with lesion development and progression [4]. The purpose of this study was to
correlate signal intensity loss in lesions seen in conventional T2W images with SWI filtered phase intensity.

Results: Conventional MRI sequences (T2W, FLAIR, T1W pre/post contrast) combined together revealed a total number of 270
lesions (113 on 1.5T, 96 on 3T and 61 on 4T). In comparison, SWI phase and magnitude images revealed more lesions, a total of
387.We found a negative correlation of T2 signal intensity with SWI filtered phase and hence the putative iron content (Figure 1).
The average phase over all lesions was 2186 ± 42 while that in the surrounding normal appearing WM was 2044 ± 20 (Figure 2).
The difference between these two values is 142 units, representing an average iron content of 47μg Fe/g tissue [5,6]. There is a
clear negative correlation between the T2 signal intensity and the putative iron deposition (Table 1).

Conclusions: SWI reveals iron deposition associated with MS lesions both in terms of its presence and characteristics compared to conventional imaging. Further, the SWI data suggests that there is a correlation between T2 signal intensity and phase changes (putative iron content). One may hypothesize that as the inflammatory component decreases, the tissue is compromised and there is an associated increase in iron deposition in the brain. Further work using SWI may provide some insight into the pathogenesis and mechanisms of disability in MS.

Oct. 22, 2003 -- Iron deposits deep in the brain may cause multiple sclerosis, new imaging studies suggest.

The findings come from studies of computer-assisted brain scans using a specialized magnetic resonance imaging ( MRI) device. University at Buffalo, N.Y., researchers Rohit Bakshi, MD, and colleagues are the first to use this technique to study multiple sclerosis. Bakshi reported the findings at this week's annual meeting of the American Neurological Association in San Francisco.

Multiple sclerosis has been considered a disease of the white matter in the brain and spinal cord -- the neural pathways that allow areas of gray matter to communicate with one another. But the new findings link iron deposits in the gray matter to movement and thinking impairments in multiple sclerosis.

"If we're going to treat this disease, we have to know where the damage is," Bakshi says in a news release. "Traditionally, we thought MS was strictly a white-matter disease. ... We were able to visualize gray matter structures deep in the brain of MS patients and found some to be atrophied."

These areas of brain damage contained abnormally high levels of iron. It's not yet clear that the iron is the cause of the brain damage. It could be that dying brain cells leave a trail of iron behind.

Walking, Thinking, and Gray Matter
Bakshi's team put 41 multiple sclerosis patients through a walking test. They also gave tests of learning, speed of information processing, and memory to 28 MS patients.

The more unnatural darkness the brain scans saw in a patient's gray matter, the worse the patient's MS symptoms. It was the only factor studied that independently predicted impaired walking and thinking.

"We suspect that MS patients have defective blood-brain barriers, the cell layer that prevents potentially toxic substances from entering the brain," Bakshi says. "Excessive iron entering the brain may damage the deep gray matter structures."

Possible Treatment
If iron is indeed the culprit, it seems possible to do something about it. Bakshi's team is exploring two ideas. The first is simply to remove excess iron from patients' bodies, and then to devise a way to prevent future iron build-up.

If that is impractical, it may be possible to prevent iron from killing brain cells. The excess iron may be causing free radicals -- extremely reactive molecules that damage brain cells. Antioxidants -- such as vitamins C and E, or even more powerful agents -- might mop up free radicals before they do their dirty work.

Even if the iron deposits are the effect, rather than the cause, of brain cell death, the study still offers a way to measure the severity of MS and the efficacy of new treatments.

Conclusions Gray matter T2 hypointensity in MS is associated with brain atrophy and is a stronger predictor of disability and clinical course than are conventional MRI findings. While longitudinal studies are warranted, these results suggest that pathologic iron deposition is a surrogate marker of the destructive disease process.

cheerleader wrote:There's your assignment, Radeck...
Do some research for us, and find other diseases in the CNS in which the immune system is affected. What happens to the CNS in HIV-AIDS? What causes the immune system to back down in stroke? Do neurologists have any theories as to PPMS and the lack of immune activation?-
get googling and get us some research and answer some of your great questions for us!
cheer

Conclusions: SWI reveals iron deposition associated with MS lesions both in terms of its presence and characteristics compared to conventional imaging. Further, the SWI data suggests that there is a correlation between T2 signal intensity and phase changes (putative iron content). One may hypothesize that as the inflammatory component decreases, the tissue is compromised and there is an associated increase in iron deposition in the brain. Further work using SWI may provide some insight into the pathogenesis and mechanisms of disability in MS.

The interesting thing about the particular study below was that they found disease course and disability had no correlation to lesions found on standard MRI....there was actually an inverse correlation. It was the SWI lesions seen that correlated to disease activity and progression. The research team hypothesizes that as inflammation decreases, iron deposition and tissue damage increase. This would correlate to what we see happening as MS becomes progressive.

cheerleader wrote:Make sure to click on all the links provided in this thread, patient...it wasn't from just one paper. Dr. Haacke used all of his volumes of research using SWIM and BOLD technology in his presentation to present the case. He also showed us new SWI pictures showing iron deposits in PPMS brains.

The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics.

Walking, Thinking, and Gray Matter
Bakshi's team put 41 multiple sclerosis patients through a walking test. They also gave tests of learning, speed of information processing, and memory to 28 MS patients.

The more unnatural darkness the brain scans saw in a patient's gray matter, the worse the patient's MS symptoms. It was the only factor studied that independently predicted impaired walking and thinking.

"We suspect that MS patients have defective blood-brain barriers, the cell layer that prevents potentially toxic substances from entering the brain," Bakshi says. "Excessive iron entering the brain may damage the deep gray matter structures."

• Plasma non-transferrin bound iron (NTBI) is potentially toxic and contributes to the generation of reactive oxygen species (ROS), consequently leading to tissue damage and organ dysfunction. Iron chelators and antioxidants are used for treatment of thalassemia patients. Green tea (GT) contains catechins derivatives that have many biological activities. The purpose of this study was to investigate the iron-chelating and free-radical scavenging capacities of green tea extract in vivo. Rats were injected ip with ferric citrate together with orally administered GT extract (GTE) for 4 months. Blood was collected monthly for measurement of iron overload and oxidative stress indicators. Plasma iron (PI) and total iron-binding capacity (TIBC) were quantified using bathophenanthroline method. Plasma NTBI was assayed with NTA chelation/HPLC. Plasma malonyldialdehyde (MDA) was determined by using the TBARS method. Erythrocyte oxidative stress was assessed using flow cytometry. Levels of PI, TIBC, NTBI and MDA, and erythrocyte ROS increased in the iron-loaded rats. Intervention with GT extract markedly decreased the PI and TIBC concentrations. It also lowered the transferrin saturation and effectively inhibited formation of NTBI. It also decreased the levels of erythrocyte ROS in week 4, 12 and 16. Therefore, green tea extract can decrease iron in plasma as well as eliminate lipid peroxidation in plasma, and destroy formation of erythrocyte ROS in the rats challenged with iron. The bifunctional effects could be beneficial in alleviating the iron and oxidative stress toxicity. In prospective, these GTE activities should be further examined in thalassemic animals or humans.

radeck wrote:The caffeine in green tea (extract) is also a vasoconstrictor though. I am under the impression that that affects arteries mostly. However as I understood other posts here vasodilators should be preferred for CCSVI?