Iron and gray matter - What do we know?

January 3, 2012 at 8:52am

As more and more MS reseachers come forward and explain how MS appears to be a disease of the gray matter first---before white matter lesions appear---it is vital that we look at gray matter structures in the MS brain, to see what is different in the MS brain when compared to normal brains.

This post will be long, but I believe it's important to understand MS research as it stands today, the beginning of 2012.

Last month, University of Texas researchers published in the Journal of Neuroscience--reporting that the thalamus, the deep gray matter of the brain, is smaller and atrophied in people with MS when compared to normal brains, and that this loss of deep gray matter tissue happens at the beginning of the disease, early on and before any white matter lesions are detected.

http://health.usnews.com/health-news/family-health/brain-and-behavior/articles/2011/12/30/multiple-sclerosis-may-cause-changes-in-thalamus-study

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A recent paper from Hubbard, Haacke, et al shows how stenotic veins creates slowed jugular return of blood in pwMS.  Blood flow thru the brains of pwMS is much less than those with non-stenotic veins.  This may be an indication of hypoperfusion and decreased oxygenation, and we'll be hearing more about that from the Hubbard Foundation later this year.

Dr. E. Haacke has also noted an early change in the gray matter of MS brains--abnormally high iron content.

Dr. E. Mark Haacke has been looking at the gray matter in MS brains for almost a decade.  He is one of the inventors of SWI technology, an imagery system that can visualize iron deposed into brain tissue.

This is from his new paper is published in the American Journal of Neuroradiology--

Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and thalamas (THA) structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep gray matter (GM) structures.

RESULTS: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor.

The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content.

Currently, there is an increased interest in studying how GM is affected and particularly deep GM involvement in MS when iron deposition has been observed.  

Brain iron accumulation in neurodegenerative diseases, including MS, is not new and has been shown histologically in the past.  In MS, its source is likely due to myelin or oligodendrocyte debris, concentrated iron in the macrophages, or as a product of local microhemorrhages following venule wall damage.  As the wall breaks down, free iron may escape outside the vessel. This process has typically been seen in the basal ganglia, neurons, oligodendrocytes, macrophages, and microglia.6 Generally, free iron is known to lead to the formation of highly reactive hydroxyl radicals that can trigger cell membrane dysfunction and chronic microglial activation. Thus, iron from any of the above-mentioned sources could lead to inflammation and a further buildup of iron, causing the system to be self-sustainable.  

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What Dr. Haacke is explaining is that we've known about iron in gray matter tissue in MS brains and other neurodegenerative diseases for awhile.   This is not new information.   Dr. Haacke explains that there are three possible causes of this iron in the MS brain.  The iron could come from one, two, or all three of these sources.

Iron in the Brain or the Immune System

September 17, 2009 at 9:36am

Many disease modifying treatments use the reduction of immune activated lesions as shown on MRI as proof a treatment is "working" in MS. This has baffled me, since we know that the number of lesions does not correlate to level of disease progression. Someone like my husband can have 20 brain lesions and function quite well. Someone else can have one or two lesions and be wheelchair-bound. Also, at a certain point, lesion progression stops when MS turns progressive. There must be another mechanism of injury, along with the immune system, at work in the MS brain.

In Bologna, Dr. Mark Haacke addressed another means of measuring brain tissue injury in MS. Susceptibility Weighted MRI. What SWI MRI shows us, is that iron deposited in the brain is a bio marker for MS progression.

What is different in SWI-MRI, according to Dr. Haacke, is that brain damage shown due to iron deposition actually CORRESPONDS to disability in MS.

The more iron deposed in the brain, the more disability, the more progressive MS is. This is different than the usual measuring of hyperintense lesions on MRI, which have no specific correlation to disease severity.

Here's the rub:
Pharma companies use the lesions shown on MRI as "proof" that their particular drug is working. Look! We've reduced hyperintensities on MRI! Our amaze-a-bub is slowing MS! Stock prices go up, investors are happy, and MS patients continue to decline.

If we look at the TRUE cause of disability- the only measurement in the brain that correlates to disability is iron deposition and brain atrophy.

This is why my husband had 20 lesions at his diagnosis and could mountain bike, and someone with one lesion is in a wheelchair. It's not just about the white matter lesions.

If we understand that the macrophages and immune system are activated as janitors to clean up the cellular death in the brain, we understand that the lesions we see on standard MRI may be secondary--just as they are a stroke patient, or someone with an ischemic brain ijury.

Thank goodness for Dr. Haacke, and other scientists who are speaking out.  It is not simply about the lesions on MRI. We will be told it is, because we can be sold drugs that halt these lesions---but that has not stopped MS progression.  There is no drug to stop reflux, iron deposition and hypoxic injury in the brain, and this is why it has not been explored since TJ Putnam in the 1940s, and will be fought.