MS: Iron levels in brain ‘predict disability’

This was the conclusion of a study that showed how a new type of MRI might help predict the likelihood of severe disease progression in multiple sclerosis (MS) patients.

In a paper about to be published in the journal Radiology, the researchers describe how they used the MRI technique — called Quantitative Susceptibility Mapping (QSM) — to measure brain levels of iron in people both with and without MS.

They found that those with MS had higher levels of iron in one part of the brain and lower levels in another, and also that this pattern was consistent with disease severity and progression.

The team suggests that the finding could lead to a diagnostic tool for earlier prediction of disability in MS.

The current “gold standard” for assessing risk of decline in mental and physical function in MS is to measure “brain atrophy,” or the amount of brain tissue that has withered. However, this has limitations.

“Brain atrophy takes a long time to see,” says lead study author Robert Zivadinov, a professor of neurology in the University at Buffalo, NY. “We need an earlier measure of who will develop MS-related disability,” he adds.

MS and iron in the brain

MS, an incurable disease, affects the brain and the rest of the central nervous system by destroying nerve tissue. Its progression is unpredictable; it can stop and start again suddenly, or persist and gradually worsen.

The symptoms range from relatively mild to severely disabling and include but are not limited to: loss of coordination and balance, impairment and loss of vision, tremors and numbness, speech difficulties, paralysis, fatigue, and problems with concentration and memory.

A number of experts believe that MS is a type of autoimmune disorder in which the immune system attacks healthy tissue as though it were a threat.

In MS, the target of immune attacks is a protective layer called myelin that surrounds the fibers that connect neurons, or working nerve cells, to one another.

Brain cells need iron to function, and the element is an important ingredient of myelin. That said, too much or too little can cause harm.

Imaging studies suggest that measuring brain iron levels might be a useful marker of MS progression.

New MRI technique maps iron levels

QSM is a new MRI technique that can estimate iron levels in different tissues by measuring their magnetic susceptibility. The more iron present in a tissue, the higher its magnetic susceptibility.

Prof. Zivadinov and team used QSM to map iron levels in the brains of 600 people with MS and 250 “healthy controls.” Of the patients, 452 had early-stage MS and 148 had a more advanced stage.

QSM revealed that individuals with MS had higher iron levels in the basal ganglia and lower levels in the thalamus, compared with the controls.

Basal ganglia are deep-seated brain structures essential for controlling movement. The thalamus helps process signals from the senses and acts as a communications hub between certain brain regions and the spinal cord.

The researchers also found that the pattern of brain iron levels in the MS group — higher in the basal ganglia but lower in thalamic structures — was consistent with longer MS duration, worse disability, and greater progression.

Tool for clinical trials

“Iron depletion or increase in several structures of the brain is an independent predictor of disability related to MS,” suggests Prof. Zivadinov.

He and his colleagues suggest that QSM might be a useful tool for clinical trials of drugs intended to prevent MS progressing to physical disability.

At present, treatments for MS use anti-inflammatory drugs, which do not halt worsening disability.

[Magnetic susceptibility] is an interesting imaging marker of disease severity that can predict which patients are at severe risk of progressing.”

Prof. Robert Zivadinov

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