Brain Iron Levels May Predict Multiple Sclerosis Disabilities

A new, highly accurate MRI technique can monitor iron levels in the brains of multiple sclerosis (MS) patients and help identify those at a higher risk for developing physical disability, according to a study in Radiology.

Brain atrophy is the current gold standard for predicting cognitive and physical decline in MS, but it has limitations, said study lead author Robert Zivadinov, MD, PhD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo (UB) in Buffalo, NY. He is director of the Buffalo Neuroimaging Analysis Center in the Jacobs School and the Center for Biomedical Imaging at UB’s Clinical and Translational Science Institute.

“Brain atrophy takes a long time to see,” Dr. Zivadinov said. “We need an earlier measure of who will develop MS-related disability.”

MRI studies of iron concentration have emerged recently as a promising measure of changes in the brain associated with MS progression.

“It is known that there is more iron in the deep gray matter structures in MS patients, but also we’ve seen in recent literature that there are regions where we find less iron in the brains of these patients,” Dr. Zivadinov said.

Using quantitative susceptibility mapping, Dr. Zivadinov and his fellow researchers performed the mapping technique on 600 MS patients, including 452 with early-stage disease and 148 whose disease had progressed.

Altered Deep Gray Matter Iron Associated with the Evolution of MS

Compared to 250 healthy control participants, MS patients had higher levels of iron in the basal ganglia (62 parts per billion (ppb) vs. 54.8 ppb; P < .001), but lower levels of iron in their thalamus (-7.5 ppb vs. -1.1 ppb; P < .002). The lower iron content in the thalamus and higher iron content in other deep gray matter structures of people with MS were associated with longer disease duration, higher disability degree and disease progression.

This association with clinical disability persisted even after adjusting for changes in the brain volumes of each individual structure.

“In this large cohort of MS patients and healthy controls, we have reported, for the first time, iron increasing in the basal ganglia but decreasing in thalamic structures,” Dr. Zivadinov said. “Iron depletion or increase in several structures of the brain is an independent predictor of disability related to MS.”

The results point to a potential role for quantitative susceptibility mapping in clinical trials of promising new drugs, Dr. Zivadinov said. Current treatments involving anti-inflammatory drugs do not prevent MS patients from developing disability.

“Susceptibility is an interesting imaging marker of disease severity that can predict which patients are at severe risk of progressing,” Dr. Zivadinov said. “To be able to act against changes in susceptibility would be extremely beneficial.”

Web Extras

• Access the study, “Brain Iron by Using Quantitative MRI Is Associated with Disability in Multiple Sclerosis,” at https://pubs.rsna.org/doi/10.1148/radiol.2018180136