Brain Iron May Distinguish Parkinson's From Other Tremors

VIENNA, Austria — Levels of iron in specific areas of the brain may help clinicians to differentiate a diagnosis of Parkinson's disease (PD) from nondegenerative tremor syndromes (ND-TS), suggests new imaging research.

The study included about 50 patients and used 3T MRI. Those with PD had significantly higher iron concentrations, as shown with R2* relaxometry, in the substantia nigra at both baseline and at the 2-year follow-up vs those with essential or dystonic tremor.

The PD group also had a significant increase in R2* values in the same area between baseline and 2 years. While the amount of increase was greater in patients with PD than in those with ND-TS, this between-group difference was not statistically significant.

Still, lead author Sebastian Franthal, MD, Department of Neurology, Medical University of Graz, Austria, told attendees here at the International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD) 2017that the overall difference in brain-iron "is a novel finding."

"Iron imaging might be useful as a cost-effective, noninvasive biomarker in differential diagnosis of tremor syndromes," said Dr Franthal.

Investigating Longitudinal Iron Changes

Brain iron, along with dopamine, "causes oxidative stress, inflammation, and neurodegeneration," Dr Franthal explained. "Past studies have proved there is a significantly higher iron deposition in substantia nigra in Parkinson's compared to healthy controls."

So for the current study, "our objective was to investigate longitudinal changes in nigral iron concentration in PD compared with other tremor syndromes."

The researchers enrolled 32 patients with PD and 15 age-matched patients with ND-TS, and they used R2* relaxometry to determine levels of nigral iron in the two groups.

They found that R2* values were significantly higher in both the substantia nigra pars compacta and pars reticulata regions for patients with PD than in those with ND-TS.

Table. Brain Iron Levels in Patients With PD and Those With ND-TS

Substantia Nigra Regions	PD Group	ND-TS Group	P Value
Baseline
Pars compacta	28.9	25.3	<.001
Pars reticulata	38.1	32.4	.001
2-year follow-up
Pars compacta	31.4	26.0	<.001
Pars reticulata	39.8	32.9	.001

No significant correlations were found "with clinical parameters of disease progression," reported Dr Franthal.

In addition, there were no significant differences in R2* increases in side dominance or between tremor-dominant or non–tremor-dominant motor phenotype in PD.

The investigators note that more research is now needed, with a greater patient population and the use of more sensitive assessment techniques.

More Substantia Nigra Findings

Two days later, Peter J. Nestor, MD, PhD, German Center for Neurodegenerative Diseases, Magdeburg, Germany, presented a study on brain dysregulation in early PD by using quantitative susceptibility mapping (QSM), a new MRI approach.

The study included 75 participants (mean age, 63.6 years): 25 patients with PD (56% men) and 50 age-matched, healthy peers to act as the control group (80% men).

"Susceptibility-weighted MRI signals were acquired with a Siemens Verio 3T scanner and were reconstructed, post-processed, and analyzed using state-of-the-art quantitative methods," explain the investigators.

Results showed a significant increase in QSM, "consistent with iron deposition," in the substantia nigra pars compacta and reticulata of the patients with PD, whereas the pallidum and striatum areas were stable.

Interestingly, iron content was decreased in the cerebellar dentate nucleus in the PD group. "That was a rather unprecedented finding as this is [normally] a very iron-rich structure," said Dr Nestor.

Although the overall findings align with past postmortem research, "extensive neocortical and cerebellar changes constituted a far more complex distribution of iron dysregulation than was originally anticipated for early clinical stages" of the disease, write the researchers, adding that QSM-measured iron-level changes could be "a proxy marker of pathological activity."

Dr Nestor told attendees that they are also starting to find differing patterns in Alzheimer's disease and amyotrophic lateral sclerosis.

"Our next prediction is that in the non-PD akinetic diseases, such as PSP [progressive supranuclear palsy] or corticobasal degeneration, we'll see qualitatively different patterns there, too," he said.

"We don't know what the clinical significance, if any, of all this is," he admitted. "So we'll be doing further investigation."

"Very Early, But Interesting"

After Dr Nestor's presentation, session co-chair Maria Grazia Spillantini, PhD, University of Cambridge, United Kingdom, told Medscape Medical News that "it's very early, but these findings were very interesting."

"There's already a lot of indications that tau could be accumulated in Parkinson's patients. And it'll be interesting to see more on what the differential effect from the accumulation of iron will demonstrate," said Dr Spillantini.

Her fellow session co-chair, Jiawei Zhou, MD, PhD, Chinese Academy of Science in Shanghai, agreed.

"I thought this presentation was terrific, very good," said Dr Zhou. "It's giving us access to the human brain in Parkinson's disease, and I think it can help us to understand the role of iron in the pathogenesis of the disease."

He noted that although brain iron has been studied for many years, it's only been recently that the door has really started opening into how it affects PD.

"The researchers have been moving forward. And I'm very optimistic because with these new technologies, we'll be able to understand more," said Dr Zhou. "This study used 3-Tesla MRI, but there are now 7-Tesla machines that will provide even higher-resolution images to let us see much more clearly these iron depositions."

Dr Franthal and Dr Nestor have disclosed no relevant financial relationships.

International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD) 2017.Poster 190, Symposium 26, and Presentation 20, presented March 30, 2017; Symposium 44, Presentation 8, presented April 1, 2017.

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