Transcranial Sonography Helps Quantify Brain Iron Levels in RLS

By Will Boggs MD

November 27, 2019

NEW YORK (Reuters Health) - Quantitative transcranial sonography of the substantia nigra identifies changes resulting from intravenous iron therapy in patients with restless legs syndrome (RLS), researchers in Spain report.

"The most prominent and promising finding is that we have an evaluation method that enables us to predict which patients might benefit most from treatment with intravenous (IV) iron, which is so far the only existing disease-modifying treatment in RLS," Dr. Celia Garcia-Malo of the Sleep Research Institute, in Madrid, told Reuters Health by email. "Transcranial sonography (TCS) could help us to know in advance which RLS patients would benefit the most from IV iron treatment."

Iron deficiency plays a central role in the pathogenesis of RLS, and reduced levels in the substantia nigra have been observed in postmortem studies of RLS patients. IV iron has been used to treat patients with RLS, but 40% to 50% of patients do not respond.

Dr. Garcia-Malo's team used quantitative TCS to measure changes in substantia nigra iron deposits as reflected by substantia nigra echogenicity indices (SNEI) before and after IV iron therapy in 30 patients with RLS.

The researchers divided these patients into two groups according to the median baseline SNEI (0.18 cm2): the severely hypoechogenic (HE) group with lower baseline SNEI and the moderately HE group with higher baseline SNEI.

Overall, SNEI increased a mean 13% following IV iron, with significant 19% increases in the severely HE group and nonsignificant 10% increases in the moderately HE group. The changes in SNEI did not differ significantly between these groups, the researchers report in Sleep Medicine, online October 30.

Following IV iron treatment, the total daily dopaminergic requirement (TDR) decreased by a mean 28.04% (42.26% in the severely HE group and 19.75% in the moderately HE group); 36.84% of patients overall reducing their TDR by more than 30% (57.14% of severely HE patients and 25% of moderately HE patients).

After IV iron treatment, International RLS Rating Scale (IRLS) scores decreased by an average 5.93 points (a 21% reduction from baseline). The average change was higher in the severely HE group (10 points, a significant 33% improvement) than in the moderately HE group (1.85 points, a nonsignificant 6.8% improvement).

The changes in TDR and IRLS scores did not differ significantly between the severely HE and moderately HE groups.

"So far we have been 'blind' in quantifying brain iron as it cannot be predicted by peripheral iron status," Dr. Garcia-Malo said. "But if we could measure brain iron deposits, we would have more evidence about when to prescribe iron replacement therapy for RLS."

"In this way, transcranial sonography could help physicians make decisions about which treatment is the most appropriate for each individual," she said. "Such tailored treatment would optimize resources and minimize therapeutic failure or adverse effects."


Sleep Med 2019.