Restless Legs Syndrome Linked to Changes in Sensory Cortex

May 03, 2018

A new study looking at neural mechanisms involved in restless legs syndrome has come up with some surprising findings — that the condition seems to be related to changes in the sensory rather than the motor area of the brain.

"Restless legs syndrome has always been considered primarily a motor problem linked to the dopaminergic system in the brain, so we were expecting to see changes in the motor cortex," senior author, Qing X. Yang, PhD, Pennsylvania State Hershey Medical Center, explained to Medscape Medical News.   

"But our results show that it is actually the somatosensory cortex that appears to be the part of the brain most affected in patients with restless legs syndrome."

"We were stunned by these findings," he added. "This shifts the area of interest to a completely different part of the brain."

The study was published online April 25 in Neurology.

Yang, who himself has restless legs syndrome, added that they found cortical thinning in the sensory cortex as well as white matter thinning in the corpus callosum, the part of the brain connecting the two hemispheres.

"These parts of the brain are not part of the dopaminergic system at all, and we didn't see any morphological changes to the motor cortex or dopaminergic system."

He said these results suggest that restless legs syndrome is both a motor and a sensory problem. 

The findings could lead to new therapeutic strategies. Yang says the study supports the idea that iron deficiency may be involved in restless legs syndrome.

"Iron is known to affect the myelination process," he said. "The somatosensory area of the brain is heavily myelinated and therefore more sensitive to myelin deficiency."

While iron supplements are often prescribed for restless legs syndrome, Yang says iron salts are not well taken up into the brain. "It might better to give ferritin — the natural substance that carries iron in the body which is thought to penetrate the brain more effectively."

Coauthor of an accompanying editorial, Robert J. Thomas, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts, commented to Medscape Medical News that this study "has brought attention back to the cortex as the focus of research into restless legs syndrome." 

"The involvement of the cortex could explain why symptoms of restless legs syndrome become permanent in severe cases," he said. "And if the cortical changes are secondary to untreated disease activity, perhaps this is an indication that we should be treating this condition earlier."

Thomas also suggested that the study raised the possibility of new therapeutic strategies, such as transcranial magnetic stimulation, which he said has been shown to change cortical activity.

The study involved 28 patients with severe restless legs symptoms who had had the disorder for an average of 13 years and 51 age-matched controls without the disorder. Each participant underwent high-resolution MRI of the brain.

Results showed morphologic changes in the brain somatosensory system in patients with restless legs syndrome compared with controls.

In patients with restless legs syndrome, average cortical thickness in the bilateral postcentral gyrus decreased 7.5% (P < .0001). The corpus callosum posterior midbody also substantially decreased (P < .008); in this area the callosal fibers are connected to the postcentral gyrus. This finding suggests altered white matter properties in the somatosensory pathway.

In the accompanying editorial, Thomas and coauthor, Tadaaki Mano, MD, Gifu University of Medical Science, Japan, note that: "While neuroimaging biomarkers are not necessary for diagnosis of RLS [restless legs syndrome], improved pathophysiologic understanding may lead to improved treatments, especially important as long-term dopaminergic therapies fall out of favor for risk of augmentation."

They add that the results also make a case for early diagnosis and treatment, before potentially irreversible changes occur in the somatosensory cortex.

The study was supported by the Pennsylvania Department of Health. Thomas has served on the scienti fi c advisory board of Jazz Pharmaceuticals; has served on the editorial board of Sleep Medicine; holds patents for electrocardiography-based assessment of sleep and sleep quality, a CO 2 device for central/complex sleep apnea, and periodic breathing detection (co-patent with DeVilbiss-Drive, used in Food and Drug Administration–approved continuous positive airway pressure); receives publishing royalties from Elsevier; has been a consultant for GLC Councils and Guidepoint Global; receives research support from the National Heart, Lung, and Blood Institute and the American Sleep Medicine Foundation; and receives license fee payments from MyCardio LLC.

Neurology. Published online April 25, 2018. Abstract, Editorial

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