01 Sep Insights into Neurobiology of Restless Legs Syndrome
MedicalResearch.com Interview with:
Rachel Marie E. Salas, MD, MEHP, FAAN
Associate Professor, Neurology and Nursing at Johns Hopkins Medicine
Director, Interprofessional Education and Interprofessional Collaborative Practice
Director, Neurology Clerkship
Director, PreDoc Program Meyer/Neuro Sleep
MedicalResearch.com: What is the background for this study? Can you briefly describe what is meant by RLS and who suffers from it?
Response: Restless Legs Syndrome (RLS) is a common neurological disorder characterized by an irritating, overwhelming urge to move (akathisia) the legs while at rest or sleep (conditions of diminished arousal), which almost immediately abates with mental or physical activity (conditions of maintained arousal).
One of the most clinically-profound and scientifically relevant consequences of this disease process is an increased arousal state producing significant wake during sleep times and a relative sustainable degree of daytime alertness despite the degree of diseased-imposed sleep loss. The focus of most previous RLS research has been on the (limb) akathisia with associated periodic movements and reduction of these with dopaminergic treatment. Little research has been done to understand the broader biological dimensions of RLS. Patients with RLS have altered sleep-wake homeostasis with increased arousal and wakefulness (hyperarousal) not only driving the signature clinical symptoms (“the urge to move” and sleep loss) but also supporting arousal over sleep drive at night and in the day. We hypothesize that there is a basic glutamate-hyperarousal process producing both disrupted sleep (increased wake time) and cortical excitability (as demonstrated by transcranial magnetic stimulation (TMS)).
MedicalResearch.com: What are the main findings?
Response: Our study gives fundamentally new insight into the neurobiology of the cortico-motor excitability of RLS. Specifically, M1 representation of the leg shows evident hyperexcitability that appears related to RLS disease severity. In contrast, the M1 hand in this study shows decreased excitability with no indication of the expected hyperarousal from RLS.
MedicalResearch.com: What should readers take away from your report?
Response: The results of this study supports an altered corticomotor excitability in the neurobiology of RLS.
The two major TMS findings here, show an interesting difference between leg and hand excitability, with strong indications for increased corticomotor excitability in M1leg but decreased in M1hand. The increased M1leg corticomotor excitability is further supported by decreased rMT for the leg, with a significant correlation between decreased rMT and RLS disease severity.
Further, a greater increase in Mlleg excitability was observed in the RLS individuals with dopaminergic RLS augmentation.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Our finding provides a specific neurobiological focus for future RLS studies (eg, fMRI connectivity and regional iron changes). Additionally, perhaps targeting cortico-motor excitabilty in the motor cortex (leg) may be a potential treatment option in the future for patients with moderate to severe RLS.
MedicalResearch.com: Is there anything else you would like to add?
Response: The study was funded by a National Institute of Neurological Disorders and Stroke grant (R01 NS075184).
COI: Earley received research funding from Luitpold Pharmaceutical. Allen has received consulting fees from AMAG and Luitpold pharmaceuticals.
Rachel Marie E. Salas, Aadi Kalloo, Christopher J. Earley, Pablo Celnik, Tiana E. Cruz, Keyana Foster, Gabriela Cantarero, Richard P. Allen. Connecting clinical aspects to corticomotor excitability in restless legs syndrome: a TMS study. Sleep Medicine, 2018; DOI: 10.1016/j.sleep.2018.05.002
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