John Hopkins researchers may have discovered why insomnia persists in patients with restless leg syndrome (RLS), despite successful treatment of the condition.
An estimated 5 per cent of the U.S. population has Restless Leg Syndrome, also known as "jimmy legs" - a common condition affecting the nervous system causing an uncontrollable urge to move the legs. The condition varies in severity and can be painful, distressing and interrupt daily activities as well as disturb sleep.
RLS patients commonly suffer from poor sleep as the actual activity of lying down and relaxing in preparation for sleep can activate RLS symptoms - relieved only by rising and moving.
The disruption of neurochemical signals has been identified as a key factor in causing the involuntary movements in RLS, often characteristic of Parkinson's disease. Neurologists have previously based treatment on the understanding that Dopamine is the main culprit in Restless Legs Syndrome.
However, despite drugs that increase the levels of dopamine levels being used in the treatment for RLS, studies have shown that they do not improve sleep outcomes and only treat the restless legs.
A research team led by associate professor of neurology Richard P. Allen, Ph.D from John Hopkins University School of Medicine has looked into solving the sleep anomaly, using MRI to image the brain in a group of 28 RLS patients and 20 non RLS patients.
Glutamate, the neurotransmitter involved in arousal, was found in abnormally high levels in the RLS group. The higher the level of glutamate recorded in the brain of those with RLS, the worse the patient’s sleep.
The research team recorded MRI images and glutamate activity in the thalamus - the part of the brain involved with the regulation of consciousness, sleep and alertness.
RLS patients included in the study had severe symptoms which exhibited:
- six to seven nights a week
- persisting for at least six months
- an average of 20 involuntary movements a night or more.
Richard P. Allen, Ph.D., is hopeful that the team may have discovered the reason why Restless Legs Syndrome also affects sleep in RSL sufferers -
“We may have solved the mystery of why getting rid of patients’ urge to move their legs doesn’t improve their sleep,” Allen says. “We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS.”
The results of the study could change the way RLS is treated and could potentially eradicate sleepless nights for patients with Restless Legs Syndrome.
Dopamine-related drugs which are currently used in the treatment of RLS do currently work, yet many patients lose the drug benefit and require ever higher doses. If the dose is too high, the medication can aggravate RLS symptoms to a state worse than prior to treatment.
Allen points out that despite drugs already on the market being available which can reduce glutamate levels in the brain, such as the anticonvulsive gabapentin enacarbil, they have not been given as a first-line treatment for RLS patients.
As more is understood about this neurobiology, the findings may not only apply to RLS, he says, but also to some forms of insomnia.
“It’s exciting to see something totally new in the field — something that really makes sense for the biology of arousal and sleep,” Allen says.
Notes:
The study was funded in part by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (R01 NS075184 and NS044862), the National Institute on Aging (P10-AG21190) and the National Center for Research Resources (M01RR02719).
Other Johns Hopkins researchers involved in the study include Peter B. Barker, D.Phil.; Alena Horska, Ph.D.; and Christopher J. Earley, M.D., Ph.D.
http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/restless-legs-syndrome/
Image: credit to xymonau at RGB Free Stock http://www.rgbstock.com/images/sleep
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