Restless Legs Syndrome

Restless legs syndrome: Study raises hope for better drugs

John Hopkins researchers may have discovered why insomnia persists in patients with restless legs syndrome (RLS), despite successful treatment of the condition.
Bottles of medication pills or pharmaceutical drugs being made in factory production line.
Few drugs effectively treat RLS while also improving sleep.

People with restless legs syndrome, sometimes called “jimmy legs,” have an uncontrollable urge to move their legs. The condition varies in severity and can be painful, distressing and interrupt daily activities as well as disturb sleep.

In spite of effective drugs to relieve RLS, studies have shown that they do not improve sleep outcomes and only treat the restless legs.

A research team led by Dr. Richard Allen, associate professor of neurology at 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:

  • On six or seven nights a week
  • Persisting for at least six months
  • With an average of at least 20 involuntary movements a night.

The second stage of the experiment involved a two-day sleep study. RLS patients were reported to have received 5.5 hours sleep on average. The researchers identified a direct link in this group between glutamate levels in the thalamus and the number of hours of sleep. There was no such association in the non-RLS control group.

Dr. Richard Allen is hopeful that the team may have discovered the reason why restless legs syndrome also affects sleep. He says:

We may have solved the mystery of why getting rid of patients’ urge to move their legs doesn’t improve their sleep.

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 lead to developments in the way RLS is treated, potentially helping to eradicate sleepless nights for people with restless legs syndrome.

Dopamine-related drugs do work for many people with RLS, yet some lose benefit and require ever-higher doses. If the dose is too high, medication can aggravate symptoms to a state worse than that prior to treatment.

Dr. Richard Allen points out that despite drugs already being available that can reduce glutamate levels in the brain, such as the anticonvulsive drug gabapentin enacarbil (Horizant), they have not been given as a first-line treatment for RLS patients.

Dr. Allen adds that as more is understood about the neurobiology, his findings could apply to some forms of insomnia as well as restless legs syndrome.

Dr. Richard Allen says:

It’s exciting to see something totally new in the field – something that really makes sense for the biology of arousal and sleep.”

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