New research suggests that insomnia caused by restless leg syndrome (RLS) is strongly linked to high levels of the brain chemical glutamate, contradicting long-held assumptions that the neurotransmitter dopamine is the main culprit of the symptoms.

"We may have solved the mystery of why getting rid of patients' urge to move their legs doesn't improve their sleep," said lead researcher Dr. Richard P. Allen, an associate professor of neurology at the John Hopkins University School of Medicine, in a news release.

"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."

Restless leg syndrome, a neurological condition in which people feel an overwhelming need to move their legs, may affect as many as one out of 10 Americans.

The symptoms are often worst when patients lie down to fall asleep, with unshakeable discomfort causing insomnia that keeps them up throughout the night. Moving the legs can temporarily relieves discomfort, but the sensations can range from merely uncomfortable to painful.

Previous evidence linked RLS to disruptions in the brain's pathways that use the neurotransmitter dopamine, which is implicated in other involuntary movement disorders like Parkinson's disease. As a result, dopamine-regulating medications are common treatments for restless leg syndrome symptoms, though such drugs tend not to reduce insomnia and can actually worsen RLS symptoms over time.

Allen's team was intrigued by previous findings that even though restless leg syndrome patients typically get less than 5.5 hours of sleep a night, few of them report daytime sleepiness as a result of their insomnia.

They decided to investigate the role of glutamate, a neurotransmitter that promotes arousal, in RLS, suspecting that high levels of the chemical might cause heightened arousal at all hours.

Using magnetic resonance imaging (MRI), the researchers scanned the brains of 28 patients with restless leg syndrome symptoms and 20 people without them. Those with RLS had symptoms keeping them awake at least six nights a week, with a five-night average of 20 or more periodic leg movements during sleep for at least six months.

The brain scans focused on glutamate activity in the thalamus, a region of the brain that regulates consciousness, sleep, and alertness.

Some of the participants also spent two consecutive nights in a sleep lab to complete polysomnography measures, allowing researchers to analyze their sleep quality and duration.

The results revealed that patients with restless leg syndrome had abnormally high glutamate levels, and that the higher their glutamate levels, the more disturbed sleep they had. Controls without sleep disturbances, however, had consistently stable glutamate levels.

"It's exciting to see something totally new in the field — something that really makes sense for the biology of arousal and sleep," said Dr. Allen.

Dr. Allen explained that the findings need to be confirmed in a larger sample, but could benefit restless leg syndrome patients if replicated.

Glutamate-reducing drugs like the anticonvulsive gabapentin enacarbil are commercially available, and it's possible that they might be able to reduce RLS symptoms and treat insomnia at the same time.

The results of the study are published in this month's issue of the journal Neurology.