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The Roots of Restless Slumber

8 July 2003 (All day)
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Lights out. Patients with sleep disorders and multiple system atrophy (right) show less brain activity in the striatum than normal (left).

To sleep, perchance to dream, said Shakespeare's Hamlet, was perhaps nobler than bearing the slings and arrows of outrageous fortune. But sleeping offers no such graceful escape for patients with obstructive sleep apnea and REM behavior disorder. Now a pair of new studies provide the first hint that faulty brain chemistry leads to these sleep disorders--a first step toward treatments that get at the roots of the problems.

Most people lie still while they dream, but patients with REM behavior disorder act out their dreams: They thrash around, fall out of bed, and occasionally pummel their partners. Similar symptoms appear in patients with a rare and fatal neurological disease called multiple symptoms atrophy (MSA); these patients sometimes lose neurons in a brain structure called the striatum that coordinates movement.

So a team led by neurologist Sid Gilman of the University of Michigan Medical School in Ann Arbor looked to see if the failure of their dopamine-producing neurons might lead to REM behavior disorder. They studied 13 patients as they slept wired to instruments that measured the extent to which their brains told muscles to contract. They also ran PET scans to measure how many dopamine-producing neurons the patients had left in the striatum. In results reported in the first of two July issues of Neurology, the MSA patients had just two-thirds the dopamine-producing neurons as normal subjects. Moreover, the patients with the fewest neurons flailed the most, suggesting that "dopamine deficiency may lead to REM behavior disorder," Gilman says.

Different neurons had gone awry in MSA patients with obstructive sleep apnea, the team reports in a companion paper. People with this condition stop breathing hundreds of times each night when their tongue, palate, and uvula relax too much and shut off their airway--symptoms that lead over the years to high blood pressure, heart attacks, and stroke. Gilman's team probed a brain structure called the pons, focusing on neurons that control the same three muscles that seal the airway. Those neurons produce a neurotransmitter called acetylcholine, and it turned out that the fewer acetylcholine-producing neurons there were in the pons, the more often patients stopped breathing while they slept.

"It was a good study, well done," says neurophysiologist Bob McCarley of Harvard Medical School in Boston. But, he cautions, today's imaging technology didn't allow the researchers to probe whether neurons were failing in the brainstem, which might be at the root of both disorders. Gilman's next step is testing otherwise healthy people with obstructive sleep apnea or REM behavior disorder.

Related sites
Background on sleep disorders from the National Library of Medicine ...
... including obstructive sleep apnea

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