MIAMI BEACH — Stimulation of the pedunculopontine nucleus could be a new target to treat excessive daytime sleepiness and other sleep disorders in people with Parkinson's disease, according to recent reports in the literature.
“Daytime sleepiness is a frequent and disabling problem in Parkinson's disease,” Dr. Isabelle Arnulf said at the World Federation of Neurology World Congress on Parkinson's Disease and Related Disorders.
Although excessive daytime sleepiness can interfere with the activities of daily life for Parkinson's disease patients, a main concern is their increased risk for a driving accident.
Dr. Arnulf, a sleep disorders specialist at H pital Piti-Salp tri re in Paris, advised telling patients to be cautious when driving. “The most dangerous for driving are those who do not feel their own sleepiness.”
In the first report of its kind, researchers at the University of Toronto demonstrated last year that deep brain stimulation of the pedunculopontine nucleus (PPN) alters human sleep patterns (Ann. Neurol. 2009;66:110-4).
They studied REM and non-REM phases for five parkinsonian patients undergoing unilateral deep brain stimulation of their PPN.
Nocturnal REM sleep time nearly doubled during stimulation, compared with periods when stimulation was turned off. The implication is that helping people with Parkinson's disease sleep better at night will decrease daytime sleepiness.
High frequency (80 Hz) PPN stimulation produces a sedative effect that “even occurs when the patient actively tries to maintain wakefulness,” Dr. Arnulf said.
In her experience, patients trying to stay awake during this stimulation demonstrate periods of microsleep. She showed meeting attendees a video of a man undergoing stimulation who, despite trying to fight off sleep, went on to establish sleep stage I and then non-REM sleep stage II within 2 minutes. The patient fell asleep 10 out of 10 times, she said.
The results that were obtained in the pilot study suggest that the PPN “could be a new target for sleep disorders,” she said.
Sleep attacks, or the sudden onset of sleep without prodroma, are primarily described in narcolepsy. Risk factors include an Epworth Sleepiness Scale score greater than 10 (range, 0-24), use of dopamine agonists, or high levodopa equivalent doses, Dr. Arnulf said.
Patients can be screened for excessive daytime sleepiness using objective measures such as the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test.
Among the possible causes of excessive daytime sleepiness in people with Parkinson's disease are the side effects of dopaminergic agents, insufficient sleep at nighttime, and lesions in arousal systems.
To treat excessive daytime sleepiness, one could decrease or switch dopamine agonists, or consider replacement of a dopamine agonist with levodopa. Combining dopamine agonist therapy with a stimulant drug is another option, Dr. Arnulf said .
Reports in the literature support sleepiness as a medication side effect. For example, in one study, researchers observed a “huge increase” in sedation effects—a decrease in sleep latency—about 3-5 hours after 12 healthy volunteers took a dopamine agonist (Br. J. Clin. Pharmacol. 2009;67:333-40).
In another study, researchers found that 22% of 929 patients with Parkinson's disease who were prescribed a dopamine agonist reported an episode of “uncontrollable somnolence” (Arch. Neurol. 2005;62:1242-8)
The risk for uncontrollable somnolence was nearly tripled in participants taking a dopamine agonist compared with other medication types.
Dr. Arnulf said that a common question is whether sustained-release dopamine agonists are less sedative. Dopamine-related sleepiness usually occurs at the peak of the dopamine agonist effect, she said, but a blunted peak does not prevent sleepiness from occurring,
Dr. Arnulf had no relevant financial disclosures.