Research Highlights
VA-UCLA team discovers link between
Parkinson's disease, narcolepsy
August 30, 2007
Parkinson's disease is usually associated with symptoms
relating to movement and muscle function: stiffness, slowness,
tremors, difficulties walking and talking. Less well-known is that
Parkinson's also shares symptoms with narcolepsy, a disorder
marked by daytime sleep attacks, nighttime insomnia, and severe
fatigue.
Now, researchers from the Greater Los Angeles VA Healthcare
System and the University of California have discovered a biosee
logical basis for the link: Both Parkinson’s and narcolepsy patients
have major deficiencies of brain cells that make a chemical called
hypocretin. The findings were published in the June issue of Brain.
"When we think of Parkinson's, the first thing that comes to
mind are the motor disorders associated with it," said Jerome
Siegel, PhD, chief of neurobiology research at the VA Medical
Center in Sepulveda and professor of psychiatry and biobehavioral
sciences at UCLA. "But sleep disruption is a major problem in
Parkinson's, often more disturbing than its motor symptoms. And
most Parkinson’s patients have daytime sleep attacks that resemble
narcoleptic sleep attacks."
In fact, said Siegel, Parkinson's disease is often preceded and
accompanied not only by daytime sleep attacks and nighttime
insomnia, but by REM sleep disorder, hallucinations and depression—all of which appear in narcolepsy.
Direct relationship between cell loss and
Parkinson's disease progression
In the study, the researchers examined 16 human brains from
cadavers—5 from normal adults and 11 in various stages of
Parkinson's. They found an increasing loss of hypocretin cells with
disease progression—up to a "massive" 62-percent loss in stage 5
Parkinson's. Said Siegel, "That leads us to believe the loss of these
cells may be a cause of the narcolepsy-like symptoms of [Parkinson’s]
and may be ameliorated by treatments aimed at reversing
the hypocretin deficit."
While no hypocretin treatments are currently available, Siegel
said he hopes such therapies will be brought to clinical trials
within the next few years. "We have had success with administration
of hypocretin to dogs with narcolepsy," he noted.
In 2000, the same group of researchers found that human brains
from narcoleptics, compared to normal brains, had up to 95-percent fewer hypocretin neurons. Before then, hypocretin had
been linked by scientists to narcolepsy in animals, but its role in
human narcolepsy had not been established.
More than one million people in the U.S. have been diagnosed
with Parkinson's disease. Narcolepsy is less common, affecting
about 150,000 people in the U.S., or 1 in 2,000 people. Patients are
excessively drowsy during the day. They fight the urge to sink into
a deep sleep while at work, walking around, or even behind the
wheel of a car. At night, their sleep is frequently interrupted. Other
symptoms include cataplexy—loss of muscle tone, where patients
can suddenly lose consciousness and fall down—and vivid
and dreamlike hallucinations that occur immediately before or after
sleep. Treatment often includes stimulants and antidepressants.
Funding for Siegel's study was provided by VA and the National
Institutes of Health. His coauthors were Thomas C. Thannickal,
PhD, and Yuan-Yang Lai, PhD, both with VA and UCLA.