Parkinson’s disease is well known for its progression of motor disorders, including stiffness, slowness, tremors, and difficulties walking and talking. Less well known is that Parkinson’s shares other symptoms with narcolepsy, characterized by sudden and uncontrollable episodes of deep sleep, severe fatigue, and general sleep disorder.
 
Now a team of University of California, Los Angeles (UCLA) and Veterans Affairs researchers think they know why the two disorders share something in common—Parkinson’s disease patients have severe damage to the same small group of neurons whose loss causes narcolepsy. The findings suggest a different clinical course of treatment for people suffering from Parkinson’s that may ameliorate their sleep symptoms.

In their report in the June issue of the journal Brain and currently online, Jerry Siegel, professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA; assistant resident neurobiologist Thomas C. Thannickal; and associate research physiologist Yuan-Yang Lai have determined that Parkinson’s disease patients have a loss of up to 60% of brain cells containing the peptide hypocretin (Hcrt). In 2000, this same group of UCLA researchers first identified the cause of narcolepsy as a loss of Hcrt, thought to be important in regulating the sleep cycle. This latest research points to a common cause for the sleep disorders associated with these two diseases and suggests that treatment of Parkinson’s disease patients with Hcrt or Hcrt analogs may reverse these symptoms.

“When we think of Parkinson’s, the first thing that comes to mind are the motor disorders associated with it,” said Siegel, who is also chief of neurobiology research at the Sepulveda Veterans Affairs Medical Center in Mission Hills, Calif. “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 by daytime sleep attacks, nocturnal insomnia, REM sleep disorder, hallucinations, and depression. All of these symptoms are also present in narcolepsy.

In the study, the researchers examined 16 human brains from cadavers—five from normal adults and 11 in various stages of Parkinson’s—and found an increasing loss of Hcrt cells with disease progression. In fact, Siegel said, the later stages of Parkinson’s were “characterized by a massive loss of the Hcrt neurons. That leads us to believe the loss of Hcrt cells may be a cause of the narcolepsy-like symptoms of Parkinson’s and may be ameliorated by treatments aimed at reversing the Hcrt deficit.”

Funding for the study was provided by the National Institutes of Health and the Medical Research Service of the US Department of Veterans Affairs.