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Saturday, June 18, 2011

Potential Cause of Severe Sleep Disorder Discovered, Implications for Parkinson's Disease

Potential Cause of Severe Sleep Disorder Discovered, Implications for Parkinson's Disease


Science Daily - Researchers at the University of Toronto are the first to identify a potential cause for a severe sleep disorder that has been closely linked to Parkinson's disease and other neurodegenerative diseases.

"Our research is the first to establish a potential genetic link to human REM sleep behaviour disorder (RBD). That's important because between 60 and 80 per cent of people diagnosed with human RBD develop Parkinson's disease or other neurodegenerative disorders later in life," says Dr. John Peever, lead author of the study that recently appeared in The Journal of Neuroscience.

Rapid-eye-movement sleep behaviour disorder (RBD) is most often characterized by violent movements that occur during dreaming sleep, also called rapid-eye-movement sleep. People who suffer from RBD do not experience normal muscle paralysis that prevents them from enacting their dreams and they often hurt themselves or their bed partners with their rapid, forceful movements. In some cases, patients need to be tied to their bed to prevent serious injury to themselves or their bedpartners.

Peever's team focused on investigating a genetic cause of RBD because the underlying cause of this disorder is unknown. There is evidence indicating that reduced brain inhibition could cause RBD, so Peever's team genetically reduced brain inhibition in mice and then recorded their sleep and muscle activity.

"We found that mice with reduced brain inhibition acted just like human RBD patients and they moved violently during REM sleep," says Peever. "This link strongly suggests that patients with RBD may also have impaired brain inhibition."

They also found that RBD symptoms in mice could be alleviated by giving them clonazepam -- a drug used to treat human RBD.

Peever's research underscores the importance of identifying a cause of RBD as 60 -- 80 per cent of RBD sufferers subsequently develop Parkinson's.

"Treating RBD could have direct implications for understanding and perhaps treating Parkinson's disease," says Peever.

Marching Through Life With Parkinson’s

Marching Through Life With Parkinson’s

JANE E. BRODY
The New York Times - Dr. Karen Jaffe, an obstetrician-gynecologist in Cleveland, was only 48 when she learned she had Parkinson’s disease. Four years later, she continues to maintain a full-time medical and surgical practice, even performing ritual circumcisions.

“I’m doing everything I can to stay healthy,” she told me in an interview. “My medications and exercises control my tremor, so doing surgery is not a problem.”

For patients with Parkinson’s disease, like Dr. Jaffe, there still is no cure. But researchers have begun to make progress in identifying causes of the disease, and a new study promises to help identify better treatments.

Until then, many patients are getting by on grit and determination. In speaking recently with several of them, two common threads emerged: an initial unwillingness to believe or reveal the diagnosis, followed by acceptance and a determination to pursue whatever it takes to remain as healthy and functional as possible.

In addition to taking medication designed to replace the brain chemical, dopamine, that is diminished in this neurological disease, each person I spoke with is dedicated to regular, often vigorous physical activity that can minimize the disabilities caused by Parkinson’s.

One, David Wolf, 51, of Buffalo, has even taken up fencing, saying (in jest, I hope), “There’s nothing like running someone through with a sword to make your day.” Another, Rena Bulkin, 68, of Manhattan, goes to a gym several times a week to do aerobics, stretching and range-of-motion and balance exercises. “If I don’t work out, my symptoms are much worse,” she said.

Dr. Jaffe dances the tango and whacks a heavy punching bag to reduce her symptoms and enhance function. “The punching bag helps my arms and relieves my frustrations,” she said. “It feels so good to hit the thing.”

She also rides an exercise bike at low resistance and high speed — 80 to 90 revolutions a minute — an activity that was shown in studies at the Cleveland Clinic to significantly reduce arm tremor.

The Parkinson’s patients also emphasized the importance of having a physician who is both expert in the disease and willing to work with patients to find treatments that produce the most benefits with the fewest side effects.

Theirs is a lesson worth learning by the growing numbers of people with Parkinson’s and their caregivers. The sooner one comes to terms with the diagnosis and starts treatment, the less rapidly the disease is likely to worsen.

More Than a Movement Disorder

Parkinson’s disease is a slowly progressive neurodegenerative condition involving a significant loss of dopamine, a neurotransmitter produced in a section of the brain called the substantia nigra that helps to control movement and emotional responses.

While manifestations of the disease can vary widely from person to person, the most common physical symptoms include tremor, or shakiness or trembling in the hands, arms, legs, jaw and face; rigidity of the muscles; slowness of movement or difficulty starting to move; and problems with balance and coordination.

Other symptoms may include fatigue, depression, anxiety, irritability, restlessness, tingling, memory problems, slowed thinking, changes in body temperature, sweating and constipation.

Although the disease usually does not produce recognizable symptoms until the seventh decade or beyond, it sometimes affects much younger people like Dr. Jaffe, Mr. Wolf and the actor Michael J. Fox, 50. Although Dr. Jaffe said she can no longer play the piano — “My left hand can’t keep up with my right hand, and I wasn’t very good in the first place” — she was able to knit a number of cotton wraps that were sold to raise money for the Michael J. Fox Foundation for Parkinson’s Research.

The foundation, in partnership with industry, is sponsoring an international study of biological markers that can help monitor progression of the disease. Results of the study, called the Parkinson’s Progression Markers Initiative, are expected to facilitate the testing of new drugs that may slow or stop the disease in its tracks.

Dr. Kenneth Marek, a neurologist at Yale University and principal investigator for the biomarkers study, said in an interview, “We need a way to keep track of whether a medicine is working or not.” Because the disease progresses very slowly in some patients and rapidly in others, different treatments are likely to be more effective in some patients than in others.

He said, “A roadblock in developing new drugs has been the inability to predict what will happen over time.”

Dr. Jaffe's husband is participating in this study, as a control subject. Two other participants, Marty Bullock, 68, of Stillwater, Okla., and his wife, Gay Lyn, plan to drive 560 miles every three months to Houston for the next five years, to be prodded and poked to give blood, urine and spinal fluid samples for analysis.

“After my diagnosis, I looked for a research program to participate in,” said Mr. Bullock. “It’s my understanding that Parkinson’s disease doesn’t get any better, so I wanted to see if perhaps I can help benefit someone else in the future.”

From Northwest Parkinson Foundation

Researchers identify why dopamine replacement therapy has a paradoxical effect on cognition


EurekAlert - Dopamine replacement therapy, which is used to manage motor symptoms associated with Parkinson's disease, can, at times, adversely affect cognition.

Dr. Oury Monchi, Ph. D. in neuronal modeling and Head of the Neurophysiological and Neuroimaging Research theme at the Centre de recherche de l'Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated with the Université de Montréal, and Dr. Penny A. MacDonald, Neurologist and postdoctoral fellow in Dr. Monchi's laboratory, have identified the reasons why within the framework of a clinical study recently published in Brain: A Journal of Neurology. This marks the second time in three months that Brain has published the results of IUGM researchers.

"The aim of our study was to understand the effects of dopamine replacement therapy on various aspects of cognition in patients with Parkinson's disease. When it comes to this particular disease, the part of the brain most affected by dopamine depletion is the striatum which is divided into several structures.

In Parkinson's disease, the dorsal striatum is more severely affected than the ventral striatum, which remains relatively unaffected, at least during the first phases of the disease. We observed that while dopamine replacement therapy enhances the functions of the dorsal striatum, it is at the expense of the ventral striatum which suffers a dopamine overdose, impairing its function", states Dr. Monchi.

Until now, the effect of dopamine replacement therapy on cognition in individuals with Parkinson's disease was controversial. The purpose of this study however, was to further investigate. This led to a series of laboratory tests and neuroimaging studies that allowed researchers to clearly define the distinct cognitive functions performed by the dorsal and ventral striatum, thereby shedding some light on the issue.

"The best treatment option for managing the motor symptoms of Parkinson's disease remains dopamine replacement therapy. In some patients however, it can have a negative effect on specific aspects of cognition.

Our discovery will therefore enable us to explore different medication and non-medication based avenues that could help improve the overall health of those affected. Our findings may contribute to helping develop personalized medicine - an avenue that is currently commanding a great deal of attention", exclaims Dr. MacDonald.