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Last Updated: Nov 17th, 2006 - 22:35:04

Sleep Disorders Channel
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Latest Research : Psychiatry : Sleep Disorders

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Genetic disease offers clues to SIDS, sleep apnea
Jul 12, 2005, 13:02, Reviewed by: Dr.

"Now that we know where the damage exists, scientists can focus on new strategies to help the brain compensate for the injury," said Harper. "For example, we may be able to inject injured areas with nerve growth factors to stimulate the regrowth of lost nerve fibers and recover some functions."

 
Imagine raising a child who stops breathing when falling asleep and has to be reminded to visit the bathroom after drinking a Big Gulp. That's the dilemma faced by parents of children born with congenital central hypoventilation syndrome (CCHS). Afflicting about 250 children in the United States, the genetic disease wreaks havoc in areas of the brain that control involuntary actions such as breathing, fluid regulation and heart function.

Now an MRI study by UCLA scientists reveals that these children's brains display stroke-like damage in regions that regulate the cardiovascular system, body temperature and urination. Published July 11 in the Journal of Comparative Neurology, the research holds important clues for unraveling the mysteries of sudden infant death syndrome (SIDS), sleep apnea and numerous other conditions.

"For a breathing researcher, this syndrome represents a rare opportunity from Mother Nature," explained Ronald Harper, Ph.D., principal investigator and professor of neurobiology at the David Geffen School of Medicine at UCLA. "By using CCHS as a model to study how the brain controls breathing, we hope not only to help children born with the disease, but also provide insights into SIDS and sleep apnea.

"These children's brains don't respond to the same cues as the rest of us, which prevents a host of involuntary mechanisms from kicking in," he added. "Younger children have to be reminded to breathe and to go to the bathroom. They will plop down to relax in front of the TV or a video game, start turning blue and not realize they are passing out."

Some children show disruption of the sympathetic nervous system, which regulates cardiovascular function. They have disturbed heart rates and blood pressure, often profusely sweat or shiver, especially at night, and sometimes faint during strenuous bowel movements. A mild fever can worsen breathing problems and quickly grow life-threatening. The pupil of one eye may constrict, while the other remains dilated.

Harper and his colleagues performed MRI brain scans on 12 children with CCHS and compared their scans to those of 28 healthy children matched by age and gender.

"We were startled to see severe tissue injury in multiple regions of the brains of children with CCHS," said Dr. Rajesh Kumar, first author and UCLA neurobiology researcher. "This damage prevents different parts of the brain from communicating with each other and blocks the nervous system from responding to involuntary reflexes."

Located primarily on the right side of the brain, the damage proved extensive. Tissue loss centered in the brain's emotion areas, which may explain the children's lack of fear to the feeling of suffocation. Damage also appeared in the anterior cingulate, which helps regulate cardiovascular function, blood pressure, heart rate and pain. This region also is involved in recognizing the urge to urinate.

The basal forebrain showed damage, as well. This area contains sensors for carbon dioxide, regulates thirst and body temperature, and plays a role in maintaining sleep.

"Now that we know where the damage exists, scientists can focus on new strategies to help the brain compensate for the injury," said Harper. "For example, we may be able to inject injured areas with nerve growth factors to stimulate the regrowth of lost nerve fibers and recover some functions."

At least 70 percent of CCHS children tested possess a mutation of PHOX2B, a gene related to brain structures that control blood vessel diameter. Harper hypothesizes that the mutated gene prevents normal development of these regions, resulting in narrowing of the blood vessels and inadequate blood flow to the brain sites that control breathing

"We think that insufficient blood flow starves cells of oxygen in the brain structures that regulate breathing," said Harper. "The breathing disorder results from the brain's inability to develop completely."

Parents of children with CCHS are desperate to call attention to the need for research of the mysterious syndrome. The condition forces most young patients to undergo a tracheotomy, an opening in the windpipe, which enables parents to quickly connect children to ventilators at bedtime. A family vacation requires lugging the ventilator on planes and to hotel rooms.

A few years ago, ventilators weren't available, and CCHS children died young. Now ventilators are enabling these children to live past adolescence, when they often unwittingly kill themselves by falling asleep after drinking alcohol. With proper care, CCHS children are now living into their 30s, marrying and having children of their own.
 

- Journal of Comparative Neurology
 

http://www.healthcare.ucla.edu

 
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The National Institute of Child Health and Development funded the research. Harper and Kumar's coauthors include Paul Macey and Jeffry Alger of the David Geffen School of Medicine at UCLA; Mary Woo of the UCLA School of Nursing; and Thomas Keens of Children's Hospital Los Angeles.

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