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CHILDREN WITH RARE DISORDER FIND HOPE AT CENTER IN SPRINGFIELD, ILL. Tina Hesman Of The Post-Dispatch St. Louis Post-Dispatch (MO) March 22, 2004 Section: NEWS Edition: FIVE STAR LATE LIFT Page A1 * Dr. Michael Pranzatelli is one of the leading authorities on treatment and research of opsoclonus-myoclonus syndrome. What seems like normal toddler play is a neurological test for Nathan. T his time, the tot passes with flying colors. But the first time Nathan visited Dr. Michael Pranzatelli's National Pediatric Myoclonus Center last July, the story was completely different. The child's eyes rolled without warning and wavered as he tried to focus on toys. A video of the visit shows Nathan staggering and stumbling down a hallway. Nathan suffers from opsoclonus-myoclonus syndrome, a disorder so rare there are no good estimates of how rare it is. The disease is Pranzatelli's specialty. There's no mistaking how rare that is. Pranzatelli's clinic is the only one of its kind in the world. His research on the rare disorder could help scientists better understand and treat other diseases, such as multiple sclerosis or Guillain-Barre syndrome, in which the immune system wages war on the nervous system. "This is an example of a non-Fortune 500 disease leading the way for a giant disease," Pranzatelli said. Opsoclonus-myoclonus syndrome is named for the darting eyes and muscle twitches that are the hallmarks of the disease. It is also called dancing eyes-dancing feet syndrome, Kinsbourne syndrome or myoclonic encephalopathy of infants. The disease is caused by an immune system gone awry, Pranzatelli says. Antibodies meant to attack tumors, called neuroblastomas, suddenly turn and assault the nervous system. Such diseases are called autoimmune diseases. Other diseases associated with inappropriate immune system attacks on the body are Type 1 diabetes, rheumatoid arthritis and lupus. About half of children diagnosed with opsoclonus-myoclonus syndrome have neuroblastomas growing somewhere in their bodies. The tumors usually start in the adrenal glands at the top of the kidneys but can grow elsewhere in the belly, neck, chest or groin. The tumors are among the most common childhood tumors - about 11,000 children in the United States are diagnosed with neuroblastoma each year, Pranzatelli said. Only about 3 percent to 4 percent of children with neuroblastoma will also get opsoclonus-myoclonus. Adults also may develop opsoclonus-myoclonus syndrome, usually in association with lung cancer or gynecological tumors. The other half of children with dancing eyes-dancing feet have no sign of neuroblastomas, Pranzatelli said. Those children are commonly thought to have developed the disease after a viral infection. But evidence is growing that all children who get the autoimmune disorder probably had tumors at one time, he said. The children's immune systems probably melted the tumors and then began attacking the brain. Most children show no sign of cancer until the autoimmune disease strikes. The first symptoms of OMS are trembling and uncoordinated movements, uncontrollable eye jerks and rolls and extreme irritability. Within weeks, sometimes only days, previously healthy children are unable to walk or talk. The longer a child waits for treatment, the worse the prognosis, Pranzatelli said. The disease is not fatal but can cause permanent brain damage, he said. And traditional treatments have not worked well to combat the disease. Only 24 percent of children given traditional therapies were enrolled in mainstream schools. About 41 percent required special education programs and 35 percent were enrolled in combined programs. Many patients are unable to live independently as adults. Pranzatelli set out to discover exactly what causes the problems and how to treat them. Nathan's story Nathan's doctors wanted to leave the tumor in and shrink it with chemotherapy, but Nathan's parents weren't comfortable with that approach. They wanted the lemon-size mass out of their son's tiny body. "You've got to remove the underlying cause," Robert Brenengen said. That is a matter of debate, Pranzatelli said. Medical researchers are trying to define when to leave a tumor in place so that the body can finish it off, and when it is safer to remove it. For patients with the disease, there's no good option About a third of patients with OMS get better when their tumors are removed. But another third actually do worse once the tumor is gone, Pranz atelli said. "It's not the tumor issue you're dealing with, it's the immune system," he said. Researchers suspect that antibodies aimed at tumor proteins kill brain cells studded with similar-looking proteins. But scientists have been unable to find the antibodies in many of the patients they examined and don't know which proteins might be serving as targets. Pranzatelli decided to look elsewhere. The doctor first examined spinal fluid from healthy people and compared it to the fluid from sick children. At first glance, there's no difference. The clear fluid contains the same number of immune cells whether it is taken from a healthy or sick child, Pranzatelli found. But he suspected that something was different. Pranzatelli developed a specialized technique to determine the name, rank and serial number of the infection-fighting cells. He found that brain and spinal fluid from healthy people contains mostly immune cells known as T-cells. About 75 percent of the cells are helper T-cells. About a quarter are cytotoxic T-cells. The fluid also contains a few B-cells (less than 1 percent) and natural killer cells. When the doctor examined spinal fluid from children with opsoclonus-myoclonus, he found an explosion of B-cells. Up to 29 percent of the cells in the fluid from OMS patients are B-cells. Those cells churn out antibodies which may attack brain cells involved in maintaining balance and coordinating movement. The patients also have more delta T-cells than normal, Pranzatelli said. Those cells are often found in plaques in the brains of people with multiple sclerosis, he said. No one knows if the delta T-cells are good or bad for people with either disease, Pranzatelli said. "In the immune system, it's hard to identify the good guys from the bad guys, because it's the same guys doing good or bad things," he said. Some therapies, including a biological agent called rituximab, can pick B-cells cleanly out of blood and spinal fluid, Pranzatelli said. The therapy is being tested for opsoclonus-myoclonus and for multiple sclerosis. He is now testing chemotherapies and biological agents of various types to tailor treatment for each of his patients. Pranzatelli has treated more than 120 children with opsoclonus-myoclonus, and has been in contact with families of at least a dozen others. His patients come from all over the United States, Canada, Mexico and other countries, including Germany and South Africa. Nathan's parents never expected to find themselves traveling to Springfield to visit the world's expert on a rare childhood disease, but they say they are pleased with the treatment Pranzatelli devised for their son. "Half of the relief in this whole thing is knowing that we're in good hands," said Nathan's mother, Kim Brenengen. Where: Southern Illinois University School of Medicine in Springfield, Ill. For more information: |
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