January 16, 2004

SIU Pediatric Neurologist Treats Patients from the U.S. and Abroad for Rare Disorder

SPRINGFIELD, Ill. -- A distraught young mother watched helplessly as her 16-month-old child, Madalin, laid on an examining table, her muscles and eyes twitching uncontrollably. Madalin had been a healthy and active toddler until the day before. Her symptoms began with a shiver, agitation and wanting to be held constantly. Forty-eight hours later she was no longer able to walk.

A physician told Madalin's mother, Jennifer Olson of Portage, Ind., that he had never seen anything like it before. "It's one of the scariest things a mother can experience," says Olson. Madalin was diagnosed later with opsoclonus-myoclonus syndrome (OMS) at a Chicago hospital.

"This very rare disorder can affect people of any age. Its first symptoms are eye and muscle jerks. It also is known as Kinsbourne syndrome or 'dancing eyes -- dancing feet'" says Dr. Michael Pranzatelli, professor of neurology and pediatrics at Southern Illinois University School of Medicine in Springfield and director of the National Pediatric Myoclonus Center.

Pranzatelli is one of the few physicians in the U.S. who treats this disorder. He has seen approximately 120 patients with OMS, about 50 of them in the past three years. "Because the disorder is so rare, some neurologists may never see a case in their entire career," explains Pranzatelli.

OMS strikes children who are perfectly normal. Overnight they start shaking and within two weeks, the child may not be able to walk or talk. "When the child is taken to a medical center, there is a good chance the disease will not be recognized. It is often misdiagnosed as a viral infection, which causes delays in starting appropriate treatment," explains Pranzatelli.

OMS can affect both children and adults and is often associated with a neuroblastoma, a cancer tumor. Although the symptoms come from the brain, the tumor is located elsewhere in the body. Children who have the disease may have a neuroblastoma in the chest, abdomen, pelvis or neck. In adults, the tumor is often a lung or gynecological cancer.

"This is an autoimmune disease which starts to fight a tumor. But the body's immune system relentlessly attacks the brain, which gets injured in the cross firing of the immune system as it tries to eradicate the tumor. Unless treatment is given to break off that attack, there will be permanent brain damage," says Pranzatelli.


SIU Pediatric Neurologist Treats Patients from the U.S. and Abroad for Rare Disorder -- add 1

In the peak of the syndrome, the child is extremely irritable and wants to be held constantly. They often scream all night, getting only a few minutes of sleep and wearing down the family. If untreated or not treated properly, behavioral problems begin including attention deficit or obsessive compulsive disorder, rage or temper tantrums, and possibly mental retardation.

For a definitive diagnosis, extensive testing is required to search for the tumor, which may include blood and urine tests as well as body CT, PET and nuclear MIBG scans. An evaluation of the patient's neurologic system follows, which includes an MRI and EEG of the brain, and a spinal fluid test to check for a high concentration of white blood cells.

"One of these white blood cells, the B cell, produces autoantibodies that attack the brain. In children with this syndrome, the B cell population is many times higher than normal," explains Pranzatelli. He has developed strategies to detect the B cells in spinal fluid and is using a new biological agent, rituximab, which attacks and destroys them. This helps prevent relapses and halts progression of the disease. "The spinal tap studies are very tricky and they are not done in many places," he explains.

Treatments for the OMS include adrenocorticotrophic hormone (ACTH) injections, which are steroids that have serious side effects including weight gain and high blood pressure. Another treatment is intravenous immunoglobulins (IVIG), which are infusions given over the period of several hours. Chemotherapy also is used to prevent relapses.

Maya Bott, of Kildeer, Ill., contracted the disease at age 2 and suffered from extreme rage attacks along with an inability to walk, uncontrollable eye movement and loss of motor skill coordination for two years. It was so severe that she couldn't be sedated with standard medication to have a CT scan. "She became dehydrated from vomiting and her skin was broken from biting herself," remembers her mother, Margo Bott.

At age 3 1/2 Maya was referred to Pranzatelli after ACTH injections made her little body balloon to 50 pounds. After a spinal tap, Pranzatelli developed a customized treatment of immunotherapy based on her cell test results. "She soon began improving and recently was able to come off the steroids after being on them for 3 1/2 years. Maya is now 6 and is still on treatment. But she now relates well to her twin sister and classmates," said Margo Bott.

The prognosis for patients with OMS depends on several factors -- how severe the patient is at the start, how much time lapses before the right treatment begins, and how many relapses they have.

"With older treatments, it was uncommon for patients with moderate or severe symptoms to be able to live independently, hold a job or have a family. With the newer treatments, we hope patients will do much better and even be mainstreamed in regular schools," explains Pranzatelli.


SIU Pediatric Neurologist Treats Patients from the U.S. and Abroad for Rare Disorder -- add 2

In 1985, after seeing a need for a systematic approach to treating the disease, Pranzatelli established the National Pediatric Myoclonus Center to provide medical and psychological support for families who are strained by the illness. It has evolved into a full-service center now based in Springfield, offering both care and advocacy for patients whose myoclonus began during childhood, partially due to the efforts of research nurse practitioner, Elizabeth Tate. The staff currently totals eight, which includes five researchers.

The non-profit center is supported by federal, pharmaceutical, institutional and private funds and has grown to be a referral center for patients in the U.S., Canada, Mexico and other countries including Germany and South Africa. Patients sometimes qualify to participate in clinical trials. The center helps arrange airfare donated by Miracle Flights and overnight accommodations in Springfield for patients and families at the Ronald McDonald House.

Patients and families are often referred to Pranzatelli and his team by other physicians. Some patients have located him after reading the numerous articles published about his research and through the center's website --http://www.omsusa.org .

Pranzatelli has been awarded more than 15 research grants to study myoclonus. His latest research project is evaluating the effects of immunotherapy on the B-cell and T-cell biomarkers of disease activity that he and his team discovered in OMS. He now is trying to identify which agent is most effective in eradicating the brain inflammation that characterizes the syndrome. He will begin a new phase I clinical trial sponsored by Genentech Inc., that will evaluate the biological agent, rituximab, this year.

As part of his teaching at SIU's medical school, Pranzatelli works with medical students and residents to help them become familiar with the disease. "It is my hope that after they finish their training, some of them will be interested in doing research on autoimmune brain disorders in children."

Pranzatelli joined the SIU faculty in 1999. He is board certified in pediatrics, psychiatry and neurology. He may be contacted through SIU's Department of Neurology in Springfield, 217-545-7635.

NOTE TO EDITORS: JPG images of Pranzatelli with his research team working in the lab and of patient Madalin Olson with research nurse, Elizabeth Tate, are available by calling SIU Public Affairs at 217-545-2155.