Monster of the Mind; SIU Neurology Group Devoted to Relieving Symptoms of Children's Disease of the Brain

The petite 8-year-old girl with a bandage around her right foot traveled halfway around the world to Springfield in October in search of treatment for a rare brain disease.

Victoria Quequet often was depressed about the balance problems that interfere with her love of dancing and riding her bicycle at home in a village near Grenoble, France.

Her parents, Catherine and Stephane, shared her sadness. Victoria recently broke her right foot in a fall when she lost her balance. The Quequets worry about other aspects of the disease, opsoclonus- myoclonus syndrome (OMS), which include Victoria's attention problems and other delays in her progress at school.

After years of being told by French doctors that nothing more was available to treat Victoria's brain disease - "Deal with it," they were told - they found hope on the Internet, and then sought help from Dr. Michael Pranzatelli, a pediatric neurologist at Springfield's Southern Illinois University School of Medicine.

Victoria, whose immune system has gone haywire and attacked her brain, told her mother she was enjoying the trip and feeling upbeat. Shortly after their flight arrived in Springfield, she said, "We are here to see a doctor to cure me."

Pranzatelli, one of the few American doctors who treats OMS, wasn't able to offer Victoria a cure, but he placed her on a drug regimen designed to halt the disease's progression.

To Victoria and about 150 other children Pranzatelli has treated since 1990 from across the country and some foreign countries, the soft-spoken doctor and his small staff of research assistants and practitioners represent the best chance for targeted, safe and effective treatment.

In addition to caring for patients directly, the Springfield group is trying to reach doctors and nurses worldwide to share their knowledge of the newest, research-based treatments - many of them developed at the medical school.

Pranzatelli said appropriate treatment, combined with early intervention in the toddler years, when the disease normally first hits, can minimize the degree of brain damage most OMS patients face.

The long hours spent treating patients and doing laboratory research have required many personal sacrifices for the Springfield team, especially Pranzatelli and his wife, Elizabeth Tate, a family nurse practitioner who is clinical manager and co-founder of their SIU-based National Pediatric Myoclonus Center.

"There's a mission involved with this," said Pranzatelli, 54, a New Jersey native who came to SIU from Washington, D.C., in 1999 to head a department at the medical school.

"For the first time in our long careers, we're in striking distance to make a major dent in this disease," he said.

An estimated 100 children and 100 adults in the United States get OMS each year. Eye and muscle jerks are the first symptoms of the disease. Symptoms typically appear in children at 18 months of age. The disease also is known as Kinsbourne syndrome or "dancing eyes- dancing feet."

Pranzatelli said OMS often is misdiagnosed, even at major medical centers and by neurologists, who may never see one case in an entire career.

OMS, it is believed, is triggered somehow by a cancer tumor, called a neuroblastoma, somewhere in the body but outside the brain. The immune system switches into gear to fight the cancer but fails to turn off after the cancer is treated. White blood cells end up damaging brain cells in what's known as "friendly fire."

The disease often causes perfectly normal children to become irritable, even inconsolable, overnight. They may want to be held constantly.

They often stop walking or talking and aren't able to feed themselves anymore. "It just takes them and knocks them out of the developmental scale," Pranzatelli said.

The initial tremors usually subside, but some children develop attention-deficit disorder or exhibit fits of rage. During the rages, called "meltdowns," they may bite themselves or their parents.

"We see rage attacks in the clinic" where patients are examined, Pranzatelli said. "I saw one kid slam the door so hard I thought it was going to come off the hinges. I saw one 2-year-old girl just scream at the top of her lungs, go into a corner under a chair and stay there crying for a half-hour."

If untreated, some children can become mentally retarded.

A study of 105 cases recently completed by Tate and research assistant Tyler Allison indicated that because of lack of knowledge among doctors, it takes an average of 11 weeks for these children to be diagnosed in the United States. In Europe or other parts of the world, the delays can be longer.

Pranzatelli would like diagnosis to be immediate so therapy - potentially with a variety of drugs - can begin right away.

About four years ago, Pranzatelli and medical technologist Anna Travelstead developed a way of analyzing spinal fluid obtained in a spinal tap to find out how white blood cells in OMS patients can be abnormally abundant or scarce.

This method, which uses computers, lasers and small amounts of spinal fluid, was a major step forward, he said. It proved long- held suspicions that OMS was caused by an immune system gone awry and identified several different "biomarkers" of disease activity.

But medical knowledge spreads slowly through medical literature. The findings about this tailored analysis of a patient's diagnosis were published only recently - in May - in the journal Neurology.

Pranzatelli is working on research that he believes will prove conclusively in several years that the drug treatments he uses are effective in the long-term or permanently.

The treatments, he said, readjust the unique imbalance of white cells in various OMS patients so different forms of "T-cells" or "B- cells" can return to normal levels.

Pranzatelli and Tate also have developed treatments beyond the steroids and chemotherapy-type drugs prescribed for the disease, and they can tailor the drugs to work on certain types of white cells without subjecting patients to as many potential complications.

He said his research, funded with state, federal and private grants, also could generate future benefits for people with more well-known autoimmune diseases, such as multiple sclerosis and lupus.

Victoria Quequet (pronounced "kay-kay") began making jerky movements with her head and feet at 1 year old, her eyes making "dancing" motions. But her pediatrician in France said the symptoms probably were a bad reaction to her Caesarean-section birth and should be ignored.

She later stopped walking and crawling. She was sent to a child psychologist, who told her parents the problem wasn't psychological. A tumor in her adrenal gland eventually was detected and treated when she was 14 months old, but chemotherapy and high-dose steroids didn't cure her symptoms.

Victoria regressed in her language skills and wanted to be held constantly - all typical symptoms of OMS. She eventually was diagnosed with OMS and received five to six drug treatments over the years, but there was no comprehensive treatment program in France, Pranzatelli said.

Now, Victoria's OMS is in the chronic stage; even minor illnesses still trigger relapses, and her symptoms get worse. She already has suffered permanent neurological damage that has set her back at least one year in school. She continues to have balance problems and attention-deficit disorder.

Pranzatelli found disturbing news in the analysis of her spinal fluid: T-cell levels indicated the disease is still causing attacks on her brain.

Pranzatelli prescribed a once-a-week low-dose pill of methotrexate, a chemotherapy medicine he has had success with before. The drug is available in France and probably will be paid for through the country's socialized medicine system.

He also prescribed a drug to better treat her attention-deficit disorder.

Victoria might be re-evaluated in six months, when her medicine will be changed if her condition doesn't improve. Pranzatelli said his hope is to stop Victoria from relapsing and to improve her balance, but her educational delays probably can't be cured.

"If we had gotten her in that first year, she would be much better now, for sure," he said. But he added that just about everyone with the disease can be helped in some way.

Victoria's father, Stephane, 39, a regional sales manager in France for an American pharmaceutical company, said the trip to Springfield was expensive but worth it.

He, his wife and Victoria, along with Victoria's 7-year-old brother, Alexandre, stayed during their visit at the Ronald McDonald House, which provides low-cost housing for families seeking medical care in Springfield.

Catherine Quequet, 40, had to quit her job as a corporate legal adviser to care for Victoria full time. Catherine said she was confident about Pranzatelli's prescribed treatment, but she will be anxious until she sees results.

"In France, we don't even have a treatment," she said through an interpreter. "It's exciting to see a doctor who takes interest in a case so rare."

Pranzatelli said he still has much work to do in treating OMS patients, conducting research and seeing other neurology patients in his regular practice. But he said he and his wife, who have no children of their own, are gratified by their work.

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

Want more info?

The National Pediatric Myoclonus Center can be reached at or by calling 545-7635.

Source: State Journal Register, December 9, 2004.

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