Lifting Barriers for Children With Movement Disorders
Clinical Savvy and High-Tech Tools Shed New Light on Motor Problems

At Packard's Movement Disorders Clinic, Terry Sanger, M.D., Ph.D., works with 17-year-old Molly Williams to unravel the cause of her severe motor problems.

FALL 2002 - The first thing you notice about Molly Williams is her smile. The pretty 17-year-old with a blond ponytail arrives with her parents at the Packard Children's Hospital Movement Disorders Clinic for a checkup with its director, Terry D. Sanger,M.D., Ph.D. But Molly wasn't always so tranquil.

The first time Molly met Sanger, she was suffering from severe clonus (brief involuntary jerking movements) that caused her to shake uncontrollably. Using a pioneering approach to treat movement disorders that combines quantitative assessment, innovative therapy, and his own clinical intuition, Sanger helped Molly when other specialists could not.

Sanger's clinic is one of the few in the world devoted exclusively to children's movement disorders, which most commonly stem from cerebral palsy and other neurological problems. In order to treat such disorders more precisely, Sanger is working to uncover the fundamental defects in brain messaging that can lead to difficulties with motor control.

A Treatable Cause

We adopted Molly when she was four days old," explains her father, Charles Williams. "By the age of 20 months we noticed that her physical development was proceeding in an unusual manner, so we took her to a neurologist, who told us she had cerebral palsy."

Over the next decade, Molly required two operations to minimize gait abnormalities and help her adapt to walking with braces. By the time she reached high school, a wheelchair had become increasingly necessary. Then, in the fall of 2001, she began to suffer from profound clonus of the arms and legs. The shaking became so violent that she couldn't concentrate in the classroom or even hold a pencil, and her breathing had become very shallow and irregular. "We were all terribly concerned," says Molly's mother, Toni, "especially after a pediatrician told us that clonus was a common byproduct of cerebral palsy and nothing could be done."

Fortunately, Molly's orthopedic surgeon at Packard, Lawrence A. Rinsky,M.D., did not agree. He felt there might be a treatable cause and urged the Williamses to take their daughter to Sanger's clinic for evaluation.

Clinic Associate Sara Sherman-Levine, R.N., P.N.P., helps assess Molly's motor control as she responds to new treatment.

As soon as Sanger saw Molly, he sensed that something unusual was happening and ordered a battery of tests. The results showed that, in addition to her movement disorder, the teenager had Graves' disease, a thyroid defect that can cause clonus in its own right. "When I started on medication for hyperthyroidism," she says, "it was like a big weight had been lifted. The clonus just about stopped, my attention span improved, and my grade-point average really shot up."

To William C.Mobley,M.D., Ph.D., chair of the Department of Neurology at Stanford,Molly Williams' story illustrates the kind of creative thinking that has made the Movement Disorders Clinic a referral center for families throughout California. "Probably nowhere in the world is the management of these conditions so advanced," he notes. "Terry Sanger sees patients that other specialists don't know how to help, and he figures out ways to help them."

An Inquiring Mind

"Too often," says Sanger, "treatable conditions like hyperthyroidism are missed because nobody has taken the trouble to look for them. There is a tendency to assume that every child who moves abnormally has cerebral palsy, and that any symptoms the child develops will not respond to treatment. But that just isn't so."

According to Sanger, childhood motor disorders may be caused by a number of other things, such as brain malformations, biochemical defects, or degenerative diseases. And while the basic injury is usually incurable, often the symptoms -- whether due entirely to the brain disease or to the brain disease plus some other, unrelated condition -- will respond to drugs or other therapy.

"We think Molly actually has an uncommon genetic disorder called hereditary spastic paraparesis (HSP) which can produce clonus of the legs, similar to cerebral palsy," says Sanger. "However, since her movements were exceptionally dramatic and also involved her arms, I suspected that something else was making her problem worse. In Molly's case, the condition turned out to be hyperthyroidism."

Mobley says that Sanger is uniquely suited to this work. "In addition to being a gifted clinician, he is an internationally respected researcher with a background that includes computer science, electrical engineering, applied mathematics, as well as neuroscience. He is using mathematical models of neural networks to try to describe exactly what happens when the brain's circuitry is impaired and a child's limbs fail to respond normally."

Sanger theorizes that each movement is composed of a limited set of "primitives," simple components that when placed in correct sequence will spell out a recognized behavior, such as grasping an object. When motor function has been damaged through birth injury or other causes, this sequence goes awry. The set may be incomplete, or the primitives may be scrambled so that the action appears purposeless (for example, rather than grasping the object, the patient's arm thrashes about). In other cases, the attempt to produce the behavior may flood the system with so many responses that the motion is frozen in midair. By defining the patterns associated with normal actions and comparing them with the faulty patterns observed in his patients, Sanger hopes to uncover clues to the fundamental defects in signal processing.

Technology Borrowed From Hollywood

Sanger applies surface EMG electrodes to measure Jake Cannon's muscle activity. Jake then is asked to perform a series of simple tasks like touching his finger to his nose. By using biofeedback training, Sanger hopes this tool will allow children like Jake to emulate normal patterns of movement.

For 13-year-old Jake Cannon, who suffered a cerebral hemorrhage in infancy that left him with motor impairment, visits to Sanger's Movement Disorders Laboratory are a "neat" opportunity to watch his skeleton come to life onscreen. Sophisticated motion-capture technology of the kind developed for animated films allows Sanger's team to analyze sequences of movement with mathematical precision. First, the youngster's extremities are wired with sensors capable of reading position in space. Then he is asked to perform a series of simple tasks, such as "reach out and try to touch your nose." The computer tracks the motion and translates it into an image of the child's skeleton.

What may seem like a game is in fact a groundbreaking tool for patient assessment that Sanger hopes eventually will lead to effective biofeedback training, in which children with motor disorders are taught to emulate normal patterns of movement as demonstrated onscreen.

"The majority of these patients have a miscommunication between brain and spinal cord," he explains. "The order to move an arm or leg is not carried out correctly but instead results in ‘negative symptoms,' in which the limb remains weak and floppy, or ‘positive symptoms,' in which muscle contractions are excessive and the patient experiences stiffness and spasticity."

While there are no good drugs yet for negative symptoms, many children do make real progress through physical therapy and repetitive exercise. For positive symptoms such as spasticity, there have been a number of recent breakthroughs--notably botulinum toxin, which in small quantities can weaken muscles just enough to ease movement. The Packard team currently is launching a clinical trial using this agent in preschoolers as young as 2, on the premise that increasing mobility during the formative years may yield benefits beyond those obtainable later.

Dystonia is another form of stiffness in which the underlying problem is not miscommunication but faulty programming. The brain orders an incorrect pattern of movement for the required task, with the result that the patient who tries to reach forward may instead find his head jerking backward and his arm shooting off to one side. Like spasticity, dystonia responds to drug therapy.

"In the past," says Sanger, "drug choices for motor disorders were often made without any real understanding of which movement patterns responded to which agents. Using surface EMG electrodes that measure muscle activity, we may be able to identify the most effective drugs for a patient's symptoms and eliminate a lot of the guesswork."

Not all of the drugs Sanger prescribes are new. Some are conventional agents that have been used for years to treat Parkinson's disease and other motor disorders in adults, without recognition that they might be suitable for children with similar symptoms.

A Team Effort

"We are breaking new ground every day," says Sara Sherman-Levine, R.N., P.N.P., who works with Sanger. "Each small achievement is a milestone, and the result of months of effort by the patient, the family, and a therapeutic team that may include specialists from four or five separate medical areas."

Molly Williams is a case in point. In addition to Drs. Sanger and Rinsky, Richard B.Moss, M.D., chief of the Pediatric Pulmonary Division at Stanford, and pediatric endocrinologist E. Kirk Neely, M.D., see Molly regularly.

"There's a constant exchange of information, which has allowed each of Molly's doctors to really understand her medical issues and get to know her as an individual," says Toni Williams. "When Molly developed severe clonus and we were all so frightened, it was enormously reassuring to know that we could bring her to this institution because we were confident the care would be outstanding."