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Previous and ongoing projects:
-The Neuroscience Institute at Stanford (NIS) Working Group on Childhood Motor Disorders
-Assistive Communications Research Program at Stanford
-Planning, Funding, and Operation of a Single-Center Clinical Trial of Botulinum Toxin Type B
-Creation and Funding of the NIH Taskforce on Childhood Motor Disorders
-Development of a Clinical Rating Scale for Hypertonia
-Creation of the Childhood Motor Study Group
-Planning, Funding, and Completion of a Multi-Center Clinical Trial of Trihexyphenidyl
1. The Neuroscience Institute at Stanford (NIS) Working Group on Childhood Motor Disorders
The working group on childhood motor disorders includes Terry Sanger, Scott Delp and Krishna Shenoy. Under Dr. Sanger’s direction, the working group is focused on developing potential new therapies for childhood motor disorders that can subsequently be tested by the Child Motor Study Group. A number of postdoctoral fellows, medical students, and engineering students have joined the working group and are bringing a wide range of innovative ideas to address children’s movement disorders.
Last year Stanford successfully recruited Dr. Jay McLelland from Carnegie Mellon University. Dr. McLelland is an internationally-known researcher in the computational basis of cognition and decision-making. Drs. Sanger, Delp, Shenoy, and McLelland have applied for an inter-departmental training grant from the National Science Foundation to support training and research in Computational Neuroscience. During first-round evaluations, the proposal was rated very highly and we will submit the final proposal this fall.
Two years ago the working group performed an “n-of-1” evaluation in which a single child participated in detailed evaluations of multiple motor and communication function. The vibration biofeedback electrode was a direct result of this program. The program also led to the development of an intelligent joystick controller that can be used to improve the communication rate for interaction with a computer. Pending financial support, we have obtained agreement from Dr. Paul Yock, who leads the Stanford BioDesign program, to continue the n-of-1 project as a fellowship training program with one or two fellows per year dedicated to finding new solutions for children with motor and communication disorders.
2. Assistive Communications Research Program at Stanford
In 2005, we completed a clinical trial in which we measured the relationship between speed and accuracy of reaching movement and used this information to redesign assistive communication software for individual children. We showed that half of the children doubled their rate of communication on an assistive device using the redesigned interface, even though they had only a few minutes of practice. This remarkable result suggests that detailed understanding of the motor function of an individual child can be used to provide customized software and hardware interfaces that are significantly better than what can be achieved otherwise. The paper describing this result is now in press in IEEE Transactions on Rehabilitation Engineering. Although the NIH has been unable to fund further study of this technique during this fiscal year, they have strongly encouraged resubmission for funding next year.
3. Planning, Funding, and Operation of a Single-Center Clinical Trial of Botulinum Toxin Type B
The use of botulinum toxin injections to relax severely stiff muscles has revolutionized the treatment of children who cannot use their arms due to cerebral palsy and other motor disorders. We obtained funding from Elan Pharmaceuticals Inc. for a clinical trial at Stanford. The trial showed that injections of botulinum toxin type B into the biceps of children with dystonia can help to increase their speed of reaching toward a target. The trial is now complete and the manuscript has been published.
4. Creation and Funding of the NIH Taskforce on Childhood Motor Disorders
In April of 2001 the National Institutes of Health (NIH) and the Carter Foundations sponsored a multidisciplinary meeting to establish a consensus on the definitions of “spasticity,” “dystonia,” and “rigidity” so that these terms could be used accurately in clinical discussion and research. Three additional meetings on this topic have culminated in a set of working groups investigating specific technology for diagnosis and quantification of hypertonia. With the assistance of the Carter Foundations and the Stanford Department of Neurology, we have funded four small grants to assist with development of this technology.
The taskforce convened in the spring of 2005, 2006, and 2007 for meetings on “negative signs”, including weakness, deficits of selective motor control, ataxia, and apraxia. A consensus document with definitions of negative signs has been published, and we hope that the consensus document will have the same impact as the consensus document on hypertonia.
We submitted an application to the NIH for continued funding of the taskforce, and we have recently received word that funding is highly likely. The application proposes to address hyperkinetic disorders in children, including chorea, choreoathetosis, and hyperkinetic dystonia. We propose a series of three meetings: the first will provide consensus definitions, the second will examine the state-of-the-art in diagnosis and quantification of hyperkinetic movement disorders, and the third will demonstrate new technologies for diagnosis and quantification.
5. Development of a Clinical Rating Scale for Hypertonia
Spasticity, dystonia, or rigidity may each contribute to a child’s movement disorder, but there is no method for determining which of these is present and which is most important. In cooperation with the NIH Taskforce on Childhood Motor Disorders, we have developed a clinical rating scale for childhood hypertonia.
We are using the results of the trihexyphenidyl clinical trial to perform initial validation of the scale, and a scale development working group has continued to provide further testing and validation.
6. Creation of the Childhood Motor Study Group
The Childhood Motor Study Group (CMSG) is a multi-center research consortium dedicated to performing clinical trials to improve movement in children. We have recently expanded the CMSG from seven to 13 sites, developed and approved by-laws, and have assigned officers and research and planning committees. We are working with a statistician in Chicago to design our next clinical trial, and we are pursuing funding opportunities for this trial.
7. Planning, Funding, and Completion of a Multi-Center Clinical Trial of Trihexyphenidyl
The topic for the initial research trial was approved by consensus at the organizational meeting in July 2001. This trial, titled “cerebral hypertonia of central origin – an open-label trial of anticholinergic treatment effects” (CHOCOLATE) tested the effectiveness of the medication Artane (trihexyphenidyl) in the treatment of childhood dystonia affecting arm movement. The results show that trihexyphenidyl is effective in an identified subset of children, and the study has now been published.