A Corticospinal Tract Model to Explain Clinical Deficits in ALS. (P4.129)

OBJECTIVE: The aim of the study was to understand the relationship between functional clinical losses and upper motor neuron (UMN) dysfunction due to loss of corticospinal tract fibers. BACKGROUND: We modeled corticospinal tract as a collection of noisy communication channels that convey kinematic and dynamic state information from neural networks responsible for control of voluntary muscle activity. DESIGN/METHODS: Triple Stimulation test (TST) was performed in 28 ALS patients to assess the number of corticospinal motor neurons. The clinical motor deficits in these subjects were measured using a combination of dexterity tests and dynamometry testing. Disease severity was measured using Appel ALS Scale and ALSFRS-R scale. RESULTS: The degree of UMN loss significantly predicted ALSFR-R (s=0.532 p=0.006) and Appel ALS Scale (AALS) (s=-0.425, p=0.034). Upper extremity evaluation of a complex task using the ‘timed propelling of a wheel chair 20ft’ (s=-0.467, p=0.021) and dexterity testings using ‘Purdue peg board test’ (s=0.317, p=0.022) and ‘block and board test’ (s=0.378, p=0.007) performances were all significantly predicted by the degree of UMN loss. UMN loss did not significantly predict dynamometry measured deficits using lateral pinch (s=0.227, p=0.113) and hand grip (s=0.204, p=0.155). CONCLUSIONS: Upper motor neuron loss can be viewed clinically as the loss of the motor cortex’s ability to convey kinematic and dynamic state information. Using neurophysiological techniques, we demonstrated that the UMN loss significantly influenced ALS patient9s ability to perform complex time sensitive tasks. Dynamometry testing did not show any significant relationship with upper motor neuron loss. The quantification of upper motor neuron loss is also a helpful parameter in predicting the disease severity as measured by Appel ALS and ALSFRS-R scales. Study Supported by: None Disclosure: Dr. Remanan has nothing to disclose. Dr. Panchal has nothing to disclose. Dr. Tohidi has nothing to disclose. Dr. Kaplan has nothing to disclose. Dr. Holzberg has nothing to disclose. Dr. Shahbazi has nothing to disclose. Dr. Lange has received personal compensation for activities with Genzyme as a consultant.