Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease

SIT is a measure of speech intelligibility that requires the participant to read aloud 11 sentences that increase in length from 5 to 10 words. Speech intelligibility is indexed in terms of percent intelligible. This is determined by calculating the mean number of correct words transcribed from the SIT transcriptions by three unfamiliar listeners and dividing this by the total number of words in the 11-sentence sample.

The MSE will include a set of tasks described by Duffy (2013) that permit consistent rating of perceptual characteristics associated with motor speech disorders. These tasks include vowel prolongation, alternating motion rates, sequential motion rates, and contextual speech (oral reading, picture description, conversational speech). These recordings will be used to complete the perceptual assessment of speech characteristics using the Mayo Clinic classification system.

To determine the effect of deutetrabenazine on facial movements at rest and during functional task performance (e.g., speaking, chewing) in individuals with HD, the investigators will utilize a 3-D optical motion capture system (Motion Analysis, Ltd.) consisting of six infrared Kestrel cameras with a sensor resolution of 2.2 million pixels at 2,048 x 1,088 full resolution. Facial movements will be captured by placing small (2mm) reflective spheres on each patient's jaw (right/left/center), mouth (right/left corner, upper/lower lip center), and cheeks (right/left zygomatic bone). Further, reflective markers will be placed on the forehead (right/left eyebrows, right/left forehead). Four head markers will serve as reference markers for head movement correction and transposition of all marker movement into a head-based coordinate system.

To determine the effect of deutetrabenazine on joint kinematics and spatiotemporal parameters using 3D motion analysis. Participants will be recording using the Xsens MVN Awinda motion capture system during a 10 meter walk test. Lower- and upper-limb kinematics will be recorded. Wireless sensors will be placed on the ankle, thigh, hand, forearm, bicep, and head. The velocity of the 10 meter walk can be compared to age and gender matched normative values. Gait speed correlates with functional ability, balance and confidence. Three trials are completed, and the average of the three scores is documented. This test will be completed using the 3D motion analysis system.

The FSST assesses dynamic balance stepping over objects forward, backwards, and sideways. The individual is required to step as fast as possible into each square, requiring the individual to step objects in varying directions. Two tests are completed, with the best time documented as the score.

The FGA assesses dynamic balance during gait and provides objective information regarding risk of falling. The FGA consists of ten items scored from 0-3, with a maximum total score of 30 points. Items include normal walking, walking with speed changes, walking with head turns, pivot turns, obstacle negotiation, tandem walking, walking with eyes closed, walking backward, and negotiating stairs. Scores less than 23/30 are predictive of falls.

The CES is an 8-item patient reported outcome measure that is designed to rate communication effectiveness in individuals with dysarthria. Each of the items presents a communication situation (e.g., talking on the phone with a familiar listener; talking while driving in a car, etc.) and the participant rates his or her perceived ability to communicate in that situation on a scale from "1" (not at all effective) to "4" (very effective).

The Nine-Hole Peg Test is an assessment of fine motor coordination that measures each hand individually. The final score reported is the time required to place and remove nine pegs with each hand. Results are compared to age and gender matched normative values. This test will assess the impact of chorea on fine motor movements and dexterity.

With the 10 Meter Walk Test, velocity can be compared to age and gender matched normative values. Gait speed correlates with functional ability, balance and confidence. Three trials are completed, and the average of the three scores is documented. This test will be completed using the 3D motion analysis system.

The investigators will be using the short-form 36 (SF-36) which is a generic patient-reported outcome measure that quantifies perceived health status. It is used as a measure of health-related quality of life. Sub sections include physical function, role limitations secondary to physical problems, general health perceptions, vitality, social functioning, role limitations due to emotional problems, mental health, and health transition. Participants respond referring to their perceived health over the past 4 weeks.

The FACIT scale has been validated in a number of chronic conditions, including cancer, Parkinson's disease, multiple sclerosis, and HIV/AIDS (Webster 2003). It includes assessments of physical, social, emotional, and functional well-being and is available in multiple condition- and treatment-specific versions. The FACIT scale is sensitive to changes in individual participants over time and can also be used to compare patient populations.