Ataxia and Exercise Disease Using MRI and Gait Analysis

The first aim is to show balance training improves DCD individual's ability to compensate for their activity limitations, but does not impact disease progression. The second aim is to demonstrate aerobic exercise improves balance and gait in DCD persons by affecting brain processes and slowing cerebellar atrophy.

Individuals with degenerative cerebellar disease (DCD) exhibit gradual loss of coordination resulting in impaired balance, gait deviations, and severe, progressive disability. With no available disease-modifying medications, balance training is the primary treatment option to improve motor skills and functional performance. There is no evidence, however, that balance training impacts DCD at the tissue level. Aerobic training, on the other hand, may modify DCD progression as evident from animal data. Compared to sedentary controls, aerobically trained DCD rats have enhanced lifespan, motor function, and cerebellar Purkinje cell survival. Numerous animal studies also document that aerobic training has a direct, favorable effect on the brain that includes production of neurotrophic hormones, enhancement of neuroplasticity mechanisms, and protection from neurotoxins. The effects of aerobic training in humans with DCD are relatively unknown, despite these encouraging animal data. A single study to date has evaluated the benefits of aerobic exercise on DCD in humans, and this was a secondary outcome of the study. Although participants performed limited aerobic training during the study, modest functional benefits were still detected. The main objective of this project will be to compare the benefits of aerobic versus balance training in DCD. We hypothesize that both aerobic and balance training will improve function in DCD subjects, but that the mechanisms in which these improvements occur differ. 1) Balance training improves DCD individual's ability to compensate for their activity limitations, but does not impact disease progression. 2) Aerobic exercise improves balance and gait in DCD persons by affecting brain processes and slowing cerebellar atrophy.

The outcome assessor will know that the participant has received balance or aerobic training, but will not be aware of which group the participant belonged.

Participants will be given a stationary exercise bike for home use. They will be instructed to use the exercise bike five times a week for thirty-minute sessions. The exercise intensity prescription will be based on the subject's VO2max determined on pre-test day. The exercise program will start at 60% of intensity per session, and then will be increased by steps of 5% intensity every 2 sessions until participants reach 30 minutes of training at 80% intensity. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be instructed to log each training session. Subjects will record duration of exercise, perceived exertion, average heart rate, maximum heart rate, and distance.

A physical therapist will tailor a home balance training program for each participant based on pre-training capabilities. Subjects will be asked to perform exercises five times a week for thirty-minute sessions. Both dynamic and static exercises will be performed in sitting and standing positions. Exercises will start with stabilizing in a challenging static position and progress to dynamic arm and leg movements in the same or modified position. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be required to log their exercise effort in terms of frequency and level of balance challenge. Individuals will be instructed to perform more difficult exercises if balance challenge scores are low.

Ataxia severity will be measured using the Scale for the Assessment and Rating of Ataxia (SARA).17 SARA evaluates the degree of ataxia by measuring gait, stance, sitting balance, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test.

For the walking assessment, participants will walk as fast as possible on a 10-meter runway six times, and we will average the times of trials 3-6. We will also collect marker position data from infrared emitting diodes placed bilaterally at the first and fifth metatarsal heads, heels, medial and lateral malleoli, medial and lateral condyles of the knee, head of the fibula, and anterior and posterior superior iliac crests pelvic crests using a three-dimensional Vicon motion capture system (Vicon, Denver, CO). Custom Nexus and Bodybuilder software will be used to calculate joint position and determine the following walking parameters: stride length, stride length variability, percent time in double limb support, and degree of pelvic rotation and tilt.

Cranial MRI will be performed in all participants using a 3-T scanner. Using each individual's T1-weighted image, structural imaging measures of cerebellar brain volume will be derived using the FreeSurfer software package (http://surfer.nmr.mgh.harvard.edu/). FreeSurfer will automatically assign a neuroanatomic label to each voxel. From this labeling, a set of volumetric regions of interest is defined. The calculated volume within the cerebellar region is adjusted for variations in individual's intracranial brain volume (ICV) which is measured using BrainWash (an automatic multi-atlas skull-striping software package). We will process the longitudinal T1-weighted images using FreeSurfer longitudinal pipeline, recently implemented to detect small or subtle changes over time.

Inclusion Criteria: Diagnosed with spinocerebellar ataxia Cerebellar atrophy on MRI Prevalence of ataxia on clinical exam Ability to safely ride a stationary exercise bike Exclusion Criteria: Other neurologic conditions Heart disease Cognitive impairment Medical instability

Barbuto S, Kuo SH, Winterbottom L, Lee S, Stern Y, O'Dell M, Stein J. Home Aerobic Training for Cerebellar Degenerative Diseases: a Randomized Controlled Trial. Cerebellum. 2023 Apr;22(2):272-281. doi: 10.1007/s12311-022-01394-4. Epub 2022 Mar 18.