ObjectiveThe purpose of this investigation was to explore if a physical therapy program involving strength, flexibility, balance, and walking can improve the uncharacteristic gait variability and overall mobility of persons living with multiple sclerosis (pwMS). DesignPre-post design to evaluate the mobility improvements after undergoing 6 weeks of a gait and balance physical therapy intervention. SettingThe initial 2 weeks were conducted at a medical center under close supervision of a physical therapist. The remaining 4 weeks were performed by the patient at their home and monitored via teleconferences. ParticipantsFifteen pwMS with relapsing-remitting (N=11) or secondary progressive multiple sclerosis (N=4) were enrolled in this study (7 women; mean age: 54.8±9 years; Kurtzke Expanded Disability Status Score range: 3.0-6.5). A group of healthy age-matched controls (N=15) were used for comparisons. InterventionsThe 6-week physical therapy intervention included exercises that targeted strength, flexibility, balance, and walking. The initial 2 weeks of the intervention were performed on-site with the remaining 4 weeks home-based. The therapy was performed twice-a-day for 5 consecutive days each week. Each session was 45 minutes in length. Main Outcome MeasuresPreferred walking speed, spatiotemporal gait kinematics, and a 6-minute walk test were completed before and after therapy. The standard deviation (SD) and sample entropy were used to evaluate the amount of variability and the regularity of the time-dependent variations in the center of mass (COM) accelerations during the 6-minute walk test. ResultsBefore the intervention, the SD of the COM was reduced, and the time-dependent variations were less regular in the pwMS than the control group. After therapy, the SD was 12% larger, and the time-dependent variations were more 7% regular in the pwMS. The effect size for these changes were large (0.91 and 0.94, respectively), suggesting these changes were meaningful. The changes in the regularity of the COM were related to the mobility improvements in the preferred walking velocity and 6-minute walk test. ConclusionsThe results suggest that pwMS have altered COM variability during gait, which can be improved with a similar physical therapy program. These changes appear to be linked with the extent of the mobility improvements.