Targeted ballet program mitigates ataxia and improves balance in females with mild-to-moderate multiple sclerosis

Background Multiple sclerosis (MS) is a disease of the central nervous system that causes ataxia and deficits in balance. Exercise-based therapies have been identified as integral to the recovery of motor function in MS, but few studies have investigated non-traditional movement interventions. We examined a targeted ballet program (TBP) designed to mitigate ataxia and improve balance in females with mild-to-moderate relapsing-remitting MS. Methods and findings Twelve females with mild-to-moderate disability due to MS were assessed for study eligibility for the study. Ten participants met the inclusion criteria. Two were lost to unrelated health complications. Eight participants completed the TBP. The TBP met twice a week for 60 minutes for 16 weeks. Assessments included (a) the International Cooperative Ataxia Rating Scale (ICARS), (b) the Mini-Balance Evaluations Systems Test (Mini-BESTest), (c) smoothness of movement during a five-meter walk, and (d) balance in a step to stand task before and after the TBP. There were no TBP-related adverse events. Single-tailed paired samples t-tests and Wilcoxon tests were conducted. Improvements were observed in ICARS (p = 7.11E-05), Mini-BESTest (p = 0.001), smoothness of movement in the left (p = 0.027) and right (p = 0.028) sides of the body, and balance in a step-to-stand task in the back (p = 0.025) direction. Results yielded 42% and 58% improvements in the mean Mini-BESTest and ICARS scores, respectively. Conclusions This study adds to current research by providing support for a TBP intervention targeting ataxia and balance in MS. The TBP was well tolerated, improved balance, and mitigated ataxia. Clinical improvements were larger than those of previous studies on physical rehabilitation in MS with similar outcome measures. Trial registration ISRCTN ISRCTN67916624.


Introduction
Background 2 Scientific background and explanation of rationale Theories used in designing behavioral interventions

Methods
Participants 3 Eligibility criteria for participants, including criteria at different levels in recruitment/sampling plan (e.g., cities, clinics, subjects) Method of recruitment (e.g., referral, self-selection), including the sampling method if a systematic sampling plan was implemented Recruitment setting Settings and locations where the data were collected Interventions 4 Details of the interventions intended for each study condition and how and when they were actually administered, specifically including: Unit of assignment (the unit being assigned to study condition, e.g., individual, group, community) Method used to assign units to study conditions, including details of any restriction (e.g., blocking, stratification, minimization) Inclusion of aspects employed to help minimize potential bias induced due to non-randomization (e.g., matching) x 2 x 2 x 2 x 2 3 x 4-5 x 4 x 4 x 6 x Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to study condition assignment; if so, statement regarding how the blinding was accomplished and how it was assessed.
Unit of Analysis 10 Description of the smallest unit that is being analyzed to assess intervention effects (e.g., individual, group, or community) If the unit of analysis differs from the unit of assignment, the analytical method used to account for this (e.g., adjusting the standard error estimates by the design effect or using multilevel analysis) Statistical Methods

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Statistical methods used to compare study groups for primary methods outcome(s), including complex methods of correlated data Statistical methods used for additional analyses, such as a subgroup analyses and adjusted analysis Methods for imputing missing data, if used Statistical software or programs used

Participant flow 12
Flow of participants through each stage of the study: enrollment, assignment, allocation, and intervention exposure, follow-up, analysis (a diagram is strongly recommended) o Enrollment: the numbers of participants screened for eligibility, found to be eligible or not eligible, declined to be enrolled, and enrolled in the study o Assignment: the numbers of participants assigned to a study condition o Allocation and intervention exposure: the number of participants assigned to each study condition and the number of participants who received each intervention o Follow-up: the number of participants who completed the followup or did not complete the follow-up (i.e., lost to follow-up), by study condition o Analysis: the number of participants included in or excluded from the main analysis, by study condition Description of protocol deviations from study as planned, along with reasons Recruitment 13 Dates defining the periods of recruitment and follow-up Baseline Data 14 Baseline demographic and clinical characteristics of participants in each study condition Baseline characteristics for each study condition relevant to specific disease prevention research Baseline comparisons of those lost to follow-up and those retained, overall and by study condition Comparison between study population at baseline and target population of interest Baseline equivalence 15 Data on study group equivalence at baseline and statistical methods used to control for baseline differences Number of participants (denominator) included in each analysis for each study condition, particularly when the denominators change for different outcomes; statement of the results in absolute numbers when feasible Indication of whether the analysis strategy was "intention to treat" or, if not, description of how non-compliers were treated in the analyses Outcomes and estimation 17 For each primary and secondary outcome, a summary of results for each estimation study condition, and the estimated effect size and a confidence interval to indicate the precision Inclusion of null and negative findings Inclusion of results from testing pre-specified causal pathways through which the intervention was intended to operate, if any Ancillary analyses 18 Summary of other analyses performed, including subgroup or restricted analyses, indicating which are pre-specified or exploratory Adverse events 19 Summary of all important adverse events or unintended effects in each study condition (including summary measures, effect size estimates, and confidence intervals)

Interpretation 20
Interpretation of the results, taking into account study hypotheses, sources of potential bias, imprecision of measures, multiplicative analyses, and other limitations or weaknesses of the study Discussion of results taking into account the mechanism by which the intervention was intended to work (causal pathways) or alternative mechanisms or explanations Discussion of the success of and barriers to implementing the intervention, fidelity of implementation Discussion of research, programmatic, or policy implications Generalizability 21 Generalizability (external validity) of the trial findings, taking into account the study population, the characteristics of the intervention, length of follow-up, incentives, compliance rates, specific sites/settings involved in the study, and other contextual issues Overall Evidence

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General interpretation of the results in the context of current evidence and current theory