Abstract
Background
Spasticity affects more than 80% of people with multiple sclerosis (MS), affecting activity, participation, and quality of life. Based on an international guideline, an MS spasticity group education and stretching program, MS Spasticity: Take Control (STC), has been developed.
Objective
The objective of this paper is to determine whether STC with home stretching is associated with greater changes in spasticity than usual care (UC), consisting of an illustrated stretching booklet and home stretching but without group instruction or support, in people with MS.
Methods
Ambulatory MS patients with self-reported spasticity interfering with daily activities were randomized to STC or UC. Individuals completed questionnaires regarding MS, spasticity, walking, fatigue and mood, and physical measures of spasticity and walking.
Results
Thirty-eight of 40 participants completed both assessments. Mean total score and scores on two subscales of the MS Spasticity Scale-88 improved more with STC than with UC (p < 0.03). There was no significant change in the Modified Ashworth Scale in either group. Mean scores on the Modified Fatigue Impact Scale, the Beck Depression Inventory-II, and the physical component of the Multiple Sclerosis Impact Scale-29 showed statistically and clinically significant improvements in the STC group only.
Conclusions
Participation in STC improved self-reported impact of spasticity more than UC and provided encouraging improvements in other measures.
Introduction
Multiple sclerosis (MS) is a common disabling disease of the central nervous system affecting approximately 400,000 Americans and 2.5 million people worldwide. 1 Spasticity occurs in 60%–80% of people with MS (PwMS) and contributes to MS disability with gait disorders, falls, fatigue, spasms, and pain potentially hastening the time to wheelchair dependence. Increased disability and dependency may lead to social isolation and depression, cardiovascular disease, muscle fibrosis, and joint contracture with secondary skin breakdown, infection, and death.2–4 In 2003, an international guideline for spasticity management in MS was published.3,4 Based on this guideline, a small-group self-management program, MS Spasticity: Take Control (STC), was developed. This program has an educational digital video disc (DVD), a lower-extremity stretching DVD, and facilitator and participant manuals. We conducted a randomized, controlled pilot trial with 40 participants to evaluate the acceptance, feasibility, and initial efficacy of the STC program.
Materials and methods
Study design
This was a single-center, single-blind, parallel, two-arm, randomized, controlled trial with 1:1 allocation comparing STC with usual care (UC) for lower-extremity spasticity in PwMS. STC includes two two-hour weekly group sessions followed by home stretching. UC used an illustrated booklet with home stretching instructions but no in-person instruction or group support. Primary outcomes were assessed for both groups following four weeks of home exercise.
Study participants
This study was approved by the joint Veterans Administration Portland Health Care System (VAPORHCS) and Oregon Health & Science University (OHSU) Institutional Review Board, registered with clinicaltrials.gov #NCT02170779, and all participants signed and received a copy of the written informed consent. Inclusion criteria were (1) physician-confirmed diagnosis of MS, 5 (2) age 18 or older, (3) able to provide informed consent and comply with study procedures, (4) able to walk 25 feet independently with or without assistive devices, (5) fluent in written and spoken English as program materials are not provided in other languages, (6) self-reported lower-extremity spasticity interfering with daily activities, and (7) willing to not change medications during the study. Exclusion criteria were (1) other medical or mental conditions that would interfere with participation.
Location and facilitators
Participants were recruited from the VAPORHCS and OHSU MS clinics and the surrounding community. Baseline and follow-up measures were completed by research assistants blinded to group assignment. STC was facilitated by a licensed physical therapist (CH) with assistance from the study coordinator.
Procedures
Participants consented and completed all physical assessments in person. A link was then emailed to participants to complete study questionnaires electronically later the same day at home or on a library computer at the study site. The statistician (YC) provided randomization in blocks of two with the first individual randomly assigned to STC or UC and the second individual assigned to the other arm. Those randomized to STC came to two two-hour classes one week apart. Those randomized to UC were mailed the stretching booklet and exercise diary with instructions to stretch daily and record all exercise. Four weeks later, all participants were sent a link to complete the study questionnaires electronically prior to completing the physical outcome measures in person. Participants were kept blind to active or control intervention assignment by being informed we were comparing different MS-specific materials for effects on MS and symptoms of MS to determine which worked best. All study visits and STC classes were held in accessible conference rooms with free parking. All participants received $100 for time and travel for each study visit attended.
Interventions
Experimental intervention
Contents of MS Spasticity: Take Control program.
MS: multiple sclerosis; DVD: digital video disc.
Control intervention/UC
Participants in the UC group did not attend the two class visits but instead were mailed the National MS Society (NMSS) booklet Stretching for people with MS: An illustrated manual and the same exercise diary given to the STC group with instructions to stretch daily and record all exercise for the same four weeks as the STC group and return for the final assessment visit. 6 We called this “usual care” because the NMSS has provided this free booklet to people with MS who ask about appropriate exercise for more than 25 years.
Outcome measures
Outcome measures were questionnaires administered electronically and physical measures collected in person. For all the questionnaires, lower scores are better (i.e. less impact of MS). The first four are MS-specific scales developed for MS and validated in MS.
The
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The physical measures, also widely used and validated in MS, were the following.
The
All participants kept an exercise diary for the four weeks of home practice and completed a knowledge test about spasticity following either intervention.
Statistical analysis
Descriptive statistical analysis was conducted for all endpoints and patient characteristics by group and as a whole. Because of the small sample size, it is not easy to determine whether the endpoints or the changes of the endpoints approximately follow a normal distribution. Therefore, we used non-parametric tests throughout the study for robustness of the testing result. We used the signed test to evaluate whether the changes following the interventions were significant within each group, and used the Wilcoxon rank sum test to compare whether the changes were significantly different between the two groups. We used McNemar’s test to determine whether participants within each group changed stretching activity from baseline to follow-up. Also, because of the small sample size, we lack the power to reliably conduct multiple regression modeling to control for the potential baseline differences for this pilot study. All testing results that had a p value less than 0.05 were considered statistically significant. SAS 9.4 (Cary, NC) was used for all data analysis.
Results
Between December 2015 and April 2016, 40 individuals were randomized and 38 completed both baseline and follow-up measurements for analysis (Figure 1). Baseline measurements did not differ between groups except more people in the STC group than in the UC group were taking MS disease-modifying medications (13 (68.4%) and five (26.3%), respectively) (Table 2). Mean MSSS-88 total scores improved more in the STC group than in the UC group between baseline and follow-up (STC –27.8, UC –3.7, p < 0.03) and on the pain and discomfort subscale (STC –3.9, UC +0.3, p < 0.02) and muscle spasms subscale (STC –5.0, UC –0.5, p < 0.03) (Figures 2 and 3 and Table 3). Other MSSS-88 subscales improved more in the STC group than in the UC group but these differences did not achieve statistical significance (Figure 3 and Table 3). Changes in MAS, MSWS-12, and the physical performance measures did not differ significantly between groups (Table 3). STC participants improved significantly in fatigue on the MFIS (p = 0.03), depression on the BDI-II (p = 0.004), physical function on the MSIS-29 physical component subscale (p = 0.002), and knowledge about spasticity on a written test (p < 0.04) but these changes were not significantly differently from those of the UC participants (p > 0.05) (Table 3). Nineteen participants reported no walking limitations with Expanded Disability Status Scale (EDSS) score < 4.5 (>500 meters without aid or rest (UC: 2.0 n = 2, 4.0 n = 7; STC 4.0 n = 10)). The other 19 individuals had walking limitations with EDSS of 4.5–6.5 with 13 of those needing an aid for walking (unilateral: UC n = 1, STC n = 2; bilateral UC n = 6 and STC n = 4). Thirteen people in the STC group were stretching at baseline. At the end of the study all 19 participants in the STC group were stretching (p = 0.023). Eight people were stretching at baseline in the UC group. At the end, 18/19 individuals in the UC group were stretching (p = 0.002) (Table 3).
Consort diagram. Baseline characteristics. STC: MS Spasticity: Take Control; EDSS: Expanded Disability Status Scale; BS: bachelor of science; DMT: disease-modifying therapy. MS Spasticity Scale (MSSS) total score. *Improvement in STC is significantly greater than in UC. MS Spasticity Scale (MSSS) subscale scores. *Improvement in STC is significantly greater than in UC. Results. MS: multiple sclerosis; MSWS: Multiple Sclerosis Walking Scale; STC: MS Spasticity: Take Control; UC: usual care; MSSS: MS Spasticity Scale; MSIS: MS Impact Scale; MFIS: Modified Fatigue Impact Scale; BDI-II: Beck Depression Inventory II; MAS: Modified Ashworth Scale; T25FW: Timed 25 foot walk; TUG: Timed Up and Go; 2MW: Two-Minute Walk.
Discussion
Participation in STC, a group MS-spasticity education and lower-extremity stretching program followed by independent home stretching for four weeks, was associated with less impact of spasticity overall and less spasticity-related pain and discomfort and muscle spasms than UC participation using written instructions for independent stretching without in-person instruction or group support. STC participation was also associated with less impact of fatigue, reduced depression, and reduced impact of physical components of MS following the intervention while UC participation was not. Neither STC nor UC participation was associated with statistically significant changes in objectively measured spasticity (MAS) or objectively measured walking tests (TUG, T25FW, 2MW). These findings suggest STC may have beneficial effects on the subjective impact of MS-related lower-extremity spasticity.
The improvements in the impact of spasticity found in this study compared to placebo are similar to those found with cannabis products and in other exercise studies. One study comparing extract of cannabis to placebo found improvements in their cannabis-treated group in all MSSS-88 subscales except the activities of daily living subscale and significant differences in three subscales: muscle stiffness, muscle spasms, and body movement. 23 Another study found significant differences on three subscales (pain and discomfort, muscle spasms, and emotional health) in patients treated with cannabinoid oromucosal spray compared to untreated individuals. 24 A study of whole-body vibration combined with exercise found significant differences only on the pain and discomfort and the muscle spasms subscales of the MSSS-88. 25 Intermittent transcranial theta burst stimulation (iTBS) combined with exercise produced significant improvement in MSSS-88 total score compared with sham iTBS with exercise therapy and iTBS alone. 26 Four weeks of unloaded leg cycling was associated with significant improvement in the MSSS-88 total score and the pain and discomfort subscale immediately after exercise and one and four weeks later and on the walking subscale only at one week after exercise. 27
The statistically significant improvements in the STC group in self-reported impact of fatigue, as reflected by scores on the MFIS: Depression, as reflected by scores on the BDI-II, and physical components of MS, as reflected by scores on the physical component subscale of the MSIS-29, found in this study are also interesting. The 6.9-point improvement in the MFIS score in the STC group (from 48 to 41.1) is very close to the seven-point change generally considered clinically significant.10,28–31 The 4.7-point improvement in BDI-II score in the STC group (from 13.7 to 9) reflects a change from “mild depression” to “minimal depression.” 12 And the 6.7-point improvement on the physical component subscale of the MSIS-29 in the STC group (from 52.3 to 45.6) is very close to the seven to eight points generally accepted as the minimal clinically important difference.32,33
Self-reported walking ability, as reflected by scores on the MSWS-12, and functional walking, as reflected by scores on the TUG, improved in the STC group but did not reach statistical significance compared to baseline scores or to the UC group. However, the –14.6 points or 17% improvement in MSWS-12 and –2.2 seconds or 21% improvement in TUG are both clinically significant. Also of interest is the UC group worsening by 10% on the TUG (+1.1 seconds) and 5% on the MSWS-12 (+4.2 points). Our –14.6-point improvement on the MSWS-12 exceeds patient- and therapist-reported clinically meaningful changes of –10.4 and –11.4 points, respectively. 34 Our 21% improvement in the TUG is the same as another study that reported 21% improvement is needed to show genuine improvement on the TUG in individuals with EDSS ≤4. 17
Participation in either the STC or UC interventions encouraged individuals to continue to stretch or to start stretching as would be hoped in a research study asking participants to stretch and then record daily stretching. More people in STC were stretching at the beginning of the study than in UC but by the end, all participants were stretching except one in UC. Even with the high participation in stretching by the UC group, the STC group demonstrated more encouraging results, possibly due to the specific instruction and group support. What remains to be seen is if participants will continue to stretch indefinitely, as recommended clinically given the ongoing and unrelenting nature of spasticity in MS, and if benefits can be sustained or extended in those who do so. Stretching may be safer and have fewer side effects than medications and may augment effects of medications. 35
The present study has several strengths. This is the first formal standardized program based on the MS spasticity guideline. The STC program includes all the recommendations of a systematic review on the effects of stretching in spasticity (body positioning, intensity, velocity, repetitions, duration, dose, and frequency). 36 We used the robust MSSS-88 to measure the impact of spasticity during daily activities from the patient perspective. 7 The MSSS-88 was developed in response to criticisms of the Ashworth scale and the MAS, the most commonly used spasticity assessments, that rely on the examiner’s subjective measuring and rating of the patient’s spasticity and capture only one component of spasticity, the resistance of tissue to passive movement from an applied quick stretch. 15 Our MSSS-88 results compare favorably to studies of cannabis or exercise therapy for MS-related spasticity. The comparison to UC controlled for non-specific effects of socialization and attention associated with participating in a research study. Our use of computer-based assessments minimized missing data. Study drop-outs were minimal (5%) and equal between groups. Adverse events were minimal with only one being study related and none severe. We used a variety of outcome measures with self-reported outcomes, the commonly used examiner-assessed MAS, and objectively measured physical performance. The outcome assessors were blind to group assignment. While the sample was small and limited to one metropolitan area, it is likely representative of people with MS and spasticity: half had unrestricted walking and the other half had walking limitations, participants were mostly women older than 50 years, most had a diagnosis of MS for more than 15 years, and most were unemployed. Advantages of the STC program include: stretching for spasticity is a familiar and logical recommendation for spasticity based on empirical evidence and years of medical practice, and group delivery is generally less expensive than one-on-one physical therapy; requires no special equipment, can be continued at home indefinitely without assistance or other support, and, while standardized, can still be customized for individual needs with the different exercises provided.
This study also has limitations. Our sample, while likely representative of PwMS and adequate for a pilot study, is very small, limiting generalizability. Many of our participants reported stretching at the beginning of the study, which may have limited potential for improvement, but the instruction may have encouraged participants to change their stretching regimens. The program also needs to be delivered in other locations to determine if benefits in this study can be reproduced. MS and spasticity last a lifetime so follow-up beyond four weeks is warranted to gather information about ongoing participation in stretching and other exercise and adverse events and to evaluate sustainability or extension of benefits seen in the present investigation.
Although this study has limitations, it is important to understand that STC, while derived from evidence and similar to other self-management programs in wide distribution and used for many conditions, needs high-quality evidence to support widespread dissemination. Daily stretching requires time and effort by PwMS and they deserve to know if it is truly beneficial. The study presented here provides an early step in evaluating this new program’s effectiveness and suggests participation in STC decreased the impact of spasticity on activities and the daily lives of people living with MS and spasticity. A larger trial with longer follow-up and careful monitoring of stretching and other exercise participation and adverse events is needed to fully assess potential benefit of this program.
Conclusion
This small study suggests that the STC education and stretching program decreases the impact of spasticity on daily activity participation and produces clinically important changes in PwMS and spasticity. STC should be subjected to a fully powered, randomized, controlled trial, with impact of spasticity from the patient’s perspective as the primary outcome, to determine its effectiveness and, therefore, value in PwMS. Having a proven program to help manage MS-related spasticity is important to optimize health-related quality of life for PwMS.
Footnotes
Acknowledgments
Thanks to: Lois Copperman, PhD, OTR, for co-producing the STC education DVD; Medtronic, the Paralyzed Veterans of America, and the VA Employee Education System and Portland VA Education Division for support of the production of STC; the National MS Society for advertising the study and the booklets used for usual care; and Kristina Wick, VA Research Coordinator.
Conflicts of interest
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Pilot Project Award # I21 RX001401 from the United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service. This work was also supported in part by Oregon Clinical and Translational Research Institute (OCTRI) (NCATS-funded CTSA grant UL1TR000128).