A task-oriented circuit training in multiple sclerosis: a feasibility study

Multiple sclerosis (MS) is a chronic and progressive neurologic disease that commonly affects young adults worldwide and it represents a major cause of disability over time [1, 2]. In this population gait and mobility impairments could have a negative impact on personal activities not only restricted to motor domains and participation but also to quality of life [3, 4]. There are several studies showing a benefit of physical therapy on walking function, mobility [5‐9] and fatigue [10‐12]; for this reason recent reviews and international guidelines recommend exercise for MS population [13, 14]. Nonetheless, the task-oriented circuit training (TOCT) approach hasn’t been studied enough in people with MS (PwMS) and gait and mobility disorders. TOCT is based on workstations that reproduce physical activities that the subject usually performs during daily living (i.e. walking, climbing stairs, maintain balance) with the aim of promoting motor learning and task retention. In addition, a major characteristic of this rehabilitative intervention is the exercise intensity that, compared to a conventional physiotherapy session, is nearer to the number of repetitions needed to achieve and maintain motor learning of these movements [15]. Moreover, TOCT has been designed for small groups of subjects requiring only one physiotherapist compared with conventional rehabilitation session in which the ratio is 1:1, giving also the advantage of reducing costs of rehabilitation. Previous studies [16, 17] have shown that TOCT is a good method to improve locomotor function and mobility in stroke survivors.

The rationale of our study is based on growing evidences [18] that demonstrate how human adult brain is capable of significant adaptations providing that the quantity (duration and frequency) and quality (task-specificity) of interventions are appropriate to facilitate enhanced neural reorganization and upper limb motor recovery in chronic stroke survivors [19]. Also, recent neuroimaging studies highlighted how adaptive brain plasticity [20, 21] and motor learning [22] are preserved even in progressive MS subjects and rehabilitative strategies that harness cortical reorganization of motor function might be an option even in this chronically disabled subjects. Task oriented circuit training (TOCT) is an intensive task-specific intervention, for this reason we designed a pilot randomized-controlled trial: (i) to test the safety, feasibility and acceptability of a two weeks high-intensity task oriented circuit training in multiple sclerosis subjects with moderate gait impairments; (ii) to assess its preliminary effects on walking, mobility, fatigue and quality of life; (iii) to evaluate the adherence to a three months home based training program that followed TOCT; (iv) to determine TOCT effect sizes and the sample needed for a future RCT study.

This is a single-blind randomized controlled pilot trial. Subjects were recruited at the outpatient clinic of the Physical Medicine and Rehabilitation Department (Ferrara University Hospital). Informed written consent was obtained from eligible subjects. The research study has been reviewed and approved by the Ferrara University Hospital Ethics Committee and registered in ClinicalTrial.gov database (NCT01464749). The inclusion criteria were: males and females, age 18 to 75, diagnosis of MS (primary or secondary progressive, relapsing-remitting), without relapses in the preceding 3 months, mild to moderate gait impairments referred to Expanded Disability Status Scale (EDSS) score between 4 and 5.5. Subjects were able to walk for at least 100 meters with no constant assistance (cane, crutch or brace) required. The exclusion criteria were: other conditions that may affect motor function, impaired cognitive functioning (Mini Mental Status Examination score less than 24). Subjects were randomized to TOCT (experimental group) or usual care (control group) through a block randomization approach. Eligible subjects were randomly assigned into a 1:1 ratio to receive experimental treatment (task-oriented circuit training), or no specific treatment (usual care). The randomization scheme was generated by using the web site Randomization.com (http://​www.​randomization.​com). The experimental group received 10 task-oriented training sessions (Monday-Friday) over 2 weeks; each session lasted 2 hours. Control group did not receive any intervention.

Twenty-four PwMS have been assessed for eligibility in an outpatient rehabilitation clinic (Ferrara University Hospital). After the preliminary visit, all subjects (17 female, 7 male, age 52.58 ± 11.21, 15.21 ± 8.68 years from MS onset) were included in the study. They were randomized into groups: twelve were allocated to TOCT and twelve to UC. Demographic and clinical characteristics are summarized in Table 2. 37.5% of subjects received disease-modifying therapy (DMT) during the entire study (8.33% immunosuppressive treatments, 16.66% interferon beta, 4.16% glatiramer acetate and 8.33% fingolimod); 20.83% of them received therapies for MS symptoms management (i.e. spasticity, depression, pain). We didn’t report significant differences in DMT or symptomatic therapies among groups at baseline or any changes in pharmacological treatments during the study.All subjects completed the 2 weeks training, while we lost 3 subjects at 3 months follow-up in UC group. The clinical study flow-chart has been reported in Figure 1.

This is a proof-of-concept study with the aim of optimizing components of a novel rehabilitative intervention for PwMS with moderate mobility impairments. We proposed a high-intensity task-specific training which includes several principles of experience-dependent neuroplasticity such as specificity, repetition and intensity [18]; for this reason we hypothesized that a sample of PwMS with moderate mobility impairments might benefit from such intervention. Previous studies on TOCT highlighted positive effects on restoring mobility in stroke survivors including a wide range of exercise doses and intensities [16]. To our knowledge (except for treadmill, body-weight support treadmill and robot-assisted gait training [34]), the only attempts to apply a task-oriented training for mobility impairments in PwMS were done by Mark et al. [35] who proposed a Constraint-Induced Movement Therapy (CIMT) for the lower extremities and Salbach et al. [36] who tested a community exercise program for people with stroke, acquired brain injury and MS. CIMT was administered to a small sample (n = 4) showing positive effects on real-world lower extremity use up to four years. Compared to our TOCT, CIMT protocol was much more intense (3.5 h/d for 3 wk), trained 15 different tasks (compared to 7) and a “transfer package” to deliver gains into the real world was administered [35]. The community exercise program was delivered to 2 MS subjects twice/week for 12 weeks with no effects on walking endurance [36]. Our two weeks high-intensity task oriented circuit training was feasible and safe in a small group of PwMS with moderate mobility impairments. We didn’t report any injuries as a consequence of falls during TOCT sessions or marked fatigability which required the interruption of the exercise; all twelve subjects concluded the 10 sessions with no drop-outs. Furthermore, looking at the feasibility patient-reported questionnaire results, we might conclude that this is a suitable intervention in this population. To test TOCT effects on walking function we did both short-distance (10MWT) than long-distance (SMWT) walking tests in addition to a patient-reported measure of walking ability (MSWS-12). Long-distance walking test and patient-reported walking ability questionnaires were considered as the best measures to detect changes after rehabilitation in MS subjects [37]. Furthermore, long-distance walking tests, such as SMWT better reflect walking performance and functional capacity in MS population [38]. A good predictor for independency and mobility in PwMS is walking endurance measured by SMWT: it has been shown that subjects have 1% increased probability of being independent for every 1 m longer they walk during SMWT [23]. In our sample we didn’t find significant effects on gait speed measured with 10MWT probably because short-distance more than long-distance walking test are due to variability. In fact, a recent study reported a within-day variability of >20% for the 10MWT when baseline gait velocity was <1.2 m/s [39]. Another reason would be that we didn’t use the 25 foot walking test, which seems to be more reliable than 10MWT in detecting changes in PwMS [40]. Our findings in SMWT gains were close to the minimally important change from a patient prospective stated as 22 m [37]. In the same way MSWS-12 score improved by 11 points, showing beneficial effects on walking ability; this patient–reported outcome measure investigates limitation on walking abilities due to MS [30] and seems to be reliable in detecting changes after rehabilitation with a minimally important change of 10.39 points [37]. Considering how health-related quality of life is strongly reduced in PwMS [4], we found positive effects of TOCT on both physical and psychological functions in MSIS-29; however we have to consider how these results are within the standard error of the measurement which is defined as 5.3-9.5 points for physical domain and 7.6-13 points for psychological domain [41, 42]. Examining fatigue which is a common MS symptom with a negative impact on mobility, activities and quality of life, in our sample we didn’t find any detrimental effects of the task-oriented circuit training (2h/d over 2 weeks). Accordingly with previous studies [10‐12] we highlighted a slight fatigue reduction after TOCT. Nevertheless, these preliminary results should be taken cautiously, considering that this is a pilot study with the aim to test the safety and feasibility of a task-oriented circuit training in PwMS.

In our sample we found a lower adherence to home-exercise program (58%) compared to other studies in MS subjects [43‐45]. We can assume that giving a diary with a home-based exercise program wasn’t sufficient to motivate subjects to continue with task-oriented exercises at home. We can also speculate that task-oriented training is less suitable at home compared to other intervention tested in the aforementioned studies (mostly resistance exercises). Moreover, depression or cognitive symptoms, that are common in MS, might have reduced subjects’ compliance to rehabilitation, as clearly highlighted for MS medications [46]. However, we didn’t find any differences in walking endurance deterioration after TOCT among good- and poor-adherence subgroups.

Finally, as long walking tests are more appropriate in detecting clinically meaningful improvement after physical rehabilitation in MS population [37, 38], we calculated a sample size for a future RCT study based on the SMWT gains (51 subjects).

In this pilot study, we assessed the safety, feasibility and preliminary effects on selected variables (gait speed, gait endurance, mobility, balance and health-related quality of life) of a task-oriented circuit training in a sample of multiple sclerosis subjects. Our main findings revealed that a 2 weeks task-oriented circuit training followed by a three months home exercise program is safe and well tolerated in multiple sclerosis subjects with moderate gait and mobility impairments. TOCT may allow a more intensive (more repetitions) and specific (task oriented) exercise in an enriched rehabilitative setting. No detrimental effects on subjective fatigue have been observed in this sample or major adverse effects (i.e. fall-related injury). Even though some positive effects on walking ability has been underlined, this trial cannot draw definitive conclusions on the effects of such intervention.