RATIONALE
Optimization of multidisciplinary clinical management, including the muscle component, cardiac and respiratory function, nutritional and gastrointestinal aspects, physiotherapy, and psychological support, has led over the past 30 years to longer life expectancy in all forms of muscular dystrophy, overall improved cardiorespiratory well-being, reduced hospitalizations, and therefore a major improvement in quality of life.
Aerobic exercise and rehabilitative treatment are the terms most frequently used to give indications to dystrophic patients with moderate-to-moderate muscle impairment, but so far data in the scientific medical literature are scarce and there are no shared treatment protocols.
Taking a step back, let us first try to define what is meant by exercise.
Exercise is defined as planned and structured physical activity practiced regularly with the goal of improving or maintaining good physical fitness.
Until about twenty years ago, it was believed that exercise in muscular dystrophies could be detrimental to the structure of the muscle fibrocell, inducing accelerated cell necrosis, just as has been shown in experimental studies in mice (Fowler,1984; Brouwer,1992; Carter GT,1995; Dupont-Versteegden EE,1994). In fact, it is now certain and validated that an active lifestyle and the practice of controlled and regular physical activity are to be considered therapeutic in neuromuscular diseases with the goal of optimizing muscle and cardio-respiratory function and preventing "nonuse" atrophy (EagleM,2002; VoetNBM,2013; Berthelsen,2014; Siciliano,2015; Preisler N,2018).
In particular, it appears that the optimal take-up is extensive and can also be performed in a safe and controlled manner at home (DeGroot, Veenhuizen,2019). It is well documented that exercise has beneficial effects on muscle with increased muscle strength and endurance. Low-intensity, aerobic muscle exercise has also been shown to improve the physical well-being of patients with muscular dystrophy and muscle strength in specific areas, without inducing muscle damage (without changes in either CK levels or muscle morphology at biopsy) and/or cardiac damage. There is also evidence that these benefits persist over time and are associated with an overall improvement in health and mental and physical well-being (Jensen BR et al 2016. Preisler N et al 2008).
It is also known that nonuse atrophy (lack of exercise), related to the lack of mechanical muscle loading, causes a reduction in muscle mass and consequently in the number of muscle fibers.
In muscular dystrophies, it is indeed possible that muscle weakness leads to a sedentary lifestyle, and that the latter induces a reduction in muscle mass and changes in metabolism and a possible increase in body weight, which leads to a further reduction in the motor activity and strength that the muscle can generate, ultimately leading to a further aggravation of muscle weakness.
IN SUMMARY
The response to exercise is specific, related to two factors: type of exercise (intensity, duration and frequency) and clinical condition of the patient. Controlled aerobic exercise is well tolerated, safe, and improves patient well-being and endurance. All activities should be monitored by a physical therapist experienced in neuromuscular disease.
This project stems precisely from the idea of providing a response to the needs of patients on the one hand about being educated to perform a physical activity/exercise "suitable" for the dystrophic muscle fiber, and on the other hand to be able to incorporate this activity into their daily life, with expert remote monitoring.
We therefore propose to offer continuity of care between the hospital facility and the home, also offering a concrete response to the inconstant care guaranteed for these chronic developmental diseases by the NHS. The drafting of a personalized therapeutic plan, to be implemented within the home, would not only support the patient's motor needs, but also ensure a positive psychological spillover, reinforcing the patient's participation in and awareness of shared therapeutic goals. This pilot project aims to evaluate the feasibility, tolerance, and effectiveness of a 6-month continuity-of-care intake program in a population of individuals with neuromuscular disease.
Each patient will undergo at the IRCCS E. MEDEA La Nostra Famiglia in Bosisio Parini a series of evaluation and training sessions (15 sessions) with a physiotherapist to draw up a personalized treatment plan that he or she can then carry out "independently" at home.
During these days, periodic clinical instrumental evaluations indicated by the specific guidelines for each form of dystrophy and in particular those of cardiorespiratory and nutritional status will also be carried out. In addition, "educational" support will also take place, educating the patient with respect to the benefits of maintaining an active lifestyle and regular practice of controlled physical activity.
The home therapy proposal will involve the use of the telerehabilitation system with virtual reality Home Kit- Virtual Reality Rehabilitation System (VRRS-Khymeia) that allows for personalized" exergames" to be performed at home. VRRS Home Kit is a device that makes home motor telerehabilitation possible in two modes:
- Online, the therapist connects via integrated video conferencing and assumes remote control of the device at the patient's home by interacting with it in real time.
- Offline, the patient performs the personalized exercise sheet, guided by the Smart Virtual Assistant, which accompanies the patient in real-time interactive mode throughout the rehabilitation session.
The software presents virtual environments in which the patient can interact. Movements made by the patient (single segment or whole body) are captured by the system using kinematic tracking sensors and displayed in real time within the virtual environment.
For each type of exercise, there is real-time monitoring of the quality of exercise execution and subsequent feedback to the subject through visual, auditory and even vocal feedback.
Patients
Ten adult patients (>18 years old) with cingulate dystrophy, Becker's dystrophy, or facio-scapulohumeral dystrophy will be recruited.
Inclusion criteria
Definite genetic diagnosis of LGMD2A/R1(calpain deficiency), LGMD2B/R2(dysferlin deficiency), LGMD2I/R9 (FKRP), LGMD2L /R11(Anoctamine5) or facio-scapulohumeral dystrophy (FSH) or Becker's dystrophy (DMB).
Patients should have a not excessively deteriorated stenico picture with strength values at the level of major antigravity muscles > or equal to 3, according to the Medical Research Council (MRC) scale.
Independent ambulation in a protected (indoor) environment, including with an aid.
Patients must have performed at least 1 clinical-functional evaluation at our Facility in the year prior to the start of the trial. They will have to express compliance of adherence to the project and should not be followed from the physiotherapy point of view elsewhere in the 6 months of participation in the project.
Exclusion criteria
Dilated or ischemic heart disease with moderate degree impairment (FE VS <50%).
Chronic respiratory failure (FVC 5% of night time spent with peripheral oxygen saturation levels < 90).
Evaluation protocol
All patients must have performed at least two clinical-functional assessments at IRCCS E. Medea in the two years prior to recruitment for this study. These evaluations are indicated by the international guidelines in relation to the pathology: a clinical neurological/neuromuscular evaluation with MRC scale, the functional motor evaluations specific to each pathology, cardiological evaluations with echocardiogram (FE VS and FA VS) and respiratory (spirometry and nocturnal peripheral oxygen saturation recording) - hematochemical examinations with CK assays (especially for dystrophic patients).
To evaluate the effectiveness of rehabilitation treatment, a specific evaluation protocol will be applied to analyze changes in the different domains proposed by the bio-psycho-social model of the International Classification of Functioning, Disability and Health (ICF, WHO 2001). Outcome measures of "Activity" and "Participation" will be used.
Clinical Outcome Measures:
- Primary (evidence of effectiveness):
Six- Minute Walk Test(6-MWT) for the assessment of endurance in walking; Timed Up and Go Test (TUG); Motor Function Measure (MFM) for the assessment of gross-motor skills and Performance Upper Limb Module (PUL) for the assessment of functional skills at the upper limb level.
- Secondary (tolerance tests):
Individual Strenght 20R Checklist (CIS-Fatigue) for quantification of global fatigue and the Short Form 36 Questionnaire (SF-36) for perception of quality of life.
At the end of the course, the patient will be required to complete 3 questionnaires to investigate acceptability and usability of the telerehabilitation system:
- NASA Task Load Test (NASA 1986. Nasa Task Load Index (TLX) v. 1.0 Manual) will be used to measure the user's perception of mental, physical, and temporal effort, as well as the level of performance and frustration
- System Usability Scale ( Brooke, “SUS: A quick and dirty usability scale,” Usability Eval. Ind., vol. 189, Nov. 1995.) will evaluate the usability of the system with a total score ranging from 0 to 100; 68 is considered the average usability value, so higher scores indicate above-average usability.
- Technology Acceptance Model 3 (TAM3: Venkatesh, V.; Bala, H. (2008), "Technology Acceptance Model 3 and a Research Agenda on Interventions," Decision Sciences 39 (2): 273-315, doi:10.1111/j.1540- 5915.2008.00192) will assess the acceptability of the tele-rehabilitation pathway.
Time Table
- evaluation in the 12 months preceding the training (T-1)
- Assessment and training in the facility, duration of 15 sessions (T0)
- 3 months after T0 (T1) assessments.
- 6 months after T0 (T2) assessments.
3 different comparisons will be performed: 1. Baseline T-1 vs T0 comparison to evaluate the normal course of pathology; 2. T0 vs T1 comparison to evaluate the effects of short-term training; 3. T0 vs T2 comparison to evaluate the effects of medium-term training.
Each patient will thus be able to be in control of himself, which is essential both for the evolutionary characteristics of the dystrophic forms that will be considered and for the personalization of treatment.
Rehabilitation protocol
The proposed exercise plan will be individualized (PRI) in both content and timing to meet different rehabilitation needs, drawing from the following macro goal areas:
- Maintenance of muscle lengths with selective and/or prolonged static stretching exercises.
- Maintenance/improvement of muscle trophism with selective and/or postural and/or functional muscle recruitment exercises at moderate intensity (approximately 65%-70% of maximum).
- Maintenance of respiratory muscle fatigue with thoracic and/or diaphragmatic breathing exercises combined with muscle exercise.
- Endurance training with walking, cycle ergometer (to be used with both upper and lower limbs) and treadmill at moderate intensity (about 65%-70% of maximum).
Home treatment will be carried out largely with the KHYMEIA telerehabilitation system. The program will involve the performance of selective, postural and functional exercises at the upper limb, lower limb and trunk levels to be performed 3 times a week for 6 consecutive months. The timing of each session will be tailored to each patient's profile. The rehabilitation proposal with VRRS Home Kit system may also be enriched by free-body exercises and cardiopulmonary training with walking and/or cycle ergometer.
During the training period, the patient will be instructed in the management of the telerehabilitation system and all activities to be performed, specifying the mode, timing, intensity, duration and frequency of training.
The patient will also be instructed in the self-administration of the Borg RPE scale and Talk Test, which should take place at home during each individual activity session to monitor "fatigue."
Upon discharge, the patient will bring home the Khymeia Home Kit case complete with everything needed to carry out the rehabilitation program independently.
Home monitoring
Supervision by the therapist of the home-initiated pathway will be carried out periodically (initially weekly, then monthly) by taking advantage of the online mode of the KHYMEIA system for a review of the patient's progress and to check execution times and exercise results, so that the work program can be redefined if necessary. Monitoring will also be facilitated by the use of a daily activity diary for reporting the time spent on motor activity with specification of exercises performed and fatigues encountered.