The validity of cardiopulmonary exercise testing for assessing aerobic capacity in neuromuscular diseases.

OBJECTIVES: To determine the content validity of cardiopulmonary exercise testing (CPET) for assessing peak oxygen uptake (VO2peak) in neuromuscular diseases (NMD). DESIGN: Baseline assessment of a randomized controlled trial. SETTING: Academic hospital. PARTICIPANTS: Eighty-six adults (age: 58.0 ± 13.9 years) with Charcot-Marie-Tooth disease (n=35), post-polio syndrome (n=26), or other NMD (n=25). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Workload, gas exchange variables, heart rate, and ratings of perceived exertion were measured during CPET on a cycle ergometer, supervised by an experienced trained assessor. Muscle strength of the knee extensors was assessed isometrically with a fixed dynamometer. Criteria for confirming maximal cardiorespiratory effort during CPET were established during 3 consensus meetings with an expert group. The percentage of participants meeting these criteria was assessed to quantify content validity. RESULTS: The following criteria were established for maximal cardiorespiratory effort; a plateau in oxygen uptake (VO2plateau) as primary criterion, or 2 out of 3 secondary criteria; 1) peak respiratory exchange ratio (RERpeak) ≥1.10, 2), peak heart rate (HRpeak) ≥85% of predicted maximal heart rate, and 3) peak rating of perceived exertion (RPEpeak) ≥17 on the 6-20 Borg scale. These criteria were attained by 71 participants (83%). VO2plateau, RERpeak ≥1.10, HRpeak ≥85%, and RPEpeak ≥17 were attained by respectively 31%, 73%, 69%, and 72% of the participants. Peak workload, VO2peak, and knee extension muscle strength were significantly higher, and body mass index was lower (all p<0.05), in participants with maximal cardiorespiratory effort compared to other participants. CONCLUSIONS: Most people with NMD achieved maximal cardiorespiratory effort during CPET. Therewith, this study provides high quality evidence of sufficient content validity of VO2peak as a maximal aerobic capacity measure. Content validity may be lower in more severely affected people with lower physical fitness.

Efficacy of a physical activity programme combining individualized aerobic exercise and coaching to improve physical fitness in neuromuscular diseases (I'M FINE): study protocol of a randomized controlled trial.

BACKGROUND: In individuals with neuromuscular diseases (NMD), symptoms of muscle weakness, fatigue and pain may limit physical activity. Inactivity leads to reduced physical fitness, which further complicates daily life functioning. Due to inconclusive evidence regarding exercise in NMD, the optimal training approach and strategies to preserve an active lifestyle remain to be determined. The physical activity programme I'M FINE, consisting of individualized aerobic exercise to improve physical fitness and coaching to preserve an active lifestyle, was therefore developed. The primary objective of this study will be to evaluate the efficacy of the I'M FINE programme in terms of improved physical fitness in individuals with slowly progressive NMD, compared to usual care. METHODS: A multicentre, assessor-blinded, two armed, randomized controlled trial will be conducted in a sample of 90 individuals with slowly progressive NMD. Participants motivated to improve their reduced physical fitness will be randomized (ratio 1:1) to the I'M FINE intervention or usual care. The I'M FINE intervention consists of a six-month physical activity programme, including individualized home-based aerobic exercise to improve physical fitness (i.e. peak oxygen uptake), and motivational interviewing coaching (e.g. goal setting, self-management) to adopt and preserve an active lifestyle. Measurements will be performed at baseline, post-intervention, and at 12- and 18-months follow-up. The primary outcome is peak oxygen uptake (VO2 peak) directly post intervention. Main secondary outcomes are physical capacity, muscle strength, self-efficacy, daily activity, quality of life and markers of metabolic syndrome. The primary analysis compares change in VO2 peak post-intervention between the intervention and usual care group, with analysis of covariance. DISCUSSION: The I'M FINE study will provide evidence regarding the efficacy of a physical activity intervention on the physical fitness and active lifestyle over the short- and long-term in individuals with slowly progressive NMD. These outcomes could potentially improve the (inter)national guidelines for efficacy of aerobic exercise programmes and provide insight in achieving a more active lifestyle in NMD. TRIAL REGISTRATION: (5/11/2018): Netherlands Trial Register NTR7609 (retrospectively registered), https://www.trialregister.nl/trial/7344. However, the Ethics Review Committee of the Amsterdam Medical Center (AMC) approved the study protocol on 7/11/2017. No adjustments were made to the approved study protocol before the first participant enrolment and registration. Registration was done after the second participant enrolment and the information in the register corresponds one on one with the approved study protocol.

Experiences and perspectives of patients with post-polio syndrome and therapists with exercise and cognitive behavioural therapy.

BACKGROUND: Many persons affected with poliomyelitis develop post-polio syndrome (PPS) later in their life. Recently, the effectiveness of Exercise Therapy (ET) and Cognitive Behavioural Therapy (CBT) for PPS has been evaluated in a randomized controlled trial, but did not show a decrease in fatigue or improvement in secondary endpoints like Quality of Life and self-perceived activity limitations. The aim of this explorative study was to gain insight in the perceived effects and experiences of the interventions from the perspectives of the patients and therapists. METHODS: Qualitative data were collected through semi-structured interviews with 17 patients and 7 therapists. All participants were involved in the trial. A thematic analysis of the data was performed. RESULTS: Some patients experienced a short term enhanced endurance and a better use of energy during the day. However, in general patients did not experience a long lasting reduction of fatigue from the CBT or ET. Mainly patients of the CBT, but also some patients of the ET described an increase of self-esteem and self-acceptance. As a result, patients were sometimes better able to perform physical activities during the day. In contrast to the CBT, the ET was in general perceived by the patients as an intensive therapy, which was difficult to fit into their daily routine. Therapists of both the CBT and the ET struggled with a low intrinsic motivation of the patients in the study. This made it sometimes difficult for the therapists to follow the protocol. CONCLUSION: Confirming the negative quantitative study outcome, the qualitative results did not demonstrate lasting effects on fatigue. Patients did, however, experience some benefits on self-esteem and acceptance of the disease. This study showed that it is of great importance to work with feasible interventions; they should fit the patients' needs on a practical (fit into their daily routine) and mental (fit their need for support) level.

Treatment for postpolio syndrome.

BACKGROUND: Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical functioning. The effectiveness of pharmacological treatment and rehabilitation management in PPS is not yet established. This is an update of a review first published in 2011. OBJECTIVES: To systematically review the evidence from randomised and quasi-randomised controlled trials for the effect of any pharmacological or non-pharmacological treatment for PPS compared to placebo, usual care or no treatment.  SEARCH METHODS: We searched the following databases on 21 July 2014: Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL Plus. We also checked reference lists of all relevant articles, searched the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment (HTA) Database and trial registers and contacted investigators known to be involved in research in this area. SELECTION CRITERIA: Randomised and quasi-randomised trials of any form of pharmacological or non-pharmacological treatment for people with PPS. The primary outcome was self perceived activity limitations and secondary outcomes were muscle strength, muscle endurance, fatigue, pain and adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 10 pharmacological (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields) studies with a total of 675 participants with PPS in this review. None of the included studies were completely free from any risk of bias, the most prevalent risk of bias being lack of blinding.There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively, and inconsistency in the evidence for effectiveness on muscle strength. IVIg caused minor adverse events in a substantial proportion of the participants. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations without generating adverse events. Data from two single trials suggested that muscle strengthening of thumb muscles (very low-quality evidence) and static magnetic fields (moderate-quality evidence) are safe and beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS. AUTHORS' CONCLUSIONS: Due to insufficient good-quality data and lack of randomised studies, it was impossible to draw definite conclusions about the effectiveness of interventions for PPS. Results indicated that IVIg, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation to clarify whether any real and meaningful effect exists.

Determining the anaerobic threshold in postpolio syndrome: comparison with current guidelines for training intensity prescription.

OBJECTIVES: To determine whether the anaerobic threshold (AT) can be identified in individuals with postpolio syndrome (PPS) using submaximal incremental exercise testing, and to compare current guidelines for intensity prescription in PPS with the AT. DESIGN: Cohort study. SETTING: Research laboratory. PARTICIPANTS: Individuals with PPS (N=82). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Power output, gas exchange variables, heart rate, and rating of perceived exertion (RPE) were measured in an incremental submaximal cycle ergometry test. Two independent observers identified the AT. Comparison of current guidelines for training intensity prescription in PPS (40%-60% heart rate reserve [HRR] or RPE of 12) with the AT was based on correlations between recommended heart rate and the heart rate at the AT. In addition, we determined the proportion of individuals that would have been recommended to train at an intensity corresponding to their AT. RESULTS: The AT was identified in 63 (77%) of the participants. Pearson correlation coefficients between the recommended heart rate and the heart rate at the AT were lower in cases of 40% HRR (r=.56) and 60% HRR (r=.50) than in cases of prescription based on the RPE (r=.86). Based on the RPE, 55% of the individuals would have been recommended to train at an intensity corresponding to their AT. This proportion was higher compared with 40% HRR (41%) or 60% HRR (18%) as criterion. CONCLUSIONS: The AT can be identified in most individuals with PPS offering an individualized target for aerobic training. If the AT cannot be identified (eg, because gas analysis equipment is not available), intensity prescription can best be based on the RPE.

Safety, walking ability, and satisfaction outcomes of the NEURO TRONIC stance-control knee-ankle-foot orthosis (SCKAFO): A comparative evaluation to the E-MAG active SCKAFO.

BACKGROUND: Stance control knee-ankle-foot orthoses (SCKAFOs) ensure knee stability by locking during stance while allowing knee flexion during swing. Differences in function of the knee joints and building principles between devices may affect their effectiveness. OBJECTIVE: To investigate the preliminary effectiveness of a NEURO TRONIC on safety outcomes, net energy cost (EC), and user experiences in individuals already using an E-MAG Active SCKAFO. STUDY DESIGN: Prospective uncontrolled intervention study. METHODS: A convenience sample of 10 subjects with flaccid lower extremity muscle weakness, including the quadriceps, due to neuromuscular disorders already using an E-MAG Active SCKAFO were provided with a newly fabricated NEURO TRONIC SCKAFO. Outcomes included knee joint locking failures and unlocking failures (ULFs) (i.e., percentage of steps the knee joint failed to lock/unlock) when walking under challenging conditions on an instrumented treadmill while wearing a safety harness; net EC (J/kg per meter) assessed with a 6-min walk test at comfortable speed; 3D gait kinematics and kinetics; and patient-reported outcomes. RESULTS: No differences between devices were found for knee joint locking failures (both devices 0%) and ULFs (9.9% for the NEURO TRONIC vs. 13.9% for the E-MAG Active SCKAFO). The mean (standard deviation) net EC with the NEURO TRONIC SCKAFO was 8.2% (from 3.68 [0.81] to 3.38 [0.75] J/kg per meter, p = 0.123) lower, although not significantly, compared with that with the E-MAG Active SCKAFO. Significant improvements with the NEURO TRONIC SCKAFO were found for ankle power ( p = 0.003), perceived walking effort ( p = 0.014), and reported falls ( p = 0.034). CONCLUSION: Both the NEURO TRONIC SCKAFO and the E-MAG Active SCKAFO were safe in terms of knee joint locking, while ULFs were frequent with both devices. The net EC with the NEURO TRONIC SCKAFO decreased, although not significantly, by 8.2%, likely due to insufficient power. Perceived walking effort was in favor of the NEURO TRONIC SCKAFO.

A Mobile Health App to Support Home-Based Aerobic Exercise in Neuromuscular Diseases: Usability Study.

BACKGROUND: Home-based aerobic exercise in people with neuromuscular diseases (NMDs) has benefits compared to exercise in the hospital or a rehabilitation center because traveling is often cumbersome due to mobility limitations, and societal costs are lower. Barriers to home-based aerobic exercise include reduced possibilities for monitoring and lack of motivation. To overcome these and other barriers, we developed a mobile health app: Keep on training with ReVi (hereafter referred to as ReVi). OBJECTIVE: We aimed to determine the usability of the ReVi app. METHODS: Patients followed a 4-month, polarized, home-based aerobic exercise program on a cycle or rowing ergometer, with 2 low-intensity sessions and 1 high-intensity session per week supported by the ReVi app. The app collected training data, including heart rate and ratings of perceived exertion, provided real-time feedback on reaching target intensity zones, and enabled monitoring via an online dashboard. Physiotherapists instructed patients on how to use the ReVi app and supervised them during their training program. Patients and physiotherapists separately evaluated usability with self-developed questionnaires, including 9 questions on a 5-point Likert scale, covering the usability elements efficiency, effectiveness, and satisfaction. RESULTS: Twenty-nine ambulatory adult patients (n=19 women; mean age 50.4, SD 14.2 years) with 11 different slowly progressive NMDs participated. Both patients and physiotherapists (n=10) reported that the app, in terms of its efficiency, was easy to use and had a rapid learning curve. Sixteen patients (55%) experienced 1 or more technical issue(s) during the course of the exercise program. In the context of effectiveness, 23 patients (81%) indicated that the app motivated them to complete the program and that it helped them to exercise within the target intensity zones. Most patients (n=19, 70%) and physiotherapists (n=6, 60%) were satisfied with the use of the app. The median attendance rate was 88% (IQR 63%-98%), with 76% (IQR 69%-82%) of time spent within the target intensity zones. Four adverse events were reported, 3 of which were resolved without discontinuation of the exercise program. CONCLUSIONS: The usability of the ReVi app was high, despite the technical issues that occurred. Further development of the app to resolve these issues is warranted before broader implementation into clinical practice.

Gait stability and the relationship with energy cost of walking in polio survivors with unilateral plantarflexor weakness.

BACKGROUND: Polio survivors often exhibit plantarflexor weakness, which impairs gait stability, and increases energy cost of walking. Quantifying gait stability could provide insights in the control mechanisms polio survivors use to maintain gait stability and in whether impaired gait stability is related to the increased energy cost of walking. RESEARCH QUESTION: Is gait stability impaired in polio survivors with plantarflexor weakness compared to able-bodied individuals, and does gait stability relate to energy cost of walking? METHODS: We retrospectively analyzed barefoot biomechanical gait data of 31 polio survivors with unilateral plantarflexor weakness and of 24 able-bodied individuals. We estimated gait stability by calculating variability (SD) of step width, step length, double support time, and stance time, and by the mean and variability (SD) of the mediolateral and anteroposterior margin of stability (MoSML and MoSAP). In addition, energy cost of walking (polio survivors only) at comfortable speed was analyzed. RESULTS: Comfortable speed was 31% lower in polio survivors compared to able-bodied individuals (p < 0.001). Corrected for speed differences, step width variability was significantly larger in polio survivors (+41%), double support time variability was significantly smaller (-27%), MoSML (affected leg) was significantly larger (+80%), and MoSAP was significantly smaller (affected leg:-17% and non-affected leg:-15%). Step width and step length variability (affected leg) were positively correlated with energy cost of walking (r = 0.502 and r = 0.552). MoSAP (non-affected leg) was negatively correlated with energy cost of walking (r = -0.530). SIGNIFICANCE: Polio survivors with unilateral plantarflexor weakness demonstrated an impaired gait stability. Increased step width and step length variability and lower MoSAP could be factors related to the elevated energy cost of walking in polio survivors. These findings increase our understanding of stability problems due to plantarflexor weakness, which could be used for the improvement of (orthotic) interventions to enhance gait stability and reduce energy cost in polio survivors.

Effects of specialist care lower limb orthoses on personal goal attainment and walking ability in adults with neuromuscular disorders.

BACKGROUND: Lower limb orthoses intend to improve walking in adults with neuromuscular disorders (NMD). Yet, reported group effects of lower limb orthoses on treatment outcomes have generally been small and heterogeneous. We propose that guideline-based orthotic care within a multidisciplinary expert setting may improve treatment outcomes. AIM: To examine the effectiveness of specialist care orthoses compared to usual care orthoses on personal goal attainment and walking ability. DESIGN: Cohort study. POPULATION: Adults with NMD who experienced walking problems due to calf and/or quadriceps muscle weakness and were provided with a specialist care lower limb orthosis between October 2011 and January 2021. METHODS: Three months after provision, the specialist care orthosis was compared to the usual care orthosis worn at baseline in terms of personal goal attainment (Goal Attainment Scaling (GAS)), comfortable walking speed (m/s), net energy cost (J/kg/m) (both assessed during a 6-minute walk test), perceived walking ability and satisfaction. RESULTS: Sixty-four adults with NMD were eligible for analysis. The specialist care orthoses comprised 19 dorsiflexion-restricting ankle-foot orthoses (AFOs), 22 stance-control knee-ankle-foot orthoses (KAFOs) and 23 locked KAFOs. Overall, 61% of subjects showed a clinically relevant improvement in GAS score. Perceived safety, stability, intensity, fear of falling and satisfaction while walking all improved (p≤0.002), and subjects were satisfied with their specialist care orthosis and the services provided. Although no effects on walking speed or net energy cost were found in combined orthosis groups, specialist care AFOs significantly reduced net energy cost (by 9.5%) compared to usual care orthoses (from mean (SD) 3.81 (0.97) to 3.45 (0.80) J/kg/m, p = 0.004). CONCLUSION: Guideline-based orthotic care within a multidisciplinary expertise setting could improve treatment outcomes in adults with NMD compared to usual orthotic care by improvements in goal attainment and walking ability. A randomized controlled trial is now warranted to confirm these results.

Measurement Properties of Aerobic Capacity Measures in Neuromuscular Diseases: A Systematic Review.

OBJECTIVE: To systematically evaluate the measurement properties of aerobic capacity measures in neuromuscular diseases. DATA SOURCES: MEDLINE, EMBASE, SportDiscus and Web of Science Conference Proceedings Citation Index - Science were systematically searched from inception until 30 June 2021. STUDY SELECTION AND DATA EXTRACTION: Screening, data extraction, risk of bias assessment and quality assessment were performed by 2 independent researchers. Studies were included if they evaluated measurement properties of aerobic capacity measures in adults with neuromuscular diseases. Risk of bias was assessed using the COnsensus based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Results were pooled and the quality of the evidence was determined using a modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. DATA SYNTHESIS: Nine studies including 187 participants were included in this review. Low quality of evidence was found for sufficient content validity of peak oxygen consumption through maximal exercise testing. Criterion validity of 4 out of 7 different measures to predict peak oxygen consumption was sufficient; however, quality of evidence was low or very low for all measures. No studies were found evaluating reliability or responsiveness. CONCLUSION: There was a lack of high-quality studies with sufficiently large sample sizes that evaluated the measurement properties of aerobic capacity measures in neuromuscular diseases.

Use and Usability Of Custom-Made Knee-Ankle-Foot Orthoses In Polio Survivors with Knee Instability: A Cross-Sectional Survey.

OBJECTIVE: To investigate the use of custom-made knee-ankle-foot orthoses in daily life and differences in usability factors of knee-ankle-foot orthoses between users and discontinued users. DESIGN: Cross-sectional survey study. SUBJECTS: A total of 163 polio survivors provided with a knee-ankle-foot orthosis at an outpatient clinic of a university hospital. METHODS: Use and usability of knee-ankle-foot orthoses in daily life were assessed with a postal questionnaire. Usability factors were formulated using the International Organization for Standardization (ISO) 9241-11 standard. RESULTS: A total of 106 respondents (65%) returned the questionnaire. Of these, 98 were eligible for analysis. Seventy-four respondents (76%) reported using their knee-ankle-foot orthosis. Compared with discontinued users (24%), users experienced more limitations when walking without an orthosis (p = 0.001), were more often experienced with wearing a previous orthosis (p < 0.001) and were more often prescribed with a locked rather than a stance-control knee-ankle-foot orthosis (p = 0.015). Furthermore, users reported better effectiveness of their knee-ankle-foot orthosis (p < 0.001), more satisfaction with goals of use and knee-ankle-foot orthosis-related aspects (p < 0.001). CONCLUSION: The majority of polio survivors used their custom-made knee-ankle-foot orthoses in daily life. Factors related to continued use, such as walking ability without orthosis, expectations of the orthosis, previous orthosis experience and type of knee-ankle-foot orthosis provided, should be considered and discussed when prescribing a knee-ankle-foot orthosis in polio survivors.

Treatment for postpolio syndrome.

BACKGROUND: Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical functioning. The effectiveness of pharmacological treatment and rehabilitation management in PPS is not yet established. OBJECTIVES: To review systematically the effects of any treatment for PPS compared to placebo, usual care or no treatment.   SEARCH STRATEGY: We searched the following databases on 1 October 2010: Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO and CINAHL Plus from inception to September 2010. SELECTION CRITERIA: Randomised and quasi-randomised trials of any form of pharmacological or non-pharmacological treatment for people with PPS. The primary outcome was self-perceived activity limitations and secondary outcomes were muscle strength, muscle endurance, fatigue, pain and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently selected eligible studies, assessed risk of bias and extracted data. MAIN RESULTS: Nine pharmacological (modafinil, intravenous immunoglobulin, pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (i.e. temperature ± 25°C, dry and sunny) and a cold climate (i.e. temperature ± 0°C, rainy or snowy), static magnetic fields) studies were included in this review. None of the included studies was completely free from any risk of bias and the most prevalent risk of bias was lack of blinding.There is moderate quality evidence that intravenous immunoglobulin has no beneficial effect on activity limitations and there is inconsistency in the evidence for effectiveness on muscle strength and pain. Results of one trial provide very low quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations. Data from two single trials suggest that muscle strengthening of thumb muscles (very low quality evidence) and static magnetic fields (moderate quality evidence) are beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there is evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS. AUTHORS' CONCLUSIONS: Due to insufficient good quality data and lack of randomised studies it is impossible to draw definite conclusions on the effectiveness of interventions for PPS. Results indicate that IVIG, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation.

A 5-year longitudinal study of fatigue in patients with late-onset sequelae of poliomyelitis.

OBJECTIVES: To study the severity and 5-year course of fatigue in patients with late-onset sequelae of poliomyelitis (LOSP) and to identify physical and psychosocial determinants of fatigue. DESIGN: Prospective cohort study with 5 measurements over 5 years. SETTING: University hospital. PARTICIPANTS: Patients with LOSP (N=168); 89% of the subjects completed the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue assessed with the Fatigue Severity Scale (FSS). Potential determinants were perceived physical functioning, bodily pain and mental health, extent of paresis, walking capacity, comorbidity, sleeping disorders, coping, and social support. Associations were investigated by multivariable longitudinal analysis using generalized estimating equations. RESULTS: The mean FSS score ± SD at baseline was 5.1±1.4, which did not change significantly during the 5-year follow-up. Reduced physical functioning, increased bodily pain, reduced sleep quality, more psychologic distress, and higher task-oriented coping were independently associated with fatigue. The extent of paresis and walking capacity were strongly associated with physical functioning. CONCLUSIONS: Fatigue is severe and persistent in patients with LOSP due to physical and psychologic factors, which has implications for counseling and treatment. In addition to the commonly applied interventions targeting physical aspects, psychologic interventions are a potential area for reducing fatigue.

Individualized Aerobic Exercise in Neuromuscular Diseases: A Pilot Study on the Feasibility and Preliminary Effectiveness to Improve Physical Fitness.

OBJECTIVE: Clear guidelines to prescribe aerobic exercise in neuromuscular diseases (NMD) are lacking, which hampers effective application in neuromuscular rehabilitation. This pilot study evaluated the feasibility and preliminary effectiveness of an individualized aerobic exercise program according to a recently developed training guide (B-FIT) to improve physical fitness in individuals with NMD. METHODS: Thirty-one individuals who were ambulatory and had 15 different slowly progressive NMD participated in a 4-month, polarized, home-based, aerobic exercise program. The program included 2 low-intensity sessions and 1 high-intensity session per week. Feasibility outcomes were the following: completion rate, proportion of followed sessions, adverse events, and participant and therapist satisfaction based on a self-designed questionnaire. Submaximal incremental exercise tests were used to assess the effects on physical fitness. RESULTS: Twenty-six participants (84%) completed the B-FIT program, and the proportion of followed sessions was >75%. Three adverse events were reported and resolved. Regarding satisfaction, participants (based on n = 9) reported feeling fitter, but training was considered insufficiently challenging. Physical therapists (n = 5) reported that B-FIT provides a clear, well-grounded guidance. They perceived the time investment for initiating the program and the carry-over to primary care as the main barriers. The mean (SD) submaximal heart rate (based on n = 20) reduced significantly by -6.5 beats per minute (95% CI = -11.8 to -1.2), from 121.7 (16.5) at baseline to 115.2 (14.3) after intervention. Submaximal ratings of perceived exertion, anaerobic threshold, and peak workload also improved significantly (P < .05). CONCLUSION: The outcomes of this pilot study suggest that individualized aerobic exercise according to B-FIT is feasible and has potential to improve physical fitness in a wide variety of slowly progressive NMD. However, some barriers must be addressed before investigating the efficacy in a randomized controlled trial. IMPACT: The outcomes of this study demonstrate the feasibility of individualized aerobic exercise according to the B-FIT training guide and the potential to improve physical fitness in NMD. Physical therapists indicated that the use of B-FIT provides a clear, well-grounded guidance. The training guide can support health care professionals in the application of aerobic exercise in adult neuromuscular rehabilitation. LAY SUMMARY: Individualized exercise according to the B-FIT training guide is feasible in a wide variety of slowly progressive NMD and might help improve physical fitness.

Exercise therapy and cognitive behavioural therapy to improve fatigue, daily activity performance and quality of life in postpoliomyelitis syndrome: the protocol of the FACTS-2-PPS trial.

BACKGROUND: Postpoliomyelitis Syndrome (PPS) is a complex of late onset neuromuscular symptoms with new or increased muscle weakness and muscle fatigability as key symptoms. Main clinical complaints are severe fatigue, deterioration in functional abilities and health related quality of life. Rehabilitation management is the mainstay of treatment. Two different therapeutic interventions may be prescribed (1) exercise therapy or (2) cognitive behavioural therapy (CBT). However, the evidence on the effectiveness of both interventions is limited. The primary aim of the FACTS-2-PPS trial is to study the efficacy of exercise therapy and CBT for reducing fatigue and improving activities and quality of life in patients with PPS. Additionally, the working mechanisms, patients' and therapists' expectations of and experiences with both interventions and cost-effectiveness will be evaluated. METHODS/DESIGN: A multi-centre, single-blinded, randomized controlled trial will be conducted. A sample of 81 severely fatigued patients with PPS will be recruited from 3 different university hospitals and their affiliate rehabilitation centres. Patients will be randomized to one of three groups i.e. (1) exercise therapy + usual care, (2) CBT + usual care, (3) usual care. At baseline, immediately post-intervention and at 3- and 6-months follow-up, fatigue, activities, quality of life and secondary outcomes will be assessed. Costs will be based on a cost questionnaire, and statistical analyses on GEE (generalized estimated equations). Analysis will also consider mechanisms of change during therapy. A responsive evaluation will be conducted to monitor the implementation process and to investigate the perspectives of patients and therapists on both interventions. DISCUSSION: A major strength of the FACTS-2-PPS study is the use of a mixed methods design in which a responsive and economic evaluation runs parallel to the trial. The results of this study will generate new evidence for the rehabilitation treatment of persons with PPS. TRIAL REGISTRATION: Dutch Trial Register NTR1371.

Stiffness-Optimized Ankle-Foot Orthoses Improve Walking Energy Cost Compared to Conventional Orthoses in Neuromuscular Disorders: A Prospective Uncontrolled Intervention Study.

In persons with calf muscle weakness, walking energy cost is commonly increased due to persistent knee flexion and a diminished push-off. Provided ankle-foot orthoses (AFOs) usually lower walking energy cost. To maximize the reduction in energy cost, AFO bending stiffness should be individually optimized, but this is not common practice. Therefore, we aimed to evaluate whether individually stiffness-optimized AFOs reduce walking energy cost compared to conventional AFOs in persons with non-spastic calf muscle weakness and, secondarily, whether stiffness-optimized AFOs improve walking speed and gait biomechanics. Thirty-seven persons with non-spastic calf muscle weakness using a conventional AFO were included. Participants were provided a new, individually stiffness-optimized AFO. Walking energy cost, speed and gait biomechanics were assessed, at delivery and 3-months follow-up. Stiffness-optimized AFOs reduced walking energy cost with 9.2% (-0.42J/kg/m, 95%CI: 0.26 to 0.57) compared to the conventional AFOs while walking speed increased with 5.2% (+0.05m/s, 95%CI: 0.03 to 0.08). In bilateral affected persons the effects were larger compared to unilateral affected persons (difference effect energy cost: 0.31J/kg/m, speed: +0.09m/s). Although individually gait biomechanics changed considerably, no significant group differences were found (p > 0.118). We demonstrated that individually stiffness-optimized AFOs considerably and meaningfully reduced walking energy cost compared to conventional AFOs, which was accompanied by an increase in walking speed. Especially in bilateral affected persons large effects of stiffness-optimization were found. The individual differences in gait changes substantiate the recommendation that the AFO bending stiffness should be individually tuned to minimize walking energy cost.

Specialised orthotic care to improve functioning in adults with neuromuscular disorders: protocol of a prospective randomised open-label blinded end-point study.

INTRODUCTION: People suffering from leg muscle weakness caused by neuromuscular disorders (NMDs) are often provided with leg orthoses to reduce walking problems such as increased walking effort, diminished walking speed, reduced balance and falls. However, evidence for the effectiveness of leg orthoses to improve walking in this patient group is limited and there is an absence of standardised practice in orthotic prescription. In 2012 a Dutch multidisciplinary guideline was developed aimed to standardise the orthotic treatment process in NMD. Although application of the guideline in expert centres (specialised orthotic care) seems beneficial regarding clinical effectiveness, larger studies are necessary to confirm results and investigate cost-effectiveness. Therefore, this study aims to examine the effectiveness and cost-effectiveness of specialised orthotic care compared with usual orthotic care in adults with slowly progressive NMD. METHODS AND ANALYSIS: A prospective randomised open-label blinded end-point study will be performed, in which 70 adults with slowly progressive NMD are randomly assigned to specialised orthotic care (intervention) or usual orthotic care (control). Outcome measures are assessed at baseline and at 3 and 6 months follow-up. The primary endpoints are gross walking energy cost (J/kg/m) assessed during a 6 min walk test and achievement of personal goals, measured with the Goal Attainment Scale. Secondary endpoints include walking speed, gait biomechanics, stability, physical functioning, falls and fear of falling, perceived fatigue and satisfaction. For the economic evaluation, societal costs and health-related quality of life will be assessed using cost questionnaires and the 5-Level version of EuroQol 5 Dimension, retrospectively. ETHICS AND DISSEMINATION: The study is registered in the Dutch trial register (NL 7511) and the protocol has been approved by the Medical Ethics Committee of the Academic Medical Center in Amsterdam. Results will be presented at national and international scientific conferences and disseminated through peer-reviewed journals and media aimed at a broad audience including patients.

Aerobic exercise in adult neuromuscular rehabilitation: A survey of healthcare professionals.

OBJECTIVE: To evaluate the current application of aerobic exercise in adult neuromuscular rehabilitation. DESIGN: Cross-sectional survey. PARTICIPANTS: Dutch rehabilitation specialists and physical therapists in specialized centres for slowly progressive neuromuscular diseases and in primary care. METHODS: Participants received a self-designed, web-based, questionnaire, including 27 close-ended questions covering 4 categories: respondent profile, application of aerobic exercise, barri-ers to prescribing aerobic exercise, and need for support to improve the application of aerobic exercise. RESULTS: All respondents (n = 52) prescribed aerobic exercise and in a wide variety of neuromuscular diseases, mostly applying sessions of more than 20 min, 2 days per week, over a period of 9-16 weeks, using different exercise modes and methods to target intensity. The majo-rity (81%) agreed that aerobic exercise should be incorporated into neuromuscular rehabilitation. However, all respon-dents perceived barriers to the application of aerobic exercise in one or more domains, and 77% of the respondents indicated needing support to improve application of this type of training, mostly with respect to screening procedures (54%) and dosing of exercise programmes (48%). CONCLUSION: Aerobic exercise is widely applied, yet our results raise awareness of the necessity of more evidence based knowledge, in order to develop and implement guidelines in adult neuromuscular rehabilitation.

Correction: Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation of a Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.0159280.].

Cognitive behavioural therapy for reducing fatigue in post-polio syndrome and in facioscapulohumeral dystrophy: A comparison.

BACKGROUND: Cognitive behavioural therapy does not reduce fatigue in post-polio syndrome, but is effective in facioscapulohumeral dystrophy. This difference in efficacy might be explained by a different role of cognitions in these conditions. OBJECTIVE: To compare fatigue-related cognitions between patients with post-polio syndrome and facio-scapulohumeral dystrophy. SUBJECTS: Patients with post-polio syndrome (n = 21) and facioscapulohumeral dystrophy (n = 24) allocated to a cognitive behavioural therapy intervention in 2 identical trials. METHODS: Assessed cognitions included: sense of control over fatigue; catastrophizing; acceptance; focusing on fatigue; and perceived social support. Group differences in cognitions (independent t-tests or Mann-Whitney U tests) and group differences in the association of cognitions with fatigue (linear regression models) were studied. RESULTS: No differences in cognitions were found between the 2 groups (p > 0.18). Furthermore, there were no cognition-by-group interaction effects, except for "perceived social support", for which a different association with fatigue was found between the 2 groups (p = 0.01). However, univariate models revealed no associations per group. CONCLUSION: Fatigue-related cognitions in severely fatigued patients with post-polio syndrome are not clearly different from that in facioscapulohumeral dystrophy. Thus, the lack of efficacy of cognitive behavioural therapy in post-polio syndrome cannot be attributed to unique cognitive characteristics of this population.