Long-term benefits of physical activity in adult patients with late onset Pompe disease: a retrospective cohort study with 10 years of follow-up.

BACKGROUND: In 2011 a 12 weeks personalized exercise training program in 23 mildly affected adult late onset Pompe patients (age 19.6-70.5 years) improved endurance, muscle strength and function. Data on long-term effects of this program or of other physical activity in Pompe disease are absent. This retrospective cohort study aimed to explore effects of long-term healthy physical activity according to the WHO norm and the former exercise training program on the disease course. RESULTS: A total of 29 adult late onset Pompe patients were included: 19 former exercise training program participants and 10 comparable control patients. Patients, who based on interviews, met the 2010 WHO healthy physical activity norm (active, n = 16) performed better on endurance (maximal cardiopulmonary exercise test), muscle strength and function compared to patients not meeting this norm (inactive, n = 13) (p < 0.05). Majority of the outcomes, including endurance and manually tested muscle strength, tended to be higher in the active patients of the 2011 training cohort who continued the program compared to active control patients (p > 0.05). CONCLUSION: In Pompe disease long-term healthy physical activity according to the 2010 WHO norm leads to physical benefits and a personalized exercise training program may have additional favorable effects and both should be recommended as standard of care.

Association of Muscle Strength and Walking Performance in Adult Patients With Pompe Disease.

Background: The loss of the ability to walk is among the most prominent signs of Pompe disease. The associations with muscle strength have not been described. Objective: The objective of this study was to estimate the associations of walking performance with muscle strength in 4 specific lower extremity muscle groups along with other factors in adult patients with Pompe disease. Design: This was a single-center, cross-sectional study. Methods: Muscle strength (hand-held dynamometry of hip flexion and abduction and knee extension and flexion) and walking performance (unable to walk, able with aids, walking without aids but with a waddling gait, or walking without aids and with a normal gait) were assessed in 107 patients at their first visit. Relationships between walking performance and muscle strength were studied through multivariate analyses and regression modeling. Age, sex, body mass index (BMI), disease duration, and use of ventilator support were taken into account as potential confounders. The results were transformed into a nomogram to allow the probability of a patient having a certain level of walking performance to be calculated based on the values of the independent variables. Results: Walking performance declined significantly with decreasing muscle strength of hip flexion and abduction and knee extension and flexion. The final selected model, including strength of the hip abductor and knee extensor, BMI, age, sex, and use of ventilation, predicted 66% of the cases accurately. Limitations: These results are based on cross-sectional data and do not predict future changes. Conclusions: In adult people with Pompe disease, walking performance can be explained by muscle strength, BMI, age, sex, and ventilation use. The proposed model gives insight into how an individual is expected to walk based on his or her risk factors and serves as a starting point to unraveling factors associated with walking performance and ultimately to developing a prognostic model.

Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study.

OBJECTIVE: To determine the effect of enzyme replacement therapy (ERT) after 5 years and to identify predictors for a favorable response because few data are available on the long-term efficacy of ERT in Pompe disease. METHODS: We included 102 adult patients with Pompe disease in a nationwide, prospective cohort study. We assessed muscle strength (manual muscle testing with Medical Research Council [MRC] grading, handheld dynamometry [HHD]), muscle function (6-minute walk test, Quick Motor Function Test), daily life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale), and pulmonary function (forced vital capacity [FVC] in upright and supine positions, maximum inspiratory and expiratory pressures) at 3- to 6-month intervals before and after the start of ERT. Data were analyzed with linear mixed-effects models for repeated measurements. RESULTS: Median follow-up duration was 6.1 years (range 0.4-7.9 years), of which 5.0 years (range 0.2-7.3 years) were during ERT. Treated patients had better muscle strength (MRC sum score +6.6 percentage points [pp]; HHD sum score +9.6 pp, both p < 0.0001), activity levels (R-PAct +10.8 pp, p < 0.002), and pulmonary function (FVC upright +7.3 pp, FVC supine +7.6 pp, both p < 0.0003) than expected for their untreated disease course. Walking distance improved (416 vs 376 m at baseline, p = 0.03). The largest increase was seen during the first 2 to 3 years of treatment. Response to treatment was similar between groups regardless of sex, age, or disease duration. CONCLUSIONS: Long-term ERT positively affects muscle strength, pulmonary function, and daily life activities in adult patients with Pompe disease, with a peak effect at ≈2 to 3 years of treatment. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with Pompe disease, long-term ERT positively affects muscle strength, pulmonary function, and daily life activities.

Safety and efficacy of exercise training in adults with Pompe disease: evalution of endurance, muscle strength and core stability before and after a 12 week training program.

BACKGROUND: Pompe disease is a proximal myopathy. We investigated whether exercise training is a safe and useful adjuvant therapy for adult Pompe patients, receiving enzyme replacement therapy. METHODS: Training comprised 36 sessions of standardized aerobic, resistance and core stability exercises over 12 weeks. Before and after, the primary outcome measures safety, endurance (aerobic exercise capacity and distance walked on the 6 min walk test) and muscle strength, and secondary outcome measures core stability, muscle function and body composition, were evaluated. RESULTS: Of 25 patients enrolled, 23 successfully completed the training. Improvements in endurance were shown by increases in maximum workload capacity (110 W before to 122 W after training, [95 % CI of the difference 6 · 0 to 19 · 7]), maximal oxygen uptake capacity (69 · 4 % and 75 · 9 % of normal, [2 · 5 to 10 · 4]), and maximum walking distance (6 min walk test: 492 meters and 508, [-4 · 4 to 27 · 7] ). There were increases in muscle strength of the hip flexors (156 · 4 N to 180 · 7 N [1 · 6 to 13 · 6) and shoulder abductors (143 · 1 N to 150 · 7 N [13 · 2 to 35 · 2]). As an important finding in secondary outcome measures the number of patients who were able to perform the core stability exercises rose, as did the core stability balancing time (p < 0.05, for all four exercises). Functional tests showed small reductions in the time needed to climb four steps (2 · 4 sec to 2 · 1, [- 0 · 54 to -0 · 04 ]) and rise to standing position (5 · 8 sec to 4 · 8, [-2 · 0 to 0 · 0]), while time to run, the quick motor function test results and body composition remained unchanged. CONCLUSIONS: Our study shows that a combination of aerobic, strength and core stability exercises is feasible, safe and beneficial to adults with Pompe disease.

Exercise training in adults with Pompe disease: the effects on pain, fatigue, and functioning.

OBJECTIVE: To assess if a 12-week exercise intervention to improve aerobic fitness, muscle strength, and core stability also had an impact on fatigue, pain, activity, and participation in adults with Pompe disease, an inherited neuromuscular disorder. DESIGN: Open-label trial. Change was assessed by the chi-square test and Wilcoxon signed-rank test. SETTING: Physiotherapy practices. PARTICIPANTS: Mildly affected adult patients with Pompe disease who were not dependent on ventilators and/or walking devices and were receiving enzyme replacement therapy. INTERVENTION: Patients participated in a 12-week exercise program, which included 36 sessions of standardized aerobic, resistance, and core stability exercises. MAIN OUTCOME MEASURES: Before and after the training program we evaluated fatigue (Fatigue Severity Scale), pain (yes/no), motor function (Quantitative Muscle Function Test, Rasch-built Pompe-specific Activity Scale), amount of physical activity (activity monitor), and health status (Medical Outcomes Study 36-Item Short-Form Health Survey). RESULTS: Of the 25 patients enrolled, 23 completed the program. At the end of the program, levels of fatigue (median, 5.33 to 4.78, P=.01) and pain (56.5% to 21.7%, P=.04) improved. The quality of motor function and the amount of physical activity patients engaged in did not change. Changes in pain and fatigue were not related to improvements in aerobic fitness or muscle strength. CONCLUSIONS: This study in mildly affected adult patients with Pompe disease suggests that a combined training program aiming to increase aerobic fitness, muscle strength, and core stability also leads to improvements in fatigue and pain.

Physiotherapy management in late-onset Pompe disease: clinical practice in 88 patients.

Pompe disease is an inherited metabolic, neuromuscular disorder. With the introduction of enzyme replacement therapy skeletal muscle and respiratory function can be stabilized or improved. Additional physiotherapy to advance physical functioning of patients might be beneficial, but evidence and guidelines are lacking. In order to get an insight into current practices of referral and treatment, and perceived benefit, we performed a survey among 88 Dutch adult Pompe patients and 31 physiotherapists. Sixty percent of patients were ever referred for physiotherapy, whereas currently less than 40% receive physiotherapy. Approximately 50% of patients were referred for loss of muscle strength; while 74% received muscle strengthening exercises, often combined with aerobic endurance training. In 47% of patients the intervention did not match the referral reason. More than two-thirds of patients and physiotherapists perceived physiotherapy as beneficial, and the majority highlighted the need for guidance. Physiotherapeutic care can be improved by tailoring interventions to referral reasons and treatment objectives. More high quality studies are urgently needed to assess which interventions are most useful in this patient group.

The Dutch version of the Knee Injury and Osteoarthritis Outcome Score: a validation study.

BACKGROUND: The Knee Injury and Osteoarthritis Outcome Score (KOOS) was constructed in Sweden. This questionnaire has proved to be valid for several orthopedic interventions of the knee. It has been formally translated and validated in several languages, but not yet in Dutch. The purpose of the present study was to evaluate the clinimetric properties of the Dutch version of the KOOS questionnaire in knee patients with various stages of osteoarthritis (OA). METHODS: The Swedish version of the KOOS questionnaire was first translated into Dutch according to a standardized procedure and second tested for clinimetric quality. The study population consisted of patients with different stages of OA (mild, moderate and severe) and of patients after primary TKA, and after a revision of the TKA. All patients filled in the Dutch KOOS questionnaire, as well as the SF-36 and a Visual Analogue Scale for pain. The following analyses were performed to evaluate the clinimetric quality of the KOOS: Cronbach's alpha (internal consistency), principal component analyses (factor analysis), intraclass correlation coefficients (reliability), spearman's correlation coefficient (construct validity), and floor and ceiling effects. RESULTS: For all patients groups Cronbach's alpha was for all subscales above 0.70. The ICCs, assessed for the patient groups with mild and moderate OA and after revision of the TKA patients, were above 0.70 for all subscales. Of the predefined hypotheses 60% or more could be confirmed for the patients with mild and moderate OA and for the TKA patients. For the other patient groups less than 45% could be confirmed. Ceiling effects were present in the mild OA group for the subscales Pain, Symptoms and ADL and for the subscale Sport/Recreation in the severe OA group. Floor effects were found for the subscales Sport/Recreation and Qol in the severe OA and revision TKA groups. CONCLUSION: Based on these different clinimetric properties within the present study we conclude that the KOOS questionnaire seems to be suitable for patients with mild and moderate OA and for patients with a primary TKA. The Dutch version of the KOOS had a lower construct validity for patients with severe OA on a waiting list for TKA and patients after revision of a TKA. Further validation studies on the Dutch version of the KOOS should also include a knee specific questionnaire for assessing the construct validity.