M.A.G.C. Schoenmakers

Physical function and fitness in long-term survivors of childhood leukaemia.

Objective: To evaluate the physical function and fitness in survivors of childhood leukaemia 5–6 years after cessation of chemotherapy. Materials and methods: Thirteen children (six boys and seven girls; mean age 15.5 years) who were treated for leukaemia were studied 5–6 years after cessation of therapy. Physical function and fitness were determined by anthropometry, motor performance, muscle strength, anaerobic and aerobic exercise capacity. Results: On motor performance, seven of the 13 patients showed significant problems in the hand-eye co-ordination domain. Muscle strength only showed a significantly lower value in the mean strength of the knee extensors. The aerobic and the anaerobic capacity were both significantly reduced compared to reference values. Conclusion: Even 5–6 years after cessation of childhood leukaemia treatment, there are still clear late effects on motor performance and physical fitness. Chemotherapy-induced neuropathy and muscle atrophies are probably the prominent cause for these reduced test results. Physical training might be indicated for patients surviving leukaemia to improve fitness levels and muscle strength.

Muscle strength, aerobic capacity and physical activity in independent ambulating children with lumbosacral spina bifida

Purpose. This cross-sectional study investigates deficits and associations in muscle strength, 6-minute walking distance (6MWD), aerobic capacity (VO2peak), and physical activity (PA) in independent ambulatory children with lumbosacral spina bifida. Method. Twenty-tree children participated (13 boys, 10 girls). Mean age (SD): 10.4 (±3.1) years. Muscle strength (manual muscle testing and hand-held dynamometry), 6MWD, VO2peak (maximal exercise test on a treadmill), and PA (quantity and energy expenditure [EE]), were measured and compared with aged-matched reference values. Results. Strength of upper and lower extremity muscles, and VO2peak were significantly lower compared to reference values. Mean Z-scores ranged from −1.2 to −2.9 for muscle strength, and from −1.7 to −4.1 for VO2peak. EE ranged from 73 – 84% of predicted EE. 6MWD was significantly associated with muscle strength of hip abductors and foot dorsal flexors. VO2peak was significantly associated with strength of hip flexors, hip abductors, knee extensors, foot dorsal flexors, and calf muscles. Conclusions. These children have significantly reduced muscle strength, 6MWD, VO2peak and lower levels of PA, compared to reference values. VO2peak and 6MWD were significantly associated with muscle strength, especially with hip abductor and ankle muscles. Therefore, even in independent ambulating children training on endurance and muscle strength seems indicated.

Spina bifida at the sacral level: more than minor gait disturbances

Objective: To investigate functional outcome in two groups of children with sacral level paralysis: myelomeningocele (MMC) versus lipomyelomeningocele (LMMC). Additionally both groups were compared with each other and when possible with reference values. Design: Cross-sectional study by means of (1) clinical assessment, and (2) disability measurement. Setting: Spina bifida outpatient clinic at a university hospital in the Netherlands. Subjects: Sample of 30 children with MMC and 14 with LMMC. Mean age (SD) 6.0 (4.9) and 8.4 (4.9) years respectively. Main measures: Muscle strength, ambulation level, motor performance (Bayley Scales of Infant Development (BSID) and Movement Assessment Battery for Children), and the Pediatric Evaluation of Disability Inventory (PEDI). Results: The majority of patients in both groups were normal ambulant, 14/21 (67%) in MMC and 9/14 (64%) in LMMC. Ambulation was strongly associated with muscle strength of hip abductors (odds ratio (OR): 13.5, 95% condfidence interval (CI) 2.5–73.7), and ankle dorsal-flexor muscles (OR: 110, 95% CI 8.9–135.9). No significant differences were found in lesion and ambulation level. Muscle strength and motor performance were significantly lower in the MMC group than in the LMMC group (p <0.05). PEDI scores were comparable in both groups. Most problems were noted in mobility skills and caregiver assistance in self-care, especially regarding bladder and bowel management. Conclusions: Gross motor and functional problems were seen in both groups. The MMC group showed more muscle weakness and motor problems. However, in both groups caregiver assistance was needed for a prolonged period, especially regarding bladder and bowel management. These dindings need special attention, particularly in children who attend regular schools.

Limiting factors in peak oxygen uptake and the relationship with functional ambulation in ambulating children with Spina Bifida

The objective of this study is to interpret the outcomes of peak oxygen uptake (VO2peak) in children with SB and explore the relationship between VO2peak and functional ambulation using retrospective cross-sectional study. Twenty-three ambulating children with SB participated at Wilhelmina’s Children’s Hospital Utrecht, the Netherlands. VO2peak was measured during a graded treadmill-test. Eschenbacher’s and Maninna’s algorithm was used to determine limiting factors in reaching low VO2peak values. Energy expenditure during locomotion (both O2 rate and O2 cost) and percentage of VO2peak and HRpeak were determined during a 6-min walking test (6MWT). Differences between community and normal ambulators were analyzed. VO2peak, VO2peak/kg, HRpeak, RERpeak and VEpeak were significantly lower compared to reference values, with significant differences between normal and community ambulators. Limiting factors according to the algorithm were mostly “muscular and/or deconditioning” (47%) and ventilatory “gasexchange” (35%). Distance walked during 6MWT was 48.5% of predicted distance. Both O2 rate and O2 cost were high with significant differences between normal and community ambulators [17.6 vs. 21.9 ml/(kg min) and 0.27 vs 0.43 ml/(kg m)]. Also %HRpeak and %VO2peak were significantly higher in community ambulators when compared to normal ambulators (resp. 97.6 vs. 75% and 90.2 vs. 55.9%). VO2peak seems to be mostly limited by deconditioning and/or muscular components and possible ventilatory factors. For both peak values and functional ambulation, community ambulators were significantly more impaired than normal ambulators. High energy expenditure, %VO2peak and %HRpeak reflect high level of strain during ambulation in the community ambulators. Future exercise testing in children with SB should include assessment of ventilatory reserve. Exercise training in ambulatory children should focus on increasing both VO2peak and muscular endurance, as well as decreasing energy cost of locomotion.

Reproducibility of Maximal and Submaximal Exercise Testing in “Normal Ambulatory” and “Community Ambulatory” Children and Adolescents With Spina Bifida: Which Is Best for the Evaluation and Application of Exercise Training?

Background With emerging interest in exercise and lifestyle interventions for children and adolescents with spina bifida, there is a need for appropriate measurements in exercise testing. Objective The purpose of this study was to assess both reliability and agreement of maximal and submaximal exercise measures in “normal ambulatory” and “community ambulatory” children and adolescents with spina bifida. Design This was a reproducibility study. Methods Twenty-three children and adolescents with spina bifida (10 normal ambulatory and 13 community ambulatory) participated in the study. Maximal exercise outcomes were measured using a graded treadmill test. Peak measures (peak oxygen uptake [V̇o2peak], peak heart rate [HRpeak], heart rate response [HRR], and oxygen pulse) were recorded. For submaximal measures, heart rate (HR) and oxygen uptake (V̇o2) at the ventilatory threshold and oxygen uptake efficiency slope (OUES) were derived from the maximal measures. Functional performance was measured as the 6-minute walking distance and the maximal speed during the treadmill test. After checking for normality and heteroscedasticity, paired t tests, intraclass correlation coefficients (ICCs), and the smallest detectable difference (SDD) or the coefficient of variation (CV) were calculated. Results Performance measures showed good reliability and agreement. For maximal measures, acceptable ICCs were found for all measures. For submaximal measures, only HR at the ventilatory threshold showed an ICC of less than .80. Agreement showed a CV of less than 10% for all measures, except for V̇o2 at the ventilatory threshold, HRR, and OUES. Limitations Limitations of the study include missing data due to equipment failure. Furthermore, the outcomes were limited to normal ambulatory and community ambulatory children and adolescents with spina bifida. Conclusions Both maximal and submaximal measures of exercise testing can be used for discriminative purposes in ambulatory children and adolescents with spina bifida. For evaluative purposes, HR measures are superior to V̇o2 measures, while taking into account the individual variation of 5% to 8%. The SDD was 0.5 km/h for peak speed and 36.3 m for 6-minute walking distance. Heart rate response, oxygen pulse, and OUES are not recommended in the evaluation of exercise testing in this population.

Reproducibility of energy cost of locomotion in ambulatory children with spina bifida

OBJECTIVES Many ambulatory children with Spina Bifida (SB) experience functional decline in ambulation despite stable or even improving motor exams. Improving or maintaining low energy cost of locomotion during childhood and throughout the teenage years, could be an important goal for children and adolescents with SB. Purpose of this study was to determine reproducibility of energy expenditure measures during gait in ambulatory children with SB. DESIGN Reproducibility study. SETTING Child Development and Exercise Center of the University Childrens Hospital in Utrecht, the Netherlands. PARTICIPANTS Fourteen ambulatory children (6 boys/8 girls) with SB. Mean age was 10.8 years (+ or - 3.4). INTERVENTIONS Net and gross energy expenditure measures during locomotion were determined during a six-minute walking test. These measures consisted of energy consumption (ECS), expressed in J/kg/min, and energy cost (EC), expressed in J/kg/m. For reliability, the intra-class coefficient (ICC) was determined. For agreement, the smallest detectable difference (SDD) was calculated. RESULTS ICCs vary from 0.86 to 0.96 for both EC and ECS. The SDD ranges from 18-24% for gross measures, up to over 30% for net values. CONCLUSION Reproducibility of energy expenditure during ambulation in children with SB should be considered carefully when using these measures in the evaluation of gait. High reliability of energy expenditure measurements makes these measurements appropriate to use as discriminative tools in children with SB, while agreement of only gross EC seems acceptable to use as a evaluative tool in children with SB. Overall, measures of reliability and agreement seem higher in young children when compared to adolescents. Further research is recommended to determine clinically relevant changes in energy expenditure in children with SB.

Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c–4

Natural history studies in spinal muscular atrophy (SMA) have primarily focused on infants and children. Natural history studies encompassing all age groups and SMA types are important for the interpretation of treatment effects of recently introduced survival motor neuron gene‐augmenting therapies.

Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2–4 (SPACE trial)

Introduction Hereditary proximal spinal muscular atrophy (SMA) is caused by homozygous loss of function of the survival motor neuron 1 gene. The main characteristic of SMA is degeneration of alpha motor neurons in the anterior horn of the spinal cord, but recent studies in animal models and patients have shown additional anatomical abnormalities and dysfunction of the neuromuscular junction (NMJ). NMJ dysfunction could contribute to symptoms of weakness and fatigability in patients with SMA. We hypothesise that pyridostigmine, an acetylcholinesterase inhibitor that improves neuromuscular transmission, could improve NMJ function and thereby muscle strength and fatigability in patients with SMA. Methods and analysis We designed a monocentre, placebo-controlled, double-blind cross-over trial with pyridostigmine and placebo to investigate the effect and efficacy of pyridostigmine on muscle strength and fatigability in patients with genetically confirmed SMA. We aim to include 45 patients with SMA types 2–4, aged 12 years and older in the Netherlands. Participants receive 8 weeks of treatment with pyridostigmine and 8 weeks of treatment with placebo in a random order separated by a washout period of 1 week. Treatment allocation is double blinded. Treatment dose will gradually be increased from 2 mg/kg/day to the maximum dose of 6 mg/kg/day in four daily doses, in the first week of each treatment period. The primary outcome measures are a change in the Motor Function Measure and repeated nine-hole peg test before and after treatment. Secondary outcome measures are changes in recently developed endurance tests, that is, the endurance shuttle nine-hole peg test, the endurance shuttle box and block test and the endurance shuttle walk test, muscle strength, level of daily functioning, quality of and activity in life, perceived fatigue and fatigability, presence of decrement on repetitive nerve stimulation and adverse events. Ethics and dissemination The protocol is approved by the local medical ethical review committee at the University Medical Center Utrecht and by the national Central Committee on Research Involving Human Subjects. Findings will be shared with the academic and medical community, funding and patient organisations in order to contribute to optimisation of medical care and quality of life for patients with SMA. Trial registration number NCT02941328.