The WE-Study: does botulinum toxin A make walking easier in children with cerebral palsy?: Study protocol for a randomized controlled trial.

BACKGROUND: Intramuscular injections of botulinum toxin A (BoNT-A) have been a cornerstone in the treatment of spasticity for the last 20 years. In Norway, the treatment is now offered to two out of three children with spastic cerebral palsy (CP). However, despite its common use, the evidence for its functional effects is limited and inconclusive. The objective of this study is to determine whether BoNT-A makes walking easier in children with CP. We hypothesize that injections with BoNT-A in the calf muscles will reduce energy cost during walking, improve walking capacity, increase habitual physical activity, reduce pain and improve self-perceived performance and satisfaction. METHODS/DESIGN: This randomized, double-blinded, placebo-controlled, multicenter trial is conducted in a clinical setting involving three health regions in Norway. Ninety-six children with spastic CP, referred for single-level injections with BoNT-A in the calf muscles, will be invited to participate. Those who are enrolled will be randomized to receive either injections with BoNT-A (Botox®) or 0.9% saline in the calf muscles. Stratification according to age and study center will be made. The allocation ratio will be 1:1. Main inclusion criteria are (1) age 4 - 17.5 years, (2) Gross Motor Function Classification System levels I and II, (3) no BoNT-A injections in the lower limbs during the past 6 months and (4) no orthopedic surgery to the lower limbs during the past 2 years. The outcome measures will be made at baseline and 4, 12 (primary endpoint) and 24 weeks after injections. Primary outcome is change in energy cost during walking. Secondary outcomes are change in walking capacity, change in activity, perceived change in performance and satisfaction in mobility tasks, and pain. The primary analysis will use a linear mixed model to test for difference in change in the outcome measures between the groups. The study is approved by the Regional Ethical Committee and The Norwegian Medicines Agency. Recruitment started in September 2015. DISCUSSION: The evaluation of effect is comprehensive and includes objective standardized tests and measures on both impairment and activity level. Results are to be expected by spring 2019. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02546999 . Registered on 9 September 2015.

High-intensity interval training to improve fitness in children with cerebral palsy.

AIM: To evaluate effects of high-intensity interval training (HIT) on aerobic exercise capacity, quality of life, and body composition in children with cerebral palsy (CP). METHODS: This was a baseline control trial. Children with CP, Gross Motor Function Classification System (GMFCS) levels I-IV, and age 10-17 years were included. The primary outcome, peak, and submaximum oxygen uptake (VO2peak, VO2submax) were measured at enrolment to the study (T0), after a pretraining period (T1), and after HIT (T2). Secondary outcomes were quality of life assessed with the KINDL questionnaire, and body composition measured using whole body dual-energy X-ray absorptiometry scanning. The exercise was performed on treadmills and consisted of 24 sessions, each with a total of 16 min of exercise at >85% of maximal heart rate. RESULTS: 20 children were included and 6 children dropped out. VO2peak increased by 10%, from a median of 37.3 (31.0-40.1) to 41.0 (36.6-48.5) mL/kg/min from T1 to T2 (p<0.01). VO2submax did not change; thereby, the percentage oxygen utilisation was reduced. Body composition was unchanged. Parent-reported quality of life improved, whereas quality of life reported by the children did not improve. CONCLUSIONS: Aerobic exercise capacity improved and per cent utilisation of VO2max declined after HIT in children with CP. Therefore, HIT can be a time efficient way to improve maximal capacity, and increase energy reserve in this patient group. TRIAL REGISTRATION NUMBER: NCT00965133.

Effectiveness of resistance training in combination with botulinum toxin-A on hand and arm use in children with cerebral palsy: a pre-post intervention study.

BACKGROUND: The aim of this pilot study was to examine the effects of additional resistance training after use of Botulinum Toxin-A (BoNT-A) on the upper limbs in children with cerebral palsy (CP). METHODS: Ten children with CP (9-17 years) with unilaterally affected upper limbs according to Manual Ability Classification System II were assigned to two intervention groups. One group received BoNT-A treatment (group B), the other BoNT-A plus eight weeks resistance training (group BT). Hand and arm use were evaluated by means of the Melbourne assessment of unilateral upper limb function (Melbourne) and Assisting Hand Assessment (AHA). Measures of muscle strength, muscle tone, and active range of motion were used to assess neuromuscular body function. Measurements were performed before and two and five months after intervention start. Change scores and differences between the groups in such scores were subjected to Mann-Whitney U and Wilcoxon Signed Rank tests, respectively. RESULTS: Both groups had very small improvements in AHA and Melbourne two months after BoNT-A injections, without differences between groups. There were significant, or close to significant, short-term treatment effects in favour of group BT for muscle strength in injected muscles (elbow flexion strength, p = .08) and non-injected muscles (elbow extension and supination strength, both p = .05), without concomitant increases in muscle tone. Active supination range improved in both groups, but more so in group BT (p = .09). There were no differences between the groups five months after intervention start. CONCLUSIONS: Resistance training strengthens non-injected muscles temporarily and may reduce short-term strength loss that results from BoNT-A injections without increasing muscle tone. Moreover, additional resistance training may increase active range of motion to a greater extent than BoNT-A alone. None of the improvements in neuromuscular impairments further augmented use of the hand and arm. Larger clinical trials are needed to establish whether resistance training can counteract strength loss caused by BoNT-A, whether the combination of BoNT-A and resistance training is superior to BoNT-A or resistance training alone in improving active range of motion, and whether increased task-related training is a more effective approach to improve hand and arm use in children with CP.

Botulinum neurotoxin treatment in children with cerebral palsy: a population-based study in Norway.

BACKGROUND/AIM: To study proportions and characteristics of children treated and un-treated with Botulinum neurotoxin (BoNT) in a population-based cohort of children with cerebral palsy (CP). METHODS: All children with CP born during 1999-2003, recorded in the Norwegian CP Register were included (N=411). Gross motor function was assessed using the gross motor classification system (GMFCS). RESULTS: Sixty-eight percent of children with bilateral spastic, 63% with unilateral spastic and 41% with dyskinetic CP had received BoNT. The percentage of children treated increased from 62% at GMFCS level I to 88% at level IV, but was only 38% among children at level V. A similar trend was seen for fine motor function. Ninety-four percent of the children received BoNT in their lower limbs. Children without significant cognitive impairment were more often treated than children with such impairment (OR: 2.61; 95% CI: 1.49-4.58). INTERPRETATION: In this first population-based study, approximately 2/3 of all children with spastic CP were treated with BoNT. The results suggest preference for treatment of children with potential for functional improvement, while treatment to relieve pain and facilitate care, and of children with cognitive impairment appeared to be less common. Whether the latter groups are treated appropriately requires further studies.

Prevalence of hip dislocation among children with cerebral palsy in regions with and without a surveillance programme: a cross sectional study in Sweden and Norway.

BACKGROUND: Hip dislocation is a serious complication among children with cerebral palsy (CP). The aim of this study was to compare the prevalence of hip dislocation among children with CP in an area providing regular care with an area providing hip surveillance services. METHODS: This is a cross-sectional study in seven Norwegian counties providing regular care and one Swedish healthcare region where a hip surveillance programme was introduced in 1994. Data were provided by the Norwegian Cerebral Palsy Register and the CP Register in Southern Sweden. Children born 1996 - 2003 with moderate to severe CP, defined as Gross Motor Classification System (GMFCS) levels III - V, were included. In all, 119 Norwegian and 136 Swedish children fulfilled the criteria. In Norway, data on hip operations and radiographs of the hips were collected from medical records, while these data are collected routinely in the Swedish register. The hip migration percentage was measured on the recent radiographs. Hip dislocation was defined as a migration percent of 100%. RESULTS: The proportion of children at GMFCS levels III - V was 34% in the Norwegian and 38% in the Swedish population. In the Norwegian population, hip dislocation was diagnosed in 18 children (15.1%; CI: 9.8 - 22.6) compared with only one child (0.7%; 95% CI: 0.01 - 4.0) in Southern Sweden (p = < 0.001). Hip surgery was performed in 53 (44.5%) of the Norwegian children and in 43 (32%) of the Swedish children (p = 0.03). The total number of hip operations was 65 in Norway and 63 in Sweden. Norwegian children were first operated at a mean age of 7.6 years (SD: 2.9) compared with 5.7 years (SD: 2.3) in Sweden (p = 0.001). CONCLUSIONS: The surveillance programme reduced the number of hip dislocations and the proportion of children undergoing hip surgery was lower. However, with the surveillance programme the first operation was performed at a younger age. Our results strongly support the effectiveness of a specifically designed follow-up programme for the prevention of hip dislocation in children with CP.