Low-dose/high-concentration localized botulinum toxin A improves upper limb movement and function in children with hemiplegic cerebral palsy

Abstract

The objective was to determine the effects of low‐dose, high‐concentration, dual localized botulinum toxin A (BTX‐A) injections on upper limb movement quality and function. Study design was an evaluator‐blinded, randomized, controlled trial. Forty‐two children (31 males, 11 females; range 2–8y, mean 4y [SD 1.6]) with hemiplegic cerebral palsy (Gross Motor Function Classification System level I) participated. All received occupational therapy. The treatment group (n=21) received one injection series (mean muscles injected 6 [SD 1.05]; total dose 82–220 units, mean 139 [SD 37.48]; dilution 100 units/0.5ml). Primary outcome of Quality of Upper Extremity Skills Test (QUEST) at 6 months was not significant (p=0.318). Secondary outcomes were average treatment effects at 1, 3, and 6 months, which favoured the treatment group: QUEST (p<0.001); Canadian Occupational Performance Measure (performance, p=0.002; satisfaction p=0.007); parent Goal Attainment Scaling (GAS; p=0.001), therapist GAS (p<0.001); Pediatric Evaluation of Disability Inventory (PEDI) functional skills (p=0.030); Ashworth (p<0.001). PEDI caregiver assistance was not significant (p=0.140). Therapy alone is effective, but at 1 and 3 months movement quality is better where BTX‐A is also used. Moreover, function is better at 1, 3, and 6 months, suggesting BTX‐A enhances therapy outcomes beyond the pharmacological effect. One‐ and 3‐month Ashworth and QUEST scores suggest precise needle placement accuracy.

Goal attainment scaling in paediatric rehabilitation: a critical review of the literature

“…Most of the goals set in the six studies were in the areas of activities and participation, but body function goals, such as gait pattern 19,23 and range of motion, 18 were also assessed. The results of these studies show that GAS is sensitive to change when used to measure an effect of BTX-A and an effect of functional training in children.…”

“…Extra caution is required when goals at both the ICF activity/participation level and body function level are used and weighted, as was done in the studies by Lowe et al 18 and Mall et al 19 For example,'knee-knee distance' 19 is not an outcome measure provided by the child itself, but it is more reliable than a GAS scale on climbing stairs.…”

“…The original GAS by 554 19 RCT Evaluation of the 61 children with CP Knee-knee distance, Significant superiority of the effects of BTX-A on Ashworth, GMFM, GAS BTX-A group (p=0.037) adductor spasticity Lowe et al 18 RCT Evaluation of the effects 42 children with QUEST, COPM, Parent GAS Significant superiority of the of specific BTX-A on hemiplegic CP and therapist GAS, PEDI, BTX-A group (GAS [parent] upper limb movement Ashworth at 1, 3, and p=0.001, GAS quality and function 6 months [therapist] p<0.001) Steenbeek RCC To determine the 11 children with CP GAS in an evaluator-blinded 9/11 participants showed significant et al 3 possibility of using GAS Kiresuk and Sherman 6 was scored before and after the intervention, and deterioration could only be scored if the start was defined as -1. This can introduce a bias for the calculation of group effects, because only three values then remain to score progress, the first of which is the expected goal (0).…”

Dose‐ and volume dependent‐response to intramuscular injection of botulinum neurotoxin‐A optimizes muscle force decrement in mice

“…2,7,9 Furthermore, the dose administered to reach clinical goals in muscle tone is highly variable. [7][8][9] Endocytotic uptake of BoNTA by the distal neuron results in a conformational change in the light chain with subsequent proteolytic cleavage of the vesicle docking protein, SNAP-25. 1,10 Cleavage of SNAP-25 prevents vesicular release of acetylcholine into the synaptic cleft of the neuromuscular junction causing muscle paralysis.…”

“…8,18 Literature to date offers little information on a systematic approach to the effects of dose and volume on the neuromuscular physiology following intramuscular administration of the toxin. [6][7][8][9] Detailed evaluation of BoNTA injections and neuromuscular physiology with an animal model would provide valuable insight into dosing techniques for the clinical administration of BoNTA. A murine model was used to test the hypothesis that the degree of muscle inhibition can be optimized by delivering the appropriate dose and volume to the targeted muscle through alteration of the independent variables, BoNTA dose and injection volume, as assessed by outcome measures of electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass.…”