Table e-3:BoNT for spasticity due to cerebral palsy in children

Reference / Class / Design / Cohort Size / Treatment (Serotype/ Brand, dose) / Follow-up / Outcome Measures (1-Primary 2-Secondary) / Drop Outs / Adverse Events /

Results/ Effect Size

/

Comments

30 / I / Randomized double blind
Spastic equinus / 20 / A/Botox
4 U/kg for both hemiplegic and diplegic pts / 3 mo / Motion analysis / 1 / 0 / Improved dynamic ankle dorsiflexion >3° (p=0.02); NNT=2 / Documented short-term efficacy
31 / I / Randomized, double blind, placebo-controlled
Spastic equinus / 40 / A/Dysport
25 U/kg for diplegics; 15 U/kg for hemiplegics / 3 mo / 1-Video gait analysis
2-GMFM / 0 / In treated group: pain in 2, increased falls in 2 / Video gait analysis improved in 50% at 12 weeks. NNT=3 / First large well-controlled study
32 / I / Randomized, double blind, placebo-controlled, dose escalation study; injection into gastrocnemius
Spastic equinus / 125 / A/Dysport
Randomized to receive placebo, 10, 20 or 30 U/kg / 4 ,mo / 1-dynamic gastroc shortening by electrogoniometry
2-passive ROM, GMFM, subjective global assessment / 1 subject in 20 U/Kg / 6-falls; 6-pain; 4-asthenia / Improved dynamic gastroc shortening at Week 4 for all 3 doses.
Improved passive ROM at Week 4 for only 30U/Kg (p<0.05).
No difference in GMFM
Parent’s subjective global improvement only at 30U/Kg (p<0.05, NNT=4.3)
33 / I / Randomized, double blind, placebo-controlled
Spastic equinus / 114 / A/ Botox
4 U/kg into gastrocnemius / 3 mo / 1- Gait analysis: physician rating scale (0-14)
2- ankle ROM / NA / 17% of BoNT group (weakness, pain, falls) / 47-61% of BoNT improved by PRS 2 or more between Week 2 and 12 (p<0.03, NNT=2.8 to 4.8)
Improved ROM (p<0.05) / Neg outcome in 17% placebo pts and 4% treated pts
35 / II / Randomized, single-blind comparison of 2 doses
Spastic equinus / 48 / A/ Dysport/ 8 U/kg vs. 24 U/kg into gastrocnemius / 1 and 3 mo / 1-gastrocnemius length
2- ankle angle / 1 / 1-received largest lose (1200 units); mild generalized weakness, lasting 4 wks / 24 units/kg slightly more effective than 8 units/kg
34 / II / Randomized, double-blind comparison of 2 doses
Spastic equinus / 33 / A/ Botox
200 U vs. 100 U independent of body wt into gastrocnemius / 1.5-2 mo / ROM, AS, gait analysis, subjective / 0 / 1-unwillingness to walk for 2 days; 2-Soreness- / Better ROM in high dose pts / Dosing was independent of weight and age.
36 / II / Randomized, double blind
With or without casting / 39 / A/Botox/ 4U/Kg into gastrocnemius / 12 mo / 1- Kinematic analysis.
2- Ashworth, ankle ROM / 5, including 3 in BTX group / 2 BoNT reported more falls / Significant change from baseline only in casting and BoNT +casting groups, and not in BoNT only group.
Comparison among the 3 groups was not presented. / Early termination due to poor enrollment.
Underpowered, only 9 subjects available for analysis in BoNT group
37 / III / Randomized, single blind. BTX vs. casting / 20 / A/Botox in 8 (6-8 U/kg)
A/Dysport in 2 (15 units/kg) / 3 mo / Clinical examination.
Physician rating.
3D gait analysis. / 0 / 1 BoNT complained of pain / Little difference between BoNT and casting groups / Underpowered: 10 in each group, only 7 BoNT and 5 casting available for 3D analysis.
Botox better tolerated and benefits lasted longer
38 / III / Randomized, single blind. Casting followed by BoNT, vs. BoNT with immediate casting / 34 / A/Botox, up to 24 units/kg into gastrocnemius / 2 mo / 1-Kinematic analysis / 0 / Incontinence in 3; weakness in 12 / Both groups improved / Study was not designed to show BoNT efficacy or to compare BoNT vs casting.
39 / III / Randomized, single blind. Casting vs. BoNT / 20 / A/Botox, 4-8 units/kg into gastrocnemius / 6 mo / Video- PRS and global impression
Ankle dorsiflexion, GMFM, AS, Parent’s Questionnaire / 0 / Not discussed / Both groups improved from baseline. No difference between groups. / Underpowered. Study was not designed to show BoNT efficacy.
40 / III / Randomized, single blind, BoNT+AFO vs. BoNT+casting / 10 / A/Dysport/ 15-20U/Kg into gastrocnemius in all patients. / 12 mo / GMFM, AS, ROM, motion analysis / NA / NA / GMFM, AS and stride length better in BoNT+casting / Underpowered. Study was not designed to show BoNT efficacy.
Small number of patients
41 / III / Randomized, single-blind, casting vs BoNT+casting / 23 / A/Botox/ 8U/Kg / 12 mo / Ankle ROM, GMFM, gait analysis, Ashworth / NA / NA / No difference between groups. / Underpowered. Study was not designed to show BoNT efficacy.
44 / I / Randomized, double-blind, BoNT vs placebo
Adductor spasticity / 61 / A/Dysport/30U/Kg into adductors and medial hamstrings / 3 ,mo / 1- Knee-knee distance
2- ROM, Ashworth, GMGM, Goal Attainment Scale / 1 in each group / 16% mild to mod weakness, 6% dysphagia / Ave increase in knee-knee distance of about 9 cm (p<0.002), and decrease in Ashworth score of 2 at week 4 (p<0.001). / Only a 3 month study. Not clear if BoNT will prevent hip subluxation.
45 / I / Pre-op injection of BoNT or placebo adductor muscles
Adductor spasticity / 16 / A/Botox
8 U/kg into adductor muscles 5-10 days prior to surgery / NA / Pain score, post-op pain medication / 0 / 0 / Mean reduction in pain scores of
74% (p<0.003), analgesic use
of about 50% (p<0.005), length of hospital stay 33% (p<0.003). / Small sample size, but results were statistically significant.
47 / II / Randomized, single blind, BoNT vs no injection (occupational therapy)
Upper extremity spasticity / 30 / A/Botox/
2-6 U/kg into at least 3 muscles / 6 mo / 1-QUEST
2-AS, ROM, PEDI, grip strength / 1 BoNT / Weakness in1 pt / Improved QUEST by 13% at 1 mo (p<0.05) but insignificant at 3 and 6 months.
No difference in other measures / Single blind design.
46 / II / Double-blind
Upper extremity spasticity / 10-Botox; 4-Dysport / A/Botox:
4-7 U/kg or Dysport 8-9 U/kg vs. placebo / 3 mo / 1-nonstandard observation
2-ROM / 0 / 0 / Improved elbow/thumb extension, & tone at wrist/ elbow.
No difference in function. / Small sample size.
Nonstandard observation
48 / III / Randomized, single blind, BoNT vs no injection
Upper extremity spasticity / 20 / A/Botox/ 2-3 U/Kg above elbow, and 1-2 U/Kg forearm / 9 mo / AS, ROM, Melbourne assessment of upper limb function, Disability Inventory, 9-hole peg. / NA / NA / Small improvement in wrist dorsal flexion and tone. No difference in functional measures. / Small sample size.
Numerous statistical comparisons without correction.

AS-Ashworth Score

GMFM-Gross Motor Function Measure

QUEST-Quality of Upper Extremity Skills Test

PEDI-Pediatric Evaluation of Disability Inventory

GAS-Goal Attainment Scale

PRS-Physician Rating Scale

OT-Occupational Therapy

COPM-Canadian Occupational Performance Measures

GAS-Goal Attainment Scale

QUEST-Quality of Upper Extremity Skills Test