Repeated BoNT-A Injections Fail to Improve Motor Function in Cerebral Palsy

Repeated botulinum neurotoxin A (BoNT-A) injections to the lower-extremity muscles did not yield significant long-term improvements in gross motor function among young children with spastic cerebral palsy (CP), according to study results published in Developmental Medicine & Child Neurology.

Although BoNT-A has long been used to manage spasticity and improve mobility in children with CP, evidence on the sustained effects of repeated injections beyond 12 months has remained limited.

Researchers conducted a multicenter, prospective observational cohort study evaluating the 3-year outcomes of BoNT-A treatment among ambulant children aged 2 to 6 years with spastic CP functioning in Gross Motor Function Classification System levels I to III. Children were recruited from 16 pediatric rehabilitation centers across Ontario and Manitoba, Canada.

[W]e did not identify greater improvement in gross motor function in children who received repeated BoNT-A injections into their lower-extremity muscles compared to children who did not receive BoNT-A.

The researchers recruited 124 participants, 65 of whom received BoNT-A within the first year after baseline assessment (BoNT-A group), and 59 of whom did not (comparison group). Participants in the BoNT-A group had a median age of 3 years and 8 months, 28% were girls, and 71% had a bilateral CP diagnosis. Participants in the comparison group had a median age of 4 years and 1 month, 49% were girls, and 56% had a bilateral CP diagnosis. Baseline gross motor ability was similar between groups (mean Gross Motor Function Measure-66 [GMFM-66] scores, 61.6 vs 64.7; P =.20). However, the BoNT-A group had lower baseline passive ankle dorsiflexion range (median, 6° vs 10°; P =.04) and lower median daily step counts (4204 vs 7294; P =.01).

Over the 3-year follow-up, 117 participants (94%) were assessed at least once beyond baseline, and 106 (85%) completed the 3-year assessment. Participants in the BoNT-A group typically received a median of 2 rounds of injections in the first year and 1 round per year thereafter. The gastrocnemius and medial hamstring muscles were the most frequently treated, with mean (SD) doses of 4.0 (1.3) and 3.7 (1.0) U/kg, respectively.

After adjusting for baseline GMFM-66 scores, the researchers observed no significant between-group differences in gross motor function over time (β̂, 0.92; 95% CI, −0.66 to 2.50; P =.256). Similarly, there were no significant differences between groups in caregiver-reported mobility skills, participation in recreation or community activities, or individualized motor performance goals.

Unexpectedly, ankle dorsiflexion range declined slightly in the BoNT-A group relative to the comparison group (β̂, −4.17; 95% CI, −7.27 to −1.08; P =.009), approaching but not exceeding the minimally important difference of 5°. A similar pattern was observed for hamstring passive range of motion (β̂, −4.96; P =.002), with both findings favoring the comparison group.

Study limitations include a nonrandomized design, baseline group differences in mobility measures, and absence of gait and/or casting data to clarify range-of-motion findings.

“[W]e did not identify greater improvement in gross motor function in children who received repeated BoNT-A injections into their lower-extremity muscles compared to children who did not receive BoNT-A,” the study authors concluded.

Disclosures: This research was supported by the Canadian Institute of Health Research, Institute of Human Development, Child and Youth Health. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.