High dose botulinum toxin A for the treatment of lower extremity hypertonicity in children with cerebral palsy.
The aim of this study was to determine the safety profile of high dose (15-25 units/kg) of botulinum toxin A (BTX-A) in children with cerebral palsy (CP) and increased lower extremity muscle tone. We performed a retrospective review of 929 patient encounters at the Movement Disorders Center at Washington University. A total of 261 patients (105 females; 156 males) were treated during these visits, ages 6 months to 21 years (mean 8 y 4 mo [SD 4 y 8 mo]). Ambulatory ability at the time of BTX-A injection was independent ambulation (36.4%, n=95), ambulation with a walker (27.6%, n=72), and non-ambulatory (31.8%, n=83). A few patients (4.2%, n=11) were able to ambulate with a cane or crutch at the time of injection. Participants were characterized according to BTX-A dose, CP etiology, motor involvement pattern, muscles injected, ambulatory ability, and use of oral tone medications. Follow-up records were searched for reported adverse events (AEs), with a mean time to AE assessment of 6.5 weeks (SD 3.38). The AE occurrence was determined for doses of 0 to 4.9 units/kg, 5 to 9.9 units/kg, 10 to 14.9 units/kg, 15 to 19.9 units/kg, and 20 to 25 units/kg. The overall AE occurrence was 4.2%. Standard doses of BTX-A had side-effect occurrences of 3.9% for 5 to 10 units/kg and 7.6% for 10 to 15 units/kg. Among higher doses (15-20 units/kg and 20-25 units/kg) the AE occurrence was 3.5% and 8.6% respectively. No patient developed botulism. AEs were randomly distributed across dosing groups, CP etiologies, clinical phenotypes, ambulatory status, and treatment duration. All doses were associated with a significant increase in passive range of motion using the Tardieu scale. We conclude that higher dose BTX-A is safe in children with a spectrum of CP phenotypes and are well tolerated over time.
Willis
Allison W
AW
Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
Crowner
Beth
B
Brunstrom
Janice E
JE
Kissel
Abigail
A
Racette
Brad A
BA
D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000627:therapeutic use*; D002547:Cerebral Palsy / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000503:physiopathology*; D008297:Male; D009122:Muscle Hypertonia / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A