Use of botulinum toxin A in management of children with cerebral palsy.
ABSTRACT QUESTION: What is the role of intramuscular botulinum toxin injections in the management of spasticity and related morbidity in children with cerebral palsy? ANSWER: When botulinum toxin A is injected into the limbs of children with spastic paresis, it induces temporary reduction in muscle tone. It also promotes better motor function when used in combination with conservative treatments such as physiotherapy. Although there is a growing body of evidence for its effective and safe treatment, there is still a lack of consensus on dose, treatment regimens, and the best integration with other clinical modalities.
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ABSTRACT: Botulinum toxin A (BTX-A) has been successfully used as a treatment for children with spastic cerebral palsy; however, the effect of BTX-A on reducing spasticity only lasts a few months, thus serial injections are required. The present study was to evaluate the efficacy and safety of serial injections of BTX-A in children with spastic cerebral palsy. Fifty-two pediatric patients with spastic cerebral palsy, 2-12 years of age (mean age, 4.79±2.70), were retrospectively analyzed. Muscle tone was assessed with the Modified Ashworth Scale, and gait was assessed with the Physician Rating Scale. Assessments were undertaken at baseline, 3 months, and 6 months after serial injections of BTX-A. The beneficial effects of BTX-A occurred 1 week after the injection, whereas the adverse side-effects appeared within 1 week and lasted <2 weeks. BTX-A significantly improved muscle tone and gait 3 and 6 months after its serial injections compared to baseline (P <0.05). Serial injections of BTX-A are effective and safe for children with spastic cerebral palsy. The sideeffects of serial injections of BTX-A are mild and selflimited.World Journal of Pediatrics 11/2013; 9(4):342-5. · 1.08 Impact Factor
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ABSTRACT: Objective: To investigate the feasibility of gamebased robotic training of the ankle in children with cerebral palsy (CP). Design: Case study, 12 weeks intervention, with no follow-up. Setting: University research laboratory. Participants: A referred sample of 3 children with cerebral palsy, age 7 to 12, all male, were enrolled. All completed the intervention. Interventions: Participants trained on the Rutgers Ankle CP system for 36 rehabilitation sessions (12 weeks, 3 times/week), playing two custom virtual reality games. The games were played while participants were seated, and trained one ankle at-a-time for strength, motor control, and coordination. Main Outcome Measures: The primary study outcome measures were for impairment (DF/PF torques, DF initial contact angle and gait speed), function (GMFM) and quality of life (Peds QL). Secondary outcome measures relate to game performance (game scores as reflective of ankle motor control and endurance). Results: Gait function improved substantially in ankle kinematics, speed and endurance. Overall function (GMFM) indicated improvements that were typical of other ankle strength training programs. Quality of life increased beyond what would be considered a minimal clinical important difference. Game performance improved in both games during the intervention. Conclusions: This feasibility study supports the assumption that game-based robotic training of the ankle benefits gait in children with CP. Game technology is appropriate for the age group and was well accepted by the participants. Additional studies are needed however, to quantify the level of benefit and compare the approach presented here to traditional methods of therapy.IEEE transactions on neural systems and rehabilitation engineering: a publication of the IEEE Engineering in Medicine and Biology Society 07/2012; · 2.42 Impact Factor
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ABSTRACT: Paralysis of the masticatory muscles using botulinum toxin (BTX) is a common treatment for cosmetic reduction of the masseters as well as for conditions involving muscle spasm and pain. The effects of this treatment on mastication have not been evaluated, and claims that the treatment unloads the jaw joint and mandible have not been validated. If BTX treatment does decrease mandibular loading, osteopenia might ensue as an adverse result. Rabbits received a single dose of BTX or saline into one randomly chosen masseter muscle and were followed for 4 or 12 weeks. Masticatory muscle activity was assessed weekly, and incisor bite force elicited by stimulation of each masseter was measured periodically. At the endpoint, strain gages were installed on the neck of the mandibular condyle and on the molar area of the mandible for in vivo bone strain recording during mastication and muscle stimulation. After termination, muscles were weighed and mandibular segments were scanned with micro CT. BTX paralysis of one masseter did not alter chewing side or rate, in part because of compensation by the medial pterygoid muscle. Masseter-induced bite force was dramatically decreased. Analysis of bone strain data suggested that at 4 weeks, the mandibular condyle of the BTX-injected side was underloaded, as were both sides of the molar area. Bone quantity and quality were severely decreased specifically at these underloaded locations, especially the injection-side condylar head. At 12 weeks, most functional parameters were near their pre-injection levels, but the injected masseter still exhibited atrophy and percent bone area was still low in the condylar head. In conclusion, although the performance of mastication was only minimally harmed by BTX paralysis of the masseter, the resulting underloading was sufficient to cause notable and persistent bone loss, particularly at the temporomandibular joint.Bone 12/2011; 50(3):651-62. · 3.82 Impact Factor
1006 Canadian Family Physician • Le Médecin de famille canadien | Vol 57: SEPTEMBER • SEPTEMBRE 2011
Question What is the role of intramuscular botulinum toxin injections in the management of spasticity and
related morbidity in children with cerebral palsy?
Answer When botulinum toxin A is injected into the limbs of children with spastic paresis, it induces temporary
reduction in muscle tone. It also promotes better motor function when used in combination with conservative
treatments such as physiotherapy. Although there is a growing body of evidence for its effective and safe
treatment, there is still a lack of consensus on dose, treatment regimens, and the best integration with other
La toxine botulique A dans la prise en charge de la paralysie cérébrale
Question Quel est le rôle des injections intramusculaires de toxine botulique dans la prise en charge de
l’hypertonie spastique et de sa morbidité afférente chez les enfants atteints de paralysie cérébrale?
Réponse Quand on injecte de la toxine botulique A dans les membres d’un enfant ayant une parésie spastique,
il se produit une réduction temporaire du tonus musculaire. Cela favorise aussi une meilleure fonction motrice
lorsqu’elle est utilisée en combinaison avec des traitements conservateurs comme la physiothérapie. Même si
les données probantes en sa faveur comme traitement sûr et efficace se multiplient, il y a toujours un manque de
consensus quant aux doses, aux régimes thérapeutiques et à son intégration optimale à d’autres interventions
posture, and results from nonprogressive brain dam-
age.1 Cerebral palsy is the most common cause of
physical disability in children, with a reported incidence
of 2 to 2.5 per 1000 live births.1 Approximately 90%
of affected children present with clinical symptoms of
spastic paresis, a muscle-tone and muscle control–regu-
lation disorder.2 Static muscle contractures and bony
deformities develop slowly over time and are second-
ary consequences of spasticity. Children with CP require
management by a multidisciplinary team to address
each child’s particular needs. A treatment program usu-
ally focuses on the reduction or normalization of tone
to prevent the development of secondary complications.
The most common interventions are physiotherapy, use
of orthotics, serial casting, electrical stimulation, and,
more recently, the intramuscular injection of botulinum
toxin type A (BtxA).
erebral palsy (CP) is a clinical syndrome character-
ized by a persistent disorder in motor control and
Botulinum toxin type A is 1 of the 7 different serotypes
of botulinum toxin (A to G) produced by the anaerobic
bacterium Clostridium botulinum.3 Botulinum toxin type
A selectively blocks the release of acetylcholine at the
cholinergic nerve terminal, ensuring a temporary reduc-
tion in muscular activity in the injected muscles.3 The
process is reversible and the return of synaptic function
to the original neuromuscular junction takes approxi-
mately 90 days. The period of clinically useful relaxation
is usually 12 to 16 weeks.4
Botulinum toxin type A injections were first given
therapeutically for strabismus in the early 1980s.5 The
treatment was adopted for other neurologic conditions,
such as blepharospasm, cervical dystonia, and hemi-
facial spasm. In 1993, Koman et al6 produced preliminary
results of the first clinical trials using BtxA for spasticity
in CP patients. The rationale for using BtxA for CP man-
agement was that the reduction of spasticity after BtxA
injection opened a “therapeutic window” for interven-
tions, enhancing both motor ability and functional skills
and preventing contracture formation.7 Although at first
BtxA was applied to one muscle at a time, it became
apparent that many of the common limb dysfunctions
Child Health Update
Use of botulinum toxin A in management
of children with cerebral palsy
Bat-Chen Friedman MD Ran D. Goldman MD FRCPC
Vol 57: SEPTEMBER • SEPTEMBRE 2011 | Canadian Family Physician • Le Médecin de famille canadien 1007
Child Health Update
and gait patterns in CP could be adequately treated only
if several muscles were treated simultaneously.
Effectiveness of BtxA in CP management
In the past 2 decades, numerous trials have assessed
the effectiveness of BtxA injections on motor function in
children with CP.8-15 While several studies found statistic-
ally significant beneficial effects,8-10,13-15 others failed to
demonstrate benefits.11,12 The use of distinct assessment
tools and primary outcome measures, in addition to the
diversity in clinical approaches, cointerventions, and
subjects’ characteristics, partly accounts for the variabil-
ity of the reports. Lack of consensus on recommended
dose and diverse pharmacokinetic properties of com-
mercially available BtxA preparations contribute to the
challenge in interpreting the results of currently avail-
In 2010, a Cochrane systematic review assessed the
effectiveness of BtxA alone or in combination with occu-
pational therapy for upper-limb treatment in children
with CP. Ten randomized controlled trials (RCTs) were
included. An analysis of data showed that a combina-
tion of BtxA and occupational therapy is more effective
than occupational therapy alone in reducing impair-
ment and improving activity-level outcomes, but not for
improving quality of life or perceived self-competence.
When BtxA was used alone there was moderate evi-
dence that it was not effective.9
Several systematic reviews also analyzed the effect-
iveness of BtxA therapy in the management of lower-
limb spasticity and gait in children with CP.10-12 In 2001,
Boyd and Hays10 summarized results of 10 RCTs and
found evidence for a moderate, dose-dependent treat-
ment effect of BtxA on gait and lower-limb function.
Koog and Min11 reviewed 15 RCTs and reported less-
favourable results. When botulinum injection was com-
pared with a non-sham control, it was effective in
improving muscle tone, ankle range of motion, gross
motor function, and gait speed; however, when sham
injection was used as control, botulinum injection had
affected gross motor function only when measured after
4 months. Koog and Min11 suggested that BtxA might
not be as effective as commonly believed and might
be overprescribed for CP patients. Recently, Ryll et al12
systematically reviewed 8 RCTs in order to assess treat-
ment effects of BtxA on gait of children with CP. When
compared with physiotherapy alone, adding BtxA treat-
ment had a moderate positive effect after 2 to 24 weeks
of follow-up. This effect was not demonstrated when
BtxA treatment was compared with casting alone.
Age and long-term effects
Spasticity most commonly develops within the first few
years of life in children with CP. Therefore, BtxA treat-
ment is recommended at 2 to 6 years of age, when
gait patterns and motor function are still flexible.8
Evidence relating to long-term outcome of treatment
with BtxA is scarce. Desloovere et al13 demonstrated
that BtxA injections delay and reduce the frequency
of surgical procedures and result in a favourable gait
pattern at 5 to 10 years of age. Similarly, Molenaers et
al14 reported that BtxA treatment can delay and reduce
the need for surgery in the follow-up of children with
CP, provided that the treatment is started while gait
patterns are still flexible. A recent prospective study
on children with CP treated with BtxA included 57
children with a mean age of 6 years who were fol-
lowed up for a year. Results demonstrated larger
reduction in spasticity and better functional prognosis
after BtxA injection in younger children. Botulinum
toxin type A treatment also correlated with improve-
ment in quality-of-life measures.15
Botulinum toxin type A is considered to be one of the
most potent poisons. However, when used in recom-
mended doses, adverse events of BtxA are usually
transient, mild, and local.16 Adverse events attributed
to systemic spread of the toxin are uncommon and
include flulike symptoms, generalized weakness, dys-
phagia, and subsequent aspiration caused by dimin-
ished airway protection.16 In 2008, the US Food and
Drug Administration expressed concern about poten-
tial severe adverse effects (respiratory compromise and
death) of BtxA based on reports of children treated for
CP-associated limb spasticity.17 These concerns were
contrary to previous safety-profile information.18 In a
meta-analysis of safety with 20 RCTs and 882 partici-
pants, BtxA use was associated with respiratory tract
infection, bronchitis, pharyngitis, muscle weakness,
urinary incontinence, falls, seizures, fever, and unspeci-
fied pain. Two deaths were reported in one study and
were found not to have causal relation to the toxin. The
authors concluded that BtxA had a good short-term
safety profile, but advocated careful monitoring, espe-
cially in children with more severe CP.19
Treatment of spastic-movement disorders associated
with CP requires an interdisciplinary team approach with
a range of conservative and surgical strategies. There is
growing evidence that BtxA is effective in reducing spas-
ticity and improving motor function when it is used in
combination with other treatment measures. However,
there is a lack of data about optimal dosing and injec-
tion schemes, and safety concerns demand strict mon-
itoring of potential adverse effects, especially in children
severely afflicted with CP.
Child Health Update
Dr Ran D. Goldman, BC Children’s Hospital, Department of Pediatrics, Room K4-226, Ambulatory Care
Bldg, 4480 Oak St, Vancouver, BC V6H 3V4; telephone 604 875-2345, extension 7333; fax 604 875-2414;
1. Stanley F, Blair E, Alberman E. Cerebral palsies: epidemiology and causal pathways. In: Clinic in
developmental medicine. No 151. London, UK: Mac Keith Press; 2000. p. 22-39.
2. Beckung E, Carlsson G, Carlsdotter S, Uvebrant P. The natural history of gross motor development
in children with cerebral palsy aged 1 to 15 years. Dev Med Child Neurol 2007;49(10):751-6.
3. Aoki KR, Guyer B. Botulinum toxin type A and other botulinum toxin serotypes: a comparative
review of biochemical and pharmacological actions. Eur J Neurol 2001;8(Suppl 5):21-9.
4. Aoki KR, Ranoux D, Wissel J. Using translational medicine to understand clinical differences
between botulinum toxin formulations. Eur J Neurol 2006;13(Suppl 4):10-9.
5. Scott AB, Rosenbaum A, Collins CC. Pharma-cologic weakening of extraocular muscles. Invest
Ophthalmol Vis Sci 1973;12(12):924-7.
6. Koman LA, Mooney JF 3rd, Smith B, Goodman A, Mulvaney T. Management of cerebral palsy with
botulinum-A toxin: preliminary investigation. J Pediatr Orthop 1993;13(4):489-95.
7. Placzek R, Siebold D, Funk FJ. Development of treatment concepts for the use of botulinum toxin A
in children with cerebral palsy. Toxins 2010;2(9):2258-71. DOI:10.3390/toxins2092258.
8. Molenaers G, Van Campenhout A, Fagard K, De Cat J, Desloovere K. The use of botulinum toxin
A in children with cerebral palsy, with a focus on the lower limb. J Child Orthop 2010;4(3):183-95.
Epub 2010 Mar 18.
9. Hoare BJ, Wallen MA, Imms C, Villanueva E, Rawicki HB, Carey L. Botulinum toxin A as an adjunct
to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE).
Cochrane Database Syst Rev 2010;(1):CD003469.
10. Boyd RN, Hays RM. Current evidence for the use of botulinum toxin type A in the management of
children with cerebral palsy: a systematic review. Euro J Neurol 2001;8(Suppl 5):1-20.
11. Koog YH, Min BI. Effects of botulinum toxin A on calf muscles in children with cerebral palsy: a
systematic review. Clin Rehabil 2010;24(8):685-700. Epub 2010 Jun 16.
12. Ryll U, Bastiaenen C, De Bie R, Staal B. Effects of leg muscle botulinum toxin A injections on
walking in children with spasticity-related cerebral palsy: a systematic review. Dev Med Child Neurol
13. Desloovere K, Molenaers G, De Cat J, Pauwels P, Van Campenhout A, Ortibus E, et al. Motor
function following multilevel botulinum toxin type A treatment in children with cerebral palsy.
Dev Med Child Neurol 2007;49(1):56-61.
14. Molenaers G, Desloovere K, Fabry G, De Cock P. The effects of quantitative gait assessment and
botulinum toxin A on musculoskeletal surgery in children with cerebral palsy. J Bone Joint Surg Am
15. Coutinho dos Santos LH, Bufara Rodrigues DC, Simões de Assis TR, Bruck I. Effective results with
botulinum toxin in cerebral palsy. Pediatr Neurol 2011;44(5):357-63.
16. O’Flaherty SJ, Janakan V, Morrow AM, Scheinberg AM, Waugh MC. Adverse events and health
status following botulinum toxin type A injections in children with cerebral palsy. Dev Med Child
Neurol 2011;53(2):125-30. DOI:10.1111/j.1469-8749.2010.03814.x.
17. FDA notifies public adverse reactions linked to botox use. Ongoing safety review of Botox, Botox
Cosmetic and Myobloc [news release]. Silver Spring, MD; February 8, 2008. Available from: www.
2011 Jun 24.
18. Goldstein EM. Safety of high-dose botulinum toxin type. A therapy for the treatment of pediatric
spasticity. J Child Neurol 2006;21(3):189-92.
19. Albavera-Hernández C, Rodrıguez JM, Idrovo AJ. Safety of botulinum toxin type A among children
with spasticity secondary to cerebral palsy: a systematic review of randomized clinical trials. Clin
Rehabil 2009;23(5):394-407. Epub 2009 Apr 23.
Pediatric Research in Emergency Therapeutics
Children’s Hospital in Vancouver, BC. Dr Friedman is a member
and Dr Goldman is Director of the PRETx program. The mission of the PRETx program is to promote
child health through evidence-based research in therapeutics in pediatric emergency medicine.
Do you have questions about the effects of drugs, chemicals, radiation, or infections in children? We
invite you to submit them to the PRETx program by fax at 604 875-2414; they will be addressed in
future Child Health Updates. Published Child Health Updates are available on the Canadian Family
Physician website (www.cfp.ca).
Child Health Update is produced by the Pediatric Research in
Emergency Therapeutics (PRETx) program (www.pretx.org) at the BC