Botulinum toxin type A for treating upper limb spasticity in children with cerebral palsy
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to assess the effectiveness and safety of botulinum toxin A (BtA) for upper limb spasticity in children with cerebral palsy.
Background
Cerebral palsy (CP) is a non‐progressive, central nervous system deficit resulting from brain damage caused by birth trauma or intra‐uterine pathology. In developed countries, cerebral palsy is the most common cause of childhood physical disability with an incidence of about 2‐2.5 per 1000 live births (Graham 2000 ). It is characterised by sensorimotor dysfunction as manifested by atypical muscle tone, posture and movement. It can also be accompanied by cognitive, psychiatric, sensory and seizure disorders. The spastic motor type is the most common comprising about 80% of reported cases (Graham 2000). Spasticity in this instance is seen as a velocity dependent increase in muscle resistance to stretch and is an important feature of cerebral palsy as it contributes to the impairment of function and reduced longtitudinal muscle growth (Dunne 1995).
Conventional management of upper limb spasticity in children with cerebral palsy has involved the use of splinting, passive stretching, and the facilitation of posture and movement (eg through occupational therapy, physiotherapy, and neurodevelopmental therapy). More recently, therapists have begun to use botulinum toxin A (BtA) as an adjunct to these therapeutic techniques in an attempt to reduce focal spasticity, increase range of motion and improve function.
BtA is produced by the anaerobic bacterium clostridium botulinum and is a powerful neuromuscular paralysing agent. BtA acts at the neuromuscular junction by inhibiting the release of the neurotransmitter acetylcholine. Injection of BtA into selected muscles produces dose dependent chemical denervation resulting in reduced muscular activity. After the sprouting of new nerve terminals, which leads to reinnervation, or restoration of the original terminal, affected muscles have the ability to recover. The period of clinically useful relaxation is usually between 12‐16 weeks (Graham 2000).
The aim of treatment with BtA is to produce selective muscle weakness with the smallest possible dose. The reduction in spasticity provides an opportunity for retraining the affected limb and the child is able to adapt and develop skills to achieve functional gains.
Objectives
The objective of this review is to assess the effectiveness and safety of botulinum toxin A (BtA) for upper limb spasticity in children with cerebral palsy.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials that evaluate the effectiveness and safety of BtA injection in to the upper limb(s) of children with spastic cerebral spasticity will be included in this review.
Types of participants
Participants will be between the ages of 0 and 19 years requiring treatment for upper limb spasticity secondary to cerebral palsy.
Types of interventions
Randomly allocated interventions that include the use of BtA injections (of any doseage) into any muscle group of the upper limb compared with placebo, no treatment or another intervention.
Types of outcome measures
The main outcomes of interest are:
1. Spasticity
2. Grip Strength
3. Active and passive range of motion
4. Quality of movement
5. Fine motor skills
6. Occupational performance
7. Individual goal setting
8. Quality of Life
9. Caregiver burden.
Search methods for identification of studies
We will search the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2001), MEDLINE< CINAHL< EMBASE and Current Contents and reference lists of articles. In MEDLINE, the following search strategy will be combined with the optium trial search strategy described in the Cochrane's Reviewer's Handbook ( Clarke MH 2001) . This strategy will be modified to search other databases.
MEDLINE(Ovid Web)
1. Botulinum toxins/
2. Botulinum toxin type a/
3. Botulin$.tw
4. Botox.tw
5. Dysport.tw
6. Or/1‐5
7. Muscle spasticity/
8. Spastic$.tw
9. Cerebral palsy
10. Cerebral pals$.tw
11. Hemiplegia/
12. Quadriplegia/
13. Hemiplegia.tw
14. Monoplegia.tw
15. Triplegia.tw
16. Quadriplegia.tw
17. Or/7‐17
18. 6 and 17
Records retrieved by the initial search will be scanned by two reviewers to identify trials that meet the inclusion criteria. Full‐text articles will be retrieved and reviewed by two reviewers for the purpose of applying inclusion criteria independently. In all instances, differences of opinion will be resolved by discussion among the reviewers.
Data collection and analysis
DATA EXTRACTION
Data from the studies will be extracted independently by two authors using standardised forms. Primary authors will be contacted to provide information if missing data is encountered. All differences will be resolved by discussion among the reviewers.
QUALITY ASSESSMENT
Study quality will be assessed using an adaptation of the method outlined in Schulz 1995. The following characteristics will be assessed:
Adequacy of the randomisation process:
A ‐ Adequate sequence generation is reported using random number tables, computer random number generator, coin tossing, or shuffling;
B ‐ Did not specify one of the adequate reported methods in (A) but mentioned randomisation method;
C ‐ Other methods of allocation that appear to be unbiased.
Adequacy of the allocation concealment process:
A ‐ Adequate measures to conceal allocations such as central randomisation; serially numbered, opaque, sealed envelopes; or other description that contained convincing elements of concealment;
B‐ Unclearly concealed trials in which the author either did not report an allocation concealment approach at all, or reported an approach that did not fall into one of the categories in (A)
C‐ Inadequately concealed trials in which method of allocation is not concealed such as alteration methods or use of case record numbers.
Potential for selection bias after allocation:
A‐ Trials where an intention to treat analysis is possible and few losses to follow‐up are noted;
B‐ Trials which reported exclusions (as listed in A but exclusions were less than 10%);
C‐ No reporting on exclusions or exclusions greater than 10% or wide differences in exclusions between groups.
Level of masking ( Treatment provider, patient, outcome assessor):
A‐ Double or triple blind;
B‐ Single blind;
C‐ Non‐blind.
DATA ANALYSIS
A statistical summary of treatment effects will proceed only in the absence of significant clinical or statistical heterogeneity. Heterogeneity will be tested using the Cochran Q statistic (Cochran 1954) with significance at p<0.10 (Boissel 1989; Fleiss 1986). Dichotomous data will be expressed as the odds ratio and a common odds ratio will be calculated with a number needed to treat being derived to help clarify the degree of benefit. Continuous data will be converted to the weighted mean difference using the inverse variance method and an overall weighted mean difference will be calculated. Overall estimates will be based on the random effects model (DerSimonian 1986). Publication bias will be tested using funnel plots or other corrective analytical methods, depending on the number of clinical trials included in the systematic review.
