Abstract
Background
Cerebral palsy is a disorder of movement and posture arising from a non-progressive lesion in the developing brain. Spasticity, a disorder of increased muscle tone, is the most common motor difficulty and is associated with activity limitation to varying degrees in mobility and self care.
Oral baclofen, a gamma-aminobutyric acid (GABA) agonist, has been used in oral form to treat spasticity for some time, but it has a variable effect on spasticity and the dose is limited by the unwanted effect of excessive sedation. Intrathecal baclofen produces higher local concentrations in cerebrospinal fluid at a fraction of the equivalent oral dose and avoids this excessive sedation.
Objectives
To determine whether intrathecal baclofen is an effective treatment for spasticity in children with cerebral palsy.
Search methods
We searched the CENTRAL, MEDLINE, EMBASE and CINAHL databases, handsearched recent conference proceedings, and communicated with researchers in the field and pharmaceutical and drug delivery system companies.
Selection criteria
We included studies which compared the effect of intrathecal baclofen treatment on spasticity, gross motor function or other areas of function with controls.
Data collection and analysis
Two authors selected studies, two authors extracted data and two authors assessed the methodological quality of included studies.
Main results
Six studies met the inclusion criteria. The data obtained were unsuitable for the conduct of a meta-analysis; we have completed a qualitative summary.
All studies were found to have high or unclear risk of bias in some aspects of their methodology.
Five of the six studies reported data collected in the randomised controlled phase of the study. A sixth study did not report sufficient results to determine the effect of intrathecal baclofen versus placebo. Of these five studies, four were conducted using lumbar puncture or other short-term means of delivering intrathecal baclofen. One study assessed the effectiveness of implantable intrathecal baclofen pumps over six months.
The four short-term studies demonstrated that intrathecal baclofen therapy reduces spasticity in children with cerebral palsy. However, two of these studies utilised inappropriate techniques for statistical analysis of results. The single longer-term study demonstrated minimal reduction in spasticity with the use of intrathecal baclofen therapy.
One of the short-term studies and the longer term study showed improvement in comfort and ease of care. The longer term study found a small improvement in gross motor function and also in some domains of health-related quality of life.
Some caution is required in interpreting the findings of the all the studies in the review due to methodological issues. In particular, there was a high risk of bias in the methodology of the longer term study due to the lack of placebo use in the control group and the absence of blinding to the intervention after randomisation for both participants and investigators.
Authors’ conclusions
There is some limited short-term evidence that intrathecal baclofen is an effective therapy for reducing spasticity in children with cerebral palsy. The effect of intrathecal baclofen on long-term spasticity outcomes is less certain.
The validity of the evidence for the effectiveness of intrathecal baclofen in treating spasticity in children with cerebral palsy from the studies in the review is constrained by the small sample sizes of the studies and methodological issues in some studies.
Spasticity is a impairment in the domain of body structure and function. Consideration must also be given to the broader context in determining whether intrathecal baclofen therapy is effective. The aim of therapy may be, for example, to improve gross motor function, to increase participation at a social role level, to improve comfort, to improve the ease of care by others or to improve the overall quality of life of the individual. Intrathecal baclofen may improve gross motor function in children with cerebral palsy, but more reliable evidence is needed to determine this.There is some evidence that intrathecal baclofen improves ease of care and the comfort and quality of life of the individuals receiving it, but again small sample sizes and methodological issues in the studies mean that these results should be interpreted with caution.
Further evidence of the effectiveness of intrathecal baclofen for treating spasticity, increasing gross motor function and improving comfort, ease of care and quality of life is needed from other investigators in order to validate these results.
The short duration of the controlled studies included in this review did not allow for the exploration of questions regarding whether the subsequent need for orthopaedic surgery in children receiving intrathecal baclofen therapy is altered, or the safety and the economic implications of intrathecal baclofen treatment when long-term therapy is administered via an implanted device. Controlled studies are not the most appropriate study design to address these questions, cohort studies may be more appropriate.
Plain language summary
Intrathecal baclofen for treating spasticity in children with cerebral palsy
Spasticity, which is an increase in muscle tone, is the most common difficulty with movement seen in children with cerebral palsy. Baclofen is a medication which acts on receptors in the brain and spinal cord to reduce abnormal muscle tone. It has been used as an oral medication for many years. The disadvantages of oral administration are that only a small amount of the medication crosses the blood-brain barrier before it can exert an effect, and that the dose is limited by the unwanted effect of excessive sedation. The administration of baclofen into the fluid surrounding the spinal cord overcomes these problems. This treatment is called intrathecal baclofen therapy and it is administered via a pump placed under the skin connected to a catheter which enters the membranes covering the spinal cord to deliver the baclofen directly into the fluid surrounding the spinal cord and brain.
This review concludes that there is a small amount of evidence from studies performed to date that intrathecal baclofen is an effective treatment for reducing spasticity in children with cerebral palsy in the short-term. The effect of intrathecal baclofen on spasticity in children with cerebral palsy over the long term is less clear.
Two short-term studies (by the same investigators) demonstrate a reduction in spasticity, but a single, longer term study shows minimal evidence for reduced spasticity with the use of intrathecal baclofen. Two further short-term studies showed reduction in spasticity with the use of intrathecal baclofen, but the authors used inappropriate methods of analysing the data, so it is uncertain whether these results are valid. All these studies had a small number of participants, making the findings less reliable.
The research also provides evidence from one short term study and one longer term study (again, by the same investigators), that intrathecal baclofen therapy improves the comfort, ease of care and some aspects of quality of life for children with cerebral palsy. However, the results of the longer term study may have been influenced by both the participants and the investigators being aware of whether they were receiving treatment or allocated to the control group. This same study found that intrathecal baclofen improves gross motor function a little in children with cerebral palsy, but again, these results may have been influenced by the way the study was conducted.
Further evidence of the effectiveness of intrathecal baclofen for treating spasticity is needed from other investigators in order to validate these results.
There is little evidence from the short-term randomised controlled trials about the safety and economic implications of this treatment when long-term therapy is administered through an implanted device. For the same reasons, we could not reach a conclusion on whether the subsequent need for orthopaedic surgery is altered in children receiving intrathecal baclofen therapy.
