Intrathecal baclofen for treating spasticity in children with cerebral palsy.

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.

Late reduction in cyclosporine dosage does not improve renal function in pediatric heart transplant recipients.

OBJECTIVE: To determine the relation between cyclosporine (CSA) dosage and late renal function in pediatric heart transplant recipients. METHODS: In this retrospective study, pediatric patients were observed for at least 3 years after transplantation, with serial measurement of renal glomerular filtration rate (GFR). Patient variables examined included pre-existing disease (cardiomyopathy or congenital heart disease), age at transplantation, duration of follow-up, and CSA dosage and trough levels at 3 months after transplantation and yearly until the latest follow-up. For each patient, the least squares regression method was used to estimate the average rate of change per year (slope value) for GFR and CSA dosage during follow-up. RESULTS: Twenty-five patients who met the study criteria underwent transplantation at a median age of 11.7 years (interquartile range [IQR], 6.8-14.5 years) and were observed for a median of 6.0 years (IQR, 4-7). The median GFR at 1 year after transplantation was 73 ml/min/1.73 m(2) (IQR, 50-89) and at latest follow-up was 75 ml/min/1.73 m(2) (IQR, 57-98). The median CSA dosage and trough level at 1 year after transplantation were 6.1 mg/kg/day and 234 ng/ml, and at latest follow-up were 3.45 mg/kg/day and 141 ng/ml, respectively. The median rate of change in GFR was +1.6 ml/year of observation (95% confidence interval, -0.9, 4.7) and was inversely related to measured GFR at 1 year after transplantation. The rate of change of GFR was unrelated to any other patient variables including CSA dosages and levels at the specified time intervals and the rate of change of CSA dosage. CONCLUSIONS: Measured GFR in pediatric cardiac transplant recipients treated with CSA is moderately depressed at 12 months after transplantation and does not change significantly during subsequent years. No evidence suggests that the usual progressive reduction in CSA dosage influences renal function beyond 1 year after transplantation.