The most common pharmaceutical used to treat cerebral palsy is botulinum toxin type A, which is a toxic protein produced by bacteria. This substance is more commonly known as Botox, and is used cosmetically to reduce the appearance of wrinkles. Another substance that is used less often for the treatment of cerebral palsy is baclofen. Both of these pharmaceuticals are used specifically to treat spasticity, one of the primary debilitating symptoms of cerebral palsy. While botulinum toxin type A decreases muscular activity by blocking the release of an activating neurotransmitter, baclofen reduces spastic movement by inhibiting neuronal activity. Other pharmaceuticals that yield similar effects can also be used in the treatment of cerebral palsy.
Spasticity is one of the most common symptoms presented by neurologic patients. Apart from surgical management, drug therapy is an important treatment of children suffering from spasticity. In this review, recent advances in the pharmacologic armamentarium are reported in detail. In particular, there are oral medications (benzodiazepines, baclofen, dantrolene sodium, alpha 2 adrenergic agonists) and parenteral medications (botulinum toxin type A and B, alcohol). Moreover, there is also baclofen that can be administered intrathecally. There are some reports supporting the use of intramuscular alcohol (45% and/or 5-7% phenol) to reduce spasticity without the loss of voluntary movement or loss of sensation. Among these drugs, intrathecal baclofen is one of the most effective substances that can reduce spasticity significantly in the upper and lower extremities. Finally, the effectiveness of therapy with botulinum toxin type A in the management of spasticity is analyzed. Botulinum toxin type A reduces hypertonia in the injected muscles for a period of 2 to 4 months without important side effects. The purpose of this article is to provide an overview of available oral and parenteral drugs for treatment of spasticity in cerebral palsy and to outline indications and contraindications.
[Verrotti, A., Greco, R., Spalice, A., Chiarelli, F. & Iannetti, P. (2006). Pharmacotherapy of spasticity with cerebral palsy. Pediatric Neurology, 34(1), 1-6.]
Local injection of botulinum toxin (BT) is a well-established treatment option for spastic movement disorders in children. BT blocks the release of acetylcholine from the axon terminal into the synaptic cleft of the motor endplate resulting in paresis of the injected musculature. Such localised, temporary chemodenervation of affected muscles can lead to functional gains and may improve the child's daily routine and rehabilitative care. We summarise state-of-the-art treatment of spasticity in children with BT type A, addressing critical issues and introducing recent advances, such as sonography-guided injection of BT and the distal injection of the psoas muscle without the need for general anaesthesia. First-hand experience with BT type B in children is presented. Copyright 2004 Movement Disorder Society
[Berweck, S. & Heinen, F. (2004). Use of botulinum toxin in pediatric spasticity (cerebral palsy). Movement Disorders, 19(Suppl. 8), S162-7.]
BACKGROUND: Cerebral palsy (CP) is a central nervous system deficit resulting from a non-progressive lesion in the developing brain. Although the brain lesions are static, the movement disorders that arise are not unchanging and are characterised by atypical muscle tone, posture and movement (Rang 1990). The spastic motor type is the most common form of CP and its conventional therapeutic management may include splinting/casting, passive stretching, facilitation of posture and movement, spasticity-reducing medication and surgery. More recently, health care professionals have begun to use botulinum toxin A (BtA) as an adjunct to interventions in an attempt to reduce muscle tone and spasticity to improve function OBJECTIVES: To assess the effectiveness of intramuscular BtA injections as an adjunct to managing the upper limb in children with spastic CP. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1966 to March Week 3 2004), EMBASE (1980 to 2003 Week 16) and CINAHL (1982 to Week 3 March 2004). SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing intramuscular BtA injections into any muscle group of the upper limb with placebo, no treatment or other interventions. DATA COLLECTION AND ANALYSIS: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity with differences resolved by discussion. Data was extracted and entered into RevMan 4.2.3. MAIN RESULTS: Two trials met the inclusion criteria, each having short-term follow up, a small number of subjects and using a single set of injections.The study by Corry 1997 compared BtA with an injection of normal saline and found promising results in elbow extension, elbow and wrist muscle tone. At three months, encouraging results for wrist muscle tone and grasp and release were noted. The trial reported median change, range of changes and the difference in these measures between groups. The study by Fehlings 2000 compared BtA with no intervention. When data were analysed no treatment effect was found for quality of upper limb function, passive range of motion, muscle tone, grip strength or self-care ability. REVIEWERS' CONCLUSIONS: This systematic review has not found sufficient evidence to support or refute the use of intramuscular injections of BtA as an adjunct to managing the upper limb in children with spastic cerebral palsy. Only one of the two identified RCTs reported some promising results in support of reduced muscle tone following BtA injections. Further research incorporating larger sample sizes, rigorous methodology, measurement of upper limb function and functional outcomes is essential.
[Wasiak, J., Hoare, B. & Wallen, M. (2004). Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database of Systematic Reviews (online), 3, CD003469.]
OBJECTIVES: To determine whether botulinum toxin (BtA) is an effective and safe treatment for lower limb spasticity in children with cerebral palsy. Functional outcomes are of particular interest. SEARCH STRATEGY: Studies for inclusion in the review were identified using the Movement Disorders Review Group trials register, the Cochrane Controlled Trials Register, MEDLINE, pharmaceutical company databases, communication with other researchers in the field and reference lists of papers found using above search strategies. SELECTION CRITERIA: Studies were considered eligible for inclusion in the review if they evaluated the efficacy of BtA for the treatment of leg spasticity in children with cerebral palsy. They must have been randomised and include a concurrent control group receiving another intervention. DATA COLLECTION AND ANALYSIS: A paper pro forma was used to collect data from the included studies using double extraction by two independent reviewers. Each trial was assessed for internal validity by each of the two reviewers. Meta-analysis was not possible because results were presented in an incompatable form. A Peto odds ratio was calculated where this was appropriate, otherwise a descriptive summary of the results of the individual studies was compiled. MAIN RESULTS: Three eligible studies were found each with small numbers of subjects. They were short term, used single injection sessions with follow-up of between 4 and 26 weeks. One study (Koman), of twelve ambulant children, compared BtA with injection of a placebo and found non-significant improvements in gait in the BtA group compared to the placebo group. Two studies (Corry, Flett) compared BtA with the use of casts. Each included 20 ambulant children and found improvements in gait, range of ankle movement and muscle tone in both the BtA and cast groups. However there were no significant differences between the groups in either trial. One of these trials (Flett) also assessed motor function using the gross motor function measure (GMFM) (Russell, 1989) and found significant improvements in each group compared to baseline but no significant differences between the groups. The other trial (Corry) performed 3D gait analysis on those children able to co-operate. Maximal plantar flexion and maximal dorsiflexion during walking were both found to be significantly greater in the BtA group compared to the cast group. In all other dimensions there were no significant differences between the groups. REVIEWER'S CONCLUSIONS: This systematic review has not revealed strong controlled evidence to support or refute the use of BtA for the treatment of leg spasticity in cerebral palsy. Ongoing randomised controlled trials are likely to provide useful data on the short term effects of BtA for leg spasticity. Future research should also assess the longer term use of BtA. Ideally studies should be pragmatic in their approach to dose and distribution of toxin to reflect practise. Outcome measures assessing function and disability would give the most useful information.
[Ade-Hall, R. A. & Moore, A. P. (2000). Botulinum toxin type A in the treatment of lower limb spasticity in cerebral palsy. Cochrane Database of Systematic Reviews (online), 2, CD001408.]
BACKGROUND: Intrathecal baclofen (ITB) is an effective treatment of spasticity in patients with cerebral palsy. However, several recent reports have raised concerns that the treatment may be associated with a rapid progression of scoliosis. The objective of this study was to further examine the effect of ITB treatment on the progression of scoliosis in patients with cerebral palsy. METHODS: Spastic cerebral palsy patients who were ITB candidates were followed radiographically. Baseline Cobb angles of the primary curve were measured during the period of ITB pump insertion and at the most recent follow-up visit. Each patient was matched with a control patient by the diagnosis of cerebral palsy, age, sex, topographic involvement, and initial Cobb angle. The mean rate of change in Cobb angle was compared between ITB and control patients using paired t test. A multiple linear regression model was used to examine the difference, controlling for age, sex, topographic involvement, and initial Cobb angle. RESULTS: Fifty ITB patients and 50 controls were included in the analysis. There was no statistically significant difference between the mean change in Cobb angle in ITB patients (6.6 degrees per year) compared with the matched control patients (5.0 degrees per year, P = 0.39). The results from the multiple regression analysis also failed to show a statistically significant difference (0.92 degrees per year difference between ITB patients and controls, P = 0.56). CONCLUSIONS: The progression of scoliosis in cerebral palsy patients with ITB treatment is not significantly different from those without ITB treatment. The findings suggest that patients receiving ITB experience a natural progression of scoliosis similar to the natural history reported in the literature. LEVEL OF EVIDENCE: Level III.
[Shilt, J. S., Lai, L. P., Cabrera, M. N., Frino, J. & Smith, B. P. (2008). The impact of intrathecal baclofen on the natural history of scoliosis in cerebral palsy. Journal of Pediatric Orthopedics, 28(6), 684-7.]
This randomized double blind AB/BA cross-over trial evaluates the effect of oral modafinil versus placebo on spasticity, function, and quality of life in children with cerebral palsy (CP). Outcomes were measured at the start and end of both 8-week treatment periods (modafinil and placebo). The order of the treatment periods was randomly assigned. There was a 4-week wash-out period between treatments. Primary outcomes include the Modified Ashworth Score (MAS), and the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), a disorder-specific quality of life measure. Ten children were randomized and eight children completed the study. The mean age of participants was 11 years 5 months (SD 1 y 5 mo, range 8 y 8 mo-12 y 11 mo). Five of the participants were male and three female. Seven children had a diagnosis of spastic quadriplegic CP and one child had spastic diplegia with overflow tone to the upper extremities. The Gross Motor Function Classification System ranged from Level III to V with one child at Level III, six children at Level IV, and one at Level V. The CPCHILD pre- to post-total scores showed a slight improvement in quality of life during the placebo period and a slight deterioration in the modafinil period (overall mean change of 7.1, SD 7.6). A t-test between post differences was statistically significant (t=2.65, p=0.03) in favor of the placebo period. The MAS for elbow flexors, ankle flexors, and hip adductors did not show any significant reduction post-modafinil or post-placebo (p values ranged from 0.41-0.79). This study did not find evidence that modafinil reduces spasticity or has a positive impact on quality of life in children with spastic CP.
[Murphy, A. M., Milo-Manson, G., Best, A., Campbell, K. A. & Fehlings, D. (2008). Impact of modafinil on spasticity reduction and quality of life in children with CP. Developmental Medicine and Child Neurology, 50(7), 510-4.]
Botulinum toxin is a neurotoxin that blocks the synaptic release of acetylcholine from cholinergic nerve terminals mainly at the neuromuscular junction, resulting in irreversible loss of motor end plates. It is being widely tried as a targeted antispasticity treatment in children with cerebral palsy. A number of studies have shown that it reduces spasticity and increases the range of motion and is particularly useful in cases with dynamic contractures. However improvement in function has not been convincingly demonstrated. It is an expensive mode of therapy and the injections need to be repeated after 3-6 months. Whereas Botulinum toxin can be a valuable adjunct in select cases, it should not be projected as a panacea for children with spastic cerebral palsy.
[Singhi, P. & Ray, M. (2004). Botulinum toxin in children with cerebral palsy. Indian Journal of Pediatrics, 71(12), 1087-91.]
OBJECTIVE: To review the efficacy and safety of various drug treatments for sialorrhea. Pharmacotherapy for drug-induced sialorrhea is not addressed. DATA SOURCES: Clinical studies were identified using PubMed (1966-October 2001). Key search terms included sialorrhea and drug therapy. DATA SYNTHESIS: Sialorrhea is a social and physical detriment to patients. Drug treatment, although not necessarily the treatment of choice for all patients, can offer some symptom relief. CONCLUSIONS: Literature has documented that benztropine, glycopyrrolate, and scopolamine can reduce the incidence of sialorrhea. Although the literature evaluating the therapeutic options has limitations (e.g., small sample size, inconsistent outcome measurements), glycopyrrolate may have an advantage over the other agents due to fewer adverse effects.
[Tscheng, D. Z. (2002). Sialorrhea -- therapeutic drug options. The Annals of Pharmacotherapy, 36(11), 1785-90.]
BACKGROUND/OBJECTIVE: Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management. METHODS: Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-microg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-microg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-microg/mL concentration. RESULTS: After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback. CONCLUSIONS: Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.
[Saval, A. & Chiodo, A. E. (2008). Effect of intrathecal baclofen concentration on spasticity control: Case series. The Journal of Spinal Cord Medicine, 31(4), 394-7.]
STUDY DESIGN: Retrospective clinical and radiographic review of complications related to intrathecal baclofen therapy (ITB) and posterior spine fusion (PSF) in patients with cerebral palsy. OBJECTIVE: To report the technical considerations and complications associated with ITB in patients undergoing PSF. SUMMARY OF BACKGROUND DATA: A common treatment for spasticity in children with cerebral palsy is ITB. This population also has a high incidence of severe spinal deformities requiring PSF. METHODS: There were 4 groups: A, 26 patients with PSF before ITB; B, 11 patients who underwent PSF and ITB concurrently; C, 25 patients with PSF after ITB; and D, the control group: 103 patients with ITB only. Complications and infections were tabulated from a retrospective chart review and ongoing surveillance data. Multiple chi analyses were used to compare the number of patients who experienced complications and infections among the groups. The operative sequence and catheter management techniques for the various scenarios are described in detail in the text. RESULTS: The outcome by group was as follows: group A had 5 catheter malfunctions and 2 infections at the pump site, group B had 2 catheter malfunctions, 1 hypermobile pump and 1 infection at the spinal site, group C had 3 catheter malfunctions, 1 infection at the pump site and 1 infection at the spinal site. The control group had 23 catheter malfunctions, 5 pump failures, 8 infections at the pump site, and 1 infection at the spinal site. Multiple chi analyses showed no difference in the number of infection or device/catheter complications among any of the groups. CONCLUSION: The rate of ITB therapy complications is not increased despite PSF in any order of the procedures. There are technical details in each situation that require attention. With understanding of the appropriate techniques of catheter management, ITB pumps can be implanted and managed without an increased complication rate before, during or after spinal fusion surgery.
[Borowski, A., Shah, S. A., Littleton, A., G., Dabney, K. W. & Miller, F. (2008). Baclofen pump implantation and spinal fusion in children: Techniques and complications. Spine, 33(18), 1995-2000.]