Management of upper limb dysfunction in children with cerebral palsy: a systematic review

Effective use of the upper limb can impact on educational outcomes, participation in activities of daily living and vocational options for many children with cerebral palsy (CP). This article presents the results of a systematic review of the literature on the management of upper limb dysfunction in children with CP. The range of management options includes therapies such as physiotherapy, occupational therapy, neurodevelopmental therapy and conductive education; peripheral splinting and casting; focal or generalized pharmacotherapy; and surgery to improve upper limb function or correct deformity. A literature search identified 60 papers, of which four were randomized controlled trials and 44 were prospective studies with objective outcome measures. Principal studies undertaken for each type of treatment and the efficacy of the different types of treatment were critically evaluated. In addition, the current level of evidence for each study was evaluated according to Sackett's (1989) model and ICIDH-2 classification. A close examination of two relatively new treatments for upper limb spasticity, constraint induced movement therapy and botulinum toxin type A (BTX-A) was conducted with reference to more extensive data on the efficacy of BTX-A in the lower limb.     

Management of spasticity in adults: practical application of botulinum toxin

Spasticity, characterized by increased muscle tone, exaggerated stretch reflexes, and abnormal limb posture, is a common sequel of central nervous system pathology. Historically, medicinal treatments have been of limited efficacy. This review discusses the clinical features of spasticity, the functional and pathological consequences, and treatment. It reviews the most common patterns of spasticity encountered in the upper and lower limbs and focuses on focal treatment of spastic muscles with the three commercially available botulinum toxins Botox®, Dysport®, and Myobloc®/NeuroBloc®. It addresses practical details such as muscle selection and identification, drug dilution, and doses.     

Long-term effects of botulinum toxin A in children with cerebral palsy

The long-term effects of botulinum toxin A (BoNT-A) treatment in children with cerebral palsy (CP) are still elusive. We studied a prospective clinical cohort of 94 children with different subtypes (50% spastic diplegic CP, 22% hemiplegic CP, 25% tetraplegic CP, 3% dyskinetic CP), sex (55% male, 45% female), severity according to Gross Motor Function Classification System (29% Level I, 15% Level II, 16% Level III, 17% Level IV, 23% Level V), and age (median 5y 4mo, range 11mo–17y 8mo). The longest follow-up time was 3 years 7 months (median 1y 6mo) and included a maximum of eight injections per muscle (median two injections to a specific muscle). Outcome measurements were muscle tone (Modified Ashworth Scale) and joint range of motion (ROM). Assessments were made at a minimum before and 3 months after each injection. Ninety-five per cent confidence intervals for differences from baseline were used to identify significant changes. BoNT-A injections induced reduction of long-term spasticity in all muscle-groups examined: the gastrocnemius, hamstring, and adductor muscles. The reduction in tone was most distinct in the gastrocnemius muscle, and each repeated injection produced an immediate reduction in muscle tone. However, improvement in ROM was brief and measured only after the first injections, whereupon the ROM declined. Thus, the results suggest that BoNT-A can be effective in reducing muscle tone over a longer period, but not in preventing development of contractures in spastic muscles. The dissociation between the effects on muscle tone and ROM indicates that development of contractures is not coupled to increased muscle tone only, but might be caused by other mechanisms.     

Neurologic uses of botulinum neurotoxin type A

This article reviews the current and most neurologic uses of botulinum neurotoxin type A (BoNT-A), beginning with relevant historical data, neurochemical mechanism at the neuromuscular junction. Current commercial preparations of BoNT-A are reviewed, as are immunologic issues relating to secondary failure of BoNT-A therapy. Clinical uses are summarized with an emphasis on controlled clinical trials (as appropriate), including facial movement disorders, focal neck and limb dystonias, spasticity, hypersecretory syndromes, and pain.     

The Leg Drop Pendulum Test performed under general anesthesia in spastic cerebral palsy

The general aim of this study was to examine the stiffness and damping characteristics (rate at which oscillations diminish) of limbs of a small population of patients with spastic cerebral palsy (CP) during the Leg Drop Pendulum Test while under general anesthesia and to compare them with patients without CP, both awake and under similar anesthetized conditions. To facilitate a quantitative comparison the authors defined a set of parameters that reflect the stiffness and damping of limbs with spasticity under general anesthesia. To give these parameters more meaning a similar set was constructed for children without disabilities under conditions of normal wakefulness and under anesthesia. The test population of 10 patients with spasticity ranged in age from 4 to 19 years and had a mean age of 10 years 9 months (SD 5 years 10 months); there were four females and six males. The control population consisted of eight patients without disabilities who ranged in age from 7 to 19 years with mean age of 13 years 9 months (SD 3 years 3 months); there were six females and two males. To even out the populations, two limbs from the non-affected sides of two patients with hemiplegic spasticity (both female) were used in the control group. The Leg Drop Pendulum Test was administered to 10 limbs with spastic CP and 10 control limbs under general anesthesia. The two test populations were chosen from patients who were previously scheduled to undergo surgery. Two measures compared limbs of those under anesthetic with those under alert conditions: the damped natural frequency and the damping ratio. The natural frequency is the frequency at which a pendulum oscillates as it comes to rest; the damping ratio is a measure of how quickly the oscillations diminish. In spasticity, active muscle tone disappeared under anesthesia. In both groups the underlying biomechanics of the limb varied considerably. In controls the variation seemed to be growth related.     

Botulinum toxin type A for the treatment of the upper limb spasticity after stroke: a meta-analysis

Muscle over-activity is one of the cardinal features of spasticity and it is a common disability of stroke patients. In this group, spasticity is responsible for several limitations that interfere in their daily activities and quality of life. To treat spasticity, neurologists usually prescribe drugs as baclofen, tizanidine or benzodiazepines or even use definitive treatment as phenol or surgery. Authors suggest the use of botulinum toxin type A (BTX-A) for spasticity in the upper limbs after stroke, but there are few papers with adequate methodology supporting this idea. In this article we summarize the data of previous double-blind, randomised clinical trials to asses, with a meta-analysis, if BTX-A is an adequate treatment for spasticity due to stroke. The results show a statistical superiority of BTX-A ov%r placebo on reducing muscle tone by the Modified Ashworth Scale (WMD= 0.95 [0.74 to 1.17]) in patients with post-stroke upper limb spasticity.     

Botulinum toxin type A injections can be an effective treatment for pain in children with hip spasms and cerebral palsy

Aim  Botulinum toxin type A (BoNT-A) injections were used in the treatment of lower-limb spasticity in children with cerebral palsy (CP). Anecdotal evidence suggests a reduction in pain after this treatment in children who had pain localized to a displaced hip joint. We report on our current clinical practice.
Method  Twenty-six children with non-ambulant quadriplegic CP (Gross Motor Function Classification System level V) were assessed as having significant spasticity and pain at the hip level. Twelve were males and 14 females, with an age range of 2 to 19 years (mean age 11y 6mo, SD 4y 9mo). Ten had functional difficulties secondary to predominant spasticity and 16 had a mix of a high-background peripheral tone with superimposed dystonia. Of the 26 children assessed, 10 had at least one hip which was dislocated and three had at least one hip which was subluxed. As part of their spasticity management programme they received targeted BoNT-A injections to the adductor magnus, medial hamstrings and iliopsoas muscle groups. The Paediatric Pain Profile was used as the primary outcome measure.
Results  All had highly significant improvement in their recorded pain profile scores measured at 3 months after treatment ( p <0.001). There was equal efficacy in response to treatment in the children with subluxed or dislocated hips. In addition, families commented on improved quality of life for the children across several areas, including sleep, postural management, and activities of daily living.
Interpretation  This report demonstrates that targeted BoNT-A injections reduced pain in children with significant spasticity and pain at the hip level. They may also improve quality of life of non-ambulant children with CP and a hip problem.     

Botulinum toxin A (BoNT-A) for spasticity in adults. What is the evidence?

There are now many reports from open, uncontrolled studies which suggest that botulinum toxin A (BoNT-A) is valuable in treating spasticity. Evidence of its benefit is also gradually accumulating from randomized controlled trials (RCTs). In this presentation I will discuss the reasons why RCT evidence is being generated, and describe the findings currently available, including preliminary results from as yet unpublished trials. RCT data have been reported for leg and arm spasticity in a variety of diseases, but predominantly in stroke and multiple sclerosis patients. In most RCTs, the effects of BoNT-A are compared with placebo over a single injection cycle. The outcomes are generally positive and support the use of BoNT-A. However, data from RCTs are less convincing than those from open studies for a variety of technical reasons. These especially reflect the difficulties of finding good outcome measures for such a heterogeneous array of patients. There is good evidence that BoNT-A has clinical benefit in treating the mechanical effects of spasticity. In order to further clarify its usefulness, future research should address the strategies of short- and longer-term use of BoNT-A, and the unresolved technical issues of how to get the best out of this new treatment.     

Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on upper and lower limb spasticity in post-stroke patients

Objectives. The purpose of this study was to examine the effects of combined botulinum toxin type A (BoNT-A) and inpatient multidisciplinary (MD) rehabilitation therapy on the improvement of upper and lower limb function in post-stroke patients. Methods. In this retrospective study, a 12-day inpatient treatment protocol was implemented on 51 post-stroke patients with spasticity. Assessments were performed on the day of admission, at discharge, and at 3 months following discharge. Results. At the time of discharge, all of the evaluated items showed a statistically significant improvement. Only the Functional Reach Test (FRT) showed a statistically significant improvement at 3 months. In subgroup analyses, the slowest walking speed group showed a significantly greater change ratio of the 10 Meter Walk Test relative to the other groups, from the time of admission to discharge. This group showed a greater FRT change ratio than the other groups from the time of admission to the 3-month follow-up. Conclusion. Inpatient combined therapy of simultaneous injections of BoNT-A to the upper and lower limbs and MD may improve motor function.     

Long-term effects of injection of botulinum toxin type A combined with home-based functional training for post-stroke patients with spastic upper limb hemiparesis

The aim of this study was to assess the effects of botulinum toxin type A (BoNT-A) injection with home-based functional training for passive and active motor function, over a 6-month period in post-stroke patients with upper limb spasticity. We studied 190 patients with at least 6-month history of stroke. They received injections of BoNT-A in upper limb muscles and detailed one-to-one instructions for home-based functional training. At baseline (before therapy), and at 1-, 3- and 6-month follow-up, Fugl-Meyer assessment (FMA) and Wolf motor function test (WMFT) were used to assess active motor function, the modified Ashworth scale (MAS) for assessment of spasticity, and the range of motion (ROM) for passive motor function. The total score for upper limb and scores of categories A and B of the FMA increased significantly at 1, 3 and 6 months, while the FMA score for category D increased significantly at 3 and 6 months, but not at 1 month. Significant decreases in the MAS scores were noted in all muscles examined at 1, 3 and 6 months, compared with baseline. The ROM for elbow joint extension significantly improved at 1, 3, and 6 months, while that for wrist joint extension increased significantly at 1 month, but not 3 or 6 months, compared with baseline. The results suggest that comprehensive improvement of motor function requires improvement of motor function in the proximal part of the upper limb and that BoNT-A followed by rehabilitation reduces spasticity and improves motor function of fingers.     

Therapeutic interventions for tone abnormalities in cerebral palsy

Cerebral palsy (CP) is a common cause of movement disorders in children. The upper motor neuron syndrome of CP leads to several types of muscle overactivity, including spasticity. Reduction of muscle overactivity may be an important treatment goal, to improve comfort, care, and active function and to prevent future musculoskeletal complications. After a comprehensive team evaluation, a treatment plan is generated. Treatments may include physical and occupational therapy, oral medications, botulinum toxin and/or phenol injections, intrathecal baclofen, selective dorsal rhizotomy, and orthopedic surgery. Successful and early prevention of contracture may reduce the need for later corrective surgery.     

The interrater and intrarater reliability of the Modified Ashworth Scale in the assessment of muscle spasticity: limb and muscle group effect

The Modified Ashworth Scale (MAS) is a clinical scale used to assess muscle spasticity. While the evidence indicates that the reliability of the MAS is better in the upper limb and in certain distal muscle groups, no investigation has compared the effect of limbs and muscle groups on the MAS reliability. This study aimed to evaluate the effect of limb and muscle group on the reliability of the MAS in patients with spastic hemiplegia. Thirty subjects with upper and lower limb muscle spasticity were recruited for this trial. Two female experienced physiotherapists participated in this examination of reliability, and rated each patient in a randomized order in a single session. For the intrarater reliability, the second rater repeated the test 1 week later. Shoulder adductor, elbow flexor, wrist flexor, hip adductor, knee extensor, and ankle plantar flexor were tested on the hemiplegic side. Results demonstrated moderate inter (kappa=0.514, SE=0.046, p < 0.001) and intrarater (kappa=0.590, SE=0.051, p<0.001) reliability. For the inter and intrarater reliability, the agreement obtained for the upper and lower limb was similar. In the upper limb, the agreement between raters on the distal wrist flexor was significantly higher than the agreement on the proximal shoulder adductor. In the lower limb, there was a similar agreement between raters on the distal ankle plantar flexor and proximal hip adductor. For within rater, the agreement on the proximal and distal muscles of both limbs was not statistically significant. The Modified Ashworth Scale had moderate reliability. The limbs had no effect on the reliability. The agreement on distal wrist flexor in the upper limb was significantly higher between rater than in the proximal shoulder adductor. The agreement obtained with the MAS was not good, which questions the validity of the measurements.     

Botulinum neurotoxins for post‐stroke spasticity in adults: A systematic review

The aim of this systematic review was to determine whether botulinum neurotoxin (BoNT) reduce spasticity or improve function in adult patients after stroke. Eleven double‐blind randomized placebo‐controlled trials met inclusion criteria. They encompassed 782 patients, 767 (98%) of whom received BoNT/A, and 15 (2%) BoNT/B. Most studies used the Ashworth scale as primary outcome measure. Differences between treated and control groups were assessed as categorical or continuous comparisons. The overall effect on upper limb spasticity was in favor of BoNT/A. A significantly higher number of patients had a reduction of upper limb spasticity at 4‐week and 8‐week evaluations in the treatment group compared with placebo. Mean changes in joint spasticity revealed improvement 3 to 6 weeks and 9 to 12 weeks after treatment. There were insufficient data to establish BoNT/A efficacy on lower limb spasticity or the effect of BoNT/B on the upper and lower limbs. Because of inconsistency and heterogeneity of the available data, it was not possible to perform a meta‐analysis on disability and patients' reported outcomes. There was an overlapping safety profile between the treatment and the placebo groups. BoNT/A reduces upper limb spasticity in patients post‐stroke, but the improvement in functional ability remains to be established. This gap needs to be filled by new studies to assess the effect of BoNT in the context of multidisciplinary patient management. © 2009 Movement Disorder Society     

Effects of ultrasound-guided botulinum toxin type-A injections with a specific approach in spastic cerebral palsy

The aim of this study was to detect effects of ultrasound-guided botulinum toxin type-A (US-guided BoNT-A) injections prepared according to lower extremity innervation zones on spasticity and motor function in 3–16 years children with diplegic and hemiplegic spastic cerebral palsy. This study included 25 patients between 3 and 16 years of age who admitted to our clinic in 2017, were being followed in our clinic with a diagnosis of cerebral palsy, had BoNT-A injections due to lower extremity spasticity. The US-guided BoNT-A injections were administered into the spastic muscles using a specific approach according to innervation zones of muscle. Modified Ashworth Scale (MAS) and Gross Motor Functional Classification System (GMFCS) were assessed at the baseline, and 4 and 12 weeks after the BoNT-A injections. Minimum and maximum ages of the patients were 45 and 192 months, and gender distribution was 8 females and 17 males. Significant decreases in the MAS scores of the knee and ankle tones were measured 4 and 12 weeks after the BoNT-A injection when compared to the baseline scores (p?<?0.025). Hip muscle tonus only decreased 12 weeks after the injection (p?<?0.025). In parallel with a reduction in spasticity GMFCS improved from 3 to 2 in the 4th and 12th weeks. US-guided BoNT-A injections with Euro-musculus approach is a practical and effective method to perform injections into proper points of proper muscles in children with spastic cerebral palsy.     

Intrathecal baclofen in severe spasticity due to multiple sclerosis

Intrathecal administration of baclofen via programmable pump is a highly effective treatment method in severe spasticity resistant to oral medications. The authors describe a case of severe spasticity with tetraplegia and painful (> 10 a day) muscle spasms in the upper and lower limbs and paraspinal muscles, in a patient with clinically definite diagnosis of multiple sclerosis (MS). The 34-year-old female patient with a 15-year history of MS, suffering from lower limb spasticity with pes equinovarus since 1995, was treated with very good results with botulinum toxin injections of calf muscles (14 sessions of Dysport 1500iu till 2002). In the early 2002 she developed tetraplegia with severe, generalized and intractable spasticity. After 4 months of ineffective polytherapy (with high doses of oral baclofen, tizanidine, gabapentine, clonidine, diazepam) and the patient's enormous sufferings (she could neither sit up nor voluntarily change her position in bed), a programmable baclofen pump (Medtronic) was implanted. As soon as a few days after the surgery she could stand, sit and move voluntarily, her painful spasms disappeared, and her bladder catheter was removed. At a 6-month follow-up the effect was stable--she was able to walk a long distance outdoors with the aid of a crutch. The daily dose of the drug is 500 micrograms. No side effects of complications were noted.     

Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review

Management of children with cerebral palsy (CP) is the focus of considerable resources in many countries, so that evaluation of the efficacy for new and established treatments is imperative. Botulinum toxin type A (BTX-A) is a relatively new method of spasticity management in children with cerebral palsy. It has been the focus of extensive research since its application to cerebral palsy 10 years ago. In a systematic review relating to the management of the lower limb in cerebral palsy 156 papers were identified. These were categorized according to Sackett and the World Health Organisation International Classification of Impairments, Disabilities and Handicaps model. We identified 10 randomized trials evaluating the use of BTX-A in the lower limb in children with cerebral palsy in a systematic review. A meta-analysis showed the pooled risk difference between BTX-A and placebo in three trials was 0.25 (95% CI 0.13, 0.37) and 0.23 (95% CI −0.06, 0.53) for two trials of BTX-A and casting using the physicians rating scale. These represent moderate treatment effects that are dosage-dependent. Outcomes were also compared for function in five studies. The type of evidence for BTX-A was graded by each treatment indication and directions for future research were then drawn from the available evidence.     

Efficacy of a child-friendly form of constraint-induced movement therapy in hemiplegic cerebral palsy: a randomized control trial

Constraint-induced (CI) movement therapy is a promising therapy for improving upper limb function in adults after stroke. It involves restraint of the non-involved limb and extensive movement practice with the involved limb. In this study, a single-blinded, randomized, control study was performed to examine the efficacy of CI therapy, modified to be child friendly, in children with hemiplegic cerebral palsy (CP). Twenty-two children (8 females, 14 males; mean age 6 y 8 mo [SD 1 y 4 mo]; range 4-8 y) were randomized to either an intervention group (n=11) or a delayed treatment control group (n=11). Children wore a sling on their non-involved upper limb for 6 hours per day for 10 out of 12 consecutive days and were engaged in play and functional activities. Children in the treatment group demonstrated improved movement efficiency and dexterity of the involved upper extremity, which were sustained through the 6-month evaluation period, as measured by the Jebsen-Taylor Test of Hand Function and fine motor-subtests of the Bruininks-Oseretsky Test of Motor Proficiency (p<0.05 in both cases). Initial severity of hand impairment and testing compliance were strong predictors of improvement. Caregivers reported significant increases in involved limb frequency of use and quality of movement. However, there was no change in strength, sensibility, or muscle tone (p>0.05 in all cases). Results suggest that for a carefully selected subgroup of children with hemiplegic CP, CI therapy modified to be child-friendly, appears to be efficacious in improving movement efficiency of the involved upper extremity.     

圆锥水平选择性脊神经后根切断术治疗痉挛型脑瘫

目的 探讨在脊髓圆锥水平施行L2～S1选择性脊神经后根切断术（selective posterior rhizotomy，SPR）治疗痉挛型脑瘫（cerebral palsy．CP）的临床价值。方法2002年5月～2005年12月，我们在圆锥水平施行SPR治疗63例痉挛型CP。术前和术后不同时间按照Ashworth痉挛评分法对下肢肌肉不同肌群的痉挛情况进行评分。结果术后下肢痉挛状态均明显缓解，术后2周、3个月和6个月的Ashworth痉挛评分与术前比较均有显著性差异（P〈0．01）。除暂时性下肢麻木、乏力外，未出现括约肌功能障碍等严重并发症。结论在圆锥水平施行SPR具有创伤小、恢复快、操作简便、疗效确切等优点，能够有效缓解痉挛型CP病人的下肢肌肉痉挛。     

Flexor and extensor muscle tone evaluated using the quantitative pendulum test in stroke and parkinsonian patients

The aim of this study was to evaluate the flexor and extensor muscle tone of the upper limbs in patients with spasticity or rigidity and to investigate the difference in hypertonia between spasticity and rigidity. The two experimental groups consisted of stroke patients and parkinsonian patients. The control group consisted of age and sex-matched normal subjects. Quantitative upper limb pendulum tests starting from both flexed and extended joint positions were conducted. System identification with a simple linear model was performed and model parameters were derived. The differences between the three groups and two starting positions were investigated by these model parameters and tested by two-way analysis of variance. In total, 57 subjects were recruited, including 22 controls, 14 stroke patients and 21 parkinsonian patients. While stiffness coefficient showed no difference among groups, the number of swings, relaxation index and damping coefficient showed changes suggesting significant hypertonia in the two patient groups. There was no difference between these two patient groups. The test starting from the extended position constantly manifested higher muscle tone in all three groups. In conclusion, the hypertonia of parkinsonian and stroke patients could not be differentiated by the modified pendulum test; the elbow extensors showed a higher muscle tone in both control and patient groups; and hypertonia of both parkinsonian and stroke patients is velocity dependent.     

Does the treatment of spastic equinovarus deformity following stroke with botulinum toxin increase gait velocity? A systematic review and meta‐analysis

While botulinum toxin‐A (BT‐A) has been used to treat lower‐limb focal spasticity successfully, its effect on characteristics of gait has not been well defined. The objective of this systematic review was to establish the treatment effect associated with the use of BT‐A for equinovarus to improve gait velocity following stroke, using a meta‐analytic technique. Relevant studies were identified through a literature search encompassing the years 1985 to November 2009. Studies were included if (i) the sample was composed of adult subjects recovering from either first or subsequent stroke, presenting with spastic equinovarus deformity of the ankle preventing full active dorsiflexion, and (ii) subjects who received BT‐A were compared with subjects who had received a placebo, or (iii) in the absence of a placebo‐controlled condition, subject had received BT‐A and was assessed before and after treatment. A standardized mean difference (SMD) ± standard error and 95% confidence interval (CI) for gait velocity between the treatment and control group was calculated for each study, using Hedges’s g, and the results pooled. Eight trials, five randomized controlled trials, and three single group intervention studies were included. Data representing 228 subjects were available for pooled analysis. Treatment with BT‐A was associated with a small improvement in gait velocity (Hedge’s g = 0.193 ± 0.081; 95% CI: 0.033 to 0.353, P < 0.018) representing an increase of 0.044 meters/s. The use of BT‐A for lower‐limb post‐stroke equinovarus because of spasticity was associated with a small, but statistically significant increase in gait velocity.