An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. Botulinum toxin A in the hemiplegic upper limb: a double-blind trial. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy. Combined botulinum toxin type A with modified constraint-induced movement therapy for chronic stroke patients with upper extremity spasticity: a randomized controlled study. Treatment of spasticity with botulinum toxin: a double-blind study. Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial. Botulinum toxin A versus fixed cast stretching for dynamic calf tightness in cerebral palsy. Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial.
In a randomized, controlled, single-blind trial, to test the hypothesis that botulinum-A toxin (BTA) injections into the upper extremity of children with spastic hemiplegia improve upper extremity function.
                Thirty children with hemiplegia, aged 2.5 to 10 years, were randomly assigned to receive: (1) a BTA injection into 1 or more of 3 muscle groups (biceps, volar forearm muscles, adductor pollicis) plus occupational therapy or (2) occupational therapy alone. Blinded outcomes obtained at baseline and at 1, 3, and 6 months included the Quality of Upper Extremity Skills Test (QUEST), goniometry measurements, grip strength, and Ashworth scores. The caregiver completed the self-care domain of the Pediatric Evaluation of Disability Inventory.
                Twenty-nine subjects completed the study. The QUEST demonstrated a significant improvement favoring the treatment group on a 2-way analysis of variance (F = 4.69, df = 1,83; P =.039). BTA treatment was also associated with an improvement in score on the self-care domain of the Pediatric Evaluation of Disability Inventory (F = 4.68, df = 1,82; P =.04).
                This study supports the effectiveness of BTA injections to improve upper extremity function of children with hemiplegia who have at least moderate spasticity. In a randomised, double-blind study, the effects of intramuscular injection of botulinum toxin type A (BtA) into the upper limb were compared with those of normal saline solution in 14 patients with cerebral palsy; their mean age was 9 years. Range of movement and function were assessed before injection and at 2 and 12 weeks after injection. BtA injection significantly increased maximum active elbow and thumb extension and significantly reduced tone at wrist and elbow. The hand grasp-and-release score improved, representing a modest functional change, but fine motor function, assessed by the ability to pick up coins, did not improve and in some cases deteriorated temporarily. The most notable subjective change was the cosmetic benefit of reduced involuntary elbow flexion. The tone-reducing effect of BtA was clinically detectable in comparison with the placebo and patients and parents perceived the change as beneficial. The median of changes in the treatment group was small but the range was large, suggesting that BtA can be useful in selected patients. Conservative therapies for equinus in cerebral palsy may help to postpone calf surgery in younger children. This study reports a prospective randomised trial of intramuscular botulinum toxin A (BtA) as an alternative to serial casting in 20 children with a dynamic component to calf equinus. Outcome was assessed in the short term to show the effect of one treatment cycle. Assessments were by clinical examination, video gait analysis, and three-dimensional gait analysis. BtA was of efficacy similar to that of serial casting. Tone reduction in the BtA group allowed a more prolonged improvement in passive dorsiflexion, which may allow more opportunity for increase in muscle length. Gait analysis showed an improved mean ankle kinematic pattern in a subsection of both groups, which was maintained at 12 weeks in the BtA group, whereas the cast group relapsed. There were fewer side effects in the BtA group. Median time to reintervention was similar. The purpose of this study was to compare the cumulative efficacy (three treatment sessions) of botulinum toxin A (BTX-A) alone, casting alone, and the combination of BTX-A and casting in the management of dynamic equinus in ambulatory children with spastic cerebral palsy (CP). Thirty-nine children with spastic CP (mean age 5y 10mo, range 3 to 9y) were enrolled in the study. A multicenter, randomized, double blind, placebo-controlled prospective study was used. Children were randomly assigned to one of three treatment groups: BTX-A only (B), placebo injection plus casting (C), or BTX-A plus casting (B+C). The dosage for the BTX-A injections was 4U/kg per extremity. Assessments were performed at baseline, 3, 6, 7.5, and 12 months with a total of three treatments administered after the evaluations at baseline, 3, and 6 months. Primary outcome measures were ankle kinematics, velocity, and stride length. Secondary outcome measures were ankle spasticity, strength, range of motion, and ankle kinetics. Group B made no significant change in any variable at any time. Groups C and B+C demonstrated significant improvements in ankle kinematics, spasticity, passive range of motion, and dorsiflexor strength. Results of this 1-year study indicate that BTX-A alone provided no improvement in the parameters measured in this study, while casting and BTX-A/casting were effective in the short- and long-term management of dynamic equinus in children with spastic CP. Botulinum toxin type A (BtxA) injection and modified constraint-induced movement therapy (mCIMT) are both promising approaches to enhance recovery after stroke. The combined application of these 2 promising modalities has rarely been studied. The aim was to investigate whether combined BtxA and mCIMT would improve spasticity and upper extremity motor function more than BtxA plus conventional rehabilitation in chronic stroke patients with upper extremity spasticity.
                In a prospective, randomized controlled, observer-blinded trial with 6-month follow-up, 32 patients (>or=1 year after stroke) with ability to actively extend >10 degrees at metacarpophalangeal and interphalangeal joints and 20 degrees at wrist of the affected upper limb were randomized to receive BtxA + mCIMT (combination group) or BtxA + conventional rehabilitation (control group) for 2 hours/day, 3 days/week for 3 months.The primary outcome assessed spasticity on the Modified Ashworth Scale. Secondary outcomes assessed real-world arm function (Motor Activity Log), laboratory motor activity (Action Research Arm Test), and patients' global satisfaction.
                A total of 32 stroke patients were recruited, and 29 completed the study. Spasticity significantly improved in all subjects at 4 weeks and 3 months postinjection without between-group differences.The combination group showed significantly greater improvements in elbow, wrist, and finger spasticity (P = .019, P = .019, and P < .001, respectively), affected upper extremity real-world arm function (P < .001) and laboratory motor activity (P < .001) than the control group at 6-month postinjection. Patients reported considerable satisfaction and no serious adverse events occurred.
                Combining BtxA and mCIMT is an effective and safe intervention for improving spasticity and motor function in chronic stroke patients. The results are promising enough to justify further studies. We recommend future research to address the likely need for including rehabilitation with BtxA to improve function in patients with poststroke spasticity. We studied the effect of botulinum-A toxin on spasticity of the leg adductors in 9 patients who were either chair-bound or bed-bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double-blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93-0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care (p = 0.009). There were no adverse effects during this short-term trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions. In order to evaluate further the efficacy of local intramuscular injections of botulinum-A toxin (BAT-A) in the management of dynamic equinus deformity associated with cerebral palsy, a randomized, double-blind, placebo-controlled study was undertaken. When evaluated using our Physician Rating Scale, 83% (five of six) of patients receiving toxin showed improvement, versus 33% (two of six) receiving placebo. There were no major complications. BAT-A injections appear to be safe and effective in children, and merit further prospective study. To compare botulinum toxin A injections with fixed plaster cast stretching in the management of cerebral palsied children with dynamic (i.e. non-fixed) calf tightness.
                The settings were the Women's and Children's Hospital (WCH) and the Crippled Children's Association of South Australia (CCA), Adelaide, South Australia. Twenty children were selected by two paediatric rehabilitation specialists. A prospective, randomized, single-blind controlled study, was carried out, with 10 children in each arm. The clinicians were blinded as to the allocated interventions. The outcome measures for 6 months post intervention were clinical assessment, modified Ashworth Scale, Gross Motor Function Measure, 2 D-video ratings using a modified Physical Rating Scale and a global scoring scale and a parent satisfaction questionnaire.
                Botulinum toxin A injections were of similar efficacy to serial fixed plaster casting in improving dynamic calf tightness in ambulant or partially ambulant children with cerebral palsy. The ease of outpatient administration, reduction of muscle tone and safety with botulinum toxin A was confirmed. Parents consistently favoured botulinum toxin A and highlighted the inconvenience of serial casting. Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study.
                This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales.
                Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group.
                BTA is significantly more effective in the treatment of ICD, with less adverse effects.
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.