The use of botulinum toxin type A in children with cerebral palsy: a retrospective study

The dosage and safety of botulinum toxin type A (BTX-A) treatments in 104 children with cerebral palsy were examined in a retrospective chart review of a 2-year period at Texas Scottish Rite Hospital for Children. Almost all of the BTX-A injections were to the muscles of the lower limbs. The average dose of BTX-A was 8–9 Ukg body weight and the interval between injections averaged 3–5 months. The average total amount of BTX-A injected at a single visit ranged from 146 to 186 U. The safety record for these treatments was excellent, with only 14 adverse events reported in 257 patient injection visits. The most commonly reported adverse event was muscle weakness, which is related to the pharmacology of BTX-A treatment     

The use of botulinum toxin type A treatment in children with spasticity

The current modalities in managing spastic children have some limitations; thus, alternative therapeutic agents are in need. The purpose of this study is to investigate whether intramuscular botulinum toxin type A administration may be an alternative agent in the treatment of children with cerebral palsy. Eighteen children who were aged between 3 and 17 years and manifested cerebral palsy were administered intramuscular botulinum toxin type A with a total dose of 6 U/kg body weight. Outcome measurements were determined with four methods, including Ashworth Spasticity Scale, standardized videotape assessments, observational gait analysis, and walking velocity. Ashworth Spasticity Scale and videotape assessments were statistically significant before and after treatment in all muscles (P < 0.001). The best improvement in video gait analysis was evident at week 8. The botulinum toxin type A injections yielded an improved walking velocity at all visits. The observational gait analysis and walking velocity demonstrated an improvement after treatment in the gastrocnemius-injected group (P < 0.001). In conclusion, intramuscular botulinum toxin type A administration may be effective in children with cerebral palsy, especially at week 4 and when injected in gastrocnemius.     

Prospective study examining remote effects of botulinum toxin a in children with cerebral palsy

We examined the remote effects on muscle strength and functional decline of lower-extremity botulinum toxin A injections in children with cerebral palsy. This prospective study enrolled 34 children (19 boys, 15 girls; mean age, 7.7 years) diagnosed with spastic cerebral palsy. Patients were examined at baseline and 1 month to determine if they experienced a change in upper-extremity strength (handheld dynamometry) or function (Pediatric Outcomes Data Collection Instrument). Subjects were analyzed in aggregate and by dosing group (low dose, 0-10 U/kg body weight; high dose, 11-25 U/kg) to determine if injection dose was associated with a change in remote muscle strength or function. We measured baseline and 1-month postinjection strength in shoulder flexor, shoulder abductor, elbow flexor, elbow extensor, and finger flexor muscles. None of these remote muscle groups was significantly weaker at 1 month after injection. No correlation was evident between change in muscle strength and toxin dose. These findings indicate that doses of botulinum toxin A in the lower extremities, at up to 21 U/kg, do not affect upper-extremity strength. This information can help guide dosages of botulinum toxin A in the management of spasticity in children with cerebral palsy.     

Spread of botulinum neurotoxin type a at standard doses is inherent to the successful treatment of spastic equinus foot in cerebral palsy: short-term neurophysiological and clinical study

To evaluate whether botulinum toxin type A at standard doses spreads to antagonist leg muscles in dynamic equinus foot, we studied 18 ambulatory children with hemiplegic cerebral palsy. The gastrocnemius muscle on the affected side was injected with botulinum toxin type A (Dysport) (mean ± standard deviation, 14.3 ± 0.9 U/kg). Compound muscle action potential areas were assessed in the lateral gastrocnemius and tibialis anterior muscles on the treated and untreated sides before botulinum toxin type A injections and on days 10 and 30 after injections. In all patients, compound muscle action potential areas recorded from both the muscles on the treated side decreased from preinjection values at day 10 (P < .05) and 30 (P < .002). After injection, ankle spasticity had diminished (P < .05), equinus foot excursion increased (P < .05), and functional gait improved (P < .05). This study shows that botulinum toxin type A spreads from foot flexors to antagonist extensors and suggests that spread may be partly responsible for improving gait in children with cerebral palsy.     

Botulinum toxin a in management of cerebral palsy

The efficacy of local injection of botulinum toxin A in selected skeletal muscles to relieve muscle hypertonia and muscle contracture, and increase range of motion in children with cerebral palsy was studied in an open ABA (baseline-treatment-posttreatment phase) type of study. The first 6 months were the baseline phase, the day of injection the treatment phase, and the next 6 months the posttreatment phase. The patients acted as their own controls. Fifteen children with cerebral palsy (mean age: 6 years, 8 months) were included in the study. All had limb deformities associated with nonfixed joint contractures that had not responded to physical therapy. Clinical assessment of passive and active muscle tone was performed using a modified Ashworth scale. The range of motion to passive movement was measured with a manual goniometer. Botulinum toxin was injected directly into the muscle at several sites. The postinjection scores of muscle hypertonia were significantly lower (P < .01) and the range-of-motion values demonstrated a significant increase (P < .001). Functional improvement was measured by decreased scissoring on standing in all 6 children with adductor muscles injected; all 6 children with knee flexor muscles injected were able to straighten the knees. The 3 children with injected gastrocnemius muscles were able to achieve heel-strike while barefooted. The study provides evidence that the intramuscular injection of botulinum toxin A in selected skeletal muscles decreases muscle tone and contractures, and increases range of motion and motor function.     

Botulinum toxin type B improves the speed of reaching in children with cerebral palsy and arm dystonia: an open-label, dose-escalation pilot study

Seven children between 2 and 15 years of age with cerebral palsy and upper extremity dystonia were enrolled in an open-label, dose-escalation pilot clinical trial of botulinum toxin type B (Myobloc), injected into the biceps and brachioradialis muscles of I or both arms. The primary outcome measure was the change in maximum speed of hand movement during attempted forward reaching. Escalating doses of 12.5, 25, and 50 U/kg per muscle were injected at each of 3 visits. Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved. There was not a dose-related effect on efficacy. There were no serious adverse events. Two children reported transient weakness. These results support the use of botulinum toxin type B as a safe and effective treatment for upper extremity dystonia in children with cerebral palsy. Larger controlled trials are needed to confirm these results.     

Parameters for predicting favorable responses to botulinum toxin in children with cerebral palsy

We sought markers for predicting a favorable outcome of botulinum toxin A injected to the lower-extremity muscles of 26 children with hemiplegic or diplegic cerebral palsy. Clinical assessment preceding and 1 month following injection included gross motor function measure, a modified Ashworth scale, and evaluation of range of motion of knee extension and ankle dorsiflexion. Response to treatment was classified based on a parent questionnaire. The 19 children (73%) considered by their parents as being good responders were compared to the 7 (27%) considered as being poor responders. In the good responders, the preinjection Ashworth scale (spasticity) was significantly higher (P < .05) and gross motor function measure scores (function) were lower (P < .05). Sixty-eight percent of the good responders were nonindependent walkers compared to 14% of the poor responders (P < .05). There were no differences in age, type of cerebral palsy, and dose of injection. An Ashworth scale indicating increased muscle tone, lower gross motor function measure scores, and nonindependent ambulatory status were predictive for a favorable response to botulinum toxin A injections and can guide patient selection and expectations of treatment outcome.     

Botulinum toxin type A on oral health in treating sialorrhea in children with cerebral palsy: a randomized, double-blind, placebo-controlled study

Intrasalivary gland injection of botulinum toxin type A is known to treat sialorrhea effectively in children with cerebral palsy. However, oral health may be compromised with escalating dose. In this randomized, double-blind, and placebo-controlled pilot trial, the authors aim to determine the therapeutic effect of low-dose, ultrasonography-controlled botulinum toxin type A injection to bilateral parotid and submandibular glands on oral health in the management of sialorrhea. Twenty children diagnosed with cerebral palsy were randomly assigned to 2 groups. The treatment group received botulinum toxin type A injections, whereas the control received normal saline in the same locations. The authors evaluated subjective drooling scales, salivary flow rate, and oral health (salivary compositions and cariogenic bacterial counts). A significant decrease was found in salivary flow rate at the 1- and 3-month follow-up in the botulinum toxin-treated group. The authors suggest that current protocol can effectively manage sialorrhea while maintaining oral health.     

Botulinum toxin type A treatment of cerebral palsy: an integrated approach

We have applied a multilevel approach to the management of spasticity associated with cerebral palsy (CP). All of the following factors are important in forming an integrated strategy for botulinum toxin type A (BTX-A) therapy: the timing of injections, patient selection, multilevel BTX-A treatment, optimal dosage and injection technique, follow-up treatment and objective measurements of functional outcome. Data on all these factors are presented here. CP patients had a mean age of 6.5 years (n = 315), and the dose of BTX-A (BOTOX®) ranged from 2 to 29 U/kg body weight ( n = 156). The combination of muscles injected in our multilevel approach differed for patients with diplegia, hemiplegia and quadriplegia: patients with hemiplegia received injections in the gastrocnemius and medial hamstrings; this combination was extended to the adductors for patients with diplegia and quadriplegia ( n = 156). For patients with quadriplegia, muscles in a three-level (gastrocnemius, medial hamstrings, adductors and iliopsoas) or two-level (excluding the gastrocnemius) combination were also frequently injected. The duration of effect of BTX-A treatment was mainly determined by follow-up treatment consisting of: serial casting, day and night orthoses and physiotherapy. No major side effects of BTX-A were reported. This integrated approach appears to prolong the duration of BTX-A treatment, resulting in a duration of about 1 year between injections.     

The effect of botulinum toxin A on gastrocnemius length: magnitude and duration of response

Thirty-nine ambulant children (22 with hemiplegia, 17 with diplegia) with spastic cerebral palsy receiving isolated gastrocnemius muscle injection with botulinum toxin A were studied prospectively. The children had a mean age of 6 years (range 3 to 13 years). Measurement of gastrocnemius muscle length was used to estimate the dynamic component of each child's spasticity and to quantify the response. There was a strong correlation between the dynamic component of spasticity before injection and the corresponding magnitude of the response after injection. Children undergoing repeated injections showed similar correlations. A strong correlation was found between the duration of response and the dynamic component. Children with hemiplegia showed twice the duration for a given dynamic component compared with those with diplegia when injected with the same total dose per unit body weight. Long-term lengthening did not occur for the cohort, although some patients showed a response at a 12-month follow-up. By delaying shortening, the injections may have a role in delaying the need for surgery. Injections were well tolerated with few side effects.     

Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, two-dose study.

BACKGROUND: Primary palmar hyperhidrosis is characterized by excessive sweating due to increased sympathetic cholinergic sudomotor nerve traffic to the palmar surface of the hands. Clinical studies suggest that intradermal injections of botulinum toxin are effective in the treatment of palmar hyperhidrosis. OBJECTIVES: To establish the effectiveness of intradermal botulinum toxin in reducing hyperhidrosis, to determine the most effective dose of toxin, and to examine its effect on muscle strength. METHODS: In a prospective, single blind, randomized trial, 24 patients with severe palmar hyperhidrosis received either a low (50 U) or a high dose (100 U) of botulinum toxin type A (Botox, Allergan) injected intradermally in 20 sites in each palm. RESULTS: Following injection with either dose, iodine starch test revealed a significant decrease in sweating within the first month. Six months after injection, the anhidrotic effect was still evident in two thirds of the patients in both groups. Handgrip strength was not affected with either dose but finger pinch strength, 2 weeks after the injection, decreased 23 +/- 27% with 50 U (p < 0.05) and 40 +/- 21% with 100 U (p < 0.001). Pinch strength improved gradually but 6 months after treatment it was still 7-11% lower than at baseline. CONCLUSIONS: Both 50 and 100 U of botulinum toxin type A, injected intradermally in each hand, decreased sweating in patients with primary hyperhidrosis for at least 2 months in all the patients, and 6 months in most patients. Weakness in the intrinsic muscles of the hand was observed.     

Functional outcomes of multilevel botulinum toxin and comprehensive rehabilitation in cerebral palsy

The objective of this study was to measure the effect of lower extremity multilevel botulinum toxin A injections and comprehensive rehabilitation on spasticity and to determine the functional gains in ambulatory children with cerebral palsy. Sixteen ambulatory children with spastic cerebral palsy (9 hemiplegic, 7 diplegic), aged between 3 and 8 years, who were able to walk with or without assistance (Gross Motor Functional Classification System I-III) were recruited to the study. Botulinum toxin A injections were applied to a total of 23 extremities, followed by a comprehensive rehabilitation program. Walking distance and walking speed (evaluated by the Six-Minute Walk Test) were significantly improved after treatment. Similarly, scores on the Observational Gait Scale (assessed by video gait analysis) increased significantly. Improvements in muscle length, spasticity, and selectivity were recorded. Reduced muscle spasticity after botulinum toxin A injections in children with cerebral palsy, with a comprehensive rehabilitation program, enabled clinically relevant improvements in functional ability.     

Iatrogenic botulism due to therapeutic botulinum toxin a injection in a pediatric patient

Botulinum toxin A is commonly used to reduce spasticity and dystonia in children with cerebral palsy. We report a pediatric patient who developed systemic botulism as a result of a severe overdose of the injected toxin (40 U/kg). This case highlights the importance of physicians having adequate knowledge of primate and human literature on the lethal dose, 50% of botulinum toxin A before injecting children.     

Medium-term response characterisation and risk factor analysis of botulinum toxin type A in the management of spasticity in children with cerebral palsy

We prospectively studied the medium-term effects of botulinum toxin type A (BTX-A) treatment in 197 children with cerebral palsy. Between one and four target muscles were selected according to functional goals and biomechanical assessments, and were injected at multiple sites with BTX-A (BOTOX®). The mean total dose administered was 10.5 U BOTOX®/Vkg body weight. In 37% of treatment episodes, children were safely treated with high doses, 12–16 Ukg body weight. Significant improvements were seen in the Modified Ashworth and Tardieu scales at 3 and 12 weeks post-injection, and in muscle length, as determined by joint range of motion, at 3,12 and 24 weeks post-treatment. Significant improvements in gait were noted using the Modified Physicians' Rating Scale, and joint kinematics and kinetics. Forty-five per cent of children were subsequently managed by repeated BTX-A injections, 17% proceeded to single-level soft tissue surgery and 38% proceeded to multi-level surgery after mean intervals of 12.8, 16.4 and 173 months, respectively. Side effects were noted in 10 children (6.2% of total treatment occasions) and included local pain (1.2%), bruising (0.7%), temporary generalised weakness (0.3%), temporary incontinence (1.2%) and pneumonia (1.2%). In summary, BTX-A was safe and effective in the management of spasticity in children with cerebral palsy. Side effects were infrequent, usually minor and self-limiting.     

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.     

Botulinum toxin treatment of sialorrhea: comparing different therapeutic preparations

In recent years, a number of potential new therapeutic indications of botulinum toxin injections have emerged, amongst which sialorrhea has attracted considerable attention. Based on open‐label and controlled studies, botulinum toxin can be used to improve sialorrhea in patients with Parkinson's disease, parkinsonian syndromes, motor neuron disease and cerebral palsy. The toxin can be injected blindly based on anatomic landmarks of the salivary glands, or localization can be facilitated by use of ultrasound guidance. There are few reported adverse effects. However, many more carefully designed, controlled studies are still required to address the specific questions related to selection of patients, the optimal injection technique, the appropriate dose of botulinum toxin and its long‐term effects.     

Use of three‐dimensional kinematic analysis following upper limb botulinum toxin A for children with hemiplegia

Background and purpose: To examine whether three‐dimensional (3‐D) kinematic analysis can detect changes in upper limb tasks (reach and hand‐to‐mouth) in children with hemiplegia, following upper limb botulinum toxin A injections. Methods: Ten children with hemiplegic cerebral palsy (7 males, 3 females, aged 9–17 years). Subjects received botulinum toxin A (Botox) injections into elbow forearm muscles combined with 6 weeks of occupational therapy. Participants completed a 3‐D kinematic analysis of two upper limb tasks, Melbourne Assessment of Unilateral Upper Limb Function and modified Ashworth scores measured at baseline, 2, 6 and 12 weeks post‐injection. Results: Post‐injections, elbow flexor muscle tone was reduced for 12 weeks (p < 0.05). Group differences in active range of motion during 3‐D analysis tasks could not be demonstrated at any time post‐intervention. However, individual analyses found that at 2 weeks post‐injection, three subjects had >15 degrees increases in active elbow extension and six subjects showed an increase of >25 degrees in forearm supination during performance of the reach and hand‐to‐mouth tasks, respectively. Conclusions: 3‐D kinematics can detect changes in active movements during functional tasks following botulinum toxin A injections, suggesting this could be a potential objective outcome measure in a clinical trial.     

Low-dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation

OBJECTIVE: To investigate the efficacy of low dose of botulinum toxin type A (BTX-A) for facial synkinesis and hyperlacrimation. MATERIAL AND METHODS: Eleven patients suffering from facial synkinesis after Bell's palsy or facial nerve injury were treated with a low dose of BTX-A, 0.5-1.25 U per point into several points. One patient showing hyperlacrimation was also treated with BTX-A. The whole observational period was 43 months. RESULTS: On average, 5.76 U of BTX-A, which was lower than that of previous reports, was injected per treatment. In seven cases, synkinesis disappeared completely after three or fewer sessions of BTX-A injection. The mean interval between treatments was 14.5 weeks. Hyperlacrimation was completely suppressed after a single subcutaneous injection of BTX-A. Only mild subcutaneous hemorrhage was observed as adverse reactions. CONCLUSION: Facial synkinesis can be treated with a lower dose of BTX-A without relevant adverse reactions.     

Botulinum toxin a injections to the upper limbs in children with cerebral palsy: duration of effect

We report our experience on the duration of effectiveness of botulinum toxin A injections to the upper extremities of children with cerebral palsy. A retrospective chart review was conducted on 30 consecutive patients (mean age, 9.9 ± 5.0 years) with spastic hemiparesis and quadriparesis. They received 1 to 5 treatments, totaling 56 treatments for the entire cohort. The injected muscles were the pronator teres (50/56), flexor carpi radialis (39/56), biceps (38/56), flexor carpi ulnaris (35/56), opponens (21/56), and adductor pollicis (17/56). Children were assessed for muscle tone and classified according to the Manual Ability Classification System before and after treatment. Functional improvement was apparent after 42 of 56 treatments, and muscle tone decreased significantly (P < .001). The mean duration of the effect was 7.0 ± 3.0 months. We conclude that the effect of botulinum toxin A to the upper limbs is retained for longer periods of time than those reported for lower limbs.     

Can we identify predictors of multilevel botulinum toxin A injections in children with cerebral palsy who walk with a flexed knee pattern?

This study evaluates whether the literature-reported potential predictors can predict the outcome of multilevel botulinum toxin A injections in children who walk with flexed knees. The associations between 11 different predictors and 2 different outcome measures (the Gross Motor Function Measure and knee angle at midstance) at different weeks of follow-up were studied in 46 children with cerebral palsy (age 4-12 years), using regression analysis. Only age was positively associated with change in the Gross Motor Function Measure at 12 weeks, and only ankle angle at midstance was positively associated with change in knee angle at midstance at 48 weeks. Of these, only the former association was found to be clinically relevant. CONCLUSION: The majority of potential predictors do not predict the outcome of multilevel botulinum toxin A injections in this patient group. The only relevant significant predictor, with regard to gross motor function, is older age.