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.     

Botulinum toxin: from spasticity reliever to a neuromotor re-learning tool

Botulinum toxin is becoming increasingly popular as the drug of choice for relief of spasticity in a wide range of conditions, from stroke to strabismus to vaginismus. Besides this role as spasticity reliever, several recent clinical reports claim that in stroke, cerebral palsy, spinal cord injury (SCI), and dystonias, BoTx brings about significant improvement in function--attributed to synaptic plasticity of the muscular afferents. The authors' research had shown that BoTx also generates synaptic plasticity in spinal alpha-motoneurons-interneurons. The article describes how BoTx facilitates relearning by Hebbian and Contrastive Hebbian modes and how it can be used as a neuro-relearning tool to enhance and hasten motor recovery in the aforementioned disorders.     

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.     

Treatment of cerebral palsy with botulinum toxin A: Functional benefit and reduction of disability. Three case reports

Three patients with cerebral palsy are described suffering, respectively, of pes equinus, spasm of the m. teres major and flexion spasm of the hand, who were treated with botulinum toxin A. These patients demonstrate not only the local reduction of the muscular hyperactivity following treatment with botulinum toxin A but also the potential functional benefit resulting from such a treatment. Thus, local intramuscular injection of botulinum toxin A in children with cerebral palsy should be considered as part of a multidisciplinary treatment concept, since reduction of the disability and the functional improvements could have high impact on daily living activities.     

Actualités et perspectives dans la prise en charge de l’hémiplégie cérébrale infantile en médecine physique et de réadaptation

Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 living births, it is the most common form of cerebral palsy among children born at term and the second most common type among preterm infants. Precocity of care at observation of the first symptoms allows preventing orthopaedic disorders and furthermore the installation of pathological patterns. Before any therapeutic intervention, it is necessary to evaluate the lower and upper limb function by means of reliable, valid and reproducible tools. This helps define precise and mutual objectives for child and family as well as therapists, therefore allowing an objective evaluation of the results. This principle applies as much in fundamental techniques (physiotherapy, occupational therapy, psychomotricity, orthesis…) as in more recent developments such as botulinum toxin, exercise programs, constraint-induced therapy, motor mental imagery or virtual reality. These recent therapies present, at various degrees, scientific evidence of their efficiency in the improvement of limb function and are now an integral part of the usual care of children with hemiplegic cerebral palsy.     

ASSESSMENT OF LINEAR GROWTH OF CHILDREN WITH CEREBRAL PALSY: USE OF ALTERNATIVE MEASURES TO HEIGHT OR LENGTH

Various linear measurements were made of 100 children with cerebral palsy to evaluate the effects of various factors on growth, and to investigate the use of alternative measurements to height or recumbent length. Linear growth was more retarded in children with spastic quadriplegia than in those with less widespread spasticity, and there was a tendency for the older children to be more growth-retarded. Upper-arm and lower-leg lengths provided useful information about linear growth. Growth charts using these alternative measurements have been developed which can be used to assess linear growth of children with cerebral palsy when it is difficult or impossible to measure height or recumbent length because of joint contractures. These charts should improve the assessment of the nutritional status of children with cerebral palsy.     

CBTX-A治疗痉挛性脑性瘫痪临床研究

目的研究国产A型肉毒毒素(CBTX-A)局部注射治疗小儿痉挛性脑瘫的疗效,副作用。方法选择1000例痉挛性小儿脑性瘫痪患儿,以每组肌肉2.5U/kg用量进行痉挛肌肉局部注射。应用PRS(physicianratingscale)法比较治疗前及治疗后1个月时运动姿势的改善情况。观察治疗中及治疗后的副作用。结果绝大多数患儿治疗后其PRS疗效指标均有不同程度的改善,其有效率为99.7%,P<0.01。除5例(0.5%)注射后短期内患肢无力外,其他均无明显副作用发生。结论CBTX-A局部注射是一种安全、有效、方便灵活、较少副作用的治疗小儿痉挛性脑瘫的好方法。     

BOTULINUM TOXIN: FROM SPASTICITY RELIEVER TO A NEUROMOTOR RE-LEARNING TOOL

Botulinum toxin is becoming increasingly popular as the drug of choice for relief of spasticity in a wide range of conditions, from stroke to strabismus to vaginismus. Besides this role as spasticity reliever, several recent clinical reports claim that in stroke, cerebral palsy, spinal cord injury (SCI), and dystonias, BoTx brings about significant improvement in function—attributed to synaptic plasticity of the muscular afferents. The authors' research had shown that BoTx also generates synaptic plasticity in spinal alpha-motoneurons-interneurons. The article describes how BoTx facilitates relearning by Hebbian and Contrastive Hebbian modes and how it can be used as a neuro-relearning tool to enhance and hasten motor recovery in the aforementioned disorders.     

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.     

干细胞在脑性瘫痪治疗中的应用

背景：干细胞在适当条件下可以分化为神经元细胞、星形胶质细胞与少突胶质细胞，可能从根本上改善脑性瘫痪患儿神经元缺失及神经胶质细胞变性，进而改善患儿脑功能障碍，从理论上达到根治目的。 目的：回顾性分析不同来源干细胞经不同途径治疗脑性瘫痪患儿的疗效。 方法：由第一作者检索1992/2011 PubMed数据及万方数据库有关脑性瘫痪的治疗及不同来源干细胞在治疗脑性瘫痪等方面的文献。 结果与结论：神经干细胞在动物神经功能损伤中的修复作用已有很多国内外报道，但目前其在人体的临床应用仍处于临床试验阶段。虽然胚胎、骨髓血、胎儿脐带血、脐带来源的干细胞已在部分医院应用到脑性瘫痪患儿中，并取得了初步的疗效，其具体评定标准及长期疗效仍有待进一步随访、观察。     

Open-label study of botulinum toxin for upper limb spasticity in cerebral palsy

The objective of this study was to assess the efficacy of botulinum toxin for upper limb spasticity in cerebral palsy. An open-label study was conducted in 11 children with cerebral palsy. Post-botulinum toxin assessment was conducted in weeks 1, 4, and 16, with averaged scores being analyzed. The Clinical Global Impression Scale of the mothers showed marked, moderate, and mild improvement in five, four, and two cases, respectively. The Modified Ashworth Spasticity Scale score showed a statistically significant decrease in the mean spasticity score (P < .003). Other tests were performed depending on the cognition of the child. Increase in joint motion occurred in all five children assessed using web space (P = .043). For the Jebson Hand Function Test, improvement occurred in all five cases assessed (P < .03). Four of five (80%) children could perform tasks that they failed before they were given botulinum toxin. Botulinum toxin is useful in decreasing spasticity and improving the upper limb function of young children with cerebral palsy with normal cognition. Motivated families should be selected with a specific target of using botulinum toxin as an adjunct in a habilitation program.     

Sudden onset odontoid fracture caused by cervical instability in hypotonic cerebral palsy

Fractures of the upper cervical spine rarely occur but carry a high rate of mortality and neurological disabilities in children. Although odontoid fractures are commonly caused by high-impact injuries, cerebral palsy children with cervical instability have a risk of developing spinal fractures even from mild trauma. We herein present the first case of an odontoid fracture in a 4-year-old boy with cerebral palsy. He exhibited prominent cervical instability due to hypotonic cerebral palsy from infancy. He suddenly developed acute respiratory failure, which subsequently required mechanical ventilation. Neuroimaging clearly revealed a type-III odontoid fracture accompanied by anterior displacement with compression of the cervical spinal cord. Bone mineral density was prominently decreased probably due to his long-term bedridden status and poor nutritional condition. We subsequently performed posterior internal fixation surgically using an onlay bone graft, resulting in a dramatic improvement in his respiratory failure. To our knowledge, this is the first report of an odontoid fracture caused by cervical instability in hypotonic cerebral palsy. Since cervical instability and decreased bone mineral density are frequently associated with cerebral palsy, odontoid fractures should be cautiously examined in cases of sudden onset respiratory failure and aggravated weakness, especially in hypotonic cerebral palsy patients.     

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.     

Spectrum of Visual Disorders in a Population-Based Cerebral Palsy Cohort

BackgroundChildren with cerebral palsy are known to be at increased risk for visual impairment.MethodsIn a population-based sample drawn from a geographically defined registry, the profile of visual impairment in children with cerebral palsy was investigated.ResultsClose to half (49.8%; 106/213) had a visual impairment. The majority of these individuals had strabismus (55.7%; 59/106) and a slightly lesser fraction had refractive errors (20.7%; 22/106) or severe visual loss (18.9%; 20/106). The vast majority of children with severe visual loss had spastic quadriplegia (83%; 17/20) or were nonambulatory (i.e., Gross Motor Function Classification Scale IV/V, 80%; 16/20).ConclusionsKnowledge of this profile will assist practitioners to heighten their appreciation of potential visual disturbances in certain subsets of children with cerebral palsy.     

Botulinum toxin and cerebral palsy: time for reflection?

Botulinum toxin A (BTX-A) is increasingly being used in early management of spasticity in ambulant children with cerebral palsy (CP), with the aim of improving function, promoting muscle growth, and delaying the need for surgical intervention. However, there is a lack of evidence about the long-term outcome of BTX-A injections. The focus on spasticity as the predominant problem in younger children with spastic CP may not fully consider the associated muscle weakness. It also raises concern that although BTX-A may improve function in the short term, it has the potential to affect muscle growth and function adversely in the long term. A cautious approach to the early use of BTX-A, with the use of objective outcome measures within a specialized multidisciplinary setting, is recommended, particularly in ambulant children with spastic diplegic CP, until further evidence is available on the long-term outcome of early BTX-A injections in children with CP.     

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 for the treatment of the spastic equinus foot in cerebral palsy

Muscle overactivity, one of the cardinal features of spasticity, is a common sequel of cerebral palsy. In this group of patients spasticity is responsible for several limitations that interfere with gait, causing variable functional disability. Drugs such as baclofen, tizanidine, or benzodiazepines, or even definitive treatments such as orthopedics or neurosurgeries are generally prescribed with uncertain results. The use of botulinum toxin type A has been frequently suggested for the treatment of spastic equinus foot in cerebral palsy, but few studies with adequate methodology support this idea. The present paper reviews and summarizes the data of published double-blind, randomized clinical trials to assess, with a meta-analysis, if botulinum toxin type A is an adequate treatment for spasticity caused by cerebral palsy. The results reveal a statistical superiority of botulinum toxin type A over placebo on gait improvement, tested using the Physician Rating Scale and Video Gait Analysis (Peto odds ratio = 3.99, 95% confidence interval = 2.20-7.22) in patients with spastic equinus foot. The botulinum toxin group also presented better results in the subjective assessment than the placebo group (Peto odds ratio = 3.49, 95% confidence interval = 1.50-8.12). Adverse events were more frequently observed after the use of botulinum toxin type A, but they were considered mild and self-limited.     

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.     

Le facteur E et ses caractéristiques neurophysiologiques et motrices : sont-elles modulables chez les enfants avec une paralysie cérébrale ? Une revue de la littérature

Although the current definition of cerebral palsy requires us to make a classification of children based on their motor abilities, other associated disorders, such as perceptual disturbances, may be the source of the main problem of our patients. These perceptual disturbances include the "startle response", commonly known in France as "Factor E". This reaction is a sudden and involuntary movement characterized by an opening motor pattern, although other autonomous and emotional components may be present. As the "Factor E" can directly impact on the autonomy and activities of the daily lives of our patients, the following problem arises: What neurophysiological and motor characteristics of factor E allow it to be modulated in children with cerebral palsy? A literature review on seven different databases was performed, finding five articles that meet the eligibility criteria. In general, we can affirm that "Factor E" has a motor pattern which is similar to that of the startle reflex found in lambda subjects and that it is habituated which can be rapid in patients with cerebral palsy.     

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.