Effect of Botulinum Toxin Injection on the Progression of Hip Dislocation in Patients with Spastic Cerebral Palsy: A Pilot Study

Hip adductor spasticity is a contributing factor to hip dislocation in patients with cerebral palsy (CP). We hypothesized that botulinum toxin injected into the hip adductor muscles would reduce spasticity and help prevent hip dislocation. Twenty patients with bilateral spastic CP aged 2 to 10 years with gross motor function classification system level IV or V were included. Botulinum toxin was injected into the hip adductor muscles at baseline and at 6-month follow-up. Muscle tone was measured with an eight-channel surface electromyography (EMG) recorder. A hip X-ray was performed, and Reimer’s hip migration index (MI) was measured. The Wilcoxon signed-rank test was used to compare the surface EMG values of the hip muscles at baseline and follow-up. The mean root mean square surface EMG value of the hip adductor muscles was significantly reduced at 1, 2, 3, and 7 months after the first injection, up to approximately 53% of the baseline. The 1-year progression of the hip MI was −0.04%. Repeated sessions of botulinum toxin injections at the hip adductor muscles significantly reduced muscle tone and hip displacement. A botulinum toxin injection may be used as an adjunctive treatment in the prevention of hip dislocation.     

Botulinum toxin treatment of adult spasticity : a benefit-risk assessment.

Injections of botulinum toxin have revolutionised the treatment of focal spasticity. Before their advent, the medical treatment for focal spasticity involved oral anti-spasticity drugs, which had decidedly non-focal adverse effects, and phenol injections. Phenol injections could be difficult to perform, could cause sensory complications and had effects that were of uncertain duration and magnitude. Furthermore, few neurologists knew how to perform them as they were mostly the province of rehabilitation specialists. Botulinum toxin can produce focal, controllable muscle weakness of predictable duration, without sensory adverse effects.Randomised clinical trials (RCTs) involving patients with spasticity resulting from a variety of diseases (mainly stroke and multiple sclerosis) have clearly shown that botulinum toxin type A (Dysport and Botox) can temporarily (for approximately 3 months) reduce spastic hypertonia in the elbow, wrist and finger flexors of the upper limbs, and the hip adductors and ankle plantar flexors in the lower limbs. The clinical benefits from this reduction of neurological impairment are best shown in the upper limb, with less disability of passive function and reduced caregiver burden. In the lower limbs, there is improved perineal hygiene from hip adductor injections. The benefits of reducing ankle plantar flexor tone are less well established. Pain is also reduced, possibly by mechanisms other than muscle weakness. Improved active function has not yet been clearly demonstrated in RCTs, only in open-label trials. The safety of botulinum toxin-A is impressive, with minimal (mainly local) adverse effects.There are little data on the use of botulinum toxin type B (Myobloc or Neurobloc) in spasticity and the only RCT that has examined this did not show tone reduction; dry mouth appeared to be a very common adverse effect. There are also very little data to allow a benefit-risk comparison of phenol and botulinum toxin injections; each have their clinical and technical advantages and disadvantages, and phenol is much less costly than botulinum toxin.     

Botulinum toxin type A for migraine. First, do no harm

Headache prevention in adults with chronic migraine is based first on oral drug therapy, preferably with propranolol, and on tapering off possible analgesic overuse. Botulinum toxin type A injections in head and neck muscles is now authorised for this purpose in the United Kingdom. It has been used off label for several years. Clinical evaluation in this indication is based on two placebo-controlled double-blind trials with identical designs. A total of 1384 patients underwent two sessions of intramuscular injections of botulinum toxin type A or placebo, 3 months apart, into at least 31 specific sites in the head and neck. Compared to baseline, patients who received botulinum toxin in one trial (but not in the other) experienced a statistically significant reduction in headache frequency at the end of the study, but the results are undermined by methodological issues. Botulinum toxin type A has not been compared with preventive oral therapy. An inherently unreliable indirect comparison suggests that botulinum toxin type A is clearly less effective than oral propranolol. In its other approved indications, botulinum toxin type A has been linked to deaths and muscle paralysis distant from the injection site, leading to swallowing difficulties and respiratory disorders. Some patients enrolled in clinical trials of botulinum toxin type A experienced transient worsening of their migraine and headache (9.3%, versus 5.8% of patients receiving placebo injections), exaggerated paralytic effects, and muscle pain and stiffness. In practice, given its uncertain efficacy, at best only modest, botulinum toxin type A is simply too risky a treatment for migraine. It is better to focus on fine tuning of standard prophylaxis.     

Alternative use of botulinum toxin in urology

Botulinum toxin A is used in the treatment of lower urinary tract symptoms due to detrusor sphincter dysynergia and detrusor hyper-reflexia (neurogenic detrusor deficiency). The toxin acts by producing paralysis of muscle tissue and has been shown to be safe and effective in the treatment of conditions caused by increased muscle tonicity and spasticity. Here the literature is reviewed chronologically, the established and emerging indications for the urological use of botulinum toxin evaluated and future applications are also considered.     

Alternative use of botulinum toxin in urology

Botulinum toxin A is used in the treatment of lower urinary tract symptoms due to detrusor sphincter dysynergia and detrusor hyper-reflexia (neurogenic detrusor deficiency). The toxin acts by producing paralysis of muscle tissue and has been shown to be safe and effective in the treatment of conditions caused by increased muscle tonicity and spasticity. Here the literature is reviewed chronologically, the established and emerging indications for the urological use of botulinum toxin evaluated and future applications are also considered.     

Electrical Stimulation of Injected Muscles to Boost Botulinum Toxin Effect on Spasticity: Rationale,Systematic Review and State of the Art

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms “electric stimulation”, “muscle spasticity” and “botulinum toxins” and strings “electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A” was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake.     

Ergonomic Recommendations in Ultrasound-Guided Botulinum Neurotoxin Chemodenervation for Spasticity: An International Expert Group Opinion

Ultrasound (US)-guided botulinum neurotoxin (BoNT) injections are becoming a mainstay in the treatment of muscle spasticity in upper motor neuron syndromes. As a result, there has been a commensurate increase in US-guided BoNT injection for spasticity training courses. However, many of these courses do not emphasize the importance of ergonomics. This paper aims to highlight the importance of ultrasound ergonomics and presents ergonomic recommendations to optimize US-guided BoNT injection techniques in spasticity management. Expert consensus opinion of 11 physicians (4 different continents; representing 8 countries, with an average of 12.6 years of practice using US guidance for BoNT chemodenervation (range 3 to 22 years)). A search using PubMed, College of Physicians and Surgeons of British Columbia database, EMbase was conducted and found no publications relating the importance of ergonomics in US-guided chemodenervation. Therefore, recommendations and consensus discussions were generated from the distribution of a 20-question survey to a panel of 11 ultrasound experts. All 11 surveyed physicians considered ergonomics to be important in reducing physician injury. There was complete agreement that physician positioning was important; 91% agreement that patient positioning was important; and 82% that ultrasound machine positioning was important. Factors that did not reach our 80% threshold for consensus were further discussed. Four categories were identified as being important when implementing ultrasound ergonomics for BoNT chemodenervation for spasticity; workstation, physician, patient and visual ergonomics. Optimizing ergonomics is paramount when performing US-guided BoNT chemodenervation for spasticity management. This includes proper preparation of the workspace and allowing for sufficient pre-injection time to optimally position both the patient and the physician. Lack of awareness of ergonomics for US-guided BoNT chemodenervation for spasticity may lead to suboptimal patient outcomes, increase work-related injuries, and patient discomfort. We propose key elements for optimal positioning of physicians and patients, as well as the optimal setup of the workspace and provide clinical pearls in visual identification of spastic muscles for chemodenervation.     

康复训练结合药物治疗儿童脑瘫的疗效观察

目的：探讨A型肉毒毒素辅助治疗儿童脑瘫的临床价值。方法：将86例双下肢痉挛脑瘫患儿随机分为两组：对照组43例,采用Vojta训练治疗;实验组43例,采用Vojta训练与肌肉注射A型肉毒毒素治疗。观察比较两组患儿的痉挛状况、运动功能及日常生活活动能力。结果：实验组治疗后的综合痉挛评分明显低于对照组（P〈0．05）,实验组治疗后的粗大运动功能D区、E区分值均明显高于对照组（P〈0．05）,实验组治疗后的日常生活活动能力评分明显高于对照组（P〈0．05）。结论：A型肉毒毒素能有效缓解脑瘫患儿的肢体肌肉痉挛,促进运动功能恢复。     

电刺激定位引导埋线治疗脑瘫患儿小腿三头肌痉挛的疗效观察

目的观察电刺激定位引导埋线治疗脑瘫患儿小腿三头肌痉挛的疗效。方法将18例脑瘫患儿随机分为电刺激定位引导埋线组（埋线组）和电刺激定位引导A型肉毒毒素（BTX．A）注射组（肉毒素组）,观察治疗1月后患儿的踝背屈曲度、综合痉挛量表CSS评分、改良Ashworth法评分。结果肉毒素和埋线治疗1月后患儿踝背屈曲度、综合痉挛量表CSS评分、改良Ashworth法评分均有明显改善（P〈0．05）,埋线组对患儿踝背屈曲度的改善弱于肉毒素组（P〈0．05）,但综合痉挛量表CSS评分、改良Ashworth法评分与肉毒素组比较差异无统计意义（P〉0．05）。结论电刺激定位引导埋线治疗脑瘫患儿小腿三头肌痉挛有较好的临床疗效。     

Potential of Botulinum toxin A to treat upper extremity spasticity in children with cerebral palsy

Abstract

Botulinum toxin type A has been used extensively to treat spasticity in children with cerebral palsy. Although the effectiveness of the toxin in the lower limbs is well established, its effectiveness in upper limbs has not been proved yet. Many studies published so far report conflicting results in terms of spasticity, function, activity and participation improvement. The scope of this review is to present the evidence from published studies, focusing on the effectiveness and the safety of botulinum toxin A.     

Unlabeled uses of botulinum toxins: a review, part 1.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.     

Unlabeled uses of botulinum toxins: a review, part 2.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.     

Management of spasticity in stroke

Spasticity treatment must be considered in relation to other impairments with functional goals defined prior to intervention. The effects of muscle co-contraction and involuntary limb movement associated with exaggerated cutaneous reflexes or effort as well as stretch reflex hyperexcitability need to be considered. Exacerbating factors such as pain must be identified. Physical therapy and conventional orthoses are the mainstays of spasticity management during acute rehabilitation. Botulinum toxin shows promise but needs further evaluation in the context of acute rehabilitation. Phenol chemodenervation can produce good results in spasticity refractory to standard treatments. Muscle strengthening exercises may be appropriate in chronic hemiparesis without adversely affecting tone. Electrical stimulation may be a useful adjunct to other spasticity treatments. Difficulty demonstrating functional benefit from antispasticity treatment may imply that interventions directed at single motor impairments whether weakness or spasticity are not likely to result in functional benefit, but it is their combination that is important.     

Botulinum toxin type A and dynamic equinus in children with cerebral palsy: new indication. Better than repeat casts

(1) Botox degrees , a product based on type A botulinum toxin, has received a new licensed indication in the local treatment of dynamic equinus in children with spasticity due to cerebral palsy. (2) Three placebo-controlled trials show that intramuscular injections of type A botulinum toxin reduce spastic equinus and substantially improve walking for at least 3 months. Two small trials, each involving 20 children, show no difference in effects between type A botulinum toxin and successive stretching casts. (3) In this setting the risk of adverse effects is smaller with type A botulinum toxin than with stretching casts. (4) Treatment with type A botulinum toxin is costly.     

A型肉毒毒素治疗脑中风和脑外伤后下肢痉挛的临床研究

目的　探讨A型肉毒毒素 (botulinumtoxinA ,BTXa)能否有效、安全地治疗下肢肌痉挛 ,改善步行能力及步行速度。方法　 2 7例中风、脑外伤患者 ,选择下肢肌肉局部注射国产BTXa。每个病人每次选择 3～ 5块肌肉 ,每块肌肉总的注射剂量介于 5 0～ 10 0U ,每次病人接受的注射总量小于或等于 40 0U。所有病人同时接受步态训练等康复治疗。注射前、注射后 2、4wk按改良式Ashworth量表 (ModifiedAsh worthScale ,MAS)评定肌张力 ,足印分析法 (footprintanaly sis)测量并记录步行时的时间距离参数的变化 ,研究各肌群肌张力变化与步态参数的关系。结果　整体比较 ,注射后 2wk(股直肌除外 )、4wk与注射前相比 ,各肌群肌张力降低 ,差异有显著性 (P <0 0 5 ) ,步态时间距离参数值 (T D值 )除步角外 ,各参数均有不同程度改善 (P <0 0 1或 <0 0 5 )。注射前与注射后 4wk比较 ,步长、步宽、步速差异均有显著性(P <0 0 5 )。注射后 2wk与 4wk比较 ,步长、步速有改善(P <0 0 5 )而步宽、步角变化不大。spearman相关分析表明各肌群肌张力降低与步长具有较好的相关性。结论　BTXa下肢肌肉局部注射结合步态训练 ,可以明显改善中风、脑外伤的痉挛步态 ,由此显示局部的化学去神经方法与康复训练相结合 ,可以使特定的功能改?     

Tetanus: Pathophysiology,Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection.     

A型肉毒毒素在治疗颈源性头痛中的临床应用

颈源性头痛是指由颈椎或颈部软组织的器质性或功能性病损所引起的一种慢性痛。目前,临床上有多种治疗方式,但无法将其治愈。A型肉毒毒素是肉毒梭菌分泌的一种细胞外毒素,具有嗜神经性,且毒力最强。A型肉毒毒素通过解除肌痉挛,抑制中枢和外周敏化和抗炎机制来治疗颈源性头痛,疗效确切,安全性高。本文通过阐述A型肉毒毒素治疗颈源性头痛的机制和用法,旨在为其在颈源性头痛治疗中的应用提供进一步的临床指导。     

Post Hoc Subgroup Analysis of the BCause Study Assessing the Effect of AbobotulinumtoxinA on Post-Stroke Shoulder Pain in Adults

AbstractBotulinum toxin type A is approved for the focal treatment of spasticity; however, the effectiveness of abobotulinumtoxinA (aboBoNT-A) in patients with shoulder pain who have set reduced pain as a treatment goal is understudied. In addition, some patients encounter delays in accessing treatment programs; therefore, the suitability of aboBoNT-A for pain reduction in this population requires investigation. These factors were assessed in aboBoNT-A-naive Brazilian patients in a post hoc analysis of data from BCause, an observational, multicenter, prospective study ({"type":"clinical-trial","attrs":{"text":"NCT02390206","term_id":"NCT02390206"}}NCT02390206). Patients (N = 49, n = 25 female; mean (standard deviation) age of 60.3 (9.1) years; median (range) time since onset of spasticity of 16.1 (0–193) months) received aboBoNT-A injections to shoulder muscles in one or two treatment cycles (n = 47). Using goal attainment scaling (GAS), most patients achieved their goal of shoulder pain reduction after one treatment cycle (72.1%; 95% confidence interval: 57.2–83.4%). Improvements in GAS T-score from baseline, clinically meaningful reductions in pain score at movement, and clinically meaningful increases in passive shoulder abduction angle further improved with repeated treatment more than 4 months later, despite treatment starting at a median of 16.1 months after the onset of spasticity. These findings support the further investigation of aboBoNT-A injections in chronic post-stroke shoulder pain.Plain Language SummaryAfter a stroke, patients often experience shoulder pain, which can lead to difficulty with arm movement and interfere with their rehabilitation. Some patients also experience difficulty or delays in receiving treatment. Botulinum toxin injections can be used to improve muscle pain and function. The BCause trial looked at how one or two doses of a specific type of botulinum toxin injection, called abobotulinumtoxinA (aboBoNT-A), into shoulder muscles could help patients with shoulder pain following a stroke. This analysis of the BCause trial included 49 Brazilian patients aged 18–80 years who had suffered a stroke in the previous year and who set reduced shoulder pain as a goal of their treatment. They had not previously received any botulinum toxin injections. The researchers looked at how helpful the injections were by using a scale that measured how well each patient achieved their treatment goal. Additionally, researchers measured pain levels, muscle tone, range of shoulder movement, and quality of life before and after treatment. The results showed that aboBoNT-A injections helped most patients to reach their goal of reduced shoulder pain. Patients receiving repeated aboBoNT-A injections experienced further improvements in how much they could move their shoulder after more than 4 months compared with at the start of the study. Patients’ and caregivers’ quality of life was also improved after treatment compared with before. The researchers considered these results to be clinically meaningful—that is, the improvements with aboBoNT-A were likely to provide a real benefit for patients, caregivers, and clinicians.     

Botulinum toxin A treatment of adult upper and lower limb spasticity

This article discusses the treatment of spasticity with botulinum toxin A as a new approach in the neurological rehabilitation of patients after stroke. Clinical studies have been reviewed to provide information about target groups, technical aspects and the advantages and disadvantages of treating spasticity with botulinum toxin A. Open and controlled studies showed that the intramuscular injection of Dysport 500 to 1,500U or Botox 100 to 300U could reversibly relieve upper limb flexor and lower limb extensor spasticity. A reduced muscle tone, pain relief, better hand hygiene and improved walking function were the main benefits. Patients tolerated the treatment well. Activity or, if not possible, electrical stimulation of the injected muscles may enhance the effectiveness of the costly toxin. Serial casting is another option. With respect to the action of botulinum toxin A, it is suggested that the effect of the toxin could be mediated by paresis of both the extrafusal and intrafusal muscle fibres, thereby altering the afferent discharge in the muscle.