Botulinum toxin injection in patients with hereditary spastic paraparesis

In an open label study, we analyzed the efficacy of botulinum toxin injection at the lower limbs of patients with hereditary spastic paraparesis (HSP). Fifteen patients who showed disabling spasticity with no or poor effect of oral treatment were recruited consecutively. Botulinum toxin was injected (400 U; Botox^®) into the spastic muscles identified by clinical examination (equinus, varus, and pathological hip adduction). Patients were regularly assessed from the first day to the fifth month: spasticity (Ashworth), motor strength, range of movements, Functional Ambulation Categories (FAC), gait parameter, Rivermead Motor Assessment, self-analysis of benefit and satisfaction. We observed a moderate and significant ( P  < 0.05) reduction of ankle plantar flexor and hip adductor spasticity, with a partial increase in the range of the active and passive motion at the ankle and in gait velocity. At an individual level, six of 15 patients showed an increase in gait velocity. The FAC and RMA did not change. Patients often reported partial improvement in foot position and lower limb propulsion, and fair satisfaction. In conclusion, botulinum toxin injection can be effective in HSP patients with relatively ancient spasticity. This technique can be introduced into the therapeutic panel, which also includes physiotherapy, oral treatment and baclofen pump.     

Botulinum toxin for treatment of spasticity in adults

Although a few hundred papers have been published on the treatment of adult spasticity with botulinum toxin, the number of randomized placebo-controlled double-blind studies, by comparison, is relatively small. Criteria of highest evidence classes are met by the following observations: 1) Botulinum toxin improves motor functions (ability to walk and stand in the presence of spastic equinus deformity and knee flexor spasticity, upper-extremity movements). 2) Botulinum toxin makes attendance of spastic adults easier (personal hygiene in patients presenting with severe adductor spasticity; self-care and dressing in the presence of arm spasticity). 3) Early initiation of treatment with botulinum toxin yields better results than delayed institution (hemispasticity).     

Botulinum toxin for treatment of spasticity in adults

Although a few hundred papers have been published on the treatment of adult spasticity with botulinum toxin, the number of randomized placebo-controlled double-blind studies, by comparison, is relatively small. Criteria of highest evidence classes are met by the following observations: 1) Botulinum toxin improves motor functions (ability to walk and stand in the presence of spastic equinus deformity and knee flexor spasticity, upper-extremity movements). 2) Botulinum toxin makes attendance of spastic adults easier (personal hygiene in patients presenting with severe adductor spasticity; self-care and dressing in the presence of arm spasticity). 3) Early initiation of treatment with botulinum toxin yields better results than delayed institution (hemispasticity).

     

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.     

Management of spasticity with botulinum toxin type A: implementing the treatment algorithm

Intramuscular injections of botulinum toxin type A (BTX-A) may successfully treat spasticity resulting from focal muscle overactivity. However, BTX-A should not be considered as a monotherapy. Physical interventions such as strengthening programmes, range-of-motion exercises or serial casting should be implemented following BTX-A injections. The likelihood of treatment success relies heavily on tailoring the treatment protocol to an individual's needs. This paper presents five case studies which describe patient management problems that have been addressed by applying an algorithm for the management of spasticity with botulinum toxin type A. The case studies are representative of patients with hand, arm, hip, leg and/or foot spasticity who have received BTX-A injections. The potential pitfalls of BTX-A treatment are presented and possible reasons for treatment failure are discussed. The case studies highlight the importance of reassessing functional objectives for each individual after treatment. The objectives of BTX-A treatment vary considerably between patients. If the treatment goals are not achieved, modification of the injection procedure and/or dose may be required. A continued failure of treatment suggests either poor patient selection or inappropriate treatment goals. Successful treatment does not obviate the need for routine re-evaluation of the goals at treatment follow-up.     

Pharmacotherapy of spasticity in children with cerebral palsy

Spasticity is one of the most common symptoms presented by neurologic patients. Apart from surgical management, drug therapy is an important treatment of children suffering from spasticity. In this review, recent advances in the pharmacologic armamentarium are reported in detail. In particular, there are oral medications (benzodiazepines, baclofen, dantrolene sodium, alpha 2 adrenergic agonists) and parenteral medications (botulinum toxin type A and B, alcohol). Moreover, there is also baclofen that can be administered intrathecally. There are some reports supporting the use of intramuscular alcohol (45% and/or 5-7% phenol) to reduce spasticity without the loss of voluntary movement or loss of sensation. Among these drugs, intrathecal baclofen is one of the most effective substances that can reduce spasticity significantly in the upper and lower extremities. Finally, the effectiveness of therapy with botulinum toxin type A in the management of spasticity is analyzed. Botulinum toxin type A reduces hypertonia in the injected muscles for a period of 2 to 4 months without important side effects. The purpose of this article is to provide an overview of available oral and parenteral drugs for treatment of spasticity in cerebral palsy and to outline indications and contraindications.     

Functional improvement in cerebral palsy patients treated with botulinum toxin A injections – preliminary results

Authors report the preliminary results of an open-label, prospective study to evaluate a functional benefit of botulinum toxin type A injections in diparetic cerebral palsy patients, using gross motor function measure (GMFM) score. In a group of 14 children (mean age 3.9 years, range 2-6) treated with Dysport 30 IU/kg, a statistically significant improvement (P < 0.05) was noticed in both simple measurements (Modified Ashworth Scale, Selective Motor Control, Passive Range of Movements, Physician Rating Scale and parental Clinical Global Impression) and complex functions (GMFM dimensions D and E) after 1 and 3 months. However, the simple measurement scores decreased (but not to the baseline) after 3 months; surprisingly, GMFM scores were still increasing (7.7% change after 3 months and 11.3% change after 6 months in nine patients). These results are in concordance with a few other data published to date. The study may support the concept of persistent functional gain in long-term treatment of spasticity caused by cerebral palsy with botulinum toxin type A.     

Botulinum toxins: pharmacology and its current therapeutic evidence for use

Botulinum toxins are, as a group, among the most potent neuromuscular toxins known, yet they are clinically useful in the management of conditions associated with muscular and glandular over-activity. Botulinum toxins act by preventing release of acetylcholine into the neuromuscular junction. While botulinum toxin type A is commonly available, different manufacturers produce specific products, which are not directly interchangeable and should not be considered as generically equivalent formulations. Type B is also available in the market. Each formulation of botulinum toxin is unique with distinct dosing, efficacy and safety profiles for each use to which it is applied. Botulinum toxin type A is the treatment of choice based on its depth of evidence in dystonias and most other conditions. Botulinum toxin type A is established as useful in the management of spasticity, tremors, headache prophylaxis and several other neurological conditions. Active research is underway to determine the parameters for which the type B toxin can be used in these conditions, as covered in this review. Botulinum toxin use has spread to several fields of medicine.     

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.     

Botulinum toxin B treatment in children with spastic movement disorders: a pilot study

The treatment of adult and pediatric patients suffering from movement disorders with elevated muscle tone includes the application of focally denervating botulinum toxins. Dystonic movement disorders in adult patients have been treated successfully using botulinum toxin type B (NeuroBloc). Thus far, there has been no systematic treatment of children with botulinum toxin type B. This study reports on the treatment of 29 children with spastic or dystonic movement disorders using botulinum toxin type B in an open-label pilot study. Sixty-two treatment sessions were performed. In 33 of these sessions, the therapy goal that had been defined before intervention was attained or surpassed. Seventeen nonresponders to botulinum toxin type A were also included in the treatment, 11 of whom attained the therapy goal. Side effects were observed in 24% of all treatments, dry mouth being the most frequent (10%), in some cases having a desirable clinical effect. With this preliminary data as a basis, we recommend a maximum dose for children of 400 U botulinum toxin type B per kg body weight, which should not exceed a total of 10,000 U botulinum toxin type B.     

Análisis descriptivo de coste de tratamiento de la espasticidad con diferentes tipos de toxina botulínica A,a lo largo de un año

IntroductionBotulinum toxin A is the first-line treatment for localised spasticity. However, the economic impact of this treatment is not fully known.This study aimed to describe the real costs of botulinum toxin A for the treatment of adult patients with spasticity at a spasticity clinic pertaining to a rehabilitation service, over a period of one year.MethodsWe retrospectively reviewed all medical procedures carried out during the year 2017. We collected data on the type of toxin used (incobotulinumtoxin A, onabotulinumtoxin A, or AAbobotulinumtoxin A), the number of units injected, the anatomical region, and the time elapsed between infiltrations. The costs of medication and indirect costs, such as staff and consumables, were also calculated.ResultsThis is the first study to describe the real costs of botulinum toxin treatment of spasticity in adult patients in Spain. In 2017, 510 infiltration procedures were performed in 164 patients. The total cost of treating spasticity in our service was €116 789.70. The mean annual cost per patient was €603.64 for onabotulinumtoxin A, €642.69 for abobotulinumtoxin A, and €707.59 for incobotulinumtoxin A.ConclusionsOur economic study of real clinical practice is consistent with the theoretical models published in the literature. The different characteristics of each toxin and the inability to establish an equivalence between the units of each drug prevents us from directly comparing these costs.     

The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences.

The increasing use of botulinum toxin type-A, especially for focal dystonia and spasticity has highlighted the issue of secondary non-responsiveness. Within the last few years botulinum toxin type-B (Myobloc/Neurobloc) has become commercially available as an alternative to type-A. This paper discusses our initial experience of botulinum toxin type-B in a total of 63 individuals who attended our botulinum clinic. Thirty-six patients had cervical dystonia and a secondary non-response to type-A toxin. Thirteen of these patients (36%) had a reasonable clinical response to Neurobloc and continue to have injections. The other 23 patients either had no response, or a poor response, or had unacceptable side effects and ceased treatment. A small number of people with blepharospasm, hemifacial spasm and foot dystonia also had a disappointing response to injection. Twenty patients with spasticity were also type-A resistant. Seven of these show some continuing response to type-B, without unacceptable side effects. These findings demonstrate that botulinum toxin type-B has a place in the management of patients who have become non-responsive to type-A, but overall the responses to type-B toxin were disappointing.     

Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review

Over the last several years, botulinum toxin type A has gained widespread use for the management of focal spasticity in children with cerebral palsy. To assess the current patterns of botulinum toxin type A use in the clinical setting, the dose, muscles injected, age at injection, and interval between injections of botulinum toxin type A treatments were examined in a retrospective chart review of children with cerebral palsy (N = 270) over a 2-year period at three major treatment centers. The average dose of botulinum toxin type A across the three centers ranged from 7.7 to 10.8 U/kg body weight, and the average total amount of botulinum toxin type A injected at a single visit ranged from 154 to 205 U. The majority of botulinum toxin type A injections were to the muscles to the lower limbs. The average age at first injection was 6.2 years, and the average interval between injections ranged from 134 to 199 days.     

Clinical utility of botulinum toxin in the treatment of cerebral palsy: comprehensive review

The physical properties, mechanism of action, and clinical evidence supporting the use of botulinum toxin in the management of spasticity in cerebral palsy are discussed. Assessment methods, patient selection criteria, and methodology for preparation and administration of botulinum toxin are discussed in detail and a treatment algorithm based on the cumulative experience of the author is provided. Botulinum toxin type A is well tolerated, safe, and effective in the treatment of patients with spastic cerebral palsy. Appropriate patient selection is imperative. Treatment goals need to be well defined and tailored to the individual patient's needs. Growth and development is a continuous and evolving process, necessitating the constant reassessment of the patient and modification of future treatment goals. The ultimate success of management in cerebral palsy is dependent on the development of a comprehensive spasticity team with complementing skills who, together, can significantly improve the quality of life of these patients.     

Expanding use of botulinum toxin

Botulinum toxin type A (BTX-A) is best known to neurologists as a treatment for neuromuscular conditions such as dystonias and spasticity and has recently been publicized for the management of facial wrinkles. The property that makes botulinum toxin type A useful for these various conditions is the inhibition of acetylcholine release at the neuromuscular junction. Although botulinum toxin types A and B (BTX-A and BTX-B) continue to find new uses in neuromuscular conditions involving the somatic nervous system, it has also been recognized that the effects of these medications are not confined to cholinergic neurons at the neuromuscular junction. Acceptors for BTX-A and BTX-B are also found on autonomic nerve terminals, where they inhibit acetylcholine release at glands and smooth muscle. This observation led to trials of botulinum neurotoxins in various conditions involving autonomic innervation. The article reviews the emerging use of botulinum neurotoxins in these and selected other conditions, including sialorrhea, primary focal hyperhidrosis, pathological pain and primary headache disorders that may be of interest to neurologists and related specialists.     

Impact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomised double blind placebo controlled trial

OBJECTIVES: After stroke, abnormal arm posture due to spasticity in a functionally useless arm may interfere with self care tasks. In these patients botulinum toxin treatment presents an opportunity to reduce disability. The purpose was to investigate whether reduction in spasticity after botulinum toxin treatment translates into reduction in disability and carer burden. METHODS: Forty patients with stroke with spasticity in a functionally useless arm (median duration 3.1 years) were randomised to receive intramuscular botulinum toxin type A (BT-A; Dysport) (n=20) or placebo (n=20) in a total dose of 1000 MU divided between elbow, wrist, and finger flexors. Spasticity (using the modified Ashworth scale), muscle power, joint movement, and pain were assessed. Disability and carer burden were measured using an eight item and a four item scale respectively. Two baseline and three post-treatment assessments (weeks 2, 6, and 12) were made. Concurrent treatments as far as possible remained unchanged and not optimised. RESULTS: Disability improved at week 6 with BT-A compared with placebo. This effect, present at week 2, wore off by week 12. Reduction in carer burden was seen at week 6 with BT-A and continued for at least 12 weeks. Forearm flexor spasticity was reduced with BT-A up to 12 weeks after treatment. Although significant improvement in elbow flexor spasticity was seen at week 2 with BT-A compared with placebo, this effect was not evident at weeks 6 and 12. Arm pain was not improved after BT-A. Grip strength was reduced with BT-A. No serious BT-A related adverse effects were reported. CONCLUSION: BT-A is useful for treating patients with stroke who have self care difficulties due to arm spasticity. The decision to treat should also include relief of carer burden. As muscle weakness may occur, its potential impact on functional activities must be assessed before intervention.     

Spasticity-induced Pectoralis minor syndrome: a case-report

ABSTRACT

Background

Pectoralis minor syndrome (PMS) develops when the neurovascular bundle compression occurs at the retropectoralis minor space. It may occur due to repetitive overhead activities, traumatic incident, structural causes, myofascial pain syndrome in the pectoralis minor muscle, as well as spasticity of the pectoralis minor muscle. In patients with hemiplegia, adductor muscles along with pectoralis minor muscle spasticity may be present in the upper extremity.Objective: We report a 19-year-old male patient with spastic hemiparesis who was diagnosed with PMS due to spasticity of the pectoralis minor muscle.Method: Diagnosis of PMS was confirmed by Ultrasound-guided 4 cc 1% lidocaine injection to the right pectoralis minor muscle and Ultrasound-guided onabotulinum toxin A injection was performed. Stretching exercises to the pectoral muscles were also added to the rehabilitation program.Result: Complaints of the patient were controlled by botulinum toxin injections at 3-month intervals.Conclusion: It should be kept in mind that spasticity in the upper extremity may develop in the pectoralis minor muscle, and may cause pressure on the neurovascular structures. Ultrasound-guided botulinum toxin injections can be a safe and effective treatment for PMS in a patent with post stroke spastic hemiparesis.     

Safety of high-dose botulinum toxin type A therapy for the treatment of pediatric spasticity

This retrospective chart review examines the safety of high-dose (> or = 15 U/kg body weight or > or = 800 total units) botulinum toxin type A (BOTOX, Allergan Inc., Irvine, CA) in children and young adults with spasticity. Ninety-four children weighing < 45 kg received a mean total dose of 334.1 U or 19.1 U/kg. Fourteen young adults weighing > or = 45 kg received a mean total dose of 927.3 U or 15.2 U/kg. Adverse events were reported by 3 of the 108 patients (2.8%) and included single instances of rash and enuresis. The only serious adverse event consisted of mild, generalized botulism in a 13-year-old patient who received a 23 U/kg dose to the hamstrings and gastrocnemius/soleus bilaterally. No serious adverse events were noted in children weighing < 45 kg who received botulinum toxin type A doses of 15 to 22 U/kg of body weight or in young adults > or = 45 kg who received total doses of 800 to 1200 U in a single injection protocol. High-dose botulinum toxin type A is safe for the treatment of spasticity in children and young adults.     

A型肉毒素局部注射结合强化运动治疗对脑卒中后下肢痉挛患者步行能力的影响

目的初步观察A型肉毒素局部注射结合强化运动治疗对脑卒中后下肢痉挛患者步行能力的影响。方法将40例脑卒中后下肢痉挛患者根据随机数字表法分为治疗组和对照组,每组20例,对照组给予下肢痉挛肌群A型肉毒素局部注射加常规康复治疗,治疗组在此基础上强化运动治疗。分别于治疗前、治疗后4周、治疗后8周对2组患者进行MAS(改良Ashworth量表)、IEMG(肌表面肌电积分值)、PROM(被动关节活动度)、10m MWS(10m最快步行速度)、FMA(Fugl-Meyer运动功能)、PCI(生理消耗指数)评分。结果治疗4周及8周后,2组MAS、IEMG、PROM、10m MWS、FMA、PCI评分较组内治疗前均显著改善,差异有统计学意义(P0.05);治疗4周后,治疗组PROM(4.39±1.25)°、10 m MWS(18.12±3.47)m/s、FMA(25.16±2.55)分、PCI(0.51±0.21)等指标显著优于对照组,差异有统计学意义(P0.05),而MAS(1.54±0.48)分、IEMG(37.95±4.48)分等指标差异无统计学意义(P0.05);治疗8周后,治疗组PROM(4.42±1.01)°、10m MWS(14.11±2.83)m/s等指标显著优于对照组,差异有统计学意义(P0.05),而MAS(1.63±0.57)分、IEMG(46.94±8.17)分、FMA(26.44±2.12)分、PCI(0.47±0.15)等指标差异无统计学意义(P0.05)。结论 A型肉毒素局部注射结合强化运动治疗可改善脑卒中后下肢痉挛患者的步行能力,可作为一种康复治疗手段应用于临床。     

Local botulinum toxin in the treatment of spastic drop foot

Summary Ten patients with spastic drop foot were treated by local injections of botulinum toxin A (botulinum toxin A haemagglutinin complex). The purpose was to improve stance and gait and/or to facilitate physiotherapy and patient care. Various calf muscles were injected using EMG guidance. The average dose used was 23 ng. Prior to and 4 weeks after treatment, positions of the upper and lower ankle joint at rest and the corresponding end positions of passive and active movement were determined. In addition, changes of spasticity and pain, the transmission phenomenon and stance and gait were evaluated. Most patients showed improvement of some aspects of the spastic drop foot. Positions of the upper and lower ankle joint were improved in most of the patients, as were the other para meters examined. Except for weakness of the injected muscles no side-effects were observed. The results appear promising and may be optimized in further trials by using higher doses of the toxin.