cover image European Journal of Neurology

European Journal of Neurology

1999 - Volume 6
Issue Supplement S4 | November 1999

Original Article

Foreword

Original Article

Abstract

Myofascial pain syndrome (MPS) is characterised by acute and specific pain affecting the piriformis, iliopsoas or scalenus anterior muscles. Tension‐type headache (TH) is a common pathological condition, which can be chronic or episodic. Based on its muscle‐relaxant properties, botulinum toxin type A (BTX‐A) has demonstrated efficacy in a variety of conditions involving dysregulated muscle contractions. Patients with MPS (= 40) or TH (n = 20) were recruited to two randomised, single‐blind studies, respectively. Each patient received either BTX‐A or methylprednisolone, injected into the affected muscles after administration of a local anaesthetic. Pain was assessed at baseline, and 30 and 60 days post‐treatment using a standard visual analogue scale. At 30 days post‐injection, the mean pain score in all treatment groups was reduced compared with baseline in both studies, although the difference between treatment groups was not significant at this time in either study. However, by 60 days post‐injection, the mean pain score has continued to fall in the BTX‐A treatment groups, compared with a waning of the steroid therapeutic activity in the controls. The net effect was a highly significant difference between the two treatments in both the MPS ( < 0.0001) and TH ( < 0.0005) studies. No major adverse events were reported. In conclusion, BTX‐A produces a more prolonged pain relief than methylprednisolone in patients suffering from MPS or TH.

Original Article

Abstract

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

Original Article

Abstract

Focal essential hyperhidrosis is a common and often disabling disorder mainly involving the palms, axillae, face, and soles of the feet. Focal hyperhidrosis may also arise from several neurological or internal diseases. Current therapeutic options include topical aluminium chloride salts, systemic anticholinergic drugs, tap‐water iontophoresis, and a number of surgical approaches. However, none of these are entirely satisfactory. In recent studies, injection of botulinum toxin type A (BTX‐A) into the hyperhidrotic area has proved very effective in reducing or abolishing focal sweating of different aetiologies without major side effects. BTX‐A therefore has the potential to replace more invasive therapies.

Original Article

Abstract

Focal hyperhidrosis is a relatively common condition in which patients experience excessive sweating, usually of the palms, axillae, face or feet. Until recently, the only effective treatment option for this chronic condition was surgery. We aimed to evaluate the efficacy and tolerability of botulinum toxin type A (BTX‐A) in the treatment of patients with hyperhidrosis, establishing optimum dosages and methods of administration. One hundred and seventy patients with focal hyperhidrosis were referred for treatment, the majority with palmar and axillary hyperhidrosis. The iodine‐starch test was used to locate and show the extent of the hyperhidrotic area. Using a template to mark the injection sites, 2 U doses of BTX‐A were injected intradermally at regular intervals. Patients received either 0.5 or 0.8 U/cm with regional anaesthesia if required. The iodine starch test and measurements of evaporation were used to assess efficacy. The majority of patients reported a marked reduction in sweating, About one‐third of the patients who received BTX‐A 0.5 U/cm requested supplementary small injections into islands of skin where they experienced residual sweating. As a result, the standard dose was increased to BTX‐A 0.8 U/cm. The median duration of treatment effect was 10 months (range, 3 to >14 months). The effectiveness of BTX‐A was not reduced by repeated use. BTX‐A treatment was well tolerated by all patients. In conclusion, chemical sudomotor denervation with BTX‐A should be recommended before surgical sympathectomy for the treatment of focal hyperhidrosis.

Original Article

Abstract

Intramuscular injections of botulinum toxin type A (BTX‐A) have been used successfully to treat disorders such as cerebral palsy and cervical dystonia for many years. New and exciting directions for the toxin are currently under clinical investigation for a number of unlicensed indications including tension‐type headache, myofascial pain and hyperhidrosis. Although research on BTX‐A is prolific, there is still much to be learnt regarding the toxin's mode of action, clinical application and perhaps more importantly, its place in the overall treatment strategy implemented by physicians to ensure treatment is a success for both the patient and the physician. This review will focus on these issues, by outlining some of the future directions for BTX‐A research.

Original Article

Abstract

Neuromuscular blockade with botulinum toxin type A (BTX‐A) injections was employed to manage equinus foot deformity in the lower extremities of paediatric cerebral palsy patients. The patients were followed to evaluate the effect of the blockade on lower extremity function and to determine the effect of treatment on the need for tendo‐Achilles lengthening (TAL) surgery. The average length of follow‐up was 3.4 years. Of the 48 patients, 17 (35%) responded to treatment witbin 6 months of initiation of therapy, as determined by a Physician Rating Scale of gait. Overall, 25 (52%) of the 48 patients underwent TAL surgery during the follow‐up period, including eight patients who responded to the BTX‐A treatment. The average age of the patients at the time of surgery was 7 years. This age compares favourably with the age at surgery reported in the recent literature. There were no significant differences by responder status, age, or gender in those patients who did and did not require TAL surgery. No adverse events relating to BTX‐A were reported. These results indicate that patients who respond to BTX‐A treatment have improved physical functioning and gait, and are able to sustain these results long term.

Original Article

Abstract

Clinicians use a range of clinical and objective measures to quantify the positive and negative features (impairments) of the upper motor neurone syndrome. These measures play an important role in the assessment and selection of suitable candidates for intervention and monitoring of outcome. Intervention strategies often focus on the positive features; however, outcome may be more contingent upon the severity of the negative features. The clinical protocol for patient selection and treatment used by our multidisciplinary team is presented, together with details of the assessment procedure. Measurement tools in routine use are described, including: the Modified Ashworth Scale, the Modified Tardieu Scale (‘R1’), muscle length by joint range of motion ‘R2’, three‐dimensional gait analysis, assessments of strength by the Medical Research Council Scale, Selective Motor Control, the Gross Motor Function Measure and the Observational Gait Scale. Three case studies of children with cerebral palsy who underwent botulinum toxin type A treatment as part of their management of gait disorder are presented, a 2‐year‐old girl with mild hemiplegia (‘true equinus’), a 3‐year‐old boy with moderate hemiplegia (‘apparent equinus’) and a 6‐year‐old girl with diplegia, where a targeted approach was used to treat a distal problem and resulted in correction Of a proximal problem.

Original Article

Abstract

Ongoing investigations evaluated clinically relevant properties of BOTOX® (botulinum toxin type A) relative to other botulinum neurotoxin preparations based on the same (type A) or different (types B, C, E and F) serotypes. The mouse Digit Abduction Scoring (DAS) assay was used to compare muscle weakening efficacy, the antigenic potential of two BOTOX® preparations was measured in rabbits, and the presence of antibodies to serotypes A and B was analysed in humans. BOTOX® and new BOTOX® produced similar degrees of dose‐related muscle weakness in mice. Both preparations of BOTOX® were approximately four times more potent than Dysport®. Preparations of serotypes B, C, and F also demonstrated lower potency than BOTOX®, with serotype F also having a shorter duration of action. Neutralising antibodies were found in rabbits 3 months post‐treatment with BOTOX®, but were undetected 8 months post‐treatment with new BOTOX®. A high incidence of antibodies to type B was observed in individuals with no known exposure to type B toxin: highest in groups with the highest incidence of type A antibodies. The safety margin for BOTOX®, calculated using DAS median effective dose (ED,) and the minimum dose producing a 10% reduction in body weight, was more than twice that of Dysport®. In conclusion, each botulinum toxin serotype tested exhibited a different muscle weakening efficacy; BOTOX® consistently exhibited the greatest eficacy. Importantly, BOTOX® and Dysport® exhibited markedly different efficacy and safety profiles, and should not be considered interchangeable. Antibody distribution in humans suggests that there may be immunological cross‐reactivity between serotypes A and B.

Original Article

Abstract

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.

Original Article

Abstract

Botulinum toxin type A (BTX‐A) has been used successfully to manage spasticity in children with cerebral palsy. Little has been done to evaluate treatment outcome and satisfaction from the patients' and parents' points of view. The aim of this study was to investigate the parents' perceptions of the benefits of BTX‐A on movement disorders in children with cerebral palsy. Twenty‐six children with adductor spasticity were enrolled into an open‐label, prospective study. Patients received intramuscular injections of BTX‐A, and assessments of joint mobility (passive range of motion), degree of spasticity (Modified Ashworth Scale) and functional benefit (Gross Motor Function Measure) were made before and 12–18 weeks after treatment. Parents' assessment of treatment outcomes were evaluated using a standardised questionnaire. BTX‐A was shown to be effective in reducing muscular hyperactivity and functional limitations. Parents' satisfaction with the treatment outcome was high. For non‐ambulatory patients, the reported benefits included facilitation of daily care, ease of positioning and reduction of pain. For patients who were disabled to a lesser extent, improvements in gait and posture included sitting with improved comfort, standing for longer periods of time and/or walking longer distances. The parents' responses supported the impressions of the therapists, demonstrating that BTX‐A produced beneficial effects on daily activities, according to both objective measures and parents' observation.

Original Article

Abstract

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 (= 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 (= 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.

Original Article

Abstract

In spasticity, flexion deformity of the hip is frequently associated with contracture or hyper‐reflexia of the psoas muscle. Botulinum toxin type A (BTX‐A) has been used for some considerable time in the management of paediatric gait disorders. We have been using a multilevel approach to manage spasticity in cerebral palsy for several years, the combination of gait analysis and clinical evaluation being important for the selection of target muscles for BTX‐A injections. Twenty cerebral palsy children (12 female) with spasticity were treated with BTX‐A injections (BOTOX® mean dose, 2 U/kg body weight) into the psoas muscle. Patients were monitored using range of motion measurements of maximal hip extension, clinical estimates of hypertonia in the hip flexors, gait analysis (three‐dimensional kinematics and kinetics) and surface electromyography of major lower limb muscles. Full gait analysis was carried out on 12 of the patients. Significant clinical improvements were observed following 15 of the 21 psoas treatments. Furthermore, the kinematics results of gait analysis showed improvement in one or more parameters in nine of the 12 patients. In conclusion, we have demonstrated the value of a multilevel approach to BTX‐A treatment in the management of spasticity in children with cerebral palsy.

Original Article

Abstract

Botulinum toxin type A (BTX‐A) injections induce a dose‐related decrease in muscle tone and increased joint mobility in adults with spasticity and children with cerebral palsy. The aim of this study was to address the question of whether BTX‐A‐related improvements in joint mobility and muscle tone are associated with changes in instrumental gait analysis in children with cerebral palsy. Ten children with cerebral palsy and equinus gait were given a single dose of BTX‐A (5 U BOTOX®/kg body weight per leg) into the gastrocnemius muscles. At follow‐up (mean, 32.6 days post‐injection), a significant ( < 0.05) increase in both passive and active ankle range of motion was observed, together with a decrease in the modified Ashworth score. Instrumental gait analysis showed improvements in ankle and knee kinematics as well as in time‐distance parameters, with a significant increase in step length observed ( < 0.05). Semi‐quantitative analysis of rectified electromyographic (EMG) recordings of the tibialis anterior muscle during gait showed a reduction in EMG activity during the stance phase and an increase in EMG activity during the swing phase. This study demonstrated the benefits of BTX‐A treatment in improving joint mobility and ambulatory function in children with cerebral palsy, and showed that changes in tibial anterior muscle activity as a result of BTX‐A injections into the gastrocnemius muscle can be measured by instrumental gait analysis.

Original Article

Abstract

Lower‐limb spasticity is one of the main features of advanced multiple sclerosis (MS), and botulinum toxin type A (BTX‐A) is known to be effective in the treatment of lower‐limb spasticity. Two hundred randomly selected MS outpatients were analysed for spasticity using clinical scores. Of the 200 randomly selected MS outpatients, 23% had marked or severe spasticity. Hence, the aims of this study were to investigate the effect of BTX‐A injections in MS patients with lower‐limb spasticity refractory to conventional treatment, and to evaluate the new method of spasmography for analysing muscle tone. Fifteen MS patients (mean MS duration, 11.2 years) with spasticity of the lower limbs were injected with BTX‐A (BOTOX®) into the affected muscles. A control group of 15 healthy volunteers was analysed by spasmography. In the 15 MS patients, the Modified Ashworth Scale scores for the left and right legs were significantly lower than baseline values ( < 0.05) at 3 and 6 weeks post‐treatment. At 6 weeks post‐treatment, the spasmography measures (= 12) of mean muscle tone and mean maximum muscle tone of both legs in passive mode were significantly reduced ( < 0.05) compared with baseline. The time to walk 10 m (n = 9) was significantly reduced compared with baseline ( < 0.05) at 3 and 6 weeks post‐treatment. No adverse events were reported for any patients treated with BTX‐A. These data indicate that BTX‐A is effective and safe in the treatment of lower‐limb spasticity, and that spasmography is a useful method for assessing therapeutic intervention in Spasticity.

Original Article

Evaluating the role of botulinum toxin type A in adults with focal spasticity

Original Article

Abstract

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.

Original Article

Abstract

The aim of this study was to evaluate the relaxant effect of two preparations (BOTOX® versus Dysport®) of botulinum toxin type A (BTX‐A) on the external urethral sphincter in patients with neurogenic voiding disorders. Ten male spinal cord injury patients with detrusor‐ external urethral sphincter dyssynergia (DSD) were clinically assessed before, and 4–6 weeks after, transurethral or transperineal BTX‐A injections (BOTOX® 100 U or Dysport® 250 U) into the external urethral sphincter. Patients with persistent difficulties in voiding or high post‐void residual volumes were re‐injected with the same product up to three times. All patients were urodynamically examined within 120 days of injection. In total, 30 BTX‐A injection cycles (one to three injections) were administered. Significant ( < 0.05) reductions in the DSD duration post‐injection, the time interval between the start of bladder contractions and voiding, and DSD seventy post‐treatment were observed. All patients who presented with a residual volume pre‐treatment showed a marked decrease post‐treatment. These effects lasted 6 months. Improvements in urodynamic parameters were significantly better following BOTOX® than DysporP treatment ( < 0.05), although the Dysport® dose used is now considered less potent than that of BOTOX®. Thus, injections of BTX‐A into the external urethral sphincter are a valuable treatment option for DSD in spinal cord injury patients. Treatment success appears to depend on the seventy of DSD before treatment.

Original Article

Abstract

Spasticity of the hip and thigh can result from spinal cord injury, multiple sclerosis, cerebral palsy and numerous other neurological conditions. Chronic hip spasticity causes the patient extreme difficulty in walking and maintaining a comfortable posture. First‐line treatment usually consists of oral anti‐spastic agents, although these are often associated with a high side‐effect burden. intramuscular injections of botulinum toxin type A (BTX‐A), particularly into the psoas major muscle, have proved to be of functional benefit to the patient. A highly reliable and reproducible method for injecting the psoas major muscle through a para‐spinal route has been developed to reduce the power of the muscle and hip flexion deformity. Injection occurs through the middle of the erector spinae muscle at L2, L3 and L4, delivering a total of 150 U BTX‐A to the psoas major muscle. Follow‐up with a substantial rehabilitation programme reliably ensures a decrease in Modified Ashworth Scores and improvements in the outcome assessment scores measured.

Original Article

Abstract

Spastic diplegia is a severely disabling condition and many current treatment options offer the patient no real therapeutic benefit. Intramuscular injection of botulinum toxin type A (BTX‐A) has demonstrated the ability to decrease spasticity, improve mobility and delay the need for surgery in patients with spastic diplegia. The study described here was a pilot to a larger study and it aimed to identify the most suitable and sensitive outcome measures to detect the benefits of BTX‐A injection. Five adolescents with hip spasticity due to cerebral palsy were injected with BTX‐A into the psoas major muscle (for thigh adduction problems) or the soleus muscle (to correct ‘toe clawing’). Assessments of gait and mobility were carried out every month for the 4‐month study period. Following injection with BTX‐A, improvement in patient mobility was most evident in subjects with thigh adduction problems. A reduction in 10‐m walking time and an increase in stride length was also more pronounced in patients injected in the psoas. Three of the five patients treated demonstrated an improved Modified Ashworth Scale score at the end of the 4‐month observation period. The results conclude that spastic diplegics with problems related to the hip, may benefit from BTX‐A. Patients who experience ‘toe clawing’ present different problems and the measures used did not pick up on the benefits gained by the patients.

Original Article

Abstract

Chronic tension‐type headache is a common condition, the pathophysiology of which is not well understood. Over‐activity of the pericranial muscles is thought to play a role, although sustained muscle contraction is probably a consequence, rather than a cause, of headache. Botulinum toxin type A (BTX‐A) is useful in many conditions involving excessive muscle contraction and may therefore be effective in relieving the pain associated with this type of headache. To investigate the efficacy of BTX‐A in relieving pain associated with chronic tension‐type headache, a double‐btind, randomised, placebo‐controlled study was carried out, in which 37 patients received BTX‐A, injected into the temporalis or cervical muscles of the neck. Clinical outcome was measured over a 4‐month study period using headache diaries and chronic pain index scores. Patients treated with BTX‐A showed an improvement in headache severity over the 4‐month study period, with 13 out of 22 patients showing a 25, 50 or >50% improvement in headache score at Month 3 compared with two out of 15 patients in the placebo group. The number of headache‐free days increased significantly in the BTX‐A‐treated patient group, and patients recorded an improvement in quality of life following BTX‐A injection. It can be concluded that intramuscular injection of BTX‐A is an effective treatment for chronic tension‐type headache.