Search

OBJECTIVE:To examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA. DESIGN:Secondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study. SETTING:Fifty-two centers (11 countries). PATIENTS:Adults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb. MAIN OUTCOME MEASUREMENTS:Muscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented. RESULTS:Of 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA. CONCLUSIONS:Patients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A pr

OBJECTIVE: To examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA. DESIGN: Secondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study. SETTING: Fifty-two centers (11 countries). PATIENTS: Adults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb. MAIN OUTCOME MEASUREMENTS: Muscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented. RESULTS: Of 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA. CONCLUSIONS: Patients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other Bo

ObjectiveTo examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA.DesignSecondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study.SettingFifty-two centers (11 countries).PatientsAdults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb.Main outcome measurementsMuscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented.ResultsOf 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA.ConclusionsPatients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A products.

Individuals with lesions of central motor pathways frequently suffer from sustained involuntary muscle activity. This symptom shares clinical characteristics with dystonia but is observable in individuals classified as spastic. The term spastic dystonia has been introduced, although the underlying mechanisms of involuntary activity are not clarified and vary between individuals depending on the disorder. This study aimed to investigate the nature and pathophysiology of sustained involuntary muscle activity in adults with cerebral palsy and stroke. Seventeen adults with cerebral palsy (Gross Motor Function Classification System I-V), 8 adults with chronic stroke and 14 control individuals participated in the study. All individuals with cerebral palsy or stroke showed increased resistance to passive movement with Modified Ashworth Scale >1. Two-minute surface EMG recordings were obtained from the biceps muscle during attempted rest in three positions of the elbow joint; a maximally flexed position, a 90-degree position and a maximally extended position. Cross-correlation analysis of sustained involuntary muscle activity from individuals with cerebral palsy and stroke, and recordings of voluntary isometric contractions from control individuals were performed to examine common synaptic drive. In total, 13 out of 17 individuals with cerebral palsy and all 8 individuals with stroke contained sustained involuntary muscle activity. In individuals with cerebral palsy, the level of muscle activity was not affected by the joint position. In individuals with stroke, the level of muscle activity significantly (P <0.05) increased from the flexed position to the 90 degree and extended position. Cumulant density function indicated significant short-term synchronization of motor unit activities in all recordings. All groups exhibited significant coherence in the alpha (6-15 Hz), beta (16-35 Hz) and early gamma band (36-60 Hz). The cerebral palsy group had lower alpha band c

This paper revisits the taxonomy of the neurophysiological consequences of a persistent impairment of motor command execution in the classic environment of sensorimotor restriction and muscle hypo-mobilization in short position. Around each joint, the syndrome involves 2 disorders, muscular and neurologic. The muscular disorder is promoted by muscle hypo-mobilization in short position in the context of paresis, in the hours and days after paresis onset: this genetically mediated, evolving myopathy, is called spastic myopathy. The clinician may suspect it by feeling extensibility loss in a resting muscle, although long after the actual onset of the disease. The neurologic disorder, promoted by sensorimotor restriction in the context of paresis and by the muscle disorder itself, comprises 4 main components, mostly affecting antagonists to desired movements: the first is spastic dystonia, an unwanted, involuntary muscle activation at rest, in the absence of stretch or voluntary effort; spastic dystonia superimposes on spastic myopathy to cause visible, gradually increasing body deformities; the second is spastic cocontraction, an unwanted, involuntary antagonist muscle activation during voluntary effort directed to the agonist, aggravated by antagonist stretch; it is primarily due to misdirection of the supraspinal descending drive and contributes to reducing movement amplitude; and the third is spasticity, one form of hyperreflexia, defined by an enhancement of the velocity-dependent responses to phasic stretch, detected and measured at rest (another form of hyperreflexia is “nociceptive spasms” following flexor reflex afferent stimulation, particularly after spinal cord lesions). The 3 main forms of overactivity, spastic dystonia, spastic cocontraction and spasticity, share the same motor neuron hyperexcitability as a contributing factor, all being predominant in the muscles that are more affected by spastic myopathy. The fourth component of the neurologic disorde

Individuals with lesions of central motor pathways frequently suffer from sustained involuntary muscle activity. This symptom shares clinical characteristics with dystonia but is observable in individuals classified as spastic. The term spastic dystonia has been introduced, although the underlying mechanisms of involuntary activity are not clarified and vary between individuals depending on the disorder. This study aimed to investigate the nature and pathophysiology of sustained involuntary muscle activity in adults with cerebral palsy and stroke. Seventeen adults with cerebral palsy (Gross Motor Function Classification System I-V), 8 adults with chronic stroke and 14 control individuals participated in the study. All individuals with cerebral palsy or stroke showed increased resistance to passive movement with Modified Ashworth Scale >1. Two-minute surface EMG recordings were obtained from the biceps muscle during attempted rest in three positions of the elbow joint; a maximally flexed position, a 90-degree position and a maximally extended position. Cross-correlation analysis of sustained involuntary muscle activity from individuals with cerebral palsy and stroke, and recordings of voluntary isometric contractions from control individuals were performed to examine common synaptic drive. In total, 13 out of 17 individuals with cerebral palsy and all 8 individuals with stroke contained sustained involuntary muscle activity. In individuals with cerebral palsy, the level of muscle activity was not affected by the joint position. In individuals with stroke, the level of muscle activity significantly (P <0.05) increased from the flexed position to the 90 degree and extended position. Cumulant density function indicated significant short-term synchronization of motor unit activities in all recordings. All groups exhibited significant coherence in the alpha (6-15 Hz), beta (16-35 Hz) and early gamma band (36-60 Hz). The cerebral palsy group had lower alpha band c

BACKGROUND: AbobotulinumtoxinA has beneficial effects on spasticity and active movements in hemiparetic adults with upper limb spasticity (ULS). However, evidence-based information on optimal dosing for clinical use is limited. OBJECTIVE: To describe joint-specific dose effects of abobotulinumtoxinA in adults with ULS. DESIGN: Secondary analysis of a phase 3 study (NCT01313299). SETTING: Multicenter, international, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 243 adults with ULS >6 months after stroke or traumatic brain injury, aged 52.8 (13.5) years and 64.3% male, randomized 1:1:1 to receive a single-injection cycle of placebo or abobotulinumtoxinA 500 U or 1000 U (total dose). METHODS: The overall effects of injected doses were assessed in the primary analysis, which showed improvement of angles of catch in finger, wrist, and elbow flexors and of active range of motion against these muscle groups. This secondary analysis was performed at each of the possible doses received by finger, wrist, and elbow flexors to establish possible dose effects. MAIN OUTCOME MEASURES: Angle of arrest (XV1) and angle of catch (XV3) were assessed with the Tardieu Scale, and active range of motion (XA). RESULTS: At each muscle group level (finger, wrist, and elbow flexors) improvements in all outcome measures assessed (XV1, XV3, XA) were observed. In each muscle group, increases in abobotulinumtoxinA dose were associated with greater improvements in XV3 and XA, suggesting a dose-dependent effect. CONCLUSIONS: Previous clinical trials have established the clinical efficacy of abobotulinumtoxinA by total dose only. The wide range of abobotulinumtoxinA doses per muscle groups used in this study allowed observation of dose-dependent improvements in spasticity and active movement. This information provides a basis for future abobotulinumtoxinA dosing recommendations for health care professionals based on treatment objectives and quantitative assessment of spast

In this review, we will work around two simple definitions of two different entities, which most often co-exist in patients with lesions to central motor pathways: Spasticity is “Enhanced excitability of velocity-dependent responses to phasic stretch at rest”, which will not be the subject of this review, while Spastic dystonia is tonic, chronic, involuntary muscle contraction in the absence of any stretch or any voluntary command (Gracies, 2005). Spastic dystonia is a much less well understood entity that will be the subject this review. Denny-Brown (1966) observed involuntary sustained muscle activity in monkeys with lesions restricted to the motor cortices . He further observed that such involuntary muscle activity persisted following abolition of sensory input to the spinal cord and concluded that a central mechanism rather than exaggerated stretch reflex activity had to be involved. He coined the term spastic dystonia to describe this involuntary tonic activity in the context of otherwise exaggerated stretch reflexes. Sustained involuntary muscle activity in the absence of any stretch or any voluntary command contributes to burdensome and disabling body deformities in patients with spastic paresis. Yet, little has been done since Denny-Brown’s studies to determine the pathophysiology of this non- stretch or effort related sustained involuntary muscle activity following motor lesions and there is a clear need for research studies in order to improve current therapy. The purpose of the present review is to discuss some of the possible mechanisms that may be involved in the hope that this may guide future research. We discuss the existence of persistent inward currents in spinal motoneurones and present the evidence that the channels involved may be upregulated following central motor lesions. We also discuss a possible contribution from alterations in synaptic inputs from surviving or abnormally branched sensory and descending fibres leading to

OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA in adults with upper limb spasticity previously treated with botulinum toxin A (BoNT-A). DESIGN: A post hoc analysis from a Phase 3, prospective, double-blind, randomized, placebo-controlled study (NCT01313299). SETTING: A total of 34 neurology or rehabilitation clinics in 9 countries. PARTICIPANTS: Adults aged 18-80 years with hemiparesis, ≥6 months after stroke or traumatic brain injury. This analysis focused on a subgroup of subjects with previous onabotulinumtoxinA or incobotulinumtoxinA treatment (n = 105 of 243 in the total trial population) in the affected limb. The mean age was 52 years, and 62% were male. INTERVENTION: Study subjects were randomized 1:1:1 to receive a single injection session with abobotulinumtoxinA 500 or 1000 U or with placebo in the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and ≥2 additional muscle groups from the upper limb. MAIN OUTCOME MEASUREMENTS: Efficacy and safety measures were assessed, including muscle tone (Modified Ashworth Scale [MAS] in the PTMG), Physician Global Assessment (PGA), perceived function, spasticity, active movement, and treatment-emergent adverse events. RESULTS: At week 4, more subjects had ≥1 grade improvement in MAS for the PTMG with abobotulinumtoxinA versus placebo (abobotulinumtoxinA 500 U, 81.1%; abobotulinumtoxinA 1000 U, 75.0%; placebo, 25.0%). PGA scores ≥1 were achieved by 75.7% and 87.5% of abobotulinumtoxinA 500 and 1000 U subjects versus 41.7% with placebo. Perceived function (Disability Assessment Scale), spasticity angle (Tardieu Scale), and active movement were also improved with abobotulinumtoxinA. There were no treatment-related deaths or serious adverse events. CONCLUSIONS: The efficacy and safety of abobotulinumtoxinA in subjects previously treated with BoNT-A were consistent with those in the total trial population. Hence, abobotulinumtoxinA is a treatment

Objective: To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections. Methods: In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius–soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint. Results: After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: −0.5 (−0.7 to −0.4) (placebo, n = 128), −0.6 (−0.8 to −0.5) (abobotulinumtoxinA 1,000 U, n = 125; p = 0.28 vs placebo), and −0.8 (−0.9 to −0.7) (abobotulinumtoxinA 1,500 U, n = 128; p = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; p = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; p = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached −1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile. Conclusions: In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and lik

Objective: To assess the efficacy and safety of abobotulinumtoxinA in adults with upper limb spasticity previously treated with botulinum toxin A (BoNT-A). Design: A post hoc analysis from a Phase 3, prospective, double-blind, randomized, placebo-controlled study (NCT01313299). Setting: A total of 34 neurology or rehabilitation clinics in 9 countries. Participants: Adults aged 18-80 years with hemiparesis, ≥6 months after stroke or traumatic brain injury. This analysis focused on a subgroup of subjects with previous onabotulinumtoxinA or incobotulinumtoxinA treatment (n = 105 of 243 in the total trial population) in the affected limb. The mean age was 52 years, and 62% were male. Intervention: Study subjects were randomized 1:1:1 to receive a single injection session with abobotulinumtoxinA 500 or 1000 U or with placebo in the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and ≥2 additional muscle groups from the upper limb. Main Outcome Measurements: Efficacy and safety measures were assessed, including muscle tone (Modified Ashworth Scale [MAS] in the PTMG), Physician Global Assessment (PGA), perceived function, spasticity, active movement, and treatment-emergent adverse events. Results: At week 4, more subjects had ≥1 grade improvement in MAS for the PTMG with abobotulinumtoxinA versus placebo (abobotulinumtoxinA 500 U, 81.1%; abobotulinumtoxinA 1000 U, 75.0%; placebo, 25.0%). PGA scores ≥1 were achieved by 75.7% and 87.5% of abobotulinumtoxinA 500 and 1000 U subjects versus 41.7% with placebo. Perceived function (Disability Assessment Scale), spasticity angle (Tardieu Scale), and active movement were also improved with abobotulinumtoxinA. There were no treatment-related deaths or serious adverse events. Conclusions: The efficacy and safety of abobotulinumtoxinA in subjects previously treated with BoNT-A were consistent with those in the total trial population. Hence, abobotulinumtoxinA is

Introduction and Objectives: Few extensive studies have assessed the effects of botulinum neurotoxin A in adults with upper limb spasticity (ULS) poststroke/traumatic brain injury (TBI) on muscle tone, spasticity, active range of motion (AROM), and function. The aim of this study was to assess the efficacy and safety of abobotulinumtoxinA (Dysport) in hemiparetic adults with ULS poststroke/TBI. Methods: In this phase 3, prospective, double-blind, placebo-controlled study, 243 patients (34 sites, 9 countries) were randomly assigned (1:1:1) to Dysport 500 or 1000 U or placebo. The primary objective was assessment of upper limb muscle tone (Modified Ashworth Scale; MAS) in the primary targeted muscle group (PTMG; finger, wrist, or elbow flexors). Other measures included spasticity (Tardieu Scale), AROM, ease of applying splint (EOS), clinical benefit (Physician Global Assessment; PGA), and subjective function (Disability Assessment Scale; DAS). Results: Four weeks postinjection, a higher proportion of patients achieved a ≥1 point improvement in MAS with both Dysport doses compared with placebo (placebo, 22.8%; 500 U, 73.8%; 1000 U, 78.5%; P<0.0001 vs placebo). Finger flexors were the most common PTMG across treatment groups (52% to 61%). For finger flexors, mean (standard error of mean; SEM) gain in spasticity angle was significantly improved with Dysport vs placebo at 500 U (27.3° [5.9]; P<0.01) and at 1000 U (29.5° [5.9]; P<0.01). This was associated with significantly improved active finger extension (23.9° [4.2]; P<0.0001 for 500 U and 17.6° [4.5]; P<0.01 for 1000 U). Similar results were observed for wrist and elbow flexors. EOS and PGA significantly improved at both doses; 50% (500 U) and 62% (1000 U) of patients improved on DAS (≥1 grade decrease from baseline) for the principal treatment target. Both doses were well tolerated, and the safety profile was consistent with previous experience with Dysport. Conclusions: Dysport improved muscle tone, spasticity, and

BACKGROUND: Resistance from antagonistic muscle groups might be a crucial factor reducing function in chronic hemiparesis. The resistance due to spastic co-contraction might be reduced by botulinum toxin injections. We assessed the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function. METHODS: In this randomised, placebo-controlled, double-blind study, we enrolled adults (aged 18-80 years) at least 6 months after stroke or brain trauma from 34 neurology or rehabilitation clinics in Europe and the USA. Eligible participants were randomly allocated in a 1:1:1 ratio with a computer-generated list to receive a single injection session of abobotulinumtoxinA 500 U or 1000 U or placebo into the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors. Patients and investigators were masked to treatment allocation. The primary endpoint was the change in muscle tone (Modified Ashworth Scale [MAS]) in the PTMG from baseline to 4 weeks. Secondary endpoints were Physician Global Assessment (PGA) at week 4 and change from baseline to 4 weeks in the perceived function (Disability Assessment Scale [DAS]) in the principal target of treatment, selected by the patient together with physician from four functional domains (dressing, hygiene, limb position, and pain). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01313299. FINDINGS: 243 patients were randomly allocated to placebo (n=81), abobotulinumtoxinA 500 U (n=81), or abobotulinumtoxinA 1000 U (n=81). Mean change in MAS score from baseline at week 4 in the PTMG was -0·3 (SD 0·6) in the placebo group (n=79), -1·2 (1·0) in the abobotulinumtoxinA 500 U group (n=80; difference -0·9, 95% CI -1·2 to -0·6; p<0·0001 vs placebo), and -1·4 (1·1) in the abobotulinu