Posts Tagged botulinum toxin

[ARTICLE] Protocol for the economic evaluation of the InTENSE program for rehabilitation of chronic upper limb spasticity – Full Text



Assessment of the costs of care associated with chronic upper-limb spasticity following stroke in Australia and the potential benefits of adding intensive upper limb rehabilitation to botulinum toxin-A are key objectives of the InTENSE randomised controlled trial.


Recruitment for the trial has been completed. A total of 139 participants from 6 stroke units across 3 Australian states are participating in the trial. A cost utility analysis will be undertaken to compare resource use and costs over 12 months with health-related quality of life outcomes associated with the intervention relative to a usual care comparator. A cost effectiveness analysis with the main clinical measure of outcome, Goal Attainment Scaling, will also be undertaken. The primary outcome measure for the cost utility analysis will be the incremental cost effectiveness ratio (ICER) generated from the incremental cost of the intervention as compared to the incremental benefit, as measured in quality adjusted life years (QALYs) gained. The utility scores generated from the EQ-5D three level instrument (EQ-5D-3 L) measured at baseline, 3 months and 12 months will be utilised to calculate the incremental Quality Adjusted Life Year (QALY) gains for the intervention relative to usual care using area-under the curve methods.


The results of the economic evaluation will provide evidence of the total costs of care for patients with chronic upper limb spasticity following stroke. It will also provide evidence for the cost-effectiveness of adding evidence-based movement therapy to botulinum toxin-A as a treatment, providing important information for health system decision makers tasked with the planning and provision of services.


People with spasticity following stroke have significantly higher care costs (particularly direct healthcare costs, and aged care costs) and lower quality of life than those survivors without spasticity [1,2,3]. Therefore, identifying effective therapies to reduce upper-limb spasticity and improve function are an important target for research.

International clinical guidelines support the use of botulinum toxin-A in conjunction with active rehabilitation as the preferred treatment [4]. However, the optimum rehabilitation strategy remains undetermined. There are a lack of adequately powered randomised controlled trials evaluating the effect of botulinum toxin-A injections alone, compared to the injection plus active rehabilitation. However, consideration of the costs of providing care for these patients and ultimately consideration of the cost effectiveness of new therapies (namely, whether they are a worthwhile spend of the constrained resources of the healthcare budget as compared to other potential therapies) is another important factor [5].

There have been few studies of the economic impact of upper-limb spasticity following stroke. Lundström et al. [2] evaluated the healthcare costs for the year following stroke in those with and without spasticity in Sweden, and identified that direct health care costs were four times higher in those with spasticity compared to those without, predominantly due to increased costs of hospital care and post hospital community care (i.e. home help services, residential care etc). However, this study only included hospitalised patients and was based on only 25 participants with spasticity. More recently in the UK, Raluy-Callado [3] evaluated costs of care in over 2900 post-stroke spasticity patients and found that those with spasticity following stroke had double the healthcare costs of those without spasticity with increased hospital care contributing to increased costs in this group, but were not able to include information on home and community care in their estimate. In addition, the potential economic impacts of spasticity following stroke are broad ranging, with loss of workforce productivity among patients and their caregivers which persisit after the event [6]. However, the potential cost-effectiveness of therapies is under-researched, with no economic evaluations to date evaluating the impact of evidence-based movement training combined with botulinum toxin-A injections [178]. Rychlik et al. 2016 evaluated the impact for the health care costs and quality of life of botulinum toxin-A treatment vs usual care without botulinum toxin-A. The study showed a significant improvement in the physical and mental health status of participants over the follow up period. Increased healthcare costs were evident for the participants who received the treatment, but despite higher incremental costs (driven by higher pharmaceutical and nursing home care costs) the study authors concluded the intervention was very likely to be considered cost effective due to the large gains in quality of life attributed to the intervention group compared to usual care. However a key limitation of this study was that it was not randomised and the results may have been influenced by confounding factors in the treatment and usual care groups [1]. Conversely, the BoTULS trial evaluated the clinical and cost effectiveness of treating upper-limb spasticity with botulinum toxin-A plus physical therapy vs physical therapy alone over a 4 week intervention period. The study authors concluded that the intervention had a low probability of cost-effectiveness compared to usual care using the UK reference care willingness to pay threshold of £20,000 for an additional QALY gained [9].

In addition, there is an absence of studies from an Australian perspective. Makino et al. 2018 [8] have published the only Australian based study which evaluated the cost-effectiveness of extending botulinum toxin-A therapy beyond the four treatments currently supported by the Pharmaceutical Benefits Scheme. This study was undertaken from the health-care payer perspective, and therefore included direct healthcare costs in the Markov-state transition model that was developed. It was found that extending the number of treatments beyond four was likely to be considered cost effective. However, the study authors didn’t include costs or benefits from rehabilitation or physical therapy in addition to the botulinum toxin-A in their analysis.

The cost of botulinum toxin-A injections is significant, calculated as $1673 Australian Dollars per treatment cycle and patients may receive multiple cycles of treatment [48]. The InTENSE trial [10] aims to determine the clinical and cost effectiveness of including evidence-based movement training with botulinum toxin-A injections. Therefore, interventions to improve the long-term effect of botulinum toxin-A injections in this group could assist in improving quality of life of patients and reducing their healthcare and broader community care costs. Here we describe in detail the protocol for the economic evaluation to occur alongside the evaluation of clinical effect for the InTENSE trial.[…]

Continue —-> Protocol for the economic evaluation of the InTENSE program for rehabilitation of chronic upper limb spasticity | BMC Health Services Research | Full Text


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[Abstract] Does Casting After Botulinum Toxin Injection Improve Outcomes in Adults With Limb Spasticity? A Systematic Review – Full Text PDF


Objective: To determine current evidence for casting as an adjunct therapy following botulinum toxin injection for adult limb spasticity.

Design: The databases MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials were searched for English language studies from 1990 to August 2018. Full-text studies using a casting protocol following botulinum toxin injection for adult participants for limb spasticity were included. Studies were graded according to Sackett’s levels of evidence, and outcome measures were categorized using domains of the International Classification of Disability, Functioning and Health. The review was prepared and reported according to PRISMA guidelines.

Results: Five studies, involving a total of 98 participants, met the inclusion criteria (2 randomized controlled trials, 1 pre-post study, 1 case series and 1 case report). Casting protocols varied widely between studies; all were on casting of the lower limbs. There is level 1b evidence that casting following botulinum toxin injection improves spasticity outcomes compared with stretching and taping, and that casting after either botulinum toxin or saline injections is better than physical therapy alone.

Conclusion: The evidence suggests that adjunct casting of the lower limbs may improve outcomes following botulinum toxin injection. Casting protocols vary widely in the literature and priority needs to be given to future studies that determine which protocol yields the best results.

Full Text PDF

via Does Casting After Botulinum Toxin Injection Improve Outcomes in Adults With Limb Spasticity? A Systematic Review – PubMed

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[WEB PAGE] Dysport is Now Approved for Upper Limb Spasticity as Well



The United States Food and Drug Administration (FDA) has expanded the use of Dysport (abobotulinumtoxinA) for injection to include the treatment of upper limb spasticity in children two years of age and older, excluding spasticity caused by cerebral palsy (CP), Ipsen Biopharmaceuticals, an affiliate of Ipsen, announces in a news release.

This approval makes Dysport the first botulinum toxin approved by the FDA for both pediatric spasticity indications, following the previous approval to treat children with lower limb spasticity aged two and older received in July 2016.

“For physicians, it is reassuring to have a botulinum toxin treatment in Dysport which demonstrated sustained symptom relief for spasticity, which can be physically challenging for children,” says Ann Tilton, MD, study investigator and Professor of Clinical Neurology at the Louisiana State University Health Sciences Center New Orleans, in the release.

“This FDA decision for Dysport means we now have an approved therapy to offer children and adolescents seeking improvements in mobility in both upper and lower limbs.”

The approval is based on a Phase 3 study with children aged two to 17 years old being treated for upper limb spasticity. Due to Orphan Drug Exclusivity, this approval excludes use in children with upper limb spasticity caused by CP. Dysport demonstrated statistically significant improvements from baseline at Week 6 with doses of 8 Units/kg and 16 Units/kg vs. 2 Units/kg, as measured by the Modified Ashworth Scale (MAS) in the elbow or wrist flexors.

Dysport demonstrated a reduction in spasticity symptoms through 12 weeks for most children for both upper and lower limbs. In the upper limb study, a majority of patients were retreated between 16-28 weeks; however, some patients had a longer duration of response (ie, 34 weeks or more). The most frequent adverse reactions observed were upper respiratory tract infection and pharyngitis, the release explains.

“This approval is a testament to Ipsen’s legacy in neurotoxin research and continued commitment to advancing patient care,” states Kimberly Baldwin, Vice President, Franchise Head, Neuroscience Business Unit, Ipsen. “We believe the data for both pediatric upper and lower limb spasticity underscore the role of Dysport as an important treatment option for patients seeking long-lasting spasticity symptom relief.”

For more information, visit Ipsen.

[Source(s): Ipsen, Business Wire]


via Dysport is Now Approved for Upper Limb Spasticity as Well – Rehab Managment

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[ARTICLE] Effectiveness of Robot-Assisted Upper Limb Training on Spasticity, Function and Muscle Activity in Chronic Stroke Patients Treated With Botulinum Toxin: A Randomized Single-Blinded Controlled Trial – Full Text

Background: The combined use of Robot-assisted UL training and Botulinum toxin (BoNT) appear to be a promising therapeutic synergism to improve UL function in chronic stroke patients.

Objective: To evaluate the effects of Robot-assisted UL training on UL spasticity, function, muscle strength and the electromyographic UL muscles activity in chronic stroke patients treated with Botulinum toxin.

Methods: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with UL spastic hemiparesis. The experimental group (n = 16) received robot-assisted UL training and BoNT treatment. The control group (n = 16) received conventional treatment combined with BoNT treatment. Training protocols lasted for 5 weeks (45 min/session, two sessions/week). Before and after rehabilitation, a blinded rater evaluated patients. The primary outcome was the Modified Ashworth Scale (MAS). Secondary outcomes were the Fugl-Meyer Assessment Scale (FMA) and the Medical Research Council Scale (MRC). The electromyographic activity of 5 UL muscles during the “hand-to-mouth” task was explored only in the experimental group and 14 healthy age-matched controls using a surface Electromyography (EMGs).

Results: No significant between-group differences on the MAS and FMA were measured. The experimental group reported significantly greater improvements on UL muscle strength (p = 0.004; Cohen’s d = 0.49), shoulder abduction (p = 0.039; Cohen’s d = 0.42), external rotation (p = 0.019; Cohen’s d = 0.72), and elbow flexion (p = 0.043; Cohen’s d = 1.15) than the control group. Preliminary observation of muscular activity showed a different enhancement of the biceps brachii activation after the robot-assisted training.

Conclusions: Robot-assisted training is as effective as conventional training on muscle tone reduction when combined with Botulinum toxin in chronic stroke patients with UL spasticity. However, only the robot-assisted UL training contributed to improving muscle strength. The single-group analysis and the qualitative inspection of sEMG data performed in the experimental group showed improvement in the agonist muscles activity during the hand-to-mouth task.


Upper limb (UL) sensorimotor impairments are one of the major determinants of long-term disability in stroke survivors (1). Several disturbances are the manifestation of UL impairments after stroke (i.e., muscle weakness, changes in muscle tone, joint disturbances, impaired motor control). However, spasticity and weakness are the primary reason for rehabilitative intervention in the chronic stages (13). Historically, spasticity refers to a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks resulting from hyperexcitability of the stretch reflex (4) while weakness is the loss of the ability to generate the normal amount of force.

From 7 to 38% of post-stroke patients complain of UL spasticity in the first year (5). The pathophysiology of spasticity is complicated, and new knowledge has progressively challenged this definition. Processes involving central and peripheral mechanisms contribute to the spastic movement disorder resulting in abnormal regulation of tonic stretch reflex and increased muscle resistance of the passively stretched muscle and deficits in agonist and antagonist coactivation (67). The resulting immobilization of the muscle at a fixed length for a prolonged time induces secondary biomechanical and viscoelastic properties changes in muscles and soft tissues, and pain (811). These peripheral mechanisms, in turn, leads to further stiffness, and viscoelastic muscle changes (28). Whether the muscular properties changes may be adaptive and secondary to paresis are uncertain. However, the management of UL spasticity should combine treatment of both the neurogenic and peripheral components of spasticity (910).

UL weakness after stroke is prevalent in both acute and chronic phases of recovery (3). It is a determinant of UL function in ADLs and other negative consequences such as bone mineral content (3), atrophy and altered muscle pattern of activation. Literature supports UL strengthening training effectiveness for all levels of impairment and in all stages of recovery (3). However, a small number of trials have been performed in chronic subgroup patients, and there is still controversy in including this procedure in UL rehabilitation (3).

Botulinum toxin (BoNT) injection in carefully selected muscles is a valuable treatment for spastic muscles in stroke patients improving deficits in agonist and antagonist coactivation, facilitating agonist recruitment and increasing active range of motion (681214). However, improvements in UL activity or performance is modest (13). With a view of improving UL function after stroke, moderate to high-quality evidence support combining BoNT treatment with other rehabilitation procedures (1915). Specifically, the integration of robotics in the UL rehabilitation holds promise for developing high-intensity, repetitive, task-specific, interactive treatment of upper limb (15). The combined use of these procedures to compensate for their limitations has been studied in only one pilot RCT reporting positive results in UL function (Fugl-Meyer UL Assessment scale) and muscular activation pattern (16). With the limits of the small sample, the results support the value of combining high-intensity UL training by robotics and BoNT treatment in patients with UL spastic paresis.

Clinical scales are currently used to assess the rehabilitation treatment effects, but these outcome measures may suffer from some drawbacks that can be overcome by instrumental assessment as subjectivity, limited sensitivity, and the lack of information on the underlying training effects on motor control (17). Instrumental assessment, such as surface electromyography (sEMG) during a functional task execution allows assessing abnormal activation of spastic muscles and deficits of voluntary movements in patients with stroke.

Moreover, the hand-to-mouth task is representative of Activities of Daily Life (ADL) such as eating and drinking. Kinematic analysis of the hand-to-mouth task has been widely used to assess UL functions in individuals affected by neurological diseases showing adequate to more than adequate test-retest reliability in healthy subjects (1819). The task involves flexing the elbow a slightly flexing the shoulder against gravity, and it is considered to be a paradigmatic functional task for the assessment of spasticity and strength deficits on the elbow muscles (1720). Although sEMG has been reported to be a useful assessment procedure to detect muscle activity improvement after rehabilitation, limited results have been reported (1621).

The primary aim of this study was to explore the therapeutic synergisms of combined robot-assisted upper limb training and BoNT treatment on upper limb spasticity. The secondary aim was to evaluate the treatment effects on UL function, muscle strength, and the electromyographic activity of UL muscles during a functional task.

The combined treatment would contribute to decrease UL spasticity and improve function through a combination of training effects between BoNT neurolysis and the robotic treatment. A reduction of muscle tone would parallel improvement in muscle strength ought to the high-intensity, repetitive and task-specific robotic training. Since spasticity is associated with abnormal activation of shortening muscles and deficits in voluntary movement of the UL, the sEMG assessment would target these impairments (281115).

Materials and Methods

Trial Design

A single-blind RCT with two parallel group is reported. The primary endpoint was the changes in UL spasticity while the secondary endpoints were changes in UL function, muscle strength and the electromyographic activity of UL muscles during a functional task. The study was conducted according to the tenets of the Declaration of Helsinki, the guidelines for Good Clinical Practice, and the Consolidated Standards of Reporting Trials (CONSORT), approved by the local Ethics Committee “Nucleo ricerca clinica–Research and Biostatistic Support Unit” (prog n.2366), and registered at clinical trial (NCT03590314).


Chronic post-stroke patients with upper-limb spasticity referred to the Neurorehabilitation Unit (AOUI Verona) and the Physical Medicine and Rehabilitation Section, “OORR” Hospital (University of Foggia) were assessed for eligibility.

Inclusion criteria were: age > 18 years, diagnosis of ischemic or hemorrhagic first-ever stroke as documented by a computerized tomography scan or magnetic resonance imaging, at least 6 months since stroke, Modified Ashworth Scale (MAS) score (shoulder and elbow) ≤ 3 and ≥1+ (22), BoNT injection within the previous 12 weeks of at least one of muscles of the affected upper limb, Mini-Mental State Examination (MMSE) score ≥24 (23) and Trunk Control Test score = 100/100 (24).

Exclusion criteria were: any rehabilitation intervention in the 3 months before recruitment, bilateral cerebrovascular lesion, severe neuropsychologic impairment (global aphasia, severe attention deficit or neglect), joint orthopedic disorders.

All participants were informed regarding the experimental nature of the study. Informed consent was obtained from all subjects. The local ethics committee approved the study.


Each patient underwent a BoNT injection in the paretic limb. The dose of BoNT injected into the target muscle was based on the severity of spasticity in each case. Different commercial formulations of BoNT were used according to the pharmaceutical portfolio contracts of our Hospitals (Onabotulinumtoxin A, Abobotulinumtoxin A, and Incobotulinumtoxin A). The dose, volume and number of injection sites were set accordingly. A Logiq ® Book XP portable ultrasound system (GE Healthcare; Chalfont St. Giles, UK) was used to inject BoNT into the target muscle.

Before the start of the study authors designed the experimental (EG) and the control group (CG) protocols. Two physiotherapists, one for each group, carried out the rehabilitation procedures. Patients of both groups received ten individual sessions (45 min/session, two sessions/week, five consecutive weeks). Treatments were performed in the rehabilitative gym of the G. B. Rossi University Hospital Neurological Rehabilitation Unit, or “OORR” Hospital.

Robot-Assisted UL Training

The Robot-assisted UL Training group was treated using the electromechanical device Armotion (Reha Technology, Olten, Switzerland). It is an end-effector device that allows goal-directed arm movements in a bi-dimensional space with visual feedback. It offers different training modalities such as passive, active, passive-active, perturbative, and assistive modes. The robot can move, drive or oppose the patient’s movement and allows creating a personalized treatment, varying parameters such as some repetitions, execution speed, resistance degree of motion. The exercises available from the software are supported by games that facilitate the functional use of the paretic arm (25). The robot is equipped with a control system called “impedance control” that modulates the robot movements for adapting to the motor behavior of the patient’s upper limb. The joints involved in the exercises were the shoulder and the elbow, is the wrist fixed to the device.

The Robot-assisted UL Training consisted of passive mobilization and stretching exercises for affected UL (10 min) followed by robot-assisted exercises (35 min). Four types of exercises contained within the Armotion software and amount of repetitions were selected as follows: (i) “Collect the coins” (45–75 coins/10 min), (ii) “Drive the car” (15–25 laps/10 min), (iii) “Wash the dishes” (40–60 repetitions/10 min), and (iv) “Burst the balloons” (100–150 balloons/5 min) (Figure 1). All exercises were oriented to achieving several goals in various directions, emphasizing the elbow flexion-extension and reaching movement. The robot allows participants to execute the exercises through an “assisted as needed” control strategy. For increment the difficulty, we have varied the assisted and non-assisted modality, increasing the number of repetitions over the study period.[…]


Figure 1. The upper limb robot-assisted training setting.

Continue —> Frontiers | Effectiveness of Robot-Assisted Upper Limb Training on Spasticity, Function and Muscle Activity in Chronic Stroke Patients Treated With Botulinum Toxin: A Randomized Single-Blinded Controlled Trial | Neurology

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[ARTICLE] Effects of a 6-month self-rehabilitation programme in addition to botulinum toxin injections and conventional physiotherapy on limitations of patients with spastic hemiparesis following stroke (ADJU-TOX): protocol study for a randomised controlled, investigator blinded study -Full Text


Introduction Home-based self-rehabilitation programmes combined with botulinum toxin injections (BTIs) appear to be a relevant approach to increase the recommended intensive rehabilitation of patients with spasticity following a stroke. The literature highlights a lack of evidence of beneficial effects of this adjuvant therapy to reduce limitations of patients with stroke. The aim of this study is to assess the effects of a 6-month self-rehabilitation programme in adjunction to BTI, in comparison with BTI alone, to reduce limitations of patients with spasticity following a stroke.


Methods and analysis 220 chronic patients will participate to this multicentre, prospective, randomised, controlled, assessor blinded study. All patients will benefit from two successive BTI (3 months apart), and patients randomised in the self-rehabilitation group will perform in adjunction 6 months of self-rehabilitation at home. All patients continue their conventional physiotherapy. The main outcome is the primary treatment goal (PTG), which will be determined jointly by the patient and the medical doctor using Goal Attainment Scaling. Impairments and functions, quality of life, mood and fatigue will be assessed. Botulinum toxin will be injected into the relevant muscles according to the PTG. Patients in the self-rehab group will be taught the self-rehabilitation programme involving respectively 10 min of stretching, 10 min of strengthening and 10 min of task-oriented exercises, corresponding to their PTG. Compliance to the self-rehabilitation programme will be monitored.

Strengths and limitations of this study

  • This study is the first to assess the effects of a self-rehabilitation in addition of usual treatments over a long period (6 months).

  • This study will include a large sample with patients from 16 hospitals across all the country.

  • The design of this study (randomised, controlled, assessor blinded study) tends to meet the highest level of evidence.

  • This study would permit to apply recommendations to improve patients limitations with little additional cost to the already limited health system budget.


Stroke is the second highest cause of death worldwide and the fourth leading cause of lost productivity (disability-adjusted life years) according to WHO. The annual incidence is around 130 000 new cases each year in France.1 Around half of survivors are left with some functional limitations as a result of multiple impairments including motor impairments with a loss of strength, stereotyped movements and changes in muscle tone.2 3 Following stroke, about one-third of people with motor deficits have complete upper limb recovery, one-third have a partial recovery, with capacity to carry a bag or to point to an object and, one-third have little to no recovery of function with often dependence for activities of daily living.4 Among impairments, positive signs of the upper motor neuron syndrome (spasticity, cocontraction and dystonia) are associated with active motor dysfunction and disabilities to use arm in daily living activities.5 6 Gait limitations following symptoms of upper motor neuron syndrome reduce also displacements and participation of patients with stroke.7 8 Although 65%–85% of stroke survivors regain the capacity to walk, their gait is slower and their cadence, step length and single support phase of gait cycle are reduced in comparison with healthy subjects.9 These spatio-temporal changes are associated with joint kinematics changes, such as reduced peak hip flexion,10 reduced peak knee flexion during swing (stiff knee gait)10 11 and reduced ankle dorsiflexion (equinus).10 Motor impairments are largely involved in these kinematic abnormalities, particularly spasticity of quadriceps reducing knee flexion in stiff knee gait11 and spasticity of the ankle plantar flexors contributing to the equinus.12

Physiotherapy has been shown to be effective for the treatment of motor impairment and the improvement of function following stroke.13 14 Different techniques have been developed, however, one has not been shown more effective than another.15 16 Nevertheless, it has been demonstrated that the intensity, the frequency and the specificity (to train specifically the task to improve) of physiotherapy is positively correlated with recovery.17–20 To increase the duration and the specificity of physiotherapy lead indeed to greater improvements in impairments and functional limitations. French et al 21 published a systematic review relating positive effects of repetitive functional task practice on upper and lower limb function in 1078 patients with stroke.21 Van de Port et al 22 showed indeed that intensive circuit training organised in specific workstations induced greater locomotor improvements than usual physiotherapy in 250 chronic outpatients with stroke.22 This likely suggests that patients do not attempt their maximal potential of recovery when they benefit of usual care. This means also that an adjuvant care might permit to the patients to reach their maximal capacity and thus reducing the impact of impairments and functional limitations. Moreover, many studies highlighted that improvements continue and are effective in chronic patients with stroke who follow intensive active rehabilitation.13 23 Currently, because of the constraints within the French health system, patients with stroke living at home usually receive only 1.7 sessions of 20–30 min of physiotherapy per week.24 These sessions, which last about 30 min, usually only consist of stretching and strengthening exercises. This contrasts with recommendations of intensive rehabilitation for chronic patients due to functional deteriorations observed when patients decrease or stop their rehabilitation.19 20 25 This suggests the necessity to develop novel approaches which could increase the intensity and specificity of rehabilitation for chronic patients with stroke living at home. A self-rehabilitation (SR) programme appears a relevant approach to increase the intensity of the oriented rehabilitation which is needed and further improve recovery of these patients.

The treatment commonly used to reduce spasticity and increase functions in patients with stroke is botulinum toxin injections (BTIs).12 26–28 In the upper limb, BTI appear associated with a global moderate treatment effect and depends of the parameters studied. A meta-analysis carried out by Foley et al 29 showed a relatively large effect size for the reduction of spasticity and the improvement of passive function and, a small effect size for the improvement of active functions such as prehension.29 This confirms the results of a previous international consensus statement in which authors consider BTI as effective for reduction of pain, deformity and improvement of washing and dressing (class I evidence, recommendation level A), but no clear benefit in active function (class III evidence, recommendations C).30 In the lower limb, several studies have evaluated the effects of BTI in the rectus femoris (RF) and triceps surae muscles in patients with stroke. Studies have shown that BTI in the triceps surae reduced passive resistance to ankle dorsiflexion, pain and the requirement of a gait aid and increased gait speed of patients with hemiparesis.31 32 An open-label study found a significant increase of 8° peak knee flexion during swing following BTI in the RF in patients with hemiparesis with inappropriate RF activity in mid-swing.33 However, there were no significant improvements in functional tests of gait capacity (gait speed, gait distance assessed during the 6 min walking test, stairs). Taken together, the results obtained in the upper and lower limbs after a single BTI session suggest that, although this treatment reduces muscle tone and increases passive function, its impact on active function is low and it does not improve activities of daily living. Some authors state that conventional outcome measures used in these previous studies are not suitable.30 34 35 They suggest using an individually based approach such as the Goal Attainment Scaling (GAS) which showed significant improvements following BTI.34 35 GAS determined the primary treatment goal which is the main treatment objective determined jointly by the patient and the therapist.

Several studies showed moreover that repeated BTI induce better improvements of muscle tone, active movements, functions and quality of life of patients with stroke than single injection.27 36–38

In view of all these studies, it appears essential to develop a combined therapy approach to improve the treatment of spasticity and functional activities in daily life. To increase the intensity of the oriented rehabilitation following BTI would be indeed relevant. Sun et al 39 highlighted greater improvements of spasticity, active function and use of the paretic upper limb of patients with stroke when a constraint-induced therapy is coupled with BTI in comparison with less intensive rehabilitation.39 Similarly, Roche et al showed that a 30 min daily SR programme of 4 weeks coupled with a single session of BTI in the lower limb significantly improved several gait-related activities compared with BTI alone.40 The SR programme was developed to combine safe and feasible exercises combining 10 min of strengthening, 10 min of stretching and 10 min of task-oriented gait-related exercises. Eighty-three per cent of the patients in the SR group carried out 33 min exercises per day more than 5 days per week.40 These results show that combining SR at home with BTI seems effective, well accepted and well tolerated. Results of these pilot studies with restricted sample suggest effectiveness of adding sessions of specific exercises following BTI in patients with stroke, which corresponds to the conclusions of two recent reviews.41 42 These reviews recommend however further study with large sample size, long duration and robust methodology.

The aim of this study is to assess the effects of a 6 months SR programme in adjunction to BTI, in comparison with BTI alone, to reduce limitations of patients with spasticity having a stroke. All previous results lead us to the hypothesis that the addition of a specific 30 min SR programme to repeated BTI and usual physiotherapy should increase the proportion of patients who attain their primary treatment goal (impairments and functions assessed with GAS) more than usual care (involving repeated BTI and conventional physiotherapy), in poststroke outpatients with spasticity. Secondary objectives are to compare the effects of the two therapeutic strategies on impairments and functional status, on quality of life, mood, fatigability and fatigue of patients with stroke and evaluate the time course of the effects. Another aim is to assess compliance with, and tolerability of the SR programme, and to define the characteristics of compliant and non-compliant patients.[…]

Continue —> Effects of a 6-month self-rehabilitation programme in addition to botulinum toxin injections and conventional physiotherapy on limitations of patients with spastic hemiparesis following stroke (ADJU-TOX): protocol study for a randomised controlled, inves… | BMJ Open

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[ARTICLE] Efficacy of physical therapy associated with botulinum toxin type A on functional performance in post-stroke spasticity: A randomized, double-blinded, placebo-controlled trial – Full Text


The aim was to investigate if botulinum toxin type A (BTx-A) associated with physical therapy is superior to physical therapy alone in post stroke spasticity. A randomized, double-blinded controlled trial was performed in a rehabilitation unit on Northeastern, Brazil. Patients with post stroke spasticity were enrolled either to BTx-A injections and a pre-defined program of physical therapy or saline injections plus physical therapy. Primary endpoint was functional performance evaluated through time up and go test, six minutes walking test and Fugl-Meyer scale for upper limb. Secondary endpoint was spasticity improvement. Confidence interval was considered at 95%. Although there was a significant decrease in upper limbs flexor tonus (P<0.05) in the BTx-A group, there was no difference regarding functional performance after 9 months of treatment. When analyzing gait speed and performance, both groups showed a significant improvement in the third month of treatment, however it was not sustained over time. Although BTx-A shows superiority to improve muscle tone, physical therapy is the cornerstone to improve function in the upper limbs of post stroke patients.


Stroke is the major cause of permanent and temporary functional incapacity worldwide among adults, affecting limb strength, motor control, balance and mobility.1 Spasticity is characterized by an increase in tonic stretch reflex movement velocity dependent and post-stroke spasticity is frequently associated with poor functional performance due to abnormal postural patterns, leading to retractions, atrophy, selective movement control loss, limb weakness, fibrosis and structured contractions.2 Moreover, impairment in activities of daily living (ADL) such as feeding, locomotion, proper hygiene and sleeping habits results in poor quality of life (QOL) and increased burden to relatives and caregivers.3

Several trials support the efficacy and safety of botulinum toxin type A (BTx-A) on spasticity treatment, reducing muscle permanent contraction and abnormal postural patterns, therefore, favoring rehabilitation process.4 Physical therapy has been described to be effective in post-stroke spastic patients through prevention of secondary incapacities and promoting behavioral reeducation, based on biomechanical and neurophysiological patterns. These techniques include physical exercises that focus on functional rehabilitation, reduction of limb spasticity, muscle strength improvement and sustained joint movement amplitude, besides proprioceptive and sensorial stimuli.5

Several trials with BTx-A show functional improvement in post-stroke spastic patients when compared to placebo, however, none have studied the impact of physical therapy alone.4

The aim of this trial was to investigate if BTx-A treatment associated with physical therapy is superior to physical therapy alone on functional performance in post-stroke spastic patients.[…]


Continue —> Efficacy of physical therapy associated with botulinum toxin type A on functional performance in post-stroke spasticity: A randomized, double-blinded, placebo-controlled trial

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[ARTICLE] Botulinum Toxin Type A Treatment Combined with Intensive Rehabilitation for Gait Poststroke: A Preliminary Study – Full Text


To examine the effects of botulinum toxin type A (BoNT-A) treatment combined with intensive rehabilitation for gait compared with intensive rehabilitation alone in patients with chronic stroke.

Materials and Methods

A comparative case series design was used. Subjects were 19 patients with chronic stroke and spastic hemiplegia. In 9 patients (group I), BoNT-A was injected into spastic muscles of the affected lower limbs, followed by a 4-week inpatient intensive rehabilitation program. In the other 10 patients (group II), a 4-week inpatient intensive rehabilitation program alone was first provided (control period) followed by the same treatment protocol in group I. The Modified Ashworth Scale (MAS) scores, range of motion (ROM), gait speed in the 10-Meter Walking Test, 6-Minute Walking Distance Test (6MD) scores, Timed Up and Go Test (TUG) scores, and Berg Balance Scale scores were evaluated every 4 weeks following baseline assessments.


All results except for the MAS score of knee flexor and the ROM of knee flexion improved in group I and the gait speed, 6MD, and TUG scores improved in group II. Intergroup comparisons at week 4 showed significantly greater improvements in the MAS score of ankle plantar flexor, ROM of ankle dorsiflexion, and 6MD in group I than in group II (P = .016, .011, and .009, respectively).


BoNT-A treatment for lower-limb spasticity, combined with intensive rehabilitation, was effective in improving spasticity and the 6MD compared with intensive rehabilitation alone in patients with chronic stroke.



Lower-limb spasticity is a major problem in the management of patients after stroke12 because it causes gait disturbance.3 Such patients often have difficulty performing ankle dorsiflexion effectively during the swing phase of the gait cycle because of muscle spasticity and the inability to activate the ankle dorsiflexors.4 Calf muscle spasticity typically causes foot deformity, which results in the loss of heel strike, reduced toe clearance, and an inadequate base of support.5 These impairments decrease gait ability: cadence, stride length, speed, capacity, and stability.678910 Thus, lower-limb spasticity causes gait disturbance, which limits activities of daily living and, eventually, quality of life. Effective treatment of lower-limb spasticity is important in improving gait ability and enhancing the independence of patients after a stroke.

One of the primary treatments for lower-limb spasticity is botulinum toxin type A (BoNT-A). Although BoNT-A has been shown to reduce lower-limb spasticity in patients after stroke,111213its effects on improving gait ability have not been consistent among different previous studies. Pittock et al,14 Kaji et al,15 and Burbaud et al1 reported that BoNT-A injection reduced lower-limb spasticity but did not significantly improve gait pattern or speed. By contrast, Hesse et al11 and Mancini et al16 reported that BoNT-A treatment was effective in improving gait speed as well as lower-limb spasticity. Similarly, a systematic review and meta-analysis recently showed that BoNT-A treatment for lower-limb spasticity was associated with a small but statistically significant increase in gait speed.17 Consequently, the effect of BoNT-A alone for improving gait ability has been considered minimal.

To improve gait ability, adjunctive rehabilitation has recently been recommended to optimize the effects of BoNT-A treatment for lower-limb spasticity in poststroke patients.181920212223Gastaldi et al21 reported that BoNT-A treatment for lower-limb spasticity combined with additional stretching and physical therapy improved gait speed and single- and double-limb support during the stance phase of the gait cycle. Similarly, Roche et al22 reported that BoNT-A treatment for lower-limb spasticity combined with self-rehabilitation improved gait speed, capacity, and time to ascend and descend a flight of stairs. By contrast, Demetrios et al23 suggested no significant improvement in gait speed for 2 groups receiving BoNT-A treatment for lower-limb spasticity combined with high- or low-intensity rehabilitation. However, they concluded that both groups received BoNT-A treatment combined with regular rehabilitation, so there may have been insufficient variation of intensity during the rehabilitation phase. Therefore, the capacity of BoNT-A treatment combined with more intensive rehabilitation to improve gait ability remains unclear in poststroke patients.

The aim of this study was to examine the effects of BoNT-A treatment for lower-limb spasticity combined with intensive rehabilitation on improving gait ability in patients with chronic stroke and spastic hemiplegia compared with intensive rehabilitation alone. This study hypothesized that BoNT-A treatment combined with intensive rehabilitation would improve lower-limb spasticity and gait ability more effectively than intensive rehabilitation alone.[…]


Continue —> Botulinum Toxin Type A Treatment Combined with Intensive Rehabilitation for Gait Poststroke: A Preliminary Study – ScienceDirect

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[Abstract] Comparative hybrid effects of combining botulinum toxin A injection with bilateral robot-assisted, mirror or task-oriented therapy for upper extremity spasticity in patients with chronic stroke


Spasticity, a common impairment after stroke, has profound negative impact on outcomes in patients with stroke. Botulinum toxin type A (BoNT-A) injection combined with rehabilitation training is suggested for spasticity treatment. However, there is no recommendation about what kind of rehabilitation training is more appropriate than others following BoNT-A injection. The purpose of this study was to compare the effects of combining BoNT-A injection with bilateral robot-assisted (RT) or mirror (MT) or task-oriented (TT) therapy for upper extremity (UE) spasticity in patients with chronic stroke.

Material and method

Participants were randomly assigned to RT, or MT, or TT group after BoNT-A injection. The participants received 45 minutes of intervention per day, 3 days/week, for 8 weeks according the allocated results. In addition, all participants received 30 minutes of functional practice training. At pre-intervention, post-intervention and 3-month follow-up a blinded research assistant did outcome measures, including body function and structures by Fugl-Meyer Assessment (FMA), and Modified Ashworth Scale (MAS); activity and participation measures by Motor Activity Log (MAL), and Nottingham Extended Activities of Daily Living Scale (EADLS).


Thirty-seven subjects met the inclusion criteria and underwent randomization, 13 were assigned to the RT; 12 to MT; and 12 to TT group. The 3 groups were well matched with regard to baseline characteristics and functional status. All groups had significant improvement in FMA, MAS and MAL post-intervention. There were no group differences in FMA, MAS, EADLs either post-intervention or at follow-up. There was a trend that TT group had higher quality of movement (QOM) in MAL post intervention than the other 2 groups (P = 0.07), at follow-up TT group had significantly higher QOM in MAL than the other 2 groups (P = 0.03).


Combining BoNT-A injection with TT resulted in better quality of UE movement in patients with spastic stroke than with RT or MT.


via Comparative hybrid effects of combining botulinum toxin A injection with bilateral robot-assisted, mirror or task-oriented therapy for upper extremity spasticity in patients with chronic stroke – ScienceDirect 

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[ARTICLE] Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges – Full Text


A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections), modulate neural activity (noninvasive brain stimulation), and enhance motivation (virtual reality) in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.

1. Introduction

Significant advances have been made in the management of stroke (including prevention, acute management, and rehabilitation); however cerebrovascular diseases remain the third most common cause of death and the first cause of disability worldwide [16]. Stroke causes brain damage, leading to loss of motor function. Upper limb (UL) function is particularly reduced, resulting in disability. Many rehabilitation techniques have been developed over the last decades to facilitate motor recovery of the UL in order to improve functional ability and quality of life [710]. They are commonly based on principles of motor skill learning to promote plasticity of motor neural networks. These principles include intensive, repetitive, task-oriented movement-based training [1119]. A better understanding of the neural substrates of motor relearning has led to the development of innovative strategies and tools to deliver exercise that meets these requirements. Treatments mostly target the neurological impairment (paresis, spasticity, etc.) through the activation of neural circuits or by acting on peripheral effectors. Robotic devices provide exercises that incorporate key elements of motor learning. Advanced robotic systems can offer highly repetitive, reproducible, interactive forms of training for the paretic limb, which are quantifiable. Robotic devices also enable easy and objective assessment of motor performance in standardized conditions by the recording of biomechanical data (i.e., speed, forces) [2022]. This data can be used to analyze and assess motor recovery in stroke patients [2326]. Since the 1990s, many other technology-based approaches and innovative pharmaceutical treatments have also been developed for rehabilitation, including virtual reality- (VR-) based systems, botulinum neurotoxin (BoNT) injections, and noninvasive brain stimulation (NIBS) (Direct Current Stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)). There is currently no high-quality evidence to support any of these innovative interventions, despite the fact that some are used in routine practice [27]. By their respective mechanisms of action, each of these treatments could potentiate the effects of robotic therapy, leading to greater improvements in motor capacity. The aim of this paper is to review studies of combined treatments based on robotic rehabilitation and to analyze the rationale behind such approaches.[…]


Continue —> Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

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[Abstract] Botulinum Toxin Injection Techniques for the Management of Adult Spasticity


Spasticity is often experienced by individuals with injury or illness of the central nervous system from etiologies such as stroke, spinal cord injury, brain injury, multiple sclerosis, or other neurologic conditions. Although spasticity may provide benefits in some patients, it more often leads to complications negatively impacting the patient. Nonpharmacologic treatment options often do not provide long-term reduction of spasticity, and systemic interventions, such as oral medications, can have intolerable side effects. The use of botulinum neurotoxin injections is one option for management of focal spasticity. Several localization techniques are available to physicians that allow for identification of the selected target muscles. These methods include anatomic localization in isolation or in conjunction with electromyography guidance, electrical stimulation guidance, or ultrasound guidance. This article will focus on further description of each of these techniques in relation to the treatment of adult spasticity and will discuss the advantages and disadvantages of each technique, as well as review the literature comparing the techniques.


via Botulinum Toxin Injection Techniques for the Management of Adult Spasticity – ScienceDirect

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