Archive for category Spasticity

[WEB SITE] What is clonus? Everything you need to know

Clonus is a neurological condition that occurs when nerve cells that control the muscles are damaged. This damage causes involuntary muscle contractions or spasms.

Clonus spasms often occur in a rhythmic pattern. Symptoms are common in a few different muscles, especially in the extremities. These include the:

  • ankles
  • knees
  • calves
  • wrists
  • jaw
  • biceps

Damaged nerves can cause muscles to misfire, leading to involuntary contractions, muscle tightness, and pain.

Clonus can cause a muscle to pulse for an extended period. This pulsing can lead to muscle fatigue, which may make it difficult for a person to use the muscle later.

Clonus can make everyday activities strenuous and can even be debilitating. In this article, learn more about the causes and treatment.


Nerve cells in muscles causing clonus

Damaged nerve cells cause clonus.

While researchers do not understand the exact cause of clonus, it appears to be due to damaged nerve passageways in the brain.

A number of chronic conditions are associated with clonus. As these conditions require specialized treatment, the outcome may vary in each case.

Conditions associated with clonus include:

Multiple sclerosis (MS) is an autoimmune disorder that attacks the protective sheath around the nerves. The resulting damage disrupts the nerve signals in the brain.

A stroke starves a part of the brain of oxygen, usually due to a blood clot. A stroke may cause clonus if it damages the area in the brain that controls movement.

Infections, such as meningitis or encephalitis, can damage brain cells or nerves if they become severe.

Major injuries, such as head trauma from a major accident, may also damage the nerves in the brain or spinal cord.

Serotonin syndrome is a potentially dangerous reaction that occurs if too much serotonin builds up in the body. This buildup could be due to drug abuse, but it may also be caused by taking high doses of medications or mixing certain medical drugs.

A brain tumor that pushes against the motor neurons in the brain or causes these areas to swell may lead to clonus.

Other causes of clonus include anything that has the potential to affect the nerves or brain cells, including:

  • cerebral palsy
  • Lou Gehrig’s disease
  • anoxic brain injury
  • hereditary spastic paraparesis
  • kidney or liver failure
  • overdoses of drugs such as Tramadol, which is a strong painkiller

Clonus tests

Clonus may be diagnosed using an MRI scan.

An MRI scan may be used to diagnose clonus.

To diagnose clonus, doctors may first physically examine the area that is most affected. If a muscle contracts while a person is in the doctor’s office, they may monitor the contraction to see how fast the muscle is pulsing and how many times it contracts before stopping.

Doctors will then order a specific series of tests to help them confirm the diagnosis. They may use magnetic resonance imaging (MRI) to check for damage to the cells or nerves.

Blood tests may also help identify markers for various conditions associated with clonus.

A physical test may also help doctors identify clonus. During this test, they will ask the person to quickly flex their foot, so their toes are pointing upward and then hold the muscle there.

This may cause a sustained pulsing in the ankle. A series of these pulses may indicate clonus. Doctors do not rely on this test to diagnose clonus, but it can help point them in the right direction during the diagnostic process.


Treatment for clonus varies depending on the underlying cause. Doctors may try many different treatment methods before finding the one that works best for each person.


Sedative medications and muscle relaxers help reduce clonus symptoms. Doctors often recommend these drugs in the first instance for people experiencing clonus.

Medications that may help with clonus contractions include:

  • baclofen (Lioresal)
  • dantrolene (Dantrium)
  • tizanidine (Zanaflex)
  • gabapentin (Neurotonin)
  • diazepam (Valium)
  • clonazepam (Klonopin)

Sedatives and anti-spasticity medications can cause drowsiness or sleepiness. People taking these medications should not drive a car or operate heavy machinery.

Other side effects may include mental confusion, lightheadedness, or even trouble walking. A person should discuss these side effects with a doctor, especially if they are likely to disrupt a person’s work or everyday activities.

Other treatments

Clonus may be treated with physical therapy.

Physical therapy may help treat clonus.

Other than medication, treatments that may help reduce clonus include:

Physical therapy

Working with a physical therapist to stretch or exercise the muscles may help increase the range of motion in the damaged area. Some therapists may recommend wrist or ankle splints for some people as they can provide structure and improve stability, reducing the risk of accidents.

Botox injections

Some people with clonus respond well to Botox injections. Botox therapy involves injecting specific toxins to paralyze muscles in the area. The effects of Botox injections wear off over time so a person will require repeat injections on a regular basis.


Surgery is often the last resort. During a procedure to treat clonus, surgeons will cut away parts of the nerve that are causing abnormal muscle movements, which should relieve symptoms.

Home remedies

While medical treatments for clonus are important, home remedies can be valuable in supporting these efforts.

Using heat packs or taking warm baths may relieve pain, while applying cold packs may help reduce muscle aches. Stretching and yoga may help promote an increased range of motion.

Some people may also find a magnesium supplement or magnesium salt bath helps relax the muscles. People should speak to a doctor before trying magnesium, as it may interact with other medications.


The outlook for clonus may vary according to the underlying cause. Where a sudden injury or illness causes clonus and muscle spasms, the symptoms will likely go away over time or respond well to physical therapy.

Chronic conditions such as multiple sclerosis, meningitis, or a stroke may require long-term treatments for symptom management.

Clonus may sometimes get worse if the underlying condition progresses. Many people find they can manage symptoms by working closely with a doctor and physical therapist.

via Clonus: Definition, causes, tests, and treatment


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[Abstract] Non-pharmacological interventions for spasticity in adults: An overview of systematic reviews



Spasticity causes significant long-term disability-burden, requiring comprehensive management. This review evaluates evidence from published systematic reviews of clinical trials for effectiveness of non-pharmacological interventions for improved spasticity outcomes.


Data sources: a literature search was conducted using medical and health science electronic (MEDLINE, EMBASE, CINAHL, PubMed, and the Cochrane Library) databases for published systematic reviews up to 15th June 2017. Data extraction and synthesis: two reviewers applied inclusion criteria to select potential systematic reviews, independently extracted data for methodological quality using Assessment of Multiple Systematic Reviews (AMSTAR). Quality of evidence was critically appraised with Grades of Recommendation, Assessment, Development and Evaluation (GRADE).


Overall 18 systematic reviews were evaluated for evidence for a range of non-pharmacological interventions currently used in managing spasticity in various neurological conditions. There is “moderate” evidence for electro-neuromuscular stimulation and acupuncture as an adjunct therapy to conventional routine care (pharmacological and rehabilitation) in persons following stroke. “Low” quality evidence for rehabilitation programs targeting spasticity (such as induced movement therapy, stretching, dynamic elbow-splinting, occupational therapy) in stroke and other neurological conditions; extracorporeal shock-wave therapy in brain injury; transcranial direct current stimulation in stroke; transcranial magnetic stimulation and transcutaneous electrical nerve stimulation for other neurological conditions; physical activity programs and repetitive magnetic stimulation in persons with MS, vibration therapy for SCI and stretching for other neurological condition. For other interventions, evidence was inconclusive.


Despite the available range of non-pharmacological interventions for spasticity, there is lack of high-quality evidence for many modalities. Further research is needed to judge the effect with appropriate study designs, timing and intensity of modalities, and associate costs of these interventions.


via Non-pharmacological interventions for spasticity in adults: An overview of systematic reviews – ScienceDirect

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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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[ARTICLE] Quantification of Upper Limb Motor Recovery and EEG Power Changes after Robot-Assisted Bilateral Arm Training in Chronic Stroke Patients: A Prospective Pilot Study – Full Text PDF

Background. Bilateral arm training (BAT) has shown promise in expediting progress toward upper limb recovery in chronic stroke patients, but its neural correlates are poorly understood.

Objective. To evaluate changes in upper limb function and EEG power after
a robot-assisted BAT in chronic stroke patients.

Methods. In a within-subject design, seven right-handed chronic stroke patients with upper limb paresis received 21 sessions (3 days/week) of the robot-assisted BAT. The outcomes were changes in score on the upper limb section of the Fugl-Meyer assessment (FM), Motricity Index (MI), and Modified Ashworth Scale (MAS) evaluated at the baseline (T0), posttraining (T1), and 1-month follow-up (T2). Event-related desynchronization/synchronization were calculated in the upper alpha and the beta frequency ranges.

Results. Significant improvement in all outcomes was measured over the course of the study. Changes in FM were significant at T2, and in MAS at T1 and T2. After training,
desynchronization on the ipsilesional sensorimotor areas increased during passive and active movement, as compared with T0.

Conclusions. A repetitive robotic-assisted BAT program may improve upper limb motor function and reduce spasticity in the chronically impaired paretic arm. Effects on spasticity were associated with EEG changes over the ipsilesional sensorimotor network.

1. Introduction

Poststroke upper limb impairment strongly influences
disability and patients’ quality of life [1, 2]. Considering that
up to two-thirds of stroke survivors suffer from upper limb
dysfunctions, one of the main goals of rehabilitation is to
improve recovery of upper limb functioning. Many
rehabilitation approaches have been put forward [3–5].
However, there is strong evidence that the conceptual evolution
of stroke rehabilitation promotes high-intensity, taskspecific,
and repetitive training [3, 5, 6]. To this end, the
application of robot-assisted therapy has steadily gained
acceptance since the 1990s [7, 8]. Robotic devices, in fact,
allow repetitive, interactive, high-intensity, and task-specific

upper limb training across all stages of recovery and neurological
severity as well [6].
A meta-analysis has shown significant, homogeneous
positive summary effect sizes (SESs) for upper limb motor
function improvements and muscle strength with the use of
elbow-wrist robots in a bilateral mode [5]. Although subgroup
analysis revealed no significant differences between
phases post stroke [5], bilateral arm training (BAT) has
shown great promise in expediting progress toward poststroke
recovery of upper limb functioning even in the chronic
phase [6, 9–11].
BAT is a form of training in which both upper limbs perform
the same movements simultaneously and independently
of each other [12]. It can be undertaken in different
modes (in-phase, antiphase) and training modalities (i.e.,
active, passive, and active-passive) [13]. The beneficial effects
of BAT are thought to arise from a coupling effect in which
both limbs adopt similar spatio-temporal movement parameters
leading to a sort of coordination [14]. Active-passive
BAT of the wrist has been investigated in behavioral and neurophysiological
studies [11, 15]. It consists of rhythmic, continuous
bimanual mirror symmetrical movements during
which the patient actively flexes and extends the “unaffected”
wrist, while the device assists the movement of the “affected”
wrist in a mirrored, symmetrical pattern via mechanical coupling
[15–19]; that is, movement of the affected upper limb is
facilitated by the unaffected one [12]. Previous studies have
reported that this pattern of coordinated movement leads
to improvements in upper limb function [11, 16, 19, 20] associated
with an increase in ipsilesional corticomotor excitability
[11]. In addition, passive BAT of the forearm and the wrist
has been shown to lead to a sustained reduction of muscle
tone in hemiparetic patients with upper limb spasticity [20].
Current evidence indicates that the neural correlates of
BAT are poorly understood [13]. The limitations of previous
studies are threefold. First, patient characteristics such as
type and site of stroke lesion were not consistently reported
[21], precluding full understanding of motor and neural
responses to BAT. Second, different BAT modalities (i.e.,
in-phase, antiphase, active, and active-passive) combined or
not with other interventions (i.e., functional tasks or free
movements with rhythmic auditory cues) have been
reported. As different training modalities are thought to
exploit different clinical effects and neural mechanisms
[22], the relationship between each of these specific modes
(delivered as a single intervention) and brain activity patterns
needs to be more precisely explored [13]. Finally, a wide
range and variation of neurophysiological and neuroimaging
measures have been used among studies.
Essentially, transcranial magnetic stimulation (TMS)
and functional magnetic resonance imaging (fMRI) studies
have been used to investigate the neural correlates of BAT.
Strength and weakness might be acknowledged for both
techniques when applied in a neurorehabilitation setting
[23]. TMS is an important tool that fits in the middle of
the functional biology continuum for assessment in stroke
recovery. However, it has the disadvantage of not being as
relevant as other biologic measures in gathering information
on brain activity during different states (or tasks) [23],
unless electroencephalography (EEG) is recorded simultaneously
Functional imaging and related techniques ((fMRI),
positron emission tomography (PET), EEG, magnetoencephalography
(MEG), and near-infrared spectroscopy (NIRS))
are important tools to determine the effects of brain injury
and how rehabilitation can change brain systems [23].
fMRI is the most widely used technique for studying brain
function. Several fMRI studies have described movementrelated
changes in motor cortical activation during partial
recovery of the affected limb in stroke patients [25], and
many studies have described the effects of various rehabilitative
treatments on motor activation.
fMRI shows difficulties when exploring brain functions
during robot-assisted sensorimotor tasks because only a few
devices are MRI compatible [26–28] and their use in the clinical
setting is limited by regulation (i.e., CE marking).
The EEG technique, conversely, has considerable
advantages over other methods in the rehabilitation setting
[17, 18, 29] being portable and readily operable with different
robotic devices. Finally, the higher temporal resolution of
EEG than fMRI signals allows monitoring brain activity during
movement execution [30–32]. EEG alpha and beta band
powers decrease during motor execution over the premotor
and primary sensorimotor cortex; at the end of the movement,
a rebound of beta activity is observed over the ipsilesional
side. These power changes are termed, respectively,
event-related desynchronization (ERD)—that is, power band
decrease—and event-related synchronization (ERS)—that is,
power band increase [33].
To the best of our knowledge, no study has addressed
changes in EEG power alongside changes in upper limb
motor function after passive robot-assisted BAT (RBAT).
Therefore, the aim of this pilot study was to evaluate
changes in both EEG power by investigating the
topographical distribution of event ERD/ERS, and upper
limb recovery of function after passive R-BAT in chronic
stroke patients. Conducting a small-scale pilot study
before the main study can enhance the likelihood of success
of the main study. Moreover, information gathered
in this pilot study would be used to refine or modify
the research methodology and to develop large-scale studies
[34]. The work hypothesis was that R-BAT would
improve recovery of upper limb function and that these
effects would be associated with an increase in activation of
the ipsilesional hemisphere.[…]

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[Abstract] Efficacy and safety of NABOTA in post-stroke upper limb spasticity: A phase 3 multicenter, double-blinded, randomized controlled trial


A phase III clinical trial was performed for a novel botulinum toxin A, NABOTA, on post-stroke upper limb spasticity.

NABOTA demonstrated non-inferiority on efficacy and safety compared to onabotulinum toxin A (Botox).

NABOTA may serve as an alternative for treatment of post-stroke upper limb spasticity using botulinum toxin A.


Botulinum toxin A is widely used in the clinics to reduce spasticity and improve upper limb function for post-stroke patients. Efficacy and safety of a new botulinum toxin type A, NABOTA (DWP450) in post-stroke upper limb spasticity was evaluated in comparison with Botox (onabotulinum toxin A). A total of 197 patients with post-stroke upper limb spasticity were included in this study and randomly assigned to NABOTA group (n = 99) or Botox group (n = 98). Wrist flexors with modified Ashworth Scale (MAS) grade 2 or greater, and elbow flexors, thumb flexors and finger flexors with MAS 1 or greater were injected with either drug. The primary outcome was the change of wrist flexor MAS between baseline and 4 weeks post-injection. MAS of each injected muscle, Disability Assessment Scale (DAS), and Caregiver Burden Scale were also assessed at baseline and 4, 8, and 12 weeks after the injection. Global Assessment Scale (GAS) was evaluated on the last visit at 12 weeks. The change of MAS for wrist flexor between baseline and 4 weeks post-injection was − 1.44 ± 0.72 in the NABOTA group and − 1.46 ± 0.77 in the Botox group. The difference of change between both groups was 0.0129 (95% confidence interval − 0.2062–0.2319), within the non-inferiority margin of 0.45. Both groups showed significant improvements regarding MAS of all injected muscles, DAS, and Caregiver Burden Scale at all follow-up periods. There were no significant differences in all secondary outcome measures between the two groups. NABOTA demonstrated non-inferior efficacy and safety for improving upper limb spasticity in stroke patients compared to Botox.


via Efficacy and safety of NABOTA in post-stroke upper limb spasticity: A phase 3 multicenter, double-blinded, randomized controlled trial – ScienceDirect

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[Abstract] Transcranial and spinal cord magnetic stimulation in treatment of spasticity: a literature review and meta-analysis

INTRODUCTION: Spasticity is associated with various diseases of the nervous system. Current treatments such as drug therapy, botulinum toxin injections, kinesitherapy, and physiotherapy are not sufficiently effective in a large number of patients. Transcranial magnetic stimulation (TMS) can be considered as an alternative method of treatment. The purpose of this article was to conduct a systematic review and meta-analysis of all available publications assessing the efficacy of repetitive TMS in treatment of spasticity.

EVIDENCE ACQUISITION: Search for articles was conducted in databases PubMed, Willey, and Google. Keywords included “TMS”, “spasticity”, “TMS and spasticity”, “non-invasive brain stimulation”, and “non-invasive spinal cord stimulation”. The difference in scores according to the Modified Ashworth Scale (MAS) for one joint before and after treatment was taken as the effect size.
EVIDENCE SYNTHESIS: We found 26 articles that examined the TMS efficacy in treatment of spasticity. Meta-analysis included 6 trials comprising 149 patients who underwent real stimulation or simulation. No statistically significant difference in the effect of real and simulated stimulation was found in stroke patients. In patients with spinal cord injury and spasticity, the mean effect size value and the 95% confidence interval were -0.80 and (-1.12, -0.49), respectively, in a group of real stimulation; in the case of simulated stimulation, these parameters were 0.15 and (-0.30, -0.00), respectively. Statistically significant differences between groups of real stimulation and simulation were demonstrated for using high-frequency repetitive TMS or iTBS mode for the M1 area of the spastic leg (P=0.0002).
CONCLUSIONS: According to the meta-analysis, the statistically significant effect of TMS in the form of reduced spasticity was demonstrated only for the developed due to lesions at the brain stem and spinal cord level. To clarify the amount of the antispasmodic effect of repetitive TMS at other lesion levels, in particular in patients with hemispheric stroke, further research is required.

via Transcranial and spinal cord magnetic stimulation in treatment of spasticity: a literature review and meta-analysis – European Journal of Physical and Rehabilitation Medicine 2018 February;54(1):75-84 – Minerva Medica – Journals

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[Abstract] Long-term safety of repeated high doses of incobotulinumtoxinA injections for the treatment of upper and lower limb spasticity after stroke


    Current guidelines suggested a dosage up to 600 units (U) of botulinum toxin type A (BoNT-A) in post-stroke spasticityHigh doses of incobotulinumtoxinA (840U) showed efficacy and safety in severe post-stroke upper and lower limb spasticityIn a 2-year follow-up on 20 patients, a reduction of spasticity/disability was found with repeated high doses of incobotulinumtoxinAOne month after the last BoNT-A administration, the efficacy on spasticity/disability was similar to that at baselineLong-term treatment with high doses of incobotulinumtoxinA was safe and effective in post-stroke upper and lower limb spasticity


Current guidelines suggested a dosage up to 600 units (U) of botulinum toxin type A (BoNT-A) (onabotulinumtoxinA or incobotulinumtoxinA) in reducing spastic hypertonia with low prevalence of complications, although a growing body of evidence showed efficacy with the use of high doses (> 800 U). The available evidence mainly referred to a single set of injections evaluating the efficacy and safety of the neurotoxin 30 days after the treatment. In a prospective, non-randomized, open-label study, we studied the safety of repeated higher doses of incobotulinumtoxinA in post-stroke upper and lower limb spasticity.

Two years after the first set of injections, we evaluated in 20 stroke survivors with upper and lower limb spasticity the long-term safety of repeated high doses of incobotulinumtoxinA (up to 840 U) for a total of eight sets of injections.

Patients reported an improvement of their clinical picture concerning a reduction of spasticity measured with the Asworth Scale (AS) for elbow, wrist, fingers and ankle flexor muscles and disability measured with the Disability Assessment Scale (DAS) 30 days after the last set of injections (eighth set) compared to the baseline (p < 0.0001). No difference in AS and DAS scores has been found between t1 (30 days after the first injection set) and t2 (30 days after the eighth set of injections), with also similar safety.

In a two-year follow-up, repeated high doses of incobotulinumtoxinA, administered for eight sets of injections, appeared to be safe in patients with upper and lower limb spasticity after stroke without general adverse effects.


via Long-term safety of repeated high doses of incobotulinumtoxinA injections for the treatment of upper and lower limb spasticity after stroke – ScienceDirect

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[ARTICLE] Treatment of Upper Limb Spasticity after Stroke: One-Year Safety and Efficacy of Botulinum Toxin Type A NT201 – Full Text PDF

A new preparation of botulinum toxin type A called NT 201, free from complexing proteins, potentially with low antigenicity has been used in the therapy of spasticity in stroke patients. This was an open-label study reported the safety and the efficacy of one-year treatment with NT 201 evaluating the therapeutic effect on functional disability and on quality of life in upper limb spasticity after stroke. Patients received a botulinum toxin therapy in the upper injected intramuscularly. After inoculation, patients were submitted to a motor rehabilitation program for upper limb injected three times/week. Re-treatment was permitted at 12 weeks after the prior treatment. Safety assessment included evaluation of adverse events and efficacy was measured by Modified Ashworth Scale for spasticity (MAS), Spasm Frequency Score (SFS) for the daily spasms, and Disability Assessment Scale (DAS) for disability. Of 35 consecutive patients (13 women and 12 men) screened for study eligibility, 20 (6 women and 14 men) patients (mean age 63,4±7,03) were included in this study and were submitted to NT 201 therapy for one year. At the baseline, botulinum toxin dose in the upper limb ranged from 160 to 450U, whereas total dose in the last treatment administrated was reduced respect the first injections ranging from 120 to 350U. All the enrolled patients completed the year-long study and reported an improvement of clinical picture. MAS, was statistically (p<0,001) reduced in all muscles at T1 (mean score ±SD: 2.65±0.67) and T2 (mean score ±SD: 2.55±0.60) in comparison to the baseline T0 (mean score ±SD: 3.9±0.78). Significant reduction (p<0,001) from baseline T0 (mean score ±SD: 3.25± 0.78) was also noted in SFS at T1 (mean score ±SD: 1.55±0.51) and T2 (mean score ±SD: 1.30±0.47). The DAS score showed a reduction of the T1score (mean score ±SD: 1.70±0.47) and T2 score (mean score ±SD: 1,40±0,50) respect to baseline T0 score (mean score ±SD: 2,65±0,48) statistically significant (p<0,001). No adverse effects were observed in these patients. NT 201 appeared to be an efficacious and well-tolerated long-term treatment option for patients with upper limb spasticity after stroke, obtaining a substantial improvement in functional disability, muscle hypertone, and daily spasms.


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via Treatment of Upper Limb Spasticity after Stroke: One-Year Safety and Efficacy of Botulinum Toxin Type A NT201 – P. Fiore, A. Santamato, M. Ranieri, R.G. Bellomo, R. Saggini, F. Panza, G. Megna, G. Cristella, M. Megna, 2012

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[ARTICLE] Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial – Full Text


Lower limb spasticity in post-stroke patients can impair ambulation and reduces activities of daily living (ADL) performance of patients. Botulinum toxin type A (BoNTA) has been shown effective for upper limb spasticity. This study assesses the treatment of lower limb spasticity in a large placebo-controlled clinical trial. In this multicenter, randomized, double-blind, parallel-group, placebo-controlled study, we evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke lower limb spasticity. One hundred twenty patients with lower limb spasticity were randomized to a single treatment with BoNTA 300 U or placebo. The tone of the ankle flexor was assessed at baseline and through 12 weeks using the Modified Ashworth Scale (MAS). Gait pattern and speed of gait were also assessed. The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS ankle score. Significant improvement in spasticity with BoNTA 300 U was demonstrated by a mean difference in the AUC of the change from baseline in the MAS ankle score between the BoNTA and placebo groups (−3.428; 95% CIs, −5.841 to −1.016; p = 0.006; t test). A significantly greater decrease from baseline in the MAS ankle score was noted at weeks 4, 6 and 8 in the BoNTA group compared to the placebo group (p < 0.001). Significant improvement in the Clinicians Global Impression was noted by the investigator at weeks 4, 6 and 8 (p = 0.016–0.048, Wilcoxon test), but not by the patient or physical/occupational therapist. Assessments of gait pattern using the Physician’s Rating Scale and speed of gait revealed no significant treatment differences but showed a tendency towards improvement with BoNTA. No marked difference was noted in the frequency of treatment-related adverse events between BoNTA and placebo groups. This was the first large-scale trial to indicate that BoNTA significantly reduced spasticity in lower limb muscles.


Spasticity is defined by Lance as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one of the components of upper motor neuron syndrome [1].

BoNTA (botulinum toxin type A, onabotulinumtoxinA1) is a specific formulation of a locally injected muscle relaxant whose active ingredient is botulinum toxin type A produced by Clostridium botulinum. Botulinum toxin type A binds to the receptors in the presynaptic, cholinergic motor nerve terminal and is taken up by the nerve cells where the light chain of toxin cleaves a synaptosome-associated protein (SNAP-25) to inhibit acetylcholine release from the nerve terminal. As its muscle relaxant effect is exerted in the hypertonic muscle, BoNTA offers an alternative treatment for spastic patients who have difficulty with oral muscle relaxants that can produce generalized weakness and drowsiness, cognitive impairment, and/or a reduced level of arousal. Locally injected BoNTA is expected to improve limb position and functional ability, and reduce pain in patients with spasticity. Moreover, BoNTA has no sedative action, unlike existing oral antispastic treatments, and therefore can be used in patients with cognitive impairment or a reduced level of arousal. Based on these considerations, BoNTA is a first-line treatment choice if the upper and lower limb spasticity is focal and reversible without contracture [2].

The efficacy and safety of BoNTA in patients with post-stroke lower limb spasticity have been suggested by randomized-controlled trials of limited scale [345678] and meta-analysis [9]. The efficacy of BoNTA in patients with severe brain injury has also been demonstrated in a randomized-control trial [10]. Approved treatments of spasticity in Japan include peripheral and central muscle relaxants, alcohol, phenol block, and intrathecal baclofen (only in cases of severe spastic paralysis). We conducted a clinical study to evaluate the efficacy and safety of BoNTA in Japanese patients with post-stroke lower limb spasticity who received a single placebo-controlled injection of BoNTA followed by open-label repeated treatment of up to three sessions. This article reports the efficacy and safety results of the double-blind phase. […]


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[Abstract] Botulinum toxin type A in post-stroke upper limb spasticity


To evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke upper limb spasticity.

Research design and methods:

In a multicentre, randomised, double-blind, parallel-group, placebo-controlled study, 109 patients with upper limb spasticity were randomised to receive a single treatment with lower-dose (120–150 U) or higher-dose (200–240 U) BoNTA or placebo into upper limb muscles.

Main outcome measures:

The tone of the wrist flexor was assessed at baseline and at weeks 0, 1, 4, 6, 8 and 12 using the Modified Ashworth Scale (MAS) for wrist, finger, thumb and disability in activities of daily living (ADL) was rated using the 4-point Disability Assessment Scale (DAS). The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS wrist score in the higher-dose groups.


Subjects were randomised with 51 in the higher BoNTA group, 26 in the higher-dose placebo group, 21 in the lower BoNTA group and 11 in the lower-dose placebo group. Significant improvement in spasticity with higher-dose BoNTA was demonstrated by a mean difference in the AUC of the change from baseline in the MAS wrist score between the higher-dose BoNTA group and the higher-dose placebo group of −6.830 (p < 0.001, t-test), no significant different was demonstrated between the lower-dose BoNTA group and the lower-dose placebo group (p = 0.215, t-test). Significant improvements with higher-dose BoNTA were also observed in the DAS scores for limb position (p = 0.001–0.022) at all time points and dressing (p = 0.018–0.038, Wilcoxon test) at weeks 6, 8 and 12. No clinically relevant difference was noted in the frequency of treatment-related adverse events between BoNTA-treated and placebo-treated patients. The long-term efficacy and safety, and the effects on rehabilitation of BoNTA on upper limb will be evaluated using the data obtained in the open-label phase.


Higher-dose BoNTA reduced spasticity in upper limb muscles and improved ADL performance in terms of limb position and dressing. BoNTA is safe and effective in the treatment of post-stroke upper limb spasticity.


via Botulinum toxin type A in post-stroke upper limb spasticity: Current Medical Research and Opinion: Vol 26, No 8

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