Posts Tagged Spasticity

[Abstract] Sporadic distant neurotoxin effects in the chronic treatment of spasticity


Neurotoxin therapy is an effective component of comprehensive spasticity management. The two cases presented demonstrate adverse effects.

Material and method

Patient S is a 60-year-old female with right spastic hemiparesis due to left hemispheric stroke (age 46) treated with therapy, bracing, oral baclofen. Patient R is a 28-year-old female with left spastic hemiparesis due to hemispherectomy (age 6).


For patient S, onabotulinumtoxinA (ONA) was initiated at 300 units (u) to the right upper extremity (RUE), advanced to 500u. She received injections every 3–3.5 months for over 9 years and continued to function independently. At routine follow-up, she related left upper extremity (LUE) weakness that she noted but did not report with her two prior injections. She denied any other symptoms. Examination revealed mild, diffuse LUE weakness, imaging was unremarkable and EMG demonstrated a chronic LUE axonal polyradiculopathy. ONA was continued at 300u to the RUE with somewhat lesser but maintained benefit without adverse effects.

For patient R, ONA was initiated at 400u to the LUE every three months for 13 rounds, advanced to 500u. Contralateral (RUE) weakness developed after the second round of 500u dosing. Diagnostic evaluation was notable only for increased insertional activity, fibrillationpotentials and decreased recruitment with subsequent long duration polyphasic motor unitpotentials. Unchanged with high dose steroids, weakness improved with IVIG. Repeat ONA with 500u resulted in good local effect, recurrent contralateral upper and lower extremity weakness. EMG demonstrated contralateral cervical, thoracic and lumbosacral axonal polyradiculopathy. Symptoms improved with IVIG. Patient declined subsequent ONA.


Both patients were treated with neurotoxin therapy for 3–9 years with good clinical response before developing the adverse reaction. Weakness distant to the injection sites is supported by electrodiagnostic findings of contralateral axonal polyradiculopathy. The clinical presentations suggest the possibility that the adverse effect of distant weakness may be immune-mediated and dose-related.


via Sporadic distant neurotoxin effects in the chronic treatment of spasticity – ScienceDirect


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[Brochure] “Spasticity Treatment Dialogue Tool” for Patients/Caregivers and Healthcare Providers

Spasticity is one of the most common post-stroke conditions affecting stroke survivors. It is caused by damage to the brain that disrupts normal communication to muscles. Muscles do not receive the message to relax which can lead to severe spasms and contractions in locations such as the wrist, elbow, knee, or foot. Untreated, it can cause painful and debilitating bone and joint deformities that may lead to balance problems, loss of coordination and muscle movement, as well as a decrease in the overall quality of life.


Some common symptoms of spasticity include:

  • Tightness in limbs
  • Pain at affected site
  • Severe charley horse/cramps
  • Involuntary movement/spasms
  • Distortion of muscles/limbs

Finding the right treatment option for each individual patient is key to managing the difficult symptoms caused by spasticity. The “Spasticity Treatment Dialogue Tool” is designed to support an honest conversation between caregivers/patients and their healthcare providers.

Download Now

via Careliving Community Roundup- June, 2018 – – Gmail

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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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[Online Game] Mobility Mission Online Game –

Mobility Mission Online Game

Mobility Mission is an entertaining online game that addresses post-stroke mobility challenges. Stroke is a serious condition, and learning to deal with the effects of surviving a stroke can be challenging. This game will help you gain a better understanding of post-stroke mobility challenges such as spasticity, paralysis, foot drop, as well as management and treatment options you can discuss with your healthcare provider. As you travel through the four levels of the game you will learn how to improve your safety at home and acquire tips to lower your risk of falling. Your journey is waiting!



via Mobility Mission Online Game |

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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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