Pharmacological interventions other than botulinum toxin for spasticity after stroke.

BACKGROUND: The long-term risk of stroke increases with age, and stroke is a common cause of disability in the community. Spasticity is considered a significantly disabling impairment that develops in people who have had a stroke. The burden of care is higher in stroke survivors who have spasticity when compared with stroke survivors without spasticity with regard to treatment costs, quality of life, and caregiver burden. OBJECTIVES: To assess if pharmacological interventions for spasticity are more effective than no intervention, normal practice, or control at improving function following stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 5), MEDLINE (1946 to May 2016), Embase (2008 to May 2016), CINAHL (1982 to May 2016), AMED (1985 to May 2016), and eight further databases and trial registers. In an effort to identify further studies, we undertook handsearches of reference lists and contacted study authors and commercial companies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any systemically acting or locally acting drug versus placebo, control, or comparative drug with the aim of treating spasticity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and extracted the data. We assessed the included studies for both quality and risk of bias. We contacted study authors to request further information when necessary. MAIN RESULTS: We included seven RCTs with a total 403 participants. We found a high risk of bias in all but one RCT. Two of the seven RCTs assessed a systemic drug versus placebo. We pooled data on an indirect measure of spasticity (160 participants) from these two studies but found no significant effect (odds ratio (OR) 1.66, 95% confidence interval (CI) 0.21 to 13.07; I(2) = 85%). We identified a significant risk of adverse events per participant occurring in the treatment group versus placebo group (risk ratio (RR) 1.65, 95% CI 1.12 to 2.42; 160 participants; I(2) = 0%). Only one of these studies used a functional outcome measure, and we found no significant difference between groups.Of the other five studies, two assessed a systemic drug versus another systemic drug, one assessed a systemic drug versus local drug, and the final two assessed a local drug versus another local drug. AUTHORS' CONCLUSIONS: The lack of high-quality RCTs limited our ability to make specific conclusions. Evidence is insufficient to determine if systemic antispasmodics are effective at improving function following stroke

The problems and limitations of cohort studies

Chronic obstructive pulmonary disease (COPD) is the third most common cause of mortality worldwide and it is important to discover whether risk factors can be identified from studies undertaken in childhood. Numerous longitudinal cohort studies have been developed in many parts of the world to better understand the long-term outcomes of chronic respiratory diseases. Using data they have generated, it should be possible to identify specific risk factors in children and develop a model to prioritise their importance when found, in order to consider ways to reduce the prevalence and/or severity of disease in adults. However, this does require the sharing of data within the field, as is happening in other related fields, such as the Virtual International Stroke Trial Archive (www.vista.gla.ac.uk). Pooling of the raw data could be very informative and an organisation such as the European Respiratory Society could play an important role in ensuring this happens. Unfortunately, cohort studies vary widely in their inclusion criteria, their methodology and the format in which lung function data are presented. The raw data required to develop a model to assess the impact of childhood risk factors on future lung function have not been made available from many of the published articles. Our initial belief that recognised risk factors are independent variables was naı¨ve and a different approach is required to better understand their interdependenc

How reproductive ecology contributes to the spread of a globally invasive fish

The work was funded by Natural Environment Research Council (NERC) (UK) and the European Research Council.Invasive freshwater fish represent a major threat to biodiversity. Here, we first demonstrate the dramatic, human-mediated range expansion of the Trinidadian guppy (Poecilia reticulata), an invasive fish with a reputation for negatively impacting native freshwater communities. Next, we explore possible mechanisms that might explain successful global establishment of this species. Guppies, along with some other notable invasive fish species such as mosquitofish (Gambusia spp.), have reproductive adaptations to ephemeral habitats that may enable introductions of very small numbers of founders to succeed. The remarkable ability of single pregnant guppies to routinely establish viable populations is demonstrated using a replicated mesocosm set up. In 86% of cases, these populations persisted for two years (the duration of the experiment). Establishment success was independent of founder origin (high and low predation habitats), and there was no loss of behavioural performance amongst mesocosm juveniles. Behavioural "signatures" of the founding locality were, however, evident in mesocosm fish. Our results demonstrate that introductions consisting of a single individual can lead to thriving populations of this invasive fish and suggest that particular caution should be exercised when introducing this species, or other livebearers, to natural water bodies.Peer reviewe

Designing a trial of early electrical stimulation to the stroke-affected arm: Qualitative findings on the barriers and facilitators

Introduction: This study aimed to explore the barriers and facilitators to implementing early therapeutic electrical stimulation (ES) treatment from both the patient and therapist perspectives as part of a feasibility study. Methods Design: Interviews were conducted with patients and their carers and focus groups with the therapists post-intervention period. Setting: Interviews were in the patient’s homes and for the focus groups in a specialist stroke unit in Nottinghamshire. Subjects: Fifteen patient participants (34% of sample) were interviewed (intervention n = 9; control group n = 3; carers n = 3). Sixteen therapists (9 occupational therapists; 7 physiotherapists) took part in the three focus groups. Intervention: Participants were randomized to receive usual care or usual care and ES to wrist flexors and extensors for 30 min, twice a day, 5 days a week for 3 months. Findings: The barriers to ES treatment cited by the therapists outweighed the barriers mentioned by patients. Therapists’ barriers included lack of confidence and staff knowledge regarding ES and time pressures of delivering the ES. No patients mentioned time as a barrier and considered the treatment regime to be acceptable; however, lack of staff support was mentioned 14 times by them. Conclusion: Although initially the perceived barrier for therapists was time restrictions, after analysing the data, it appears that confidence/knowledge is the real barrier, and time is the manifestation of this underlying self-doubt. Patients were able to confidently self-manage treatment, and although efficacy was not measured, patients volunteered information regarding its perceived benefit, and no adverse effects were reported

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56

The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial.

BACKGROUND: Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain, stiffness and contractures. The abnormal muscle activity, associated with post-stroke spasticity, is thought to be causally associated with the development of these complications. Treatment of spasticity is currently delayed until a patient develops signs of these complications. METHODS/DESIGN: This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA (BoNT-A) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial. All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm. Those who have no function will be appropriate for further screening. Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline. The primary outcome measure is the action research arm test - a measure of arm function. Further measures include spasticity, stiffness, muscle strength and fatigue as well as measures of quality of life, participation and caregiver strain. TRIAL REGISTRATIONS: ISRCTN57435427, EudraCT2010-021257-39, NCT01882556

Upper limb impairments associated with spasticity in neurological disorders

<p>Abstract</p> <p>Background</p> <p>While upper-extremity movement in individuals with neurological disorders such as stroke and spinal cord injury (SCI) has been studied for many years, the effects of spasticity on arm movement have been poorly quantified. The present study is designed to characterize the nature of impaired arm movements associated with spasticity in these two clinical populations. By comparing impaired voluntary movements between these two groups, we will gain a greater understanding of the effects of the type of spasticity on these movements and, potentially a better understanding of the underlying impairment mechanisms.</p> <p>Methods</p> <p>We characterized the kinematics and kinetics of rapid arm movement in SCI and neurologically intact subjects and in both the paretic and non-paretic limbs in stroke subjects. The kinematics of rapid elbow extension over the entire range of motion were quantified by measuring movement trajectory and its derivatives; i.e. movement velocity and acceleration. The kinetics were quantified by measuring maximum isometric voluntary contractions of elbow flexors and extensors. The movement smoothness was estimated using two different computational techniques.</p> <p>Results</p> <p>Most kinematic and kinetic and movement smoothness parameters changed significantly in paretic as compared to normal arms in stroke subjects (p < 0.003). Surprisingly, there were no significant differences in these parameters between SCI and stroke subjects, except for the movement smoothness (p ≤ 0.02). Extension was significantly less smooth in the paretic compared to the non-paretic arm in the stroke group (p < 0.003), whereas it was within the normal range in the SCI group. There was also no significant difference in these parameters between the non-paretic arm in stroke subjects and the normal arm in healthy subjects.</p> <p>Conclusion</p> <p>The findings suggest that although the cause and location of injury are different in spastic stroke and SCI subjects, the impairments in arm voluntary movement were similar in the two spastic groups. Our results also suggest that the non-paretic arm in stroke subjects was not distinguishable from the normal, and might therefore be used as an appropriate control for studying movement of the paretic arm.</p

Development of spasticity with age in a total population of children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>The development of spasticity with age in children with cerebral palsy (CP) has, to our knowledge, not been studied before. In 1994, a register and a health care program for children with CP in southern Sweden were initiated. In the programme the child's muscle tone according to the modified Ashworth scale is measured twice a year until six years of age, then once a year. We have used this data to analyse the development of spasticity with age in a total population of children with cerebral palsy.</p> <p>Methods</p> <p>All measurements of muscle tone in the gastrocnemius-soleus muscle in all children with CP from 0 to 15 years during the period 1995–2006 were analysed. The CP subtypes were classified according to the Surveillance of Cerebral Palsy in Europe network system. Using these criteria, the study was based on 6218 examinations in 547 children. For the statistical analysis the Ashworth scale was dichotomized. The levels 0–1 were gathered in one category and levels 2–4 in the other. The pattern of development with age was evaluated using piecewise logistic regression in combination with Akaike's An Information Criterion.</p> <p>Results</p> <p>In the total sample the degree of muscle tone increased up to 4 years of age. After 4 years of age the muscle tone decreased each year up to 12 years of age. A similar development was seen when excluding the children operated with selective dorsal rhizotomy, intrathecal baclofen pump or tendo Achilles lengthening. At 4 years of age about 47% of the children had spasticity in their gastro-soleus muscle graded as Ashworth 2–4. After 12 years of age 23% of the children had that level of spasticity. The CP subtypes spastic bilateral and spastic unilateral CP showed the same pattern as the total sample. Children with dyskinetic type of CP showed an increasing muscle tone up to age 6, followed by a decreasing pattern up to age 15.</p> <p>Conclusion</p> <p>In children with CP, the muscle tone as measured with the Ashworth scale increases up to 4 years of age and then decreases up to 12 years of age. The same tendency is seen in all spastic subtypes. The findings may have implications both for clinical judgement and for research studies on spasticity treatment.</p

The relation between neuromechanical parameters and Ashworth score in stroke patients

Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin