Mohamed Sakel

RATIoNAle ANd deSIGN oF A MulTICeNTRe, douBle-BlINd, pRoSpeCTIve, RANdoMIzed, euRopeAN ANd CANAdIAN STudy: evAluATING pATIeNT ouTCoMeS ANd CoSTS oF MANAGING AdulTS WITH poST-STRoke FoCAl SpASTICITy

OBJECTIVE This report describes the design of a study aiming to provide evidence for the extended use of botulinum toxin A in focal post-stroke upper and lower limb spasticity and to evaluate the impact of incorporating botulinum toxin treatment into the rehabilitation of patients with spasticity. DESIGN International, prospective, randomized, double-blind, placebo-controlled study with an open-label extension. METHODS Approximately 300 adults with a stroke occurring ≥ 3 months before screening, presenting with symptoms and signs of an upper motor neuron syndrome and focal spasticity-related functional impairment, were randomized to botulinum toxin (BOTOX®, Allergan Inc.) + standard care or placebo + standard care. Study medication was administered at baseline and again at Week 12 if required, with follow-up to 52 weeks. The primary endpoint was the number of patients who achieved their investigator-rated principal active functional goal (as measured by Goal Attainment Scaling), at 10 weeks after the second injection (Weeks 22-34) or at the 24-week visit if no second injection was administered. Secondary endpoints included changes from baseline in level of goal achievement, health-related quality of life and resource utilization. CONCLUSION Botulinum toxin A Economic Spasticity Trial (BEST) will provide information regarding clinical and cost-effectiveness of botulinum toxin + standard care vs standard care alone in patients with upper and/or lower limb post-stroke spasticity typically seen in clinical practice. TRIAL REGISTRATION ClinicalTrials.gov number NCT-00549783.

Galvanic vestibular stimulation in hemi-spatial neglect

Hemi-spatial neglect is an attentional disorder in which the sufferer fails to acknowledge or respond to stimuli appearing in contralesional space. In recent years, it has become clear that a measurable reduction in contralesional neglect can occur during galvanic vestibular stimulation, a technique by which transmastoid, small amplitude current induces lateral, attentional shifts via asymmetric modulation of the left and right vestibular nerves. However, it remains unclear whether this reduction persists after stimulation is stopped. To estimate longevity of effect, we therefore conducted a double-blind, randomized, dose-response trial involving a group of stroke patients suffering from left-sided neglect (n = 52, mean age = 66 years). To determine whether repeated sessions of galvanic vestibular stimulation more effectively induce lasting relief than a single session, participants received 1, 5, or 10 sessions, each lasting 25 min, of sub-sensory, left-anodal right-cathodal noisy direct current (mean amplitude = 1 mA). Ninety five percent confidence intervals indicated that all three treatment arms showed a statistically significant improvement between the pre-stimulation baseline and the final day of stimulation on the primary outcome measure, the conventional tests of the Behavioral Inattention Test. More remarkably, this change (mean change = 28%, SD = 18) was still evident 1 month later. Secondary analyses indicated an allied increase of 20% in median Barthel Index (BI) score, a measure of functional capacity, in the absence of any adverse events or instances of participant non-compliance. Together these data suggest that galvanic vestibular stimulation, a simple, cheap technique suitable for home-based administration, may produce lasting reductions in neglect that are clinically important. Further protocol optimization is now needed ahead of a larger effectiveness study.

Functional goal achievement in post-stroke spasticity patients : The BOTOX® Economic Spasticity Trial (BEST)

OBJECTIVE Evaluate changes in active and passive function with onabotulinumtoxinA + standard of care within goal-oriented rehabilitation programmes in adults with focal post-stroke spasticity. METHODS Prospective, 24-week double-blind study with an open-label extension. Subjects were randomized to onabotulinumtoxinA + standard of care or placebo + standard of care, at baseline and at 12 weeks, if judged appropriate, with follow-up to 52 weeks. The primary endpoint was the number of patients achieving their principal active functional goal at 24 weeks (or 10 weeks after an optional second injection). Secondary endpoints included achievement of a different active or a passive goal at this timepoint. RESULTS The intent-to-treat population comprised 273 patients. The proportion of patients achieving their principal active functional goal and secondary active functional goal with onabotulinumtoxinA + standard of care was not statistically different from placebo + standard of care. Significantly more patients achieved their secondary passive goal with onabotulinumtoxinA + standard of care (60.0%) vs. placebo + standard of care (38.6%) (odds ratio, 2.46; 95% confidence interval, 1.18-5.14) as well as higher Goal Attainment Scaling levels for upper limb and ankle flexor subgroups. CONCLUSIONS Addition of onabotulinumtoxinA to standard of care as part of goal-oriented rehabilitation in post-stroke spasticity patients significantly increased passive goal achievement and was associated with higher levels of active function.

The effect of repeated sessions of galvanic vestibular stimulation on target cancellation in visuo-spatial neglect: Preliminary evidence from two cases

Objective: In recent years it has emerged that the attentional disorder of visuo-spatial neglect can be overcome via artificial stimulation of the balance system. One means of achieving this is via galvanic vestibular stimulation (GVS), a simple procedure in which tiny, electrical currents are discharged to the part of the scalp overlying the vestibular nerves. Attempts to remediate neglect with GVS have utilized only a single session of stimulation and, although this can induce spontaneous recovery, symptoms resurface soon after stimulation. This study assessed whether repeated sessions induce longer carry-over. Methods: Two individuals diagnosed with neglect post-stroke received 5 days of sub-sensory, left anodal GVS. Performance was assessed via the letter and star cancellation tasks of the Behavioural Inattention Test on four occasions; 3 days before the start of stimulation, on the first and last day of stimulation and 3-days after stimulation. Results: Analyses of variance indicated that both participants missed significantly fewer targets in both tasks on the fifth day of stimulation compared to baseline. More so, this improvement was still evident at follow-up 3 days later. Conclusion: The results strengthen the need for a larger, sham-controlled trial to establish whether repeated GVS provides lasting relief from neglect.

Safety of repeated sessions of galvanic vestibular stimulation following stroke: A single-case study

Primary objective: Galvanic vestibular stimulation (GVS) involves the delivery of small electrical current to the part of the scalp that overlies the vestibular nerves. A single, brief session transiently reduces certain types of stroke impairment with no reported side-effects. It is anticipated that further reductions will occur if the duration and frequency of stimulation is increased. The aim of the present study was to assess whether this increased exposure is well-tolerated and consistent with patient well-being. Methods and procedures: GVS was administered to a stroke sufferer on 5 consecutive days, each for 30 minutes at an intensity of 1 milliamp. Tolerability was monitored via a range of behavioural scales sensitive to side-effects experienced during and after stimulation. Results: No unpleasant sensations were reported during stimulation and no deterioration in global function was observed over the 5-day period. Conclusion: The results imply that repeated applications of GVS are tolerable at the parameter settings applied and provide the basis for larger-scale investigations of safety and efficacy.

Quantitative Assessment of Upper Limb Motion in Neurorehabilitation Utilizing Inertial Sensors

Two inertial sensor systems were developed for 3-D tracking of upper limb movement. One utilizes four sensors and a kinematic model to track the positions of all four upper limb segments/joints and the other uses one sensor and a dead reckoning algorithm to track a single upper limb segment/joint. Initial evaluation indicates that the system using the kinematic model is able to track orientation to 1 degree and position to within 0.1 cm over a distance of 10 cm. The dead reckoning system combined with the “zero velocity update” correction can reduce errors introduced through double integration of errors in the estimate in offsets of the acceleration from several meters to 0.8% of the total movement distance. Preliminary evaluation of the systems has been carried out on ten healthy volunteers and the kinematic system has also been evaluated on one patient undergoing neurorehabilitation over a period of ten weeks. The initial evaluation of the two systems also shows that they can monitor dynamic information of joint rotation and position and assess rehabilitation process in an objective way, providing additional clinical insight into the rehabilitation process.

Application of low cost inertial sensors to human motion analysis

In this paper the feasibility of utilizing low cost inertial sensors for human motion analysis is presented. The Xsens MTx sensor is used as the standard for comparison with the Sony Move and the Nintendo Wii (Wii Remote with Wii MotionPlus). Initial tests have been carried out by measuring upper limb range of motion and position tracking. Initial measurements utilizing kinematic modeling indicates that the MTx, whose static angle accuracy is 0.3°, can measure a movement of 10 cm with an error less than 0.05 cm. The low cost inertial sensors are capable of measuring the range of elbow flexion motion whose typical range is 150° with an error no greater than 1° and the Sony Move can track movement of 10 cm with an error less than 0.2 cm. In order to track position the system must include tri-axial accelerometers, rate gyros and magnetometers. This requirement is met by the Sony Move. The outcome is that Wii can be used for measuring upper limb range of motion and the Move for range of motion and position tracking based on the kinematic model.

Patients With Hemispatial Neglect Are More Prone to Limb Spasticity, but This Does Not Prolong Their Hospital Stay

OBJECTIVE To determine whether stroke patients who suffer from hemispatial neglect tend to stay in hospitals longer because they are prone to limb spasticity. DESIGN Retrospective analysis of inpatient medical notes. SETTING Inpatient neurorehabilitation unit of a regional UK teaching hospital. PARTICIPANTS All patients (N=106) admitted to the neurorehabilitation unit between 2008 and 2010 who had suffered a stroke, as confirmed by computed tomography or magnetic resonance imaging. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Statistical coincidence of hemispatial neglect and spasticity; length of hospital stay. RESULTS Chi-square analyses indicated that individuals with left neglect were nearly one third more likely to develop spasticity than those without neglect (87% vs 57%), while nearly one half of those with left-sided spasticity showed neglect (44% vs 13%). Individuals with neglect stayed in the hospital 45 days longer than those without neglect, but the presence or absence of spasticity did not affect length of stay. CONCLUSIONS The results provide the first statistical evidence, to the best of our knowledge, that neglect and limb spasticity tend to co-occur poststroke, though it is only the former that significantly prolongs stay. Diagnostic value aside, these results are important because they tell us that the treatment of neglect should not be overshadowed by efforts to reduce comorbid spasticity. Despite its poor prognosis, hemispatial neglect continues to receive little targeted therapy in some units.

Caloric vestibular stimulation in aphasic syndrome

Caloric vestibular stimulation (CVS) is commonly used to diagnose brainstem disorder but its therapeutic application is much less established. Based on the finding that CVS increases blood flow to brain structures associated with language and communication, we assessed whether the procedure has potential to relieve symptoms of post-stroke aphasia. Three participants, each presenting with chronic, unilateral lesions to the left hemisphere, were administered daily CVS for four consecutive weeks. Relative to their pre-treatment baseline scores, two of the three participants showed significant improvement on both picture and responsive naming at immediate and 1-week follow-up. One of these participants also showed improved sentence repetition, and another showed improved auditory word discrimination. No adverse reactions were reported. These data provide the first, albeit tentative, evidence that CVS may relieve expressive and receptive symptoms of aphasia. A larger, sham-controlled study is now needed to further assess efficacy.

Experiences of patients with traumatic brain injury and their carers during transition from in-patient rehabilitation to the community: a qualitative study

Abstract Purpose: To explore the experiences of individuals who have had a severe traumatic brain injury (TBI) and their carers in the first month post-discharge from in-patient rehabilitation into living in the community. Method: Using a qualitative approach underpinned by critical realism, we explored the narratives of 10 patients and nine carers using semi-structured interviews approximately one month post-discharge. Thematic analysis was carried out independently by two researchers. Results: Firstly, perceptions of support were mixed but many patients and carers felt unsupported in the inpatient phase, during transitions between units and when preparing for discharge. Secondly, they struggled to accept a new reality of changed abilities, loss of roles and loss of autonomy. Thirdly, early experiences post-discharge exacerbated fears for the future. Conclusions: Most patients and carers struggled to identify a cohesive plan that supported their transition to living in the community. Access to services required much persistence on the part of carers and tended to be short-term, and therefore did not meet their long-term needs. We propose the need for a case manager to be involved at an early stage of their rehabilitation and act as a key point for information and access to on-going rehabilitation and other support services. Implications for Rehabilitation Traumatic Brain Injury (TBI) is a major cause of long-term disability. It can affect all areas of daily life and significantly reduce quality of life for both patient and carer. Professionals appear to underestimate the change in abilities and impact on daily life once patients return home. Community services maintain a short-term focus, whereas patients and carers want to look further ahead – this dissonance adds to anxiety. The study’s findings on service fragmentation indicate an urgent need for better integration within health services and across health, social care and voluntary sectors. A link person/case manager who oversees the patient journey from admission onwards would help improve integrated care and ensure the patient, and carer, are at the center of service provision.