CLINICAL SPASTICITY ASSESSMENT USING THE MODIFIED TARDIEU SCALE DOES NOT REFLECT JOINT ANGULAR VELOCITY OR RANGE OF MOTION DURING WALKING: ASSESSMENT TOOL IMPLICATIONS

ObjectiveSpasticity assessment is often used to guide treatment decision-making. Assessment tool limitations may influence the conflicting evidence surrounding the relationship between spasticity and walking. This study investigated whether testing speeds and joint angles during a Modified Tardieu assessment matched lower-limb angular velocity and range of motion during walking.DesignObservational study.SubjectsThirty-five adults with a neurological condition and 34 assessors.MethodsThe Modified Tardieu Scale was completed. Joint angles and peak testing speed during V3 (fast) trials were compared with the same variables during walking in healthy people, at 0.40–0.59, 0.60–0.79 and 1.40–1.60 m/s. The proportion of trials in which the testing speed, start angle, and angle of muscle reaction matched the relevant joint angles and angular velocity during walking were analysed.ResultsThe Modified Tardieu Scale was completed faster than the angular velocities seen during walking in 88.7% (0.40–0.59 m/s), 78.9% (0.60– 0.79 m/s) and 56.2% (1.40–1.60 m/s) of trials. When compared with the normative dataset, 4.2%, 9.5% and 13.7% of the trials met all criteria for each respective walking speed.ConclusionWhen applied according to the standardized procedure and compared with joint angular velocity during walking, clinicians performed the Modified Tardieu Scale too quickly.LAY ABSTRACTSpasticity is an abnormal increase in muscle tightness, which is common following neurological injury. Spasticity has been shown to have a profound impact on an individual’s independence and quality of life. The main goal reported by patients in this population is to return to independent, normal walking. Yet, despite this there is a lack of consensus regarding the relationship between spasticity and walking outcomes. This may be due to a disconnect between clinical, bed-based assessment methods and how spasticity manifests during walking. This study aimed to establish how well a routine clinical assessment (the Modified Tardieu Scale) matched the speed and range of joint movement during walking. The findings suggest that, currently, clinicians performed the assessment too fast, which may lead to “false-positive” assessment findings. This may result in the identification and treatment of spasticity that is not impacting walking, leading to sub-optimal patient outcomes and significant healthcare wastage.Key words: muscle spasticity, patient outcome assessment, rehabilitation, brain injuries, gait, walking

Spasticity is a common impairment following neurological injury (1–5). The effective assessment and management of spasticity receives significant attention due to the detrimental effects it has on patient outcomes, carer burden, and quality of life (6, 7). Current spasticity guidelines recommend that only spasticity impacting function should receive intervention (8). As such, the role of a clinical assessment is to identify the presence of spasticity and decipher whether the spasticity warrants intervention, such as botulinum toxin-A (BoNT-A).Walking limitations are the most significant selfperceived, functional problem reported by individuals following neurological injury (9). A primary rehabilitation goal is often to improve walking independence, quality, speed, and endurance (10–12). In relation to spasticity, the clinician’s role is to identify whether spasticity is present, and subsequently determine if a patient’s walking may benefit from spasticity-related interventions.A definition of spasticity published by Pandyan et al. (13); “disordered sensori-motor control, resulting from an upper motor neurone lesion, presenting as intermittent or sustained involuntary activation of muscles’’, encompasses all the positive features of upper motor neurone syndrome (UMNS) under an umbrella term of spasticity. This terminology defines spasticity as a broader sensori-motor phenomenon (13), when compared with the more constrained, velocity-dependent definition published by Lance (14);”a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflexes, as one component of the UMNS” (14). For the purpose of this study, Lance’s definition has been used to define spasticity, since, with this definition, spasticity can be assessed as an individual construct. The Modified Tardieu Scale (MTS) is an often-recommended spasticity assessment, aligning with Lance’s (14) definition of spasticity (15–17). The MTS classifies the response of a relaxed muscle to a fast, passive stretch (V3). The assessment protocol involves a clinician moving the joint “as fast as possible” through its full range of motion (ROM) without specifying or measuring the speed of completion. The MTS is applied according to this standardized protocol regardless of the functional status or goals of the patient. For example, a household ambulator walking at ≤ 0.30 m/s is assessed at the same speed as a community ambulator walking at ≥ 0.80 m/s, whose muscles and joints are moving much faster when walking (18). This “one-size-fits” all approach does not take into account the variability in joint ROM and angular velocity (or speed of lowerlimb movement) with changes in walking speed (19). As such, the MTS may not sensitively discriminate individuals who have spasticity impacting their walking.While it is well established that interventions, such as BoNT-A, reduce spasticity at an impairment-based level, current treatment modalities for spasticity do not necessarily lead to improved walking outcomes (20–22). This may be because standardized protocols for scales such as the MTS do not reflect joint movement during walking (23–25). For example, if clinicians test at a speed that is slower than the joint angular velocity seen during walking, they may fail to identify spasticity that is affecting walking (i.e. false-negative). Conversely, if clinicians test at a speed that exceeds the joint angular velocity seen during walking, they may identify spasticity that is not impacting walking (i.e. false-positive).Matching the joint angles and testing speed of the MTS to the ROM and angular velocity seen during walking may assist in identifying patients who have spasticity impacting functional performance, leading to treatment decisions that optimize patient outcomes and healthcare resources. This study aimed to compare the joint start angle, angle of muscle reaction, and testing speed during a standardized MTS assessment of 4 major muscle groups of the lower-limb, collected in people with neurological conditions, with joint ROM and angular velocity in a healthy population walking at a range of speeds.     

SUSTAINED EFFICACY OF INCOBOTULINUMTOXINA FOLLOWING REPEATED INJECTIONS FOR UPPER-LIMB POST-STROKE SPASTICITY: A POST HOC ANALYSIS

ObjectiveThis post hoc analysis assessed the impact of repeated incobotulinumtoxinA injections on muscle tone, disability, and caregiver burden in adults with upper-limb post-stroke spasticity.DesignData from the double-blind, placebo-controlled main period and three open-label extension cycles of two Phase 3, randomized, multicentre trials were pooled.MethodsSubjects received incobotulinumtoxinA 400 Units at 12-week intervals (±3 days) (study 3001, {"type":"clinical-trial","attrs":{"text":"NCT01392300","term_id":"NCT01392300"}}NCT01392300) or ≤ 400 Units at ≥12-week intervals based on clinical need (study 0410, {"type":"clinical-trial","attrs":{"text":"NCT00432666","term_id":"NCT00432666"}}NCT00432666). Ashworth Scale (AS) arm sumscore (sum of elbow, wrist, finger and thumb flexor, and forearm pronator AS scores), Disability Assessment Scale (DAS), and Carer Burden Scale (CBS) scores were assessed.ResultsAmong 465 subjects, from study baseline to 4 weeks post-injection, mean (standard deviation) AS arm sumscore improved continuously: main period, –3.23 (2.55) (placebo, –1.49 (2.09)); extension cycles 1, 2, and 3, –4.38 (2.85), –4.87 (3.05), and –5.03 (3.02), respectively. DAS principal target domain responder rate increased from 47.4% in the main period (placebo 27.2%) to 66.6% in extension cycle 3. Significant improvements in CBS scores 4 weeks post-injection accompanied improved functional disability in all cycles.ConclusionIncobotulinumtoxinA conferred sustained improvements in muscle tone, disability, and caregiver burden in subjects with upper-limb poststroke spasticity.LAY ABSTRACTSpasticity (muscle overactivity) often occurs in patients after stroke and may lead to further disability. The results of 2 clinical trials were used to assess the effect of incobotulinumtoxinA injections (maximum dose used per injection session 400 Units) on arm and hand spasticity in patients after stroke. This study looked at the impact of treatment on disability and the burden on carers. The results from 4 treatment cycles were assessed. There was a continuous decrease in spasticity, together with improvements in disability in all treatment cycles. The burden on those who cared for patients also decreased. We showed that repeated incobotulinumtoxinA treatment across 4 cycles led to a decrease in spasticity, patient disability and burden on carers.Key words: botulinum neurotoxin, duration of effect, incobotulinumtoxinA, upper limb, spasticity, caregiver burden, rehabilitation

Stroke is an increasing cause of disability globally (1), and the development of spasticity in stroke survivors may contribute to further disability (2, 3). The prevalence of post-stroke spasticity ranges from 4.0% to 42.6% (2, 4, 5) and may be associated with reduced ability to perform the basic activities of daily living, and detrimental effects on quality of life (4, 6, 7). In addition to the loss of independence experienced by those affected, post-stroke spasticity can also result in a considerable burden on caregivers (6).The safety and efficacy of botulinum neurotoxin type A (BoNT-A) injections have been well established for the treatment of upper-limb post-stroke spasticity (8–13). Notably, the 24-week BEST study evaluated the efficacy and safety of onabotulinumtoxinA in adults with upper-limb or lower-limb post-stroke spasticity (n = 273), and the addition of onabotulinumtoxinA to the existing standard of care demonstrated improvements in passive goal-oriented activities compared with placebo, as well as additional benefits in active functional goals with no new safety signals (14).IncobotulinumtoxinA (Xeomin^®, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) is a BoNTA approved for the treatment of upper-limb spasticity at doses up to 400 Units (U) at intervals no sooner than every 12 weeks in the USA (15); while in Europe doses of up to 500 U at intervals of at least 12 weeks are approved, enabling treatment of a greater number of muscles (16). Two Phase 3 studies have confirmed the efficacy and safety of incobotulinumtoxinA in subjects with upper-limb post-stroke spasticity (17, 18); both studies included a placebo-controlled main period (MP) comprising a single injection cycle, followed by an open-label extension (OLEX) period with 3 fixed, 12-week incobotulinumtoxinA injection cycles (study 3001) (17), or a maximum of 5 flexible-duration injection cycles (study 0410) (19), respectively. Compared with placebo, incobotulinumtoxinA resulted in significant improvements in muscle tone (Ashworth Scale; AS) and functional disability (Disability Assessment Scale, DAS, for the principal target domain) 4 weeks post-treatment in the MP of both studies (17, 18). These improvements were sustained during the OLEX period of both studies (19–21) and associated with significant improvement in caregiver burden from the study baseline to the end of the OLEX period in study 3001 (21).We report here the results of a post hoc analysis, using data pooled from the MP and the first 3 OLEX injection cycles of both studies, to assess the efficacy of incobotulinumtoxinA in a large subject population using the AS sumscore; a novel approach that allows for a holistic clinical assessment of arm spasticity. In addition, we assess the impact of repeated incobotulinumtoxinA injections on caregiver burden in this large population.     

EARLY BRAIN IMAGING PREDICTORS OF POST-STROKE SPASTICITY

BackgroundPost-stroke spasticity is a major factor disturbing rehabilitation and functional recovery in stroke survivors. Clinical predictors of post-stroke spasticity have often been discussed, but brain image predictors for spasticity have been insufficiently researched. The aim of this study was to use magnetic resonance imaging data to identify early brain imaging predictors for potential development of spasticity after stroke.MethodsConsecutive patients admitted to a stroke unit were screened prospectively over 22 months. Patients with first-ever supratentorial ischaemic stroke were included in the study. Standardized clinical assessments for post-stroke spasticity were prospectively performed within 7 days and at 3 months. Brain imaging data (3 Tesla magnetic resonance imaging (3T MRI)) were collected at the baseline and evaluated.ResultsBrain imaging data from 103 stroke patients were collected in the hyperacute phase (< 7 days after stroke onset). A total of 23 patients developed post-stroke spasticity. The volumes of brain lesions involving motor network areas were significantly larger in patients with post-stroke spasticity compared with those without post-stroke spasticity (p < 0.01). Supratentorial lesion of < 0.5 cm³ were not associated with risk of post-stroke spasticity, except when the internal capsule and striatum was affected.ConclusionLesions involving motor network areas are considered to be a precondition of post-stroke spasticity. There is, however, a low risk of developing post-stroke spasticity with < 0.5 cm³ volumes of supratentorial brain lesions involving motor network areas. Larger volume brain lesions involving motor network areas, e.g. > 3 cm³, were significantly more common in patients with post-stroke spasticity. Pure cortical lesions has no risk of post-stroke spasticity in stroke survivors.LAY ABSTRACTPost-stroke spasticity is a major factor disturbing rehabilitation and functional recovery in stroke survivors. However, few studies have examined brain imaging predictors of post-stroke spasticity. Among patients with first-ever supratentorial ischaemic stroke, association between developing post-stroke spasticity, lesion site and lesion size were analysed in this prospective study. Every patient was clinically evaluated at baseline (7 days) and at 3 months. In magnetic resonance imaging (MRI) of the brain, small brain lesion volumes (< 0.5 cm³) were found to be associated with a low risk of developing post-stroke spasticity in patients with stroke. Larger lesion sizes (> 3 cm³) were significantly more common in patients with post-stroke spasticity and can be a positive predictor of post-stroke spasticity.Key words: spasticity, stroke, predictor

The earlier the complications of stroke are identified, the greater is the likelihood that patients will avoid secondary and tertiary complications, and the better their prognosis. Therefore the earlier the risk of development of post-stroke spasticity (PSS) is predicted or detected after a stroke, as one of the “plus symptom” following stroke, the more responsive patient management can be to avoid complications and improve prognosis (1, 2). If severe PSS is not managed early it will impair functional activity in affected patients, through complications, e.g. muscle shortening, contractures, pressure sores, additional to the PSS itself (1–5).Likewise, complications of PSS can lead to severe changes within a short period of time, even within a few weeks or months. If during this period PSS is not appropriately managed or treated, this, together with its complications, may detrimentally impact on patients’ physical posture, and positioning of affected joints, and thus their active freedom of movement (1, 6, 7). At a later stage, restriction in passive range of motion (ROM), hardening, or even contractures of the joint capsule may occur, which often prove irreversible in their final stage, so that surgical interventions have to be considered (8).The definition of spasticity, by Lance in 1980 (9), as a velocity-dependent increase in muscle tone, represents only one “positive” component of the upper motor neuron syndrome (UMNS), but more recent definitions include all positive symptoms (increased tendon reflexes, Babinski group reflexes, clonus, spasm, spastic dystonia and velocity-dependent increase in muscle tone) as spasticity (10), while excluding the “negative” components of the UMNS (e.g. paresis) and the complications of the UMNS (e.g. contractures, loss of muscle fibres).The pathogenesis of PSS is incompletely understood, thus only symptomatic therapies have been studied and suggested. Therefore the difficulty of management of PSS comes from detecting it at an early stage. It frequently develops gradually, building up with time, and fully manifests itself after weeks and months (11–14).Therefore, it is essential to find predictors, or their “red flags”, which indicate the potential development of spasticity with a high probability at early stages following stroke. Using such predictors, patients could be identified early following stroke and managed or treated with an appropriate approach (1, 2, 8, 11).To date, a number of studies have discussed clinical predictors for subsequent stroke-associated spasticity. Those studies include clinical predictors, such as poor functional status in the acute phase (low Barthel Index, higher modified Rankin scale, severe affected functions of the limbs), severe paresis, sensitivity loss to sensory stimuli, and young patient age (3, 12, 13, 15–17). These clinical predictors, which are associated with severe paresis and functional disorders, imply that certain locations and the size of brain lesions may be good predictors of developing PSS.Clinical predictors are considered to be an important and effective approach for the prediction of PSS (11– 13); however, the performance of clinical assessments, which are needed in order to predict more accurately, can often be limited in the hyperacute or acute phases following stroke, due to individual and clinical limitation. Therefore, analysis of brain imaging, which is a routine procedure in stroke evaluation, will be a good additional option for predicting early risk of development of PSS.There are a few studies that have investigated early brain imaging predictors of spasticity following stroke, and have suggested large volume and multiple lesion locations as possible brain imaging predictors of PSS in stroke survivors (18–23). However, these studies have suggested larger or extensive lesions as possible predictors with no mention of cut-off values for lesion size, and have suggested various possible lesion sites in the brain.The current study analysed 3 Tesla magnetic resonance imaging (3T MRI) data in order to identify early brain imaging predictors for potential development of spasticity after stroke, such as the sites and “red flags” values (sizes) of brain lesions. Patients admitted to a stroke unit were prospectively clinically examined in the acute stage (within 7 days of stroke onset) and at 3 months, for the occurrence of PSS, and MRI findings were analysed to correlate with clinical data.     

EFFECTIVENESS AND SAFETY OF CERVICAL CATHETER TIP PLACEMENT IN INTRATHECAL BACLOFEN TREATMENT OF SPASTICITY: A SYSTEMATIC REVIEW

ObjectiveTo evaluate the effectiveness and safety of intrathecal baclofen treatment of spasticity, administered via a cervical catheter tip.DesignA review of PubMed and the Cochrane Library up to September 2020. No restriction in study design. Two reviewers independently evaluated eligibility, extracted data and evaluated risk of bias. Studies were included in which patients were treated with intrathecal baclofen for spasticity, with the catheter tip at or above the first thoracic level, independent of diagnosis and age.ResultsThirteen studies were eligible, with a moderate to critical risk of bias. Improvement in spasticity was seen only in the upper extremity in 6% of subjects, only in the lower extremity in 2%, in both upper and lower extremities in 50% and without specification of location in 41%. Upper extremity function improved in 88% of cases. Neither drug-related (1%) nor technical (21%) complications occurred more often than in lower placement of the tip. Effects on respiratory function and sleep apnoea were not investigated.ConclusionCervically administered intrathecal baclofen seems to improve upper extremity spasticity and function, without causing more complications than thoracolumbar intrathecal baclofen. However, the mainly drug-related complications have not been thoroughly investigated and the available literature is of poor methodological quality. Further research is needed to confirm the efficacy and safety of this procedure.LAY ABSTRACTSpasticity is a common complication in central neurological disorders. It can lead to discomfort and functional limitations. To reduce spasticity, administration of baclofen via a catheter into the spinal canal has been used successfully for several years. However, this treatment often has limited effects on the upper limbs. The catheter tip is often situated in the thoracolumbar region. This review suggests that baclofen treatment via a cervically located catheter tip reduces spasticity of both arms and legs. Also, arm function improved in patients with a cervical catheter tip. Neither drug-related nor technical complications occurred more often than in lower placement of the cervical catheter tip. Few studies were found on this subject, and the available literature is of poor quality. Therefore, more research is needed to confirm the positive effect of this procedure on spasticity of the arms and to monitor for complications.Key words: intrathecal baclofen, tip placement, cervical, upper extremity, spasticity

Spasticity is a common complication after central nervous system injury with involvement of the upper motor neuron. The prevalence varies from 45% in stroke, 65% in spinal cord injury to 80% in multiple sclerosis (1–3).Spasticity is most commonly defined as “velocity-dependent increase in the tonic stretch reflex”, but has been redefined in 2005 by the European working group EUSPASM as “disordered sensori-motor control, resulting from an upper motor neuron lesion, presenting as intermittent or sustained involuntary activation of muscles” (4, 5). Depending on the severity, spasticity can negatively influence voluntary movement and lead to discomfort and functional limitations (5, 6).In functionally limiting spasticity, non-invasive treatment options, such as elimination of spasm provoking stimuli and physical therapy, should be considered first. In case of insufficient effect, oral medication can be started for general spasticity, or botulinum toxin, phenol or surgery for focal spasticity (7). Baclofen is the most commonly used oral antispasmodic (8). It is a centrally-acting gamma aminobutyric acid (GABA)-B agonist that works as muscle relaxant by diminishing reflex transfer at the spinal cord level. As orally provided baclofen poorly crosses the blood–brain barrier, high doses may be needed to achieve a functional effect, which may induce side-effects, such as fatigue, respiratory depression and confusion. Baclofen can also be administered locally via an intrathecal catheter, resulting in fewer side-effects than systemic baclofen treatment (6). The lower occurrence of side-effects can be explained, on the one hand, by a lower required baclofen dose (as the blood–brain barrier no longer has to be crossed), resulting in fewer general side-effects, and, on the other hand, by a lower cerebral baclofen concentration, resulting in fewer central nervous side-effects.The effect of intrathecal baclofen (ITB) on spasticity of the lower extremity (LE) has been well described in numerous studies, whereas the effect on spasticity of the upper extremity (UE) is less certain (9, 10). This difference in effectiveness might be related to the position of the intrathecal catheter tip and the baclofen gradient in the cerebrospinal fluid. The catheter tip is often positioned at the thoracic or lumbosacral level, assuming that the cerebrospinal fluid flow distributes baclofen in the intrathecal space to the required site of action. However, 2 studies that have been conducted on ITB distribution in humans show a steep concentration gradient of baclofen (11, 12). Kroin et al. found a lumbar-to-cisternal decrease in concentration of approximately 75% (11), and Heetla et al. reported a decrease in concentration from T10 to 30% at 5 cm tip distance, 12% at 10 cm and 0.7% at cerebral level (12). This baclofen concentration gradient suggests that, for optimal treatment of UE spasticity, the catheter tip should be located at the high thoracic or cervical level.Balsara et al. and Albright et al. suggest that catheter tip position should be dependent on treatment goal: T10–12 for diplegia and C5–T2 for tetraplegia (8, 13). However, in clinical studies there is no consensus on the relationship between catheter tip position and the effect on spasticity (14, 15).The demand for adequate treatment of UE spasticity has increased, as there is a growing number of patients with cervical spinal cord injury (16–18). A cervically positioned catheter tip could ameliorate spasmolytic effects on the UE due to higher cervical concentration of baclofen. However, it might lead to an insufficient effect on LE spasticity. Cervical ITB could also influence respiratory function and sleep-related disorders, either positively or negatively (19–21). Furthermore, a high cervical concentration of baclofen could increase cerebral side-effects and thereby influence cognitive and emotional functions. In this systematic review, the effectiveness and safety of baclofen treatment via a cervical catheter tip is analysed.     

CORRELATION OF N30 SOMATOSENSORY EVOKED POTENTIALS WITH SPASTICITY AND NEUROLOGICAL FUNCTION AFTER STROKE: A CROSS-SECTIONAL STUDY

ObjectiveTo test whether the presence of N30 somatosensory evoked potentials, generated from the supplementary motor area and premotor cortex, correlate with post-stroke spasticity, motor deficits, or motor recovery stage.DesignA cross-sectional study.PatientsA total of 43 patients with stroke hospitalized at Maoming People’s Hospital, Maoming, China.MethodsForty-three stroke patients underwent neurofunctional tests, including Modified Ashworth Scale (MAS), Brunnstrom stage, manual muscle test and neurophysiological tests, including N30 somatosensory evoked potentials, N20 somatosensory evoked potentials, motor evoked potentials, H-reflex. The results were compared between groups. Correlation and regression analyses were performed as well. Results: Patients with absence of N30 somatosensory evoked potential exhibited stronger flexor carpi radialis muscle spasticity (r = –0.50, p < 0.05) and worse motor function (r = 0.57, p < 0.05) than patients with presence of N30 somatosensory evoked potential. The generalized linear model (GLM) including both N30 somatosensory evoked potentials and motor evoked potentials (Akaike Information Criterion (AIC) = 121.99) better reflected the recovery stage of the affected proximal upper limb than the models including N30 somatosensory evoked potentials (AIC = 125.06) or motor evoked potentials alone (AIC = 127.45).ConclusionN30 somatosensory evoked potential status correlates with the degrees of spasticity and motor function of stroke patients. The results showed that N30 somatosensory evoked potentials hold promise as a biomarker for the development of spasticity and the recovery of proximal limbs.LAY ABSTRACTImpair motor function and spasticity adversely affect the ability to conduct the activities of daily life. Somatosensory evoked potentials and motor evoked potentials are essential to differential evaluation of degree of post-stroke spasticity and stage of motor recovery. This is the first study of the correlations between somatosensory evoked potentials N30, components of somatosensory evoked potentials related to the supplementary motor area and dorsolateral premotor cortex combined with motor evoked potentials and motor function. The results indicate that the N30 somatosensory evoked potential status is correlated with the degrees of spasticity and motor function of stroke patients. The conclusion showed that N30 Somatosensory evoked potentials hold promise as a biomarker for the development of spasticity and the recovery of proximal limbsKey words: stroke, hemiparesis, spasticity, N30 somatosensory evoked potential, motor evoked potential, function recovery

Stroke is the leading cause of disability worldwide (1). Most patients with stroke experience motor deficits, which impair motor function and adversely affect their ability to perform activities of daily living (ADL). Spasticity, one of the motor deficits that appears after stroke, is accompanied by an increased risk of falling and resulting fractures, and is associated with increased morbidity and mortality (2). Both post-stroke recovery and the development of spasticity are associated with neural plasticity of different anatomical regions, such as the reticulospinal tracts, supplementary motor area (SMA) and dorsolateral premotor cortex (PMC) (3–5).Precise biomarkers of motor function are critical for early intervention. The identification of somatosensory evoked potentials (SEPs) is essential for the accurate diagnosis of patients with focal brain disorders, and SEP components reflect the activities of different neural structures (6). N30 SEPs are somatosensory evoked potential components. Anatomically, N30 SEPs are generated from the SMA and PMC (7), from which the corticoreticular tracts radiate (8–10). Pathophysiologically, N30 SEPs present apparent inhibition in individuals with other myotonic disorders (11). Continuous theta burst stimulation of the SMA reduces the amplitude of the N30 (12). Moreover, SMA impairment leads to myodystonia and is closely associated with motor outcomes (13, 14).Thus, it was hypothesized that the presence of N30 SEPs is related to the degree of spasticity and functional status in people with stroke. The aims of the study were to test: (i) whether the presence of N30 SEPs correlates with post-stroke spasticity (PSS), motor deficits and stage of motor recovery; and (ii) whether the combination of N30 SEPs and motor evoked potentials (MEPs) can be used for the differential evaluation of degree of PSS and stage of motor recovery.     

A PRACTICAL GUIDE TO OPTIMIZING THE BENEFITS OF POST-STROKE SPASTICITY INTERVENTIONS WITH BOTULINUM TOXIN A: AN INTERNATIONAL GROUP CONSENSUS

This consensus paper is derived from a meeting of an international group of 19 neurological rehabilitation specialists with a combined experience of more than 250 years (range 4–25 years; mean 14.1 years) in treating post-stroke spasticity with botulinum toxin A. The group undertook critical assessments of some recurring practical challenges, not yet addressed in guidelines, through an extensive literature search. They then discussed the results in the light of their individual clinical experience and developed consensus statements to present to the wider community who treat such patients. The analysis provides a comprehensive overview of treatment with botulinum toxin A, including the use of adjunctive therapies, within a multidisciplinary context, and is aimed at practicing clinicians who treat patients with post-stroke spasticity and require further practical guidance on the use of botulinum toxin A. This paper does not replicate information published elsewhere, but instead aims to provide practical advice to help optimize the use of botulinum toxin A and maximize clinical outcomes. The recommendations for each topic are summarized in a series of statements. Where published high-quality evidence exists, the recommendations reflect this. However, where evidence is not yet conclusive, the group members issued statements and, in some cases, made recommendations based on their clinical experience. LAY ABSTRACTA group of doctors from around the world, who are experts in treating muscle stiffness and spasm (also called spasticity), reviewed the current scientific evidence supporting the effectiveness of using botulinum toxin injections in treatment of spasticity that results from a stroke. When evidence is not available, they discussed and agreed on the best way to treat spasticity using botulinum toxin. The recommendations made by these expert doctors can be used by less-experienced doctors as a guide to how best to use botulinum toxin injection in treating spasticity after a stroke. Key words: spasticity, botulinum toxin, consensus guideline

Botulinum toxin A (BoNT-A) has been in clinical use for treating post-stroke spasticity for approximately 30 years and is the accepted standard of care for focal post-stroke spasticity (1). It is currently known that BoNT-A treatment is safe and effective for use in both upper and lower limb spasticity, where it can result in both active and passive functional gains (2). Furthermore, BoNT-A is a first-line pharmacological treatment in the management of post-stoke focal and multi-focal spasticity, which, along with a multidisciplinary team (MDT) approach, should be part of a rehabilitation programme to promote optimal clinical effect (3–5). In addition, the Royal College of Physicians’ (RCP) guidelines for management of adult spasticity using BoNT-A (6) recommend that patient selection and management should be based on individualized criteria, resulting in a patient-centred approach to management.Despite the ever-expanding literature base on this topic, it is clear that further clinical research is necessary to increase understanding and fill gaps in post-stoke spasticity treatment protocols. The group felt that, in the intervening time, there remained a need to provide practical advice on how best to tailor treatment regimens using BoNT-A for individual patients in order to optimize care.Although BoNT-A is an established treatment for focal spasticity, there is little consensus on how to improve efficacy, and there is a need to increase prescribers’ confidence in its use, share current best practice, and identify reasons for sub-optimal responses (e.g. injection technique, dosing, muscle selection).The group agreed 3 key areas in which additional practical guidance and/or personal training and supervision is required: (i) individualized approach to spastic upper limb in stroke; (ii) optimal injection technique and preparation of the toxin; and (iii) adjunctive treatments. They examined the evidence for each topic, obtained from literature searches using the College of College of Physicians and Surgeons of British Columbia review, Medline, CINAHL and PubMed databases. They subsequently met on 2 separate occasions for full-day discussions to agree consensus statements on the topics. The gaps in the literature were filled with the knowledge acquired from the combined clinical experience of the group (6).Table IConsensus statements from the international group of experts

EFFECTS OF β-HYDROXY-β-METHYLBUTYRATE SUPPLEMENTATION ON MUSCLE MASS AND STRENGTH IN ONABOTULINUMTOXIN TYPE-A-INJECTED AND CONTRALATERAL QUADRICEPS FEMORIS IN RABBITS

ObjectiveTo determine the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits.MethodsA total of 21, female rabbits were divided into 3 groups (n = 7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs.ResultsInjected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p < 0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p <0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively.ConclusionWhile HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.LAY ABSTRACTOnabotulinum toxin A (BoNT-A) is currently approved for cosmetic procedures and for the treatment of many conditions, such as migraine headaches and neuromuscular conditions associated with spasticity, such as cerebral palsy or post-stroke in USA. Once injected into the muscle BoNT-A causes muscle paralysis, which is reversible. The current study examined the local and distant detrimental effects of BoNT-A on decreasing muscle wasting and muscle function in a rabbit model, and the effects of dietary use of HMB (β-hydroxy-βmethylbutyrate), a leucine metabolite, on these detrimental effects. BoNT-A was injected into 1 leg of a rabbit model and muscle mass and strength measured in both the injected and non-injected legs. BoNT-A caused a loss of muscle mass in the injected legs. It also caused a loss of strength in the injected legs and a somewhat reduced loss of strength in the non-injected legs. This suggests that BoNT-A injections can cause a decrease in function in distant, non-target muscles. HMB partially reversed some of the detrimental side-effects of BoNT-A, being shown to be effective in maintaining muscle strength in the non-injected leg.Key words: botulinum toxin, Botox®, β-hydroxy-β-methylbutyrate supplementation, muscle strength, muscle mass, skeletal muscle

Muscle mass is maintained by a balance between protein synthesis and degradation. However, when this balance is disturbed by either an increase in protein breakdown or a reduction in protein synthesis, muscle wasting occurs. Muscle wasting has significant clinical consequences, including muscle weakness, fatigue, morbidity, and it is an important contributing factor for reduced quality of life (QoL). Treatment modalities to prevent muscle wasting include exercise, inhibitors of inflammatory cytokines, and anti-inflammatory cytokines (1). Recently, there has been an increase in dietary supplement use aimed at increasing muscle mass, or preventing muscle atrophy in healthy, active, and sedentary people, in high-performance athletes, and in patients exposed to prolonged bed rest (2–5). However, the efficacy of dietary supplements in preventing strength loss and atrophy is a matter of debate (3).Onabotulinumtoxin type-A (BoNT-A) is a potent neurotoxins (6, 7). Once injected into the target muscle, BoNT-A binds with high affinity to the neuromuscular junction, preventing acetylcholine release, and thereby inducing dose-dependent muscle paralysis (8, 9). Due to its extreme potency and specificity, BoNT-A has been used for both therapeutic and scientific interventions (10–12).Localized BoNT-A injections are used clinically in an increasing number of neuromuscular disorders, with the primary aim of relaxing the hyperexcitability of peripheral nerve terminals; for example, in patients with cerebral palsy or following a stroke (11, 13). In experimental settings BoNT-A has been used to induce muscle weakness in an attempt to mimic muscle atrophy following injury, denervation, in elderly patients (14–16), or to determine the effects of muscle weakness on bone and joint health (17, 18). BoNT-A-induced muscle weakness can also be used to investigate strategies for the prevention of, or the reverting of, strength loss and muscle atrophy (19).β-Hydroxy-β-methylbutyrate (HMB) is naturally produced from the amino acid leucine (20). As a dietary supplement, HMB has been used to improve strength and gain lean body mass, reduce muscle protein degradation, and improve recovery following exercise in trained, untrained, and elderly people (5, 21–24). Supplemental HMB has also been shown to increase lean body mass in elderly subjects without exercise (2) and to retain lean body mass during bed rest (4). Other studies have shown HMB can improve protein turnover in muscle atrophy conditions, such as AIDS (25), trauma (26) and cancer (27), and in endotoxininduced septic rats (28).Despite the increasing use of HMB as a dietary supplement, there have been no definitive studies showing the efficacy of HMB to prevent muscle weakness under conditions known to produce muscle paralysis and consequent atrophy.The objective of the current study was to evaluate the effects of supplemental HMB on strength, muscle mass, and contractile material following BoNT-Ainduced weakness in the quadriceps femoris of New Zealand white (NZW) rabbits. It was hypothesized that HMB supplementation would reduce the loss of strength and atrophy in both BoNT-A-injected target muscles and non-injected, non-target muscles.     

IMPLEMENTATION OF EVIDENCE-BASED ASSESSMENT OF UPPER EXTREMITY IN STROKE REHABILITATION: FROM EVIDENCE TO CLINICAL PRACTICE

ObjectiveThere is an evidence–practice gap in assessment of the upper extremities during acute and subacute stroke rehabilitation. The aim of this study was to target this gap by describing and evaluating the implementation of, and adherence to, an evidence-based clinical practice guideline for occupational therapists and physiotherapists.MethodsThe upper extremity assessment implementation process at Sahlgrenska University Hospital comprised 5 stages: mapping clinical practice, identifying evidence-based outcome measures, development of a guideline, implementation, and evaluation. A systematic theoretical framework was used to guide and facilitate the implementation process. A survey, answered by 44 clinicians (23 physiotherapists and 21 occupational therapists), was used for evaluation.ResultsThe guideline includes 6 primary standardized assessments (Shoulder Abduction, Finger Extension (SAFE), 2 items of the Actions Research Arm Test (ARAT-2), Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Box and Block Test (BBT), 9-Hole Peg Test (9HPT), and grip strength (Jamar hand dynamometer)) performed at specified time-points post-stroke. More than 80% (35 to 42) clinicians reported reported being content with the guideline and the implementation process. Approximately 60–90% of the clinicians reported good adherence to specific assessments, and approximately 50% reported good adherence to the agreed time-points. Comprehensive scales were more difficult to implement compared with the shorter screening scales. High levels of work rotation among staff, and the need to prioritize other assessments during the first week after stroke, hindered to implementation.ConclusionThe robustness of evidence, adequate support and receptive context facilitated the implementation process. The guideline enables a more structured, knowledge-based and consistent assessment, and thereby supports clinical decision-making and patient involvement.LAY ABSTRACTCurrently available clinical practice guidelines do not specify which outcome measures should be used at which time-points for people after stroke. This study describes the implementation process and evaluation of a clinical practice guideline developed for the assessment of upper extremity function after stroke. The guideline is based on recent research evidence and defines the assessments, and the time-points at which the assessments should be performed. An evaluation survey showed that clinicians valued the clear structure of the guideline and found it useful for prognosis and treatment planning. Robust evidence, and active involvement of clinicians and leaders, were important elements of implementation. The guideline will potentially improve the quality of rehabilitation through increased knowledge of prognosis and treatment effects, based on the assessment of arm function in people with stroke, thereby enabling a more evidence-based, consistent, and individually tailored rehabilitation.Key words: clinical practice guideline, evidence-based practice, implementation science, stroke, rehabilitation, knowledge translation, upper extremity, assessment

Considerable efforts have been made recently in the field of stroke rehabilitation to develop evidence-based agreed guidelines for upper extremity assessment (1–4). Advances in predicting stroke outcomes, in terms of motor function and activity, have been the primary driver of this development (5–7). There is, however, a clear evidence–practice gap, since the use of recommended upper extremity outcome measures in day-to-day clinical practice is sparse. It is well recognized that valid, reliable and responsive outcome measures, performed at pre-defined time-points after stroke, are required for effective rehabilitation (2–4). Currently available clinical guidelines recommend the use of standardized outcome measures, but often do not specify what outcome measures should be used, at what frequency, or in what settings (2).The implementation of standardized recommended upper extremity outcome measures in clinical routine practice takes time and effort. Increased and consistent use of such measures is, however, required to enable person-centred informed clinical decision-making throughout the rehabilitation pathway, and thereby improve patient outcomes. Overall adherence to stroke guidelines varies, but, in general, it is greater when the implementation process includes systematic and well-defined activities (8–10). There are no recognized “gold standard” implementation activities, although multifaceted interventions involving educational outreach and a structured theoretical approach have been suggested to work best (8, 9). Organizational and multidisciplinary team factors, staff beliefs regarding the guidelines, integration of patient-centred recommendations into practice, awareness of guidelines, changing routines, and necessary time investment, are known factors affecting adherence (8, 10).The successful implementation of evidence into practice is dependent on the quality of evidence, the context, and how the evidence is introduced into practice (facilitators) (11). These 3 key elements, being part of the Promoting Action on Research Implementation in Health Services (PARIHS) theoretical framework, have been employed widely in different implementation activities (11, 12). This theoretical model prerequisites that the evidence is robust, practitioners agree with it, and the context is receptive, including the formal leaders, and that appropriate facilitation is ensured (11, 13). The Knowledge to Action (KTA) framework is another theoretical tool that has been widely used to make the process of knowledge translation into practice more systematic (14). The KTA emphasizes the importance of adapting knowledge to the local context, of involving stakeholders, and of being aware of barriers, facilitators and user needs (14).The literature is extensive regarding the implementation of stroke guidelines into clinical practice (8, 9), but only a few studies have specifically targeted assessment and use of standardized outcome measures (15, 16). More recent work on recommendations regarding upper extremity outcome measures (3) also imply a need to move this research evidence into stroke rehabilitation practice.The aim of this study was to describe and evaluate the implementation process and adherence to an evidence-based clinical practice guideline (CPG) for physical therapists (PT) and occupational therapists (OT) in the assessment of upper extremity function and activity during acute and subacute stroke rehabilitation.     

REHABILITATION IN PATIENTS WITH LYMPHOMA: AN OVERVIEW OF SYSTEMATIC REVIEWS

ObjectiveTo evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation interventions in patients with lymphoma.Data sourcesA comprehensive literature search was conducted using medical/health science databases up to 1 October 2020. Bibliographies of pertinent articles, journals and grey literature were searched.Data extraction and synthesisTwo reviewers independently selected and reviewed potential reviews for methodological quality and graded the quality of evidence for outcomes using validated tools. Any discrepancies were resolved by final group consensus.ResultsTwelve systematic reviews (n = 101 studies, 87,132 patients with lymphoma) evaluated 3 broad categories of rehabilitation interventions (physical modalities, nutrition and complementary medicine). Most reviews were of moderate-to-low methodological quality. The findings suggest: moderate-quality evidence for exercise programmes for improved fatigue and sleep disturbance; low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and an inverse association between sunlight/ultraviolet radiation exposure and incidence of non-Hodgkin’s lymphoma; and very low-quality evidence for beneficial effects of yoga for sleep disturbances. Association between physical activity and lymphoma risk is indistinct.ConclusionDespite a range of rehabilitation modalities used for patients with lymphoma, high-quality evidence for many is sparse. Beneficial effects of exercise programmes were noted for fatigue, psychological symptoms and quality of life. More research with robust study design is required to determine the effective rehabilitation approaches.LAY ABSTRACTLymphoma and its treatment cause significant disability and morbidity, often requiring comprehensive rehabilitation. Currently, a range of rehabilitation interventions are applied in patients with lymphoma. This review systematically evaluated evidence from published systematic reviews of clinical trials to determine the effectiveness of rehabilitation interventions in patients with lymphoma. The findings suggest that there is moderate-quality evidence for exercise programmes in improving fatigue and sleep disturbance. There was low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and very low-quality evidence for beneficial effects of yoga for sleep disturbances. The evidence for association of vitamin D or physical activity and lymphoma risk is limited.Key words: lymphoma, rehabilitation, systematic review, critical appraisal

Lymphomas are a heterogeneous group of malignant neoplasms of the haematopoietic system, characterized by the aberrant proliferation of mature lymphoid cells or their precursors (1). Traditionally lymphoma is classified broadly into 2 major groups: non-Hodgkin’s lymphoma (NHL, 90%) and Hodgkin’s lymphoma (HL) (1); however, lymphomas can also be stratified by cell of origin, as in the World Health Organization (WHO) classification (B-cell, T-cell/natural killer-cell (T/NK) and HL), or clinical behaviour (aggressive or indolent) (2, 3). An estimated 590,000 new cases of lymphoma (3.2% of all cancers) were diagnosed worldwide in 2018, the majority being NHLs (509,590 cases, 2.8% of all cancers) (4). NHL is a leading cause of death amongst the haematological malignancies globally, estimated to cause over 248,000 deaths (2.6% of all cancers) in 2018 (4). The incidence of lymphoma is increasing, with total worldwide incidence projected to reach approximately 919,000 by 2040 (5).The total global economic burden of lymphoma is unknown; however, treatments and supportive care requirements are resource-intensive and associated with significant financial costs for patients/families and healthcare systems. Productivity losses arise from disease and treatment-associated morbidity and premature mortality (6). In 2018, the mean monthly healthcare and utilization costs per patient for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the USA were approximately US$11,890 and $10,460, respectively (6). In Spain, in 2017 lymphoma represented 45.4% of productivity losses due to haematological malignancies, resulting in €121 million in losses due to premature mortality (7).Current therapeutic advances and cancer detection/diagnosis have improved survival rates for patients with lymphoma (PwL). The age-standardized 5-year net survival of lymphoid malignancies in adults ranges from 40% to 70% globally in 2010–14, with a 5–10% increase in trend for the period 2000–04 (8). The 5-year survival rate in the US in 2010–16 was estimated to be 72.7% for NHL and 87.4% for HL (9). As the incidence of NHL is strongly associated with increasing age, improved supportive care and availability of reduced intensity chemotherapy regimens (such as prednisone, etoposide, procarbazine, and cyclophosphamide – ‘PEP-C’; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone – ‘R-miniCHOP’, rituximab, cyclophosphamide, vincristine, prednisolone – ‘R-CVP’) are critical to facilitate deliverable therapy to older patients. Despite these factors, certain lymphomas and their treatment are associated with short- and medium-term residual neurological deficits, leading to physical, cognitive, psychosocial and behavioural impairments, limiting activities of daily living (ADL) and participation (10–13). Treatment procedures can be extensive (e.g., radiotherapy, chemotherapy and/or surgery), and associated with a range of side-effects/complications, such as neuropathy, cardiotoxicity, cachexia, fatigue, deconditioning, myopathy, etc. (14–16). Furthermore, in the transitional period, various adjustment issues are reported, such as increased care needs, inability to drive and return to work, financial constraints, relationship stress, and limitation in societal participation (11, 14, 17, 18). Distressing symptoms, such as fatigue, is a major complaint, reported in 60–100% of patients during or after cancer treatment, which persists for several years after treatment (19–21). Therefore, patients require routine surveillance to monitor complications and relapse and integrated longer-term management, including rehabilitation (22–24).Rehabilitation is an integral part of any cancer management, and there is evidence suggesting the beneficial effect of comprehensive rehabilitation (25–31). Furthermore, a major limitation of delivery of chemotherapy and predictor of inferior outcome is poor performance status (32). As the incidence of older patients treated for lymphoma requiring rehabilitation before or after anti-lymphoma therapy increases, effective evidence-based rehabilitation strategies are expected to play critical and expanding roles in best practice. Currently, a range of rehabilitation interventions are trialled in the management of lymphoma pre-treatment, during adjuvant therapies, and late phases of care, and, for the longer-term, care continuum in the community. The aim is to maximize patient function, promote independence and participation, and improve psychological well-being and quality of life (QoL) (28, 29). Reports suggest that patients with haematological malignancies, including lymphomas, can make functional gains in inpatient rehabilitation settings (31). Maximal exercise capacity seems to decrease before treatment in PwL, especially in patients with advanced disease, and tends to return to close to normal during and/or after treatment (33). Furthermore, comprehensive exercise programmes were found to be effective in reducing disability and symptoms (depression, anxiety, fatigue, pain, etc.), improving functional capacity, muscular strength and QoL (19, 31, 34, 35). One systematic review reported that NHL survivors who met public health exercise guidelines defined by the American College of Sports Medicine (i.e. engaging in >30 min/day of at least moderate physical activity (PA) on ≥ 5 days/week, or > 150 min a week) reported a clinically important better health-related quality of life (HRQoL) than their counterparts who did not meet exercise guidelines (11). Aerobic exercise training interventions were associated with positive effects on cardiorespiratory fitness, fatigue and self-reported physical functioning, and were feasible and safe in PwL (33). Other complementary and alternative therapies, such as mindfulness-based cognitive therapy, meditation, yoga, and tai chi, have shown improvement in cognitive function and QoL (36–38). Another recent systematic review reported that a combination of PA together with mental exercise may be more beneficial to PwL (39). There remains, however, an unmet need in the cancer population, and only a limited number of survivors receive the appropriate rehabilitation intervention that they need (40, 41). Furthermore, despite acknowledging rehabilitation as an integral component of the management of cancer patients, rehabilitation-specific guidelines for many cancer groups are limited, and many general cancer guidelines do not incorporate recommendations for specific rehabilitation interventions (42–44).As mentioned above, various systematic reviews have evaluated the current evidence regarding the effectiveness and safety of different rehabilitation interventions in PwL. However, these published reviews vary in scope, methodology and quality, with diverse, and occasionally discordant, conclusions. The heterogeneity of the lymphoma rehabilitation literature warrants a comprehensive review, with a focus on the evidence for efficacy and potential harm of various rehabilitative strategies. A systematic review of systematic reviews is a new approach to synthesize current evidence across the same or similar interventions, to summarize treatment effect in a much broader concept (45). This approach allows comparison of results from multiple reviews, thereby providing a comprehensive evidence-based summary (45, 46). To our knowledge, systematic reviews of rehabilitation strategies for PwL have not been thoroughly and qualitatively appraised to date. Therefore, this review aimed to systematically evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation strategies for improved function, impairments and participation in PwL. Specific questions addressed include: Are rehabilitation interventions effective in minimizing impairment, activity limitation, participation restriction and treatment-related complications in PwL?, and: What specific types of rehabilitation interventions are effective in PwL, and in which setting?     

RECOVERY OF ARM FUNCTION DURING ACUTE TO CHRONIC STAGES OF STROKE QUANTIFIED BY KINEMATICS

ObjectiveTo quantify the longitudinal changes in upper limb kinematics within the first year after stroke and to identify the factors that are associated with these changes.MethodsA total of 66 individuals with stroke from the Stroke Arm Longitudinal Study at the University of Gothenburg (SALGOT) cohort were included if they were able to perform the target-to-target task. Data from a virtual reality haptic target-to-target task at 6 time-points between 3 days and 12 months after stroke were analysed by linear mixed models, while controlling for the impact of cofactors (stroke severity, age, type and side of stroke, sex and presence of diabetes).ResultsKinematic variables of movement time, mean velocity and number of velocity peaks improved over time and were positively associated with younger age, less severe stroke and ischaemic compared with haemorrhagic stroke. Most of the improvement occurred within 4 weeks after stroke, although movement time and number of velocity peaks also improved between 3 and 6 months after stroke.ConclusionKinematic variables of movement time, mean velocity and number of velocity peaks were effective in quantifying the longitudinal changes in upper limb kinematics within the first year after stroke.LAY ABSTRACTRecovery of arm function after stroke can be measured using virtual reality technology, which, in contrast to traditional clinical assessments, enables objective and highly precise measurement of different aspects of movement, such as speed and smoothness, termed kinematics. This study aimed to measure the recovery of arm movements between 3 days and 12 months after stroke using kinematic measures, and to identify factors that affect recovery. The results showed that movement time, mean velocity and smoothness improved with time after stroke. These data also suggest that younger stroke survivors, those with less severe stroke, and those with stroke caused by a clot, as opposed to a bleed, undergo greater improvements. Most of the improvement was seen early after stroke, within the first 4 weeks, but both movement time and smoothness also continued to improve between 3 and 6 months. The results show that kinematic analysis can effectively show the changes in arm movement within the first year after stroke.Key words: upper extremity, kinematics, outcome assessment, virtual reality, stroke recovery

Upper limb motor impairment occurs in approximately 50–80% of individuals in the acute stage of stroke (1–3) and continues in 40–50% in the chronic stage (2, 4). Approximately 65% of hospitalized individuals with initial motor deficits show some degree of motor recovery, while complete motor recovery occurs in less than 15% of individuals (5). Clinical recovery of upper limb motor function is most rapid during the first 4 weeks following stroke, and most recovery occurs during the first 3 months post-stroke (5, 6). Additional recovery has also been shown to occur after 3 months following stroke, usually in combination with intensive rehabilitation (5–7).The time course of functional recovery after stroke is dependent on several factors. There is a strong negative association of initial grade of stroke paresis and age with functional recovery after stroke (5, 8, 9). According to a retrospective observational study, individuals with haemorrhagic stroke had higher initial impairment compared with those with ischaemic stroke, as demonstrated by Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) scores at admission (10). However, the haemorrhagic stroke group showed greater recovery in arm function and activity capacity, such that individuals in both groups had similar function at 3 months after stroke (11). It is not clear whether the same factors are reflected in the change in kinematic variables of arm function during the recovery of upper limb in individuals with stroke.Kinematic measurements of movement performance are recommended as core measures to be included in every stroke recovery trial (12). Kinematic assessment of upper limbs after stroke is often performed using optoelectronic cameras (13–15), robotic techniques (16) and virtual reality (VR) (17, 18). VR coupled with haptic devices can provide sensitive assessment of the kinematic function of the upper limb after stroke (19, 20). Haptic-enabled VR can measure end-point kinematics of common daily tasks, such as pointing, while allowing free arm movements in a 3D space (17). Despite VR systems being in use in stroke rehabilitation (21), there are sparse data from longitudinal studies, although some data on the responsiveness of upper limb kinematics are available from robotic studies (22–24). Haptic devices coupled with VR systems are suitable for use in the assessment and rehabilitation of post-stroke individuals, even in telemedicine settings (25).Longitudinal studies of upper limb recovery after stroke using optoelectronic cameras have shown that movement time and smoothness improved up to 3 months after stroke (14, 15, 26). Kinematic movement deficits observed at 3 months post-stroke remained unchanged at 12 months in individuals with mild stroke impairment (13). Thus, the recovery of kinematics seems to follow a similar recovery pattern as observed in clinical assessments, although the evidence in kinematics remains sparse and varies between studies. In addition, longitudinal changes in the kinematics of the upper limb after stroke have not been studied using the pointing task in 3D virtual space.The aims of this study were to quantify the longitudinal changes in upper limb kinematics between day 3 and month 12 after stroke, and to identify the factors that affect this change, using the target-to-target pointing task performed in VR.     

REHABILITATION SETTINGS DURING AND AFTER COVID-19: AN OVERVIEW OF RECOMMENDATIONS

ObjectiveThe aim of this review is to identify the best evidence to define rehabilitative approaches to acute and post-acute phases of coronavirus 2019 (COVID-19) disease.MethodsA literature search (of PubMed, Google Scholar, PEDro and Cochrane databases) was performed for relevant publications from January to April 2020.ResultsA total of 2,835 articles were retrieved, and the search resulted in a final total 31 published articles. A narrative synthesis of the selected articles was then performed. Some studies examine the effect of the pandemic on rehabilitation services and provide suggestions for a new reorganization of these services. Other studies focus on COVID-19 sequelae, formulating recommendations for rehabilitative interventions.ConclusionFor COVID-19 patients, an integrated rehabilitative process is recommended, involving a multidisciplinary and multi-professional team providing neuromuscular, cardiac, respiratory, and swallowing interventions, and psychological support, in order to improve patients’ quality of life. The intervention of a physician expert in rehabilitation should assess the patient, and a dedicated intervention set up after thorough assessment of the patient’s clinical condition, in collaboration with all rehabilitation team professionals.LAY ABSTRACTRehabilitation, in a multidisciplinary and multi-professional setting, plays a pivotal role in the management of Covid-19 patients, focusing on respiratory and motor functions and it is therefore crucial to establish treatment strategies to guarantee an optimal recovery of these patients. We performed a review of the scientific literature. All the studies concerning respiratory rehabilitation treatments for Covid-19 patients were included. Respiratory rehabilitation has the goal of improve respiratory symptoms, preserve function and reduce complications and disability; it also has positive effects on the psychological sphere, reducing anxiety and depression that can frequently develop in this context.Key words: rehabilitation, COVID-19, recommendation

In late December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan, the capital city of Hubei province, China, and spread rapidly throughout the world, causing a large global outbreak and becoming a major health concern (1). In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic and public health emergency (2).The causative agent is the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initially named 2019 novel coronavirus (2019-nCoV) (3). It is a non-segmented, enveloped, positive-sense single-strand RNA β-coronavirus (4), which may have been transmitted to humans from a potential reservoir in bats, through as-yet unknown intermediate hosts (5). Human-to-human transmission of COVID-19 occurs mainly through the respiratory tract, by inhalation of infected droplets (from symptomatic, but also asymptomatic people) and through direct contact (6, 7). The estimated incubation period is 1–14 days, mainly in the range 3–7 days (8).COVID-19 infection displays a prevalence of respiratory involvement, being responsible for interstitial pneumonia, the major manifestation of the disease, which first led to identification of the pathogen (3, 9). It causes various degrees of illness, with a clinical picture ranging from asymptomatic cases to acute respiratory distress syndrome (ARDS) and multi-organ failure (10).Symptoms include fever and dry cough (dominant manifestations), anosmia, sore throat, upper airway congestion, fatigue, headache, muscle ache, shortness of breath, and other signs of upper respiratory tract infection. Progression to pneumonia (mainly occurring in the second or third week of a symptomatic infection) (10, 11) is associated with a reduction in oxygen saturation, reduction in arterial blood gas exchange, extreme increase in inflammatory markers, and lymphopaenia (10). The clinical picture also correlates with bilateral ground glass opacities and patchy consolidations, seen on chest computed tomography (CT) (12, 13).Diagnosis of COVID-19 infection can be made only through nucleic acid detection by real-time polymerase chain reaction (RT-PCR) in respiratory tract samples.Since there is currently no approved treatment for COVID-19, management of the disease is based on symptomatic and supportive treatments, mainly targeted at preserving hydration and nutrition and controlling fever and respiratory symptoms. Oxygen or non-invasive ventilation are necessary for hypoxic patients. In most severe cases mechanical ventilation is required, and even extra-corporeal membrane oxygen (ECMO), which is recommended by the WHO for patients with refractory hypoxaemia (14). Elderly people and patients with underlying comorbidities are more susceptible to developing complications, including ARDS, acute kidney injury, arrhythmias, cardiac injury, and liver dysfunction (15, 16).Patients may undergo prolonged bed rest, leading to immobilization syndrome (17) associated with respiratory dysfunction, both of which might require rehabilitation interventions. Prolonged immobilization leads to muscle weakness, motor deconditioning, balance and postural impairment, and joint stiffness, pain and limitation, which have a strong impact on patients’ general condition (17, 18).Post-intensive care syndrome (PICS) refers to a new or worsening impairment of patient’s physical, cognitive, or mental health status arising during stay in the intensive care unit (ICU) and persisting beyond ICU discharge or hospital discharge. These patients undergo various degrees of respiratory, physical and psychological distress (19, 20). It is essential that any rehabilitative intervention is customized to the specific condition of each patient, and that this should take into account, as already observed in SARS-CoV and MERS-CoV, that SARS-CoV-2 may also have a neurotropic effect, leading to neurological involvement, which may be partially responsible for acute respiratory failure in COVID-19 patients (21).Indeed, it has recently been observed that SARSCoV-2 is involved in neurological manifestations (22) in COVID-19 patients, including in the central nervous system (CNS) (e.g. dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system (PNS) (e.g. impairments of taste, smell and vision, and nerve pain), and skeletal muscle injury (23). Cases of viral encephalitis and infectious toxic encephalopathy have been reported (24). Patients who had cerebrovascular disease were older, developed severe COVID-19 and underlying disorders, an increased inflammatory response, and a hypercoagulable state (25, 26). Neurological manifestations, apart from cerebrovascular disease and impairment of consciousness, have been reported early in the illness prior to the onset of COVID-19-related symptoms (23). Hence it is important to evaluate patients who present with neurological symptoms, to assess risk factors (25) and underlying disorders that indicate an early diagnosis of COVID-19 (23), enabling the recognition and management of complications and improving the prognosis (24).The ongoing COVID-19 pandemic is placing great stress on healthcare systems, especially acute care departments, and is already having an impact on the rehabilitation community (17, 18, 27). In a multidisciplinary and multi-professional setting, rehabilitation plays a pivotal role in the management of patients with COVID-19, focusing on respiratory and motor functions. It is therefore crucial to establish rehabilitation treatment strategies that enable optimal recovery of these patients.The aim of this study was to review the literature on COVID-19, in order to identify best evidence to define rehabilitative approaches to acute and post-acute phases of the disease.     

ARM IMPAIRMENT AND WALKING SPEED EXPLAIN REAL-LIFE ACTIVITY OF THE AFFECTED ARM AND LEG AFTER STROKE

ObjectiveTo determine to what extent accelerometer-based arm, leg and trunk activity is associated with sensorimotor impairments, walking capacity and other factors in subacute stroke.DesignCross-sectional study.PatientsTwenty-six individuals with stroke (mean age 55.4 years, severe to mild motor impairment).MethodsData on daytime activity were collected over a period of 4 days from accelerometers placed on the wrists, ankles and trunk. A forward stepwise linear regression was used to determine associations between free-living activity, clinical and demographic variables.ResultsArm motor impairment (Fugl-Meyer Assessment) and walking speed explained more than 60% of the variance in daytime activity of the more-affected arm, while walking speed alone explained 60% of the more-affected leg activity. Activity of the less-affected arm and leg was associated with arm motor impairment (R² = 0.40) and independence in walking (R² = 0.59). Arm activity ratio was associated with arm impairment (R² = 0.63) and leg activity ratio with leg impairment (R² = 0.38) and walking speed (R² = 0.27). Walking-related variables explained approximately 30% of the variance in trunk activity.ConclusionAccelerometer-based free-living activity is dependent on motor impairment and walking capacity. The most relevant activity data were obtained from more-affected limbs. Motor impairment and walking speed can provide some information about real-life daytime activity levels.LAY ABSTRACTActivity data from accelerometers can help clinicians to better understand factors limiting physical activity levels. This study aimed to determine to what degree arm, leg and trunk activity, measured with accelerometers, is associated with sensorimotor impairments, walking and other factors in people with stroke in the subacute stage of recovery. Real-life activity, measured by accelerometers, was primarily associated with motor impairment and walking speed. Spasticity, dependency in walking, and disability level also showed association with real-life activity, although to a lesser degree. Accelerometers, placed on the more-affected wrist and ankle, provided most relevant clinical information and are therefore recommended for research and clinical practice. The strong associations observed in this study suggest that when accelerometers are not available, clinical assessments of arm motor function and walking speed can provide some information on real-life activity levels in people with stroke.Key words: stroke, accelerometry, clinical research, rehabilitation, ambulatory monitoring, wearable technology, outcome assessment (healthcare), outcome measures

Individuals with stroke spend approximately 70–80% of their daytime in sedentary activities, and, when active, their activity level seldom reaches moderate-to-vigorous levels of intensity (1–3). To better understand which factors limit activity levels, wearable devices for movement monitoring, such as accelerometers, can be used effectively (4–6). Interest in using wearable technology for quantification of activity and motor function in real-life activities after stroke is increasing within the field of neurorehabilitation (7–9), although application in clinical practice is sparse (7, 10, 11).The Fugl-Meyer Assessment (FMA) is one of the most widely used clinical scales to assess sensorimotor function after stroke. The FMA has excellent psychometric properties (12, 13) and is commonly used as reference when validating new instruments. In addition to motor impairment, sensory function, spasticity, walking ability and speed are commonly assessed in clinical practice after stroke. In general, clinical assessments rely on therapists’ observational skills, and the scoring is limited to predefined categories of the scale. Traditional clinical assessments provide a snapshot of how the patient is functioning at the time of testing, which does not always overlap with the real-life functioning in daily activities (7, 8). Here accelerometers can offer several advantages, by measuring movements and activity continuously over a defined period of time in free-living conditions, and providing an objective measure of motor functioning (9, 14). Such measurements are complicated by the fact that there are numerous different accelerometer devices available, the placement of devices differs, and the metrics obtained are diverse. To overcome this limitation, the use and reporting of accelerometer data in acceleration metrics (m/s²) is advocated to allow comparison between systems, studies and conditions (10). Even though the number of studies using accelerometers is increasing, the validation of the obtained measures is critical for meaningful use in clinical research and practice (14, 15).Moderate-to-strong correlations have been reported between accelerometer-based activity measures and FMA scores (16, 17) as well as Action Research Arm Test (18) among stroke-survivors at different phases of recovery after stroke. Accelerometer-based arm ratio (i.e. the ratio between more-affected and less-affected arm) showed strong correlation with FMA, after controlling for cofactors, such as age, sex, time since stroke, sensory deficit, neglect, apraxia or lower extremity function (17). Knowledge is, however, limited regarding how different relevant cofactors might be associated with real-life activity in people with stroke in a multifactor model. Such knowledge is necessary to advance the routine use of technology-based assessment in clinical practice (19–21).The aim of this study was to determine to what degree arm, leg and trunk activity, measured with accelerometers, is associated with sensorimotor impairments and activity limitations as well as clinical and demographic characteristics in individuals with subacute stroke.     

MEASUREMENTS OF THE CENTRE OF PRESSURE OF INDIVIDUAL LEGS REVEAL NEW CHARACTERISTICS OF REDUCED ANTICIPATORY POSTURAL ADJUSTMENTS DURING GAIT INITIATION IN PATIENTS WITH POST-STROKE HEMIPLEGIA

ObjectivesTo determine whether individual measurements of the centre of pressure for the stance and stepping legs can reveal new characteristics of reduced anticipatory postural adjustments during gait initiation in post-stroke hemiplegic patients.MethodsSubjects included 30 stroke patients and 10 healthy age-matched controls. The acceleration of the trunk, and the centre of pressure of each leg, were measured during gait initiation, 3 times each with the paretic and non-paretic legs leading. Anticipatory postural adjustments were characterized using trunk acceleration and centre of pressure displacement data.ResultsLatency of the posterior displacement peak of the paretic leg centre of pressure with either the paretic or non-paretic leg leading was significantly longer in stroke patients compared with controls, and was also longer than that of the non-paretic leg. The magnitude of the posterior displacement peak of the paretic leg centre of pressure was smaller than that of the non-paretic leg. Peak latency of the paretic stepping leg centre of pressure correlated with the clinical measures of motor dysfunction, postural balance, and gait ability.ConclusionMeasurements of the latency and magnitude of centre of pressure displacement peak individually for the paretic and non-paretic legs can help elucidate the mechanism behind reduced anticipatory postural adjustments. This information will be useful in designing new treatment strategies for stroke patients.LAY ABSTRACTMeasuring the centre of pressure individually for the stance and stepping legs can reveal what happens during initiation of gait in stroke patients. The latency and magnitude of the centre of pressure displacement peak showed characteristic differences between stroke patients and control subjects, and between paretic and non-paretic legs. The peak latency of the paretic stepping leg centre of pressure correlated significantly with clinical measures of motor dysfunction, postural balance, and gait ability. These findings may contribute to the development of effective rehabilitation exercises for stroke patients.Key words: postural control, balance, posture, kinematics, gait

Balance control during gait initiation is crucial for starting stable gait, both in healthy individuals and in people with neuromuscular limitations (1, 2). Motion analyses of electromyograms, accelerations, and ground reaction forces during gait initiation can provide important clinical information for understanding the balance control mechanism. In post-stroke hemiplegic patients, sensory and motor impairments often make good balance control challenging (3–6). In particular, spasticity interferes not only with balance and gait, but also leads to suppression of the soleus muscle, which is required for gait initiation, and makes initiation of gait more difficult (4, 7, 8). The basic problems include motion asymmetry and unstable weight shift to the stance side during gait initiation. The unstable gait initiation is thought to be due to hypometric anticipatory postural adjustments (APAs) (8–10).APAs are changes in posture prior to voluntary movement, which contribute to postural adjustments during gait initiation (11). Gait initiation APAs include activation of the tibialis anterior and suppression of the soleus prior to the start of movement (12, 13), along with posterior shift of the centre of pressure (COP) (14, 15). APAs might account for the time required for the combined COP, i.e. the mean COP of both legs, to shift from the centre of both soles to the posterior part of the stepping leg and then to the posterior part of the stance leg (16). APA occurs in the postural phase, and some reports have determined COP changes until heel-off of the stepping leg (17), while other reports have used COP changes until foot-off as the end of the APA period (16). Lateral and posterior shifts of the combined COP, which are typical measures of APAs during gait initiation, are known to be smaller in stroke patients (3, 10). Furthermore, in stroke patients, inactivation of the tibialis anterior on the paretic side, prolonged latent suppression of the soleus, and smaller shifts of the combined COP indicate reduced APA function (3, 8).To the best of our knowledge, there are no detailed reports of the relationship between reduced APA function and the COP of the stance and stepping legs or of the paretic and non-paretic legs during gait initiation in stroke patients. Assessing COP in each leg individually might provide a better understanding of reduced APAs in stroke patients, with a view to devising better treatments while noting that asymmetry between the stance and stepping legs during gait initiation, and non-uniformity in the vertical component of the ground reaction force have been reported in healthy adults and elderly people (18, 19). Therefore, in post-stroke hemiplegic patients also, it is necessary to look for the details of reduced APA in individual COPs. The latency of muscle activity is important in assessing APA, and has been reported in many studies (17). On the other hand, when assessing APA, changes on each side in individual COPs remain unclear. Investigating factors in the reduced APAs with a focus on individual COPs is thus important in obtaining clinical treatment suggestions for post-stroke hemiplegic patients. The stabilometers used to assess individual COPs are compact and inexpensive, and are widely used even in clinical practice to quantify posture and balance. Electromyograms are often used to analyse APAs (8, 20), but accelerometers and stabilometers are also coming into widespread use because of the low burden on the patient and the simplicity of clinical measurements (10, 21).The aim of the current study was therefore to investigate whether individual COPs show new characteristics of reduced APAs in post-stroke hemiplegic patients. The initial hypothesis was that the peak latency and the peak magnitude of displacement in individual COPs, as characteristics of the reduced APAs in post-stroke hemiplegic patients, are asymmetrically prolonged and decreased, respectively. The second hypothesis was that the characteristic changes in individual COPs are associated with motor impairments, balance indices, and gait ability in post-stroke hemiplegic patients.     

TEMPORAL EVOLUTION AND PREDICTORS OF SUBJECTIVE COGNITIVE COMPLAINTS UP TO 4 YEARS AFTER STROKE

ObjectiveTo examine the temporal evolution of subjective cognitive complaints in the long-term after stroke, and to identify predictors of long-term subjective cognitive complaints.MethodsProspective cohort study including 395 stroke patients. Subjective cognitive complaints were assessed at 2 months, 6 months and 4 years post-stroke, using the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24). The temporal evolution of subjective cognitive complaints was described using multilevel growth modelling. Associations between CLCE-24 cognition score at 4 years post-stroke and baseline characteristics, depression, anxiety, cognitive test performance, and adaptive and maladaptive psychological factors were examined. Significant predictors were entered in a multivariate multilevel model.ResultsA significant increase in subjective cognitive complaints from 2 months up to 4 years (mean 3.7 years, standard deviation (SD) 0.6 years) post-stroke was observed (p≤0.001). Two months post-stroke, 76% of patients reported at least one cognitive complaint, 72% at 6 months, and 89% at 4 years post-stroke. A higher level of subjective cognitive complaints at 2 months and lower scores on adaptive and maladaptive psychological factors were significant independent predictors of a higher level of subjective cognitive complaints at 4 years post-stroke.ConclusionPost-stroke subjective cognitive complaints increase over time and can be predicted by the extent of subjective cognitive complaints and the presence of adaptive and maladaptive psychological factors in the early phases after stroke.LAY ABSTRACTMany people suffer a stroke in the brain leading to consequences in different areas of functioning. Complaints in the domain of thinking (memory, attention, planning and organization) are frequent post-stroke. This study investigated the occurrence and type of complaints experienced in the first years after a stroke. The study found that these complaints increase over time. Longterm complaints are found in those people who already have problems early after stroke.Key words: stroke, rehabilitation, cognition, cognitive complaints

Subjective cognitive complaints (SCC) are common after stroke, with prevalence rates varying between 28.6% (1) and 90.2%, (2), depending on stroke characteristics, time since stroke, SCC definitions and the instruments used. The most commonly reported complaints are mental slowness (in 46–80% of patients) and difficulties in concentration and memory (in 38–68% and 38–94% of patients, respectively) (3). Previous cross-sectional studies showed that SCC are present in both the early stages after stroke (1–6 months after stroke) (4–6), and in the long-term (> 1 year after stroke) (1, 7, 8). To date only a few studies have examined the temporal evolution of SCC. Tinson & Lincoln observed an increase in SCC between 1 and 7 months post-stroke (n = 95) (9). The authors used the Everyday Memory Questionnaire (10), focusing on memory-related complaints. Wilz & Barskova also found an increase in SCC over time after stroke (3 vs 15 months post-stroke, n = 81) (11). SCC were measured with the Patient Competency Rating Scale cognition subscale (12). Van Rijsbergen et al., who used the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24) (13), recently found that SCC remained stable between 3 and 12 months after stroke (n = 155) (14). Long-term results on the course of post-stroke SCC are lacking. Since SCC were found to be independently related to lower quality of life in patients with mild cognitive impairment (15), and patients with subarachnoid haemorrhage (16), it is important to assess SCC after stroke. Furthermore, earlier research showed that SCC were most strongly associated with participation after stroke, compared with cognitive tests in a neuropsychological test battery, and the Montreal Cognitive Assessment (MoCA) (17, 18). Hence, in order to improve participation and integration in society after stroke, it is important to take the patients’ perspective into account, rather than only determining objective cognitive measures.The presence and severity of SCC is expected to be a direct reflection of the presence and severity of cognitive deficits. However, previous studies investigating the relationship between SCC and cognitive performance in stroke patients have shown conflicting results (1–4, 7, 8, 13, 19, 20). Other factors have shown to be related to SCC, in particular psychological factors, such as depressive symptoms (2, 4, 6, 7, 21), anxiety (21, 22), perceived stress (14), personality traits (7, 22), and coping style (23). To date, only one study on SCC used a longitudinal design (14), which prevents conclusions on the temporal evolution of SCC in stroke patients in the long term. Since more stroke patients survive, recover well and are discharged home nowadays, it is important to address predictors of SCC in the early phases after stroke, in order to identify patients who need more intensive monitoring at follow-up. Once identified, it is possible to investigate whether the patients will benefit from more focused rehabilitation programmes.The aim of this longitudinal study was to examine the temporal evolution of SCC, from 2 months until 4 years post-stroke. Furthermore, the study assessed which factors are predictive of SCC at 4 years post-stroke, taking into account demographic and stroke-related characteristics at baseline, and cognitive deficits and psychological factors measured at 2 months post-stroke.     

FATIGUE IN MEN AND WOMEN WHO HAVE RETURNED TO WORK AFTER STROKE: ASSESSED WITH THE FATIGUE SEVERITY SCALE AND MENTAL FATIGUE SCALE

ObjectiveTo assess the occurrence of self-reported fatigue among men and women who have returned to work after stroke, and the association between 2 fatigue rating scales.DesignA cross-sectional study.SubjectsA total of 91 adults (58 men/33 women, mean age 53 years) with mild to moderate disability. Methods: Questionnaires were posted to participants approximately one year after stroke. Fatigue was assessed with the Fatigue Severity Scale (FSS) and the Mental Fatigue Scale (MFS).ResultsIn total, 58% of the women and 33% of the men reported fatigue on the FSS (total score ≥ 4), and 46% of the women and 28% of the men reported mental fatigue on the MFS (total score ≥ 10.5). Being easily fatigued, decreased motivation, mental fatigability and sensitivity to stress were the most reported problems. FSS and MFS were moderately associated (rho 0.517–0.732).ConclusionFatigue is common among persons who have returned to work after stroke, and interferes with daily life. The long-term consequences of fatigue should be addressed after stroke, especially in women. The FSS and the MFS can be used in combination, as they provide information on different aspects of fatigue.LAY ABSTRACTFatigue can be a long-lasting and disabling impairment following stroke. There is a need for increased knowledge of how fatigue affects people who have returned to work after stroke, and which fatigue rating scales capture their problems most appropriately. The aim of this study was to assess the occurrence of self-reported fatigue among men and women who have returned to work after stroke, and to determine the association between 2 fatigue rating scales. The study was based on a postal survey and includes 91 participants. Fatigue was found to be common 1 year after stroke, especially in women, and interfered with daily life. The 2 fatigue rating scales could be used in combination, as they provide different information on fatigue. The findings could be used to develop support that enables people with stroke to return to and to stay at work long-term.Key words: cerebral stroke, data correlation, disability evaluation, mental fatigue, return to work, self-assessment, stroke rehabilitation

Stroke is one of the most common causes of long- lasting disability among adults (1, 2). In Sweden, approximately 26,000 persons have a stroke annually (3). Because of an increasing incidence of stroke among young people (4) many live with its consequences for a significant part of their lives. Common impairments following stroke include reduced sensorimotor and cognitive functions, as well as fatigue (5–7). Due to advances in acute treatments and rehabilitation, more people recover from their initial neurological impairments. Despite this, post-stroke fatigue can be a persisting and severely disabling problem (8).Fatigue is defined as a subjective lack of physical and/or mental energy that interferes with various activities (9). It is related to reduced quality of life (10, 11), increased dependence in ADL (12) and increased mortality (12, 13). Fatigue can also have a negative impact on social participation, driving, reading, sleeping and return to work (8). Although fatigue is reported by 25–85% of stroke survivors during the first 2 years after stroke, the occurrence of post-stroke fatigue remains unclear due to large heterogeneity between studies (9). Women may experience more fatigue than men (7, 14), although the mechanisms behind this, or in what situations fatigue occurs, are poorly described.In addition, people with mild stroke (15, 16) who have returned to work (17) may experience fatigue, which could lead to difficulties in maintaining work (18). Our previous study (19) revealed that ”invisible” impairments, including fatigue, contributed to people feeling uncertain about their working capacity after stroke. They also had difficulties expressing what kind of help they needed to deal with their problems. Overall, knowledge regarding the occurrence of fatigue among people who have returned to work and its influence on daily life and work capacity is limited. Such knowledge is important to be able to provide adequate rehabilitation and support that enables people to return to work and stay at work after stroke.Fatigue is most often assessed using self-reported rating scales. Several scales are available, but no consensus exists regarding which scale should be preferred after stroke. Currently, the Fatigue Severity Scale (FSS) is the most used in stroke research (9). The FSS mainly targets fatigue defined as a sense of physical tiredness and lack of energy (20). However, people with stroke also commonly experience mental fatigue; characterized by difficulties performing mentally strenuous tasks for more than short periods, increased irritability, sensitivity to stress, concentration difficulties and emotional instability (21). The Mental Fatigue Scale (MFS) was constructed to capture the impact of mental fatigue on various life situations (22).Taken together, there is a need for increased knowledge of how fatigue affects people who have returned to work after stroke, and which fatigue rating scales most appropriately capture their problems. Therefore, the aims of this study were to assess: (i) the occurrence of self-reported fatigue among men and women who have returned to work after stroke; and (ii) the association between FSS and MFS (i.e. whether these measures can replace or complement each other).     

COGNITIVE FUNCTION AND PERFORMANCE OF EVERYDAY ACTIVITIES IN ADULTS WITH SPINA BIFIDA

Background and objectiveIndividuals with spina bifida often have cognitive impairments leading to difficulties in education and daily activities. The aims of this study were to explore cognitive impairments in adults with spina bifida and to consider associations between impairments, educational outcome and performance of daily activities, comparing individuals with and without intellectual disability.MethodsData were collected on 35 adults with spina bifida via cognitive tests and Assessment of Motor and Process Skills (AMPS). Participants were divided into 3 groups: individuals without intellectual disability who completed compulsory education (NID-C); those without intellectual disability, who failed to successfully pass compulsory education (NID-F); and those with intellectual disability failed to successfully pass compulsory education (ID-F).ResultsAll individuals with intellectual disability failed to successfully pass compulsory education (group ID-F) and had poorer scores across almost all measures than group NID-F and significantly poorer scores than group NID-C. All except 6 individuals scored below cut-off levels for effort and safety on both AMPS motor and process scales; more significant associations were seen between the cognitive tests and the motor rather than process scale.ConclusionCognitive impairments, irrespective of intellectual disability, impact on the performance of everyday activities and on educational achievement, and thus need to be considered in assessments and interventions to improve outcomes and promote independence in people with spina bifida.LAY ABSTRACTIndividuals with spina bifida often have cognitive impairments, resulting in difficulties in performing their everyday life activities at home, in education, training and social life. These difficulties are often not recognized, and the individuals do not receive the support they need from society. This study investigated the relationship between cognitive impairments, school achievements and performance of daily life activities of 35 adults with spina bifida. The study examined whether individuals had an intellectual disability, and whether they had completed compulsory education, and compared this with their cognitive function and performance in everyday activities. The results confirm that individuals with cognitive impairments, even those without intellectual disabilities, often have considerable difficulties in school achievements, and performance of daily life activities, reducing their ability to live independently.Key words: disability evaluation, intellectual disability, cognitive function, activities of daily living, spina bifida

Spina bifida (SB) is caused by the incomplete closing of the embryonic neural tube, which can affect brain development, with consequent sensory and motor difficulties (1, 2). Hydrocephalus is present at birth in 80–85% of individuals with SB (3), and by adulthood 63% are estimated to have hydrocephalus (4). Hydrocephalus leads to structural anomalies in the brain (1), which seem to contribute to a cognitive phenotype with relative strengths and weaknesses (5) and differing degrees of cognitive impairments amongst individuals with SB (6). One in 5 individuals with SB and hydrocephalus are reported to have an intellectual disability (ID) (intelligence quotient (IQ) < 70) (7). Furthermore, according to several studies many other individuals with SB show impaired executive functions (EF)¹, which become more evident when performing more complex activities (5). Impaired working memory (9), a part of EF (8), and prospective memory (10) are also common, as well as attention disorders (11), impaired processing speed, timing deficits (5), problems with time management (12) and with getting things done (13). Impaired visuospatial function is also common (11). In general, individuals with SB have no limitations in reading, vocabulary, grammar, and sentence structure, but may have difficulties in understanding the underlying meaning of words and in drawing conclusions (5). Reduced reading comprehension and reduced numeracy are also common (5). Learning capacity is often unaffected, but individuals may have difficulties in processing and retrieving information (5). These cognitive impairments can be observed in childhood and become more evident during adolescence and adulthood, when activities of daily living (especially taking care of your own household), education, work and relations put increased demands on the person (14). Several studies found that cognitive impairments in individuals with SB do not decrease with maturity, but persist into adulthood (9, 14). Furthermore, impairments in prospective memory have also been shown to increase for persons over 32 years of age (10). Few studies have examined the effects of ageing on cognitive function in individuals with SB (9).Cognitive impairments are associated with quality of life (15) and affect performance of daily activities negatively for adults with SB (16), with potential impact on health and wellbeing (4, 17). Impaired EF may limit young adults in achieving milestones of independence in life, like education, work, relationships and assuming responsibility for their own household (18). Many individuals with SB do not reach secondary education and have difficulties in obtaining a job (19). Further challenges may appear in adulthood with the need to manage contacts with authorities regarding special transportation services, housing, and community-based support services, etc. (20). Moreover, management of personal hygiene and medication due to complex SB-related disabilities put additional demands on EF (20). Consequently, impaired EF increases risks for complications, such as pressure ulcers, urinary infections, incontinence, and constipation (21). However, individuals with SB are often highly verbal, giving the impression of managing everyday life well (22). Thus, healthcare professionals and others not specialized in the field seldom recognize these cognitive limitations (23). The need for support may go unrecognized, and interventions may be insufficient or even fail (24).In order to provide appropriate support, there is a need for assessments to recognize the range of cognitive impairments in individuals with SB and to consider how these impact on educational outcomes (completion of compulsory education²) and performance of daily activities (especially household activities). The aims of the current study were to explore cognitive impairments in adults with SB and to consider associations between these impairments, educational outcome, and performance of daily activities, comparing individuals with and without intellectual disabilities (ID).     

E–Z isomerization of 3-benzylidene-indolin-2-ones using a microfluidic photo-reactor

Here, we report controlled E–Z isomeric motion of the functionalized 3-benzylidene-indolin-2-ones under various solvents, temperature, light sources, and most importantly effective enhancement of light irradiance in microfluidic photoreactor conditions. Stabilization of the E–Z isomeric motion is failed in batch process, which might be due to the exponential decay of light intensity, variable irradiation, low mixing, low heat exchange, low photon flux etc. This photo-μ-flow light driven motion is further extended to the establishment of a photostationary state under solar light irradiation.

(E)-3-Benzylidene-indolin-2-ones were efficiently converted to their corresponding (Z) -isomers at low temperature in the presence of light.

Functionalized 3-benzylidene-indolin-2-ones are an important structural motif in organic chemistry and are embedded in many naturally occurring compounds.¹ They found wide applications in molecular-motors,² energy harvesting dyes,³ pharmaceutical chemistry (sunitinib, tenidap),⁴ protein kinase inhibitors,⁵ pesticides,⁶ flavors,⁷ and the fragrance industry.⁸ In the last few decades, numerous protocols have been developed for the synthesis of novel indolin-2-ones. For instance, palladium (Pd)-catalysed intramolecular hydroarylation of N-arylpropiolamides,⁹ Knoevenagel condensation of oxindole and aldehyde,¹⁰ two-step protocols such as Ni-catalyzed CO₂ insertion followed by coupling reaction,¹¹ Pd-catalysed C–H functionalization/intramolecular alkenylation,¹² Pd(0)/monophosphine-promoted ring–forming reaction of 2-(alkynyl)aryl isocyanates with organoboron compound, and others.¹³Knoevenagel condensation is one of the best methods for the preparation of 3-benzylidene-indolin-2-ones, but often it gives mixture of E/Z isomeric products. Otherwise, noble metal-catalysed protocols received enormous interest. However, the limited availability, high price, and toxicity of these metals diminished their usage in industrial applications. Therefore, several research groups have been engaged in search of an alternative greener and cleaner approach under metal-free conditions. To address the diastereoisomeric issue, Tacconi et al. reported a thermal (300–310 °C) isomerization reaction of 3-arylidene-1,3-dihydroindol-2-ones,¹⁴ which suffers from poor reaction efficiency and E/Z selectivity. Therefore, transformations controlling E/Z ratio of 3-benzylidene-indolin-2-ones remains a challenging task and highly desirable (Scheme 1).Open in a separate windowScheme 1Functionalized 3-benzylidene-indolin-2-ones and alkenes in bioactive compounds and the accessible methods.On the other hand, selective E/Z stereo-isomerization of alkenes has been well established using various methods in the presence of light stimuli,^15a cations,^15b halogens or elemental selenium,¹⁶ palladium-hydride catalyst,¹⁰ cobalt-catalyst,¹⁷ Ir-catalyst,¹⁸ organo-catalysts.¹⁹ Among these, light-induced photostationary E/Z stereoisomerization is very attractive, due to its close proximity towards the natural process. In recent years, several light-driven molecular motors (controlled motion at the molecular level), molecular propellers,²⁰ switches,²¹ brakes,²² turnstiles,²³ shuttles,²⁴ scissors,²⁵ elevators,²⁶ rotating modules,²⁷ muscles,²⁸ rotors,²⁹ ratchets,³⁰ and catalytic self-propelled objects have been developed.³¹ Further, equipment''s relying on molecular mechanics were rapidly developed, particularly in the area of health care.Till date, controlled photo-isomerization of functionalized 3-benzylidene-indolin-2-ones is one of the puzzling problems to the scientific community. Photochemical reactions in batch process have serious drawbacks with limited hot-spot zone due to inefficient light penetration with increasing light path distance through the absorbing media, and the situation becomes poorer when the reactor size increases.^32,33 In contrast, the capillary microreactor platform has emerged as an efficient the artificial tool with impressive advantages, such as excellent photon flux, uniform irradiation, compatibility with multi-step syntheses, excellent mass and heat transfer, which lead to significant decrease the reaction time with improved yield or selectivity over batch reactors.^33a,34 To address the aforementioned challenges, it is essential to develop a highly efficient photo-microchemical flow approach for the controlled isomerization of functionalized 3-benzylidene-indolin-2-ones in catalyst-free and an environment friendly manner.     

INCREASED SATELLITE CELL APOPTOSIS IN VASTUS LATERALIS MUSCLE AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION

ObjectiveRecovery of the quadriceps femoris muscle after anterior ligament reconstruction is impaired. The aim of this study was to investigate satellite cell content and function of the vastus lateralis muscle after anterior ligament reconstruction.MethodsBiopsies were obtained from the vastus lateralis muscle of 16 recreational athletes immediately before and again 12 weeks after anterior ligament reconstruction. Total satellite cell number (Pax7⁺), activated (Pax7⁺/MyoD⁺), differentiating (Pax7^–/MyoD⁺), and apoptotic (Pax7⁺/TUNEL⁺) satellite cells, myofibers expressing myosin heavy chain (MHC) I and II, and neonatal MHC (MHCneo) were determined immunohistochemically.ResultsAfter anterior ligament reconstruction, the number of apoptotic satellite cells was significantly (p = 0.019) increased, concomitant with a significant (p < 0.001) decrease in total satellite cell number, with no change in activated and differentiating satellite cell number. MHCneo⁺ myofibers tended towards an increase.CONCLUSIONSatellite cell apoptosis and the reduction in the satellite cell pool might provide an explanation for prolonged quadriceps muscle atrophy after anterior ligament reconstruction.LAY ABSTRACTProtracted muscle atrophy is common after anterior ligament reconstruction, even if athletes adhere to a structured rehabilitation programme. Satellite cells, the stem cells of skeletal muscle, play an important role in recovery of an atrophied muscle. Exercise can activate satellite cells, induce their proliferation, and probably also differentiation of these stem cells. The current study evaluated satellite cell content and function in biopsies from the vastus lateralis muscle of 16 recreational athletes immediately before and 12 weeks after anterior ligament reconstruction. After anterior ligament reconstruction, an increased number of satellite cells showed signs of apoptosis (cell death). Furthermore, total satellite cell number was decreased, with no change in the numbers of activated and differentiating satellite cells. The number of regenerating myofibers expressing neonatal myosin tended to increase. In conclusion, satellite cell apoptosis and the reduced satellite cell number might provide an explanation for the impaired muscle recovery after anterior ligament reconstruction.Key words: satellite cells, apoptosis, muscle regeneration, developmental myosin heavy chain, muscular atrophy, quadriceps muscle

Protracted atrophy and weakness of the quadriceps muscle are common after anterior cruciate ligament (ACL) injury and/or anterior cruciate ligament reconstruction (ACL-R), even if the patients undergo guided rehabilitation programmes (1–4). Muscle recovery is compromised due to negative changes in the knee extensor muscles, most likely due to impaired neuromuscular function (5), post-surgery inflammation (6) and immobilization (7). After ACL injury, fibrogenic alterations were observed in biopsies obtained from the vastus lateralis muscle of the injured leg (8, 9). Satellite cell (SC) abundance was also reduced compared with biopsies taken from the vastus lateralis muscle of the uninjured leg (8, 10). Furthermore, there was a surprising lack of increase in SC number after regular rehabilitation training (10), as well as after 12 weeks of supervised quadriceps strength training during rehabilitation after ACL-R (3).SCs play an important role in skeletal muscle growth and regeneration (11, 12). Increases in SC number occur after 11–12 weeks of quadriceps strength training in healthy subjects (13–15). The role of SCs in atrophy of human skeletal muscle, however, has scarcely been investigated. In the very few studies on the role of SCs in atrophy of human skeletal muscle (8, 10, 16), loss of SCs with atrophy is not a consistent finding. However, there is some evidence that a particularly severe atrophic environment, as is found, for example, after severe burn injury, has a negative impact on SC number and SC function and can induce SC apoptosis (17). With regard to findings in animal studies, it has been hypothesized that muscle wasting in old age (sarcopaenia) could at least partly be explained by SC dysfunction with increased SC apoptosis due to chronic low-grade systemic inflammation (18). The significantly reduced SC number in biopsies from the vastus lateralis muscle after ACL injury (8, 10) and the lack of increase in SC number after resumption of muscular training after ACL-R (3, 10) suggest that ACL injury and/or ACL-R with quadriceps tendon or semitendinosus tendon autografts, respectively, might generate a severe atrophic environment with negative effects on SC number and function.The primary aim of this study was to further investigate the effects of ACL-R on SCs and to determine whether the previously described reduction in SC number might be due to SC apoptosis. The study analysed muscle biopsies from the vastus lateralis muscle of recreational athletes immediately before ACL surgery and again after 12 weeks of early rehabilitation.     

EFFECTS OF VIRTUAL REALITY-BASED NECK-SPECIFIC SENSORIMOTORTRAINING IN PATIENTS WITH CHRONIC NECK PAIN: A RANDOMIZED CONTROLLED PILOT TRIAL

ObjectiveTo evaluate the effects of neck-specific sensorimotor training using a virtual reality device compared with 2 standard rehabilitation programmes: with, and without general sensorimotor training, in patients with non-traumatic chronic neck pain.DesignPilot randomized control study.Patients and methodsA total of 51 participants were randomly assigned to 1 of 3 groups: 1: control group; 2: sensorimotor group; 3: virtual reality group. All 3 groups received the clinic’s standard rehabilitation programme. Group 2 also received “general sensorimotor training” in the form of group therapy, for a total of 120 min. Group 3 received additional virtual reality-based “neck-specific sensorimotor training” for a total of 120 min. Participants’ neck pain, headaches, active cervical range of motion, and Neck Disability Index were determined before and after 3 weeks of intervention.ResultsCompared with the control group, the virtual reality group showed significant (p < 0.05) advantages in relief of headaches, and active cervical range of motion in flexion and extension. Compared with the sensorimotor group, the virtual reality group showed significant improvements in cervical extension.ConclusionVirtual reality-based sensorimotor training may increase the effects of a standard rehabilitation programme for patients with non-traumatic chronic neck pain, especially active cervical range of motion in extension.LAY ABSTRACTThe aim of this study was to evaluate the effectiveness of neck-specific coordination training using a virtual reality device, in comparison with general coordination training and a standard exercise programme as part of inpatient rehabilitation for patients with chronic neck pain. Pain, disability and mobility of the neck were determined before and after 3 weeks of training intervention in 51 patients. The virtual reality training group exhibited greater effects in relief of headaches, and bending the neck forwards and backwards compared with the standard exercise group, and an increased ability to bend the neck backwards compared with the coordination training group. The results suggest that neck-specific coordination training using a virtual reality device increases the benefits of standard inpatient rehabilitation in patients with chronic neck pain, particularly in bending the neck backwards.Key words: neck pain, rehabilitation, virtual reality, kinematics

Neck pain is a widespread problem; 60–80% of individuals develop neck pain during their life-time, with 30–50% of the general population reporting neck pain annually (1–3). Many patients experience neck pain as a complex biopsychosocial disorder, with problematic physical and psychological symptoms (3), such as reduced cervical range of motion, headaches, lack of concentration, emotional and cognitive disorders (4, 5). Aside from the decreased quality of life, these complaints are a major cause of inability to work (6, 7) and lead to considerable economic damage (8). Hence, the demand for an effective treatment is indisputable.According to a recently published review (9), the strongest treatment effects for neck pain are those associated with exercise. However, the evidence for this claim is only of moderate quality. Since there is no data available at present to show that any one form of exercise is evidentially more effective than another, multimodal care is concordantly recommended by leading experts (3, 9).Sensorimotor training methods are a current trend in exercise therapy, and for the first time they take into account the special function of the neck, by including connections between the perceptions of sensory organs located in the head and neck muscles (10–14). Alterations of sensorimotor control have been identified in many patients with neck pain, and are thought to play an important role in the aetiology and maintenance of associated disorders (14, 15).To date, there are only a few sensorimotor training concepts that have been specially developed for the neck region. Initial studies found that patients undergoing these training methods experienced reduced neck pain, as well as improvements in cervical range of motion, self-reported disability, and general health (11, 13, 14, 16). However, a systematic review from 2014 (17) revealed very little evidence for eye-neck coordination and proprioceptive exercises. Furthermore, a randomized controlled trial (RCT) found that neck coordination exercises did not produce a larger effect than strength training and massages (18).Application of a virtual reality (VR) device is a novel and promising option for training cervical kinematics (10, 12, 19). In theory, this technique provides several advantages: distracting attention and therefore reducing pain and kinesiophobia (20, 21), engaging and motivating physical activities, and improving the effectiveness of exercise (22, 23).To date, only one RCT has compared the effects of VR-based training with conventional kinematic training using laser beams in patients with chronic neck pain (12). The VR group exhibited significant improvements in motion velocity, pain intensity, health status, and accuracy of neck motion.Due to the conflicting evidence and lack of research, there is a need for more studies that consider the effectiveness of VR-based sensorimotor training concepts, especially in combination with other effective therapeutic exercises or as part of individually tailored programmes (12).The aim of this study was therefore to evaluate the effects of neck-specific sensorimotor training using a VR device, in comparison with standard rehabilitation programmes, both with and without general sensorimotor training, in patients with non-traumatic chronic neck pain.