Motor response to amphetamine treatment, task-specific training, and limited motor experience in a postacute animal stroke model No benefit from D-amphetamine when added to physiotherapy after stroke: a randomized, placebo-controlled study Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333) What’s New in Stroke Rehabilitation Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial. Enhanced physical therapy improves recovery of arm function after stroke. A randomised controlled trial. Effect of Thermal Stimulation on Upper Extremity Motor Recovery 3 Months After Stroke From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke A New Method for Predicting Recovery After Stroke Safety of Dexamphetamine in Acute Ischemic Stroke: A Randomized, Double-Blind, Controlled Dose-Escalation Trial Amphetamine paired with physical therapy accelerates motor recovery after stroke. Further evidence. Music listening enhances cognitive recovery and mood after middle cerebral artery stroke. Arm rehabilitation in post stroke subjects: A randomized controlled trial on the efficacy of myoelectrically driven FES applied in a task-oriented approach
Despite advances in acute treatment of ischemic cerebrovascular events , the most common clinical outcome is disabling neurological impairment . Despite experimental evidence that psychostimulant treatment can positively affect recovery rate after focal brain lesions , beyond rehabilitation therapies there are no currently accepted medical treatments indicated for diminishing neurological impairment after clinical ly established stroke . To test the effect of amphetamine , task-specific training , limiting motor experience , and their interaction on motor recovery in a postacute animal model of stroke , animals were nonaversively trained in beam walking before a unilateral photochemical sensorimotor cortex lesion and tested for 10 days after lesion . Animals were r and omized to groups receiving : a single session of motor training 24 h after lesion ; a single injection of amphetamine 2 mg/kg 24 h after lesion ; beam-walking experience limited to testing on days 1 and 10 after lesion ; and groups that received amphetamine treatment combined with training or combined with limited experience .  Motor recovery was maximally enhanced by training , delayed by amphetamine treatment , and most negatively affected by limiting beam-walking experience during the recovery period . These findings support physical training after stroke , indicating that limiting physical activity negatively affects motor recovery and raises questions about the role of stimulant treatment to enhance motor recovery in the postacute phase after stroke Objective : To assess the effect of D-amphetamine on the recovery of activities of daily living and motor functions after stroke , Design : R and omized , placebo-controlled study , Setting : Inpatient rehabilitation centre , Subjects : Twenty-four stroke survivors after a first ischaemic supratentorial stroke within six weeks before study onset , severely to moderately affected , with a Barthel Index ( 0–100 ) ranging from 25 to 50 , no severe concomitant internal , neurological or psychiatric diseases , and participating in a comprehensive rehabilitation programme of 10–12 weeks , Interventions : Ten sessions with 10 mg D-amphetamine ( or placebo ) every fourth day totalling 100 mg in a time period of 36 days combined with physical therapy according to the neurodevelopmental concept within 60 minutes after drug intake . Main outcome measures : Barthel Index ( 0–100 ) served as the primary outcome measure and the Rivermead Motor Assessment Score with its three sections ( gross function , leg and trunk , and arm ) as the secondary outcome measure , assessed at days 0 , 20 , 36 , 90 , 180 and 360 . Results : The two groups did not differ with respect to clinical data and outcome measures at study onset . All patients improved significantly except for arm function over the intervention period and up to day 90 after study onset . The comparison between groups did not reveal any difference at any time ; amphetamine-treated patients did not show any increase in motor function or ADL compared with the control group . Conclusions : The placebo-controlled study failed to show any effect of D-amphetamine on stroke recovery compared with control . The small number of patients , the timing and content of physical therapy were limiting factors of the present study . Further trials are warranted Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation . Amphetamine , a sympathomimetic , might have haemodynamic effects in stroke patients , although limited data have been published . Subjects were recruited 3–30 days post-ischaemic stroke into a phase II r and omized ( 1:1 ) , double-blind , placebo-controlled trial . Subjects received dexamphetamine ( 5 mg initially , then 10 mg for 10 subsequent doses with 3- or 4-day separations ) or placebo in addition to inpatient physiotherapy . Recovery was assessed by motor scales ( Fugl – Meyer ( FM ) ) , and functional scales ( Barthel index ( BI ) and modified Rankin score ( mRS ) ) . Peripheral blood pressure ( BP ) , central haemodynamics and middle cerebral artery blood flow velocity were assessed before , and 90 min after , the first two doses . Thirty-three subjects were recruited , aged 33–88 ( mean 71 ) years , males 52 % , 4–30 ( median 15 ) days post stroke to inclusion . Sixteen patients were r and omized to placebo and seventeen to amphetamine . Amphetamine did not improve motor function at 90 days ; mean ( s.d . ) FM 37.6 ( 27.6 ) vs control 35.2 ( 27.8 ) ( P=0.81 ) . Functional outcome ( BI , mRS ) did not differ between treatment groups . Peripheral and central systolic BP , and heart rate ( HR ) , were 11.2 mm Hg ( P=0.03 ) , 9.5 mm Hg ( P=0.04 ) and 7 beats per minute ( P=0.02 ) higher , respectively , with amphetamine , compared with control . A nonsignificant reduction in myocardial perfusion ( BUI ) was seen with amphetamine . Other cardiac and cerebral haemodynamics were unaffected . Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and HR without altering cerebral haemodynamics Stroke rehabilitation has been revolutionized in the last decade through a combination of new imaging techniques looking at brain recovery and clinical trials into what is working in stroke rehabilitation . The fear that rehabilitation was a long way from being rooted in science1 has been overcome by an increasing underst and ing of neuronal recovery processes and their modulation by various physical and pharmacological interventions . More than 300 r and omized controlled trials provide a sound foundation for evidence -based practice in stroke rehabilitation , supplementing and often confirming decades of clinical experience . This growing body of knowledge has been enriched by several studies in 2003 . Advances in basic sciences and clinical research are beginning to merge and show that the human brain is capable of significant recovery after stroke , provided that the appropriate treatments and stimuli are applied in adequate amounts and at the right time . What is particularly exciting is the introduction s of new technologies such as robotic enhancement of therapies and virtual reality to further enhance that recovery . Stroke rehabilitation is therapy intensive and one of the unresolved debates has been around the issues of quality and quantity . Evidence is building that intensity of therapy is important . This is particularly true for language recovery . Bhogal et al2 identified 8 r and omized controlled trials ( RCTs ) , which compared the intensity of speech and language therapy ( SLT ) delivered by a trained therapist versus a non-therapist or a non-SLT control . Four of the studies were positive and these studies provided a mean of 8.8 hours of therapy per week for 11.2 weeks when compared with the 4 negative trials that provide approximately 2 hours of therapy per week for a total of 22.9 weeks . On average , positive RCTs provided 98.4 hours of therapy over half the time that the negative RCTs provided 43.6 hours . Intensive therapy PURPOSE To assess the effects of d-amphetamine on motor facilitation and recovery in stroke patients with mild arm paresis receiving the Arm Ability training . METHODS Thirty-one stroke patients with mild arm paresis were r and omly assigned to either ( a. ) receiving placebo or ( b. ) d-amphetamine twice a week 2 hours before Arm Ability training sessions for three weeks . MAIN OUTCOME MEASURE time needed to perform TEMPA tasks , a measure of upper extremity performance reflecting everyday life tasks . Secondary measures : aim ed movements , tapping , and a 10 m walkway as well as motor performance during training sessions . RESULTS The interim efficacy analysis of 26 stroke patients who completed the study intervention showed overall arm motor recovery both from pre to post test after 3 weeks of training and from pre test to follow-up 1 year later . No superior effect of d-amphetamine over placebo could be substantiated for either motor facilitation during training or motor recovery ( post training or long-term ) . D-amphetamine exerted mild effects on blood pressure . Serious adverse events were not observed . CONCLUSIONS d-Amphetamine failed to facilitate motor performance during training sessions , to promote skill acquisition with training tasks , and most importantly to enhance motor recovery among patients with mild arm paresis after stroke Previous research on stroke rehabilitation has not established whether increase in physical therapy lead to better intrinsic recovery from hemiplegia . A detailed study was carried out of recovery of arm function after acute stroke , and compares orthodox physiotherapy with an enhanced therapy regime which increased the amount of treatment as well as using behavioural methods to encourage motor learning . In a single-blind r and omised trial , 132 consecutive stroke patients were assigned to orthodox or enhanced therapy groups . At six months after stroke the enhanced therapy group showed a small but statistically significant advantage in recovery of strength , range and speed of movement . This effect seemed concentrated amongst those who had a milder initial impairment . More work is needed to discover the reasons for this improved recovery , and whether further development of this therapeutic approach might offer clinical ly significant gains for some patients Background and Purpose — To examine the effect of thermal stimulation ( TS ) on upper extremity ( UE ) motor recovery in patients at least 3 months after stroke . Methods — Participants were r and omly assigned to either the experimental group or the control group . In addition to regular rehabilitation programs , the experimental group received an UE-TS protocol for 30 minutes per day ( 3 days/week for 8 weeks ) ; the control group received the same TS protocol on lower extremity . The UE subscale of the Stroke Rehabilitation Assessment of Movement and the Action Research Arm Test were primary outcome measures . The Modified Ashworth Scale and the Barthel Index were secondary outcome measures . All measures were administered at baseline , after TS , and at 1-month follow-up . Results — Twenty-three participants ( 12 in the experimental group ) completed the study . After treatment , the experimental group showed significant improvement compared to the control group in the scores of the UE subscale of the Stroke Rehabilitation Assessment of Movement and Action Research Arm Test . At follow-up examination , a significant improvement in the experimental group was observed on the UE subscale of the Stroke Rehabilitation Assessment of Movement . Conclusions — The 8-week additional UE-TS protocol improved UE motor recovery for stroke patients 3 months after onset Background There is much discourse in healthcare about the importance of client-centred rehabilitation , however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal -directed practice that reflects patients ' valued activities . In addition , the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear . In community based rehabilitation , interventions based on patients ' perceived needs may be more likely to alter such outcomes . In this paper , we describe the methodology of a r and omised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke . The effectiveness of this intervention in reducing the severity of post-stroke depression , improving participation status and health-related quality of life is examined . The impact on carers is also examined . Methods / Design Patients ( and their primary carers , if available ) are r and omly allocated to an intervention or control arm of the study . The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities . Intervention methods include : telephone contacts , written information provision , home visitation , and contact with treating health professionals , with further relevant health service referrals as required . The control involves treatment as usual , as determined by inpatient and community rehabilitation treating teams . Formal blinded assessment s are conducted at discharge from inpatient rehabilitation , and at six and twelve months post-stroke . The primary outcome is depression . Secondary outcome measures include participation and activity status , health-related quality of life , and self-efficacy . Discussion The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers , with emphasis on goal -directed practice to enhance home and community participation status . Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression , as well as enhancing the individual 's perception of their health-related quality of life . The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : Background and Purpose — Several prognostic factors have been identified for outcome after stroke . However , there is a need for empirically derived models that can predict outcome and assist in medical management during rehabilitation . To be useful , these models should take into account early changes in recovery and individual patient characteristics . We present such a model and demonstrate its clinical utility . Methods — Data on functional recovery ( Barthel Index ) at 0 , 2 , 4 , 6 , and 12 months after stroke were collected prospect ively for 299 stroke patients at 2 London hospitals . Multilevel models were used to model recovery trajectories , allowing for day-to-day and between-patient variation . The predictive performance of the model was vali date d with an independent cohort of 710 stroke patients . Results — Urinary incontinence , sex , prestroke disability , and dysarthria affected the level of outcome after stroke ; age , dysphasia , and limb deficit also affected the rate of recovery . Applying this to the validation cohort , the average difference between predicted and observed Barthel Index was −0.4 , with 90 % limits of agreement from −7 to 6 . Predicted Barthel Index lay within 3 points of the observed Barthel Index on 49 % of occasions and improved to 69 % when patients ’ recovery histories were taken into account . Conclusions — The model predicts recovery at various stages of rehabilitation in ways that could improve clinical decision making . Predictions can be altered in light of observed recovery . This model is a potentially useful tool for comparing individual patients with average recovery trajectories . Patients at elevated risk could be identified and interventions initiated Background and Purpose — Amphetamine is reported to enhance recovery after experimental stroke , but results from the first few trials in humans are inconclusive . Limited information is available on treatment safety . This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia . Methods — Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms . Patients were r and omized to 1 of 3 dose levels ( 2.5 , 5 , or 10 mg orally twice daily ) or placebo for 5 consecutive days . Adverse events , blood pressure , heart rate , body temperature , consciousness level , and functional outcome measures were followed up daily during treatment . Follow-ups were made at day 7 and 1 and 3 months after stroke . Results — Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg , 8 mm Hg , and 9 bpm , respectively , with dexamphetamine treatment compared with placebo ( P ≤0.01 ) . There was no difference between dexamphetamine and placebo  regarding adverse events , body temperature , or consciousness level . During treatment , there was a benefit of dexamphetamine in neurological and functional outcome ( P < 0.05 ) , but differences were not maintained at follow-up . Conclusions — Overall , dexamphetamine was safe and well tolerated by patients with acute cerebral ischemia , but blood pressure and heart rate increased during treatment in comparison to placebo . These observations may be important in the future planning of amphetamine trials because changes in these variables have been observed to interfere with clinical outcome . The suggestions of improvement in outcome must be confirmed in further studies BACKGROUND AND PURPOSE In animal models of brain injury , administration of numerous pharmaceuticals is reported to facilitate functional recovery . However , only drugs that increase the release of norepinephrine have been shown to promote recovery when administered late ( days to weeks ) after injury . To determine whether these findings were applicable to humans , we administered the norepinephrine stimulant dextroamphetamine , paired with physical therapy , to hemiplegic stroke patients . METHODS Ten hemiplegic patients who suffered an acute ischemic infa rct ion were entered between days 16 and 30 after onset and r and omly assigned to receive either 10 mg of dextroamphetamine or a placebo orally every fourth day for 10 sessions paired with physical therapy . The Fugl-Meyer Motor Scale was used at baseline , within each session , and for 12 months after onset as the dependent measure . Confounding medications such as alpha-adrenergic antagonists or agonists were excluded in all subjects . RESULTS Although there were no differences between the groups at baseline ( P = .599 ) , there was a significant ( P = .047 ) difference between the groups when the drug had been discontinued for 1 week and at the 12-month follow-up visit ( P = .047 ) . CONCLUSIONS Administration of dextroamphetamine paired with physical therapy increased the rate and extent of motor recovery in a small group of hemiplegic stroke patients . These data support and extend previous findings of the facilitatory aspects of certain types of drugs on recovery from brain injury . The use of neuromodulation may allow the nervous system to adapt previously unused or alternative pathways to relevant external input We know from animal studies that a stimulating and enriched environment can enhance recovery after stroke , but little is known about the effects of an enriched sound environment on recovery from neural damage in humans . In humans , music listening activates a wide-spread bilateral network of brain regions related to attention , semantic processing , memory , motor functions , and emotional processing .  Music exposure also enhances emotional and cognitive functioning in healthy subjects and in various clinical patient groups . The potential role of music in neurological rehabilitation , however , has not been systematic ally investigated . This single-blind , r and omized , and controlled trial was design ed to determine whether everyday music listening can facilitate the recovery of cognitive functions and mood after stroke . In the acute recovery phase , 60 patients with a left or right hemisphere middle cerebral artery ( MCA ) stroke were r and omly assigned to a music group , a language group , or a control group . During the following two months , the music and language groups listened daily to self-selected music or audio books , respectively , while the control group received no listening material . In addition , all patients received st and ard medical care and rehabilitation . All patients underwent an extensive neuropsychological assessment , which included a wide range of cognitive tests as well as mood and quality of life question naires , one week ( baseline ) , 3 months , and 6 months after the stroke . Fifty-four patients completed the study . Results showed that recovery in the domains of verbal memory and focused attention improved significantly more in the music group than in the language and control groups . The music group also experienced less depressed and confused mood than the control group . These findings demonstrate for the first time that music listening during the early post-stroke stage can enhance cognitive recovery and prevent negative mood . The neural mechanisms potentially underlying these effects are discussed Purpose Motor recovery of persons after stroke may be enhanced by a novel approach where residual muscle activity is facilitated by patient-controlled electrical muscle activation . Myoelectric activity from hemiparetic muscles is then used for continuous control of functional electrical stimulation ( MeCFES ) of same or synergic muscles to promote restoration of movements during task-oriented therapy ( TOT ) . Use of MeCFES during TOT may help to obtain a larger functional and neurological recovery than otherwise possible . Study design Multicenter r and omized controlled trial . Methods Eighty two acute and chronic stroke victims were recruited through the collaborating facilities and after signing an informed consent were r and omized to receive either the experimental ( MeCFES assisted TOT ( M-TOT ) or conventional rehabilitation care including TOT ( C-TOT ) . Both groups received 45 minutes of rehabilitation over 25 sessions . Outcomes were Action Research Arm Test ( ARAT ) , Upper Extremity Fugl-Meyer Assessment ( FMA-UE ) scores and Disability of the Arm Shoulder and H and question naire . Results Sixty eight subjects completed the protocol ( Mean age 66.2 , range 36.5–88.7 , onset months 12.7 , range 0.8–19.1 ) of which 45 were seen at follow up 5 weeks later . There were significant improvements in both groups on ARAT ( median improvement : MeCFES TOT group 3.0 ; C-TOT group 2.0 ) and FMA-UE ( median improvement : M-TOT 4.5 ; C-TOT 3.5 ) . Considering subacute subjects ( time since stroke < 6 months ) , there was a trend for a larger proportion of improved patients in the M-TOT group following rehabilitation ( 57.9 % ) than in the C-TOT group ( 33.2 % ) ( difference in proportion improved 24.7 % ; 95 % CI -4.0 ; 48.6 ) , though the study did not meet the planned sample size . Conclusion This is the first large multicentre RCT to compare MeCFES assisted TOT with conventional care TOT for the upper extremity . No adverse events or negative outcomes were encountered , thus we conclude that MeCFES can be a safe adjunct to rehabilitation that could promote recovery of upper limb function in persons after stroke , particularly when applied in the subacute phase
No evidence exists at present to support the use of amphetamine after stroke .
INTRODUCTION The use of drugs to enhance recovery ( " rehabilitation pharmacology " ) has been assessed .
Amphetamine can improve outcome in experimental models of stroke , and several small clinical trials have assessed its use in stroke .