Amphetamine Paired With Physical Therapy Accelerates Motor Recovery After Stroke

Walker-Batson, Delaina; Smith, Patricia S.; Curtis, Sandra; Unwin, Hal; Greenlee, Ralph G.

doi:10.1161/01.str.26.12.2254

Cited by 356 publications

(172 citation statements)

References 16 publications

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“…Additionally, there were no effects on other measures of impairment, disability, mood and quality of life. Early studies of amphetamine after stroke suggested motor impairment might be reduced, 16,17,19,25 data we used to power the present trial. However, more recent studies have not supported this finding.…”

Section: Discussionmentioning

confidence: 99%

“…A sample size of 42 was required based on an unpublished meta-analysis of four small trials, 16,17,19,25 which showed a beneficial effect of amphetamine on motor impairment assessed as the Fugl-Meyer (FM) motor scale: randomization ratio of 1:1, mean treatment difference 16 …”

Section: Designmentioning

confidence: 99%

“…Dexamphetamine sulphate (initial 5 mg dose followed by 10 mg thereafter) or placebo was administered orally twice a week with alternating 3-or 4-day separations. 17,23,24,26,35,36 The dose of 10 mg is unlikely to cause dependency or extreme vascular instability. There were a total of 11 doses covering a treatment period of 35 days.…”

Section: Interventionmentioning

confidence: 99%

“…5,9,10 However, timing and dose of administration appears important; high doses and early administration being associated with a poor outcome, 5,11 whereas pretreatment with amphetamine led to increased ischaemic insult. 12 The evidence in normal subjects [13][14][15] and in clinical stroke is less clear, [16][17][18][19][20][21][22][23][24][25][26][27] numerous small trials, utilising varying dosage and timing of treatment, showing conflicting results, overall demonstrating no evidence of benefit on motor recovery. Although treatment appears feasible and well tolerated, a trend towards increased death in the treatment group exists on meta-anlaysis.…”

Section: Introductionmentioning

confidence: 99%

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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)

et al. 2007

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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 randomized (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 randomized 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 ¼ 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 ¼ 0.03), 9.5 mm Hg (P ¼ 0.04) and 7 beats per minute (P ¼ 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.

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Section: Discussionmentioning

confidence: 99%

Section: Designmentioning

confidence: 99%

Section: Interventionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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)

et al. 2007

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“…An accurate prediction of recovery is essential to target medications and therapies appropriately toward ambulation or toward wheelchair use, as well as to advise patient and family. Preliminary observations in animals and humans suggest that there may be a critical period during acute rehabilitation when CNS stimulants, 36 aggressive active exercise, 37 electrical stimulation 38 and training, such as body weight support 39 ± 43 can enhance recovery of voluntary movement. As these new rehabilitation interventions develop, failure by rehabilitation physicians to recognize these favorable prognostic signs and failure to initiate these new therapies may result in suboptimal functional outcomes.…”

Section: Discussionmentioning

confidence: 99%

The pattern of reflex recovery during spinal shock

et al. 1999

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Study Design: A prospective descriptive study of the course of recovery of re¯exes following acute spinal cord injury (SCI). Objectives: The purpose of the study was to observe the pattern of re¯ex recovery following acute SCI in order to determine the prognostic signi®cance of re¯exes for ambulation and their relationship to spinal shock. Setting: A regional spinal cord injury center in Philadelphia, Pennsylvania, USA. Methods: Fifty subjects admitted consecutively over a 9 month period and on the day of injury were observed for the following re¯exes; bulbo-cavernosis (BC), delayed plantar response (DPR), cremasteric (CRM), ankle jerk (AJ), knee jerk (KJ), and normal plantar response for 5 ± 7 days a week and 6 ± 8 weeks duration. The 50 subjects were assessed for ambulation of 200 feet at time of discharge. MRI studies were reviewed on 13/28 complete (ASIA A) injuries. Results: Thirty-®ve subjects (28 ASIA A, 4 ASIA B, 3 ASIA C) had a DPR of 2 days or longer duration and these subjects were not ambulatory. The fourteen subjects (12 ASIA D and 2 ASIA C), who were ambulatory, either had no DPR (11/14) or had a DPR of only 1 days duration (3/14). One subject (ASIA B) was not ambulatory and had a DRP of 1 days duration. The DPR was the ®rst re¯ex to recover most often, followed by the BC, CRM in the ®rst few days and later followed by the deep tendon re¯exes (AJ & KJ) by 1 ± 2 weeks respectively. Less than 8% of subjects had no re¯exes on the day of injury and the re¯exes did not follow a caudal-rostral pattern of recovery. Conclusions: Prognosis for ambulation based on re¯exes early after SCI should not be linked to current descriptions of spinal shock. In fact, the view of spinal shock, based on the absence of re¯exes and the recovery of re¯exes in a caudal to rostral sequence, is of limited clinical utility and should be discarded. The evolution of re¯exes over several days following injury may be more relevant to prognosis than the use of the term spinal shock and the presence or absence of re¯exes on the day of injury.

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New Therapies for Stroke

Caplan¹

1997

Archives of Neurology

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The treatment of patients with stroke and cerebrovascular disease has entered a new era. During the 1990s there has been a revolution in technology able to define quickly, safely, and accurately stroke pathophysiological characteristics and the cardiovascular lesions that cause stroke in individual patients. Advanced brain imaging with computed tomography, magnetic resonance imaging, and newer magnetic resonance modalities, including fluid attenuating inversion recovery imaging, diffusion, perfusion, functional magnetic resonance imaging, and magnetic resonance spectroscopy, show clinicians the localization, severity, and potential reversibility of ischemia. Vascular lesions can be defined using spiral computed tomographic angiography, magnetic resonance angiography, and extracranial and transcranial ultrasonography. Cardiac and aortic sources of stroke are now better studied using transesophageal echocardiography. More sophisticated hematologic testing gives new insights into the role of altered coagulability in causing or contributing to thromboembolism. Clinicians can now recognize the key data elements needed to logically treat brain ischemia, including the following: The nature, location, and severity of cardiac and cerebrovascular lesions. The mechanism by which these lesions cause ischemia--hypoperfusion? embolism? functional changes such as vasoconstriction? The cellular and serologic components of the blood that relate to coagulability, viscosity, and blood flow. The state of the brain--normal, reversibly ichemic ("stunned"), or infarcted. With these diagnostic advances have come new treatments, new ideas about treatment, and more and new information about conventional treatments.

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Amphetamine Paired With Physical Therapy Accelerates Motor Recovery After Stroke

Cited by 356 publications

References 16 publications

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)

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)

The pattern of reflex recovery during spinal shock

New Therapies for Stroke

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