Neurostimulant Use for Rehabilitation and Recovery After Stroke: A Narrative Literature Review

 I see nothing here that even remotely states what should be done to get recovered! You got published but DID NOTHING for getting survivors recovered!

Neurostimulant Use for Rehabilitation and Recovery After Stroke: A Narrative Literature Review

Helene Chesnais, BA https://orcid.org/0000-0002-3936-726X, Kelly L. Sloane, MD https://orcid.org/0000-0001-9680-9565, Jens Witsch, MD https://orcid.org/0000-0001-8924-851X, Christopher Favilla, MD https://orcid.org/0000-0003-0871-9549, Scott E. Kasner, MD https://orcid.org/0000-0003-0418-6917, and Aaron Rothstein, MD https://orcid.org/0000-0002-8480-8220 aaron.rothstein@pennmedicine.upenn.eduAuthor Info & Affiliations

Stroke

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https://doi.org/10.1161/STROKEAHA.124.048677

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Abstract

BACKGROUND:

Stroke often results in significant impairments across various domains, including movement, language, cognition, and mood. Neurostimulants have been proposed as potential therapeutic interventions to enhance recovery in these areas.

METHODS:

This narrative literature review examines clinical trials investigating the efficacy of neurostimulants in poststroke recovery. It evaluates outcomes related to aphasia, motor deficits, cognition, fatigue, and depression.

RESULTS:

The qualitative analysis included 34 trials testing the following neurostimulants: methylphenidate (n=6), amphetamines (n=8), memantine (n=2), modafinil (n=2), levodopa (n=14), amantadine (n=1), bromocriptine (n=3), and ropinirole (n=1). Of the 34 studies, 31 were randomized, placebo-controlled (double-blind, n=27; single-blind, n=2; unblinded n=2), 2 were randomized and not placebo-controlled, and 1 was not randomized. Study design was either multiarm (n=23), crossover (n=10), or used subjects as their own control (n=1). Mean sample size was 49.4 (5–593).

CONCLUSIONS:

Current evidence suggests that memantine may be effective for aphasia, although few phase III trials exist, whereas bromocriptine and amphetamines lack sufficient evidence for long-term recovery of aphasia. Levodopa may improve motor aphasias but has not shown long-term benefits for motor recovery. Similarly, ropinirole has not been shown to improve poststroke motor outcomes. Methylphenidate has limited efficacy for cognitive improvement but may enhance poststroke functionality and mood. Modafinil may help with poststroke fatigue. In conclusion, there are promising results of positive effects of neurostimulants with few side effects, though studies are limited by heterogeneous designs and small sample sizes. Neurostimulant efficacy must be assessed in conjunction with specific rehabilitation modalities as part of larger, well-designed studies to best understand their effects on impairment.

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Amphetamine regimen does not improve post-stroke motor recovery

So explain this then.

Motor recovery and axonal plasticity with short-term amphetamine after stroke

They achieved full motor recovery in rats.

The negative research here: 

Amphetamine regimen does not improve post-stroke motor recovery

A pilot clinical trial exploring the benefit of d-amphetamine combined with physical therapy for stroke patients found no evidence that the regimen improved post-stroke motor recovery.
The results, which were published in the August 27, 2018 issue of JAMA Neurology, are "another step to better understand an approach that may or may not eventually lead to a new way of improving recovery," said Dr. Larry Goldstein, chairman of Neurology at the University of Kentucky and the study's lead author.
Amphetamines were first synthesized in 1887 by Romanian chemist Lazar Edeleanu, but it wasn't until the late 1920's that amphetamines were identified as a medically useful mood and energy booster. By World War II, soldiers were using amphetamines to combat fatigue and improve morale; the military routinely distributed the drug to pilots flying long missions. In the 1960's, however, the medical community's enthusiasm for the drug as a safe and popular remedy for depression and fatigue faded.
Two decades later, the question came full circle when Sciencepublished the results of a complex, placebo-controlled study demonstrating that rats with brain injuries who were given amphetamines in conjunction with physical therapy showed notable improvement in motor function. Other studies in cats and mice suggested similar improvements.
Since then, the scientific community has worked to extend these successes to humans and further define the parameters for optimal efficacy, e.g. dose, timing/frequency/intensity of physical therapy, but with inconsistent results.
Goldstein et al aimed to further inform the debate. Their study screened 1665 ischemic stroke patients in five rehabilitation hospitals or inpatient units. Sixty-four participants were randomized to receive either 10mg of d-amphetamine or placebo combined with a one-hour physical therapy session every four days for six sessions, in addition to standard rehabilitation. Treatment began between ten and 30 days after ischemic stroke.

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The primary outcome was defined as a difference in the change in Fugl-Meyer Motor scores, an impairment index assessing motor function, balance, and sensation. The study also assessed changes in the NIH-Stroke Scale, Canadian Neurological Scale, Action Research Arm test, Rankin Score, Functional Independence Measure, Ambulation Speed and Endurance, Mini Mental State examination, Beck Depression Index and the Stroke Impact Scale as secondary measures. Participants were tested at baseline, the end of treatment and again at three months post-stroke.
Resulting data showed no overall treatment-related difference in Fugl-Meyer Motor scores between baseline and 3-month post-stroke in the two test groups (18.65+2.27 points with d-amphetamine vs. 20.83+2.94 points with placebo). The two groups were equally comparable on all secondary outcome measures as well, and there was no difference in subgroups based on stroke location or baseline severity.
Goldstein said the next step is to explore other dosing regimens, treatment intervals and times between stroke and beginning treatment -- all factors that are important based on animal studies.
"The concept of using amphetamines as part of a regimen for stroke recovery is biologically complex, and this pilot was specifically designed to explore some of that complexity," he said. "This data should help elucidate the parameters for continued study."

Source:

http://www.uky.edu/

Motor recovery and axonal plasticity with short-term amphetamine after stroke

They achieved full motor recovery in rats. FUCKING HEY.  This should have generated immediate clinical testing in humans. I don't give a damn if they were using amphetamines. But hey once again I'm 100% sure our fucking failures of stroke associations did nothing with this.

Motor recovery and axonal plasticity with short-term amphetamine after stroke

Papadopoulos CM, et al. Stroke. 2009.

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Abstract

BACKGROUND AND PURPOSE: There is considerable debate regarding the efficacy of amphetamine to facilitate motor recovery after stroke or experimental brain injury. Different drug dosing and timing schedules and differing physical rehabilitation strategies may contribute to outcome variability. The present study was designed to ascertain (1) whether short-term amphetamine could induce long-term functional motor recovery in rats after an ischemic lesion modeling stroke in humans; (2) how different levels of physical rehabilitation interact with amphetamine to enhance forelimb-related functional outcome; and (3) whether motor improvement was associated with axonal sprouting from intact corticoefferent pathways originating in the contralesional forelimb motor cortex.

METHODS: After permanent middle cerebral artery occlusion, rats received vehicle or amphetamine during the first postoperative week (2 mg/kg, subcutaneously on Postoperative Days 2, 5, and 8). In both treatment groups, separate cohorts of rats were exposed to different levels of "physical rehabilitation" represented by a control environment, enriched environment, or enriched environment with additional sessions of focused activity. Skilled forelimb performance was assessed using the forelimb reaching task and ladder rung walk test. Anterograde tracing with biotinylated dextran amine was used to assess new fiber outgrowth to denervated motor areas.

RESULTS: All treatment groups showed significant motor improvement as compared with control-housed, vehicle-treated animals. However, animals housed in an enriched environment that received amphetamine paired with focused activity sessions performed significantly better than any other treatment group and was the only group to achieve complete motor recovery (ie, reached preoperative performance) by 8 weeks. This recovery was associated with axonal sprouting into deafferentated subcortical areas from contralesional projection neurons.

CONCLUSIONS: This study suggests that, after stroke, short-term pairing of amphetamine with sufficiently focused activity is an effective means of inducing long-term improvement in forelimb motor function. The anatomic data suggests that corticoefferent plasticity in the form of axonal sprouting contributes to the maintenance of motor recovery.

PMID

19038917 [PubMed - indexed for MEDLINE]

PMCID

PMC3806086

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Comment in

• Stroke. 2009 Jan;40(1):8-9.

Amphetamine and post-stroke rehabilitation: indications and controversies

Another problem of our stupid war on drugs. We have a hard time even getting this into clinical trials.
Amphetamine and post-stroke rehabilitation: indications and controversies

There is robust evidence for amphetamine (AMPH) facilitated recovery from behavioral deficits in animal models of stroke. Following experimental lesions, numerous studies of motor, somatosensory and vision recovery show AMPH accelerates the rate of recovery when paired with relevant behavioral experience. While the experimental literature continues to mount for an AMPH effect, the translation to clinical studies has been far less clear. This is due in part to the inherent difficulty of extrapolating results in animals to humans; however, there is much controversy regarding how the basic science data is interpreted for the design of human clinical trials. This review will: overview noteworthy experimental studies that have strong implications for human rehabilitation; describe the blinded drug/placebo clinical trials administering AMPH to enhance recovery of motor and language deficits post-stroke published to date; discuss the various complexities and controversies of designing clinical trials which may affect response/non-response to pharmacologic agents and conclude with suggestions of critical questions still to be answered for the rehabilitation specialist.

Early Promise For Stroke Patients Given - levodopa

My god, from Sept. 2001. Thats plenty of time to get this translated into a therapy protocol. Innovative doctors should have been giving this off-label  within a year, Never mind my doctor by 2006, no innovation seen there.

Early Promise For Stroke Patients Given - levodopa

A preliminary study published in this week’s issue of THE LANCET suggests that the neurotransmitter precursor levodopa used in combination with physiotherapy could improve motor recovery for patients after stroke.
Hemiplegia (paralysis to one side of the body) causes functional disability after stroke. Physiotherapy used to be the only way of improving motor function in such patients. However, administration of amphetamines in addition to exercise has been found to improve motor recovery in animals, probably by increasing the concentration of the neurotransmitter norepinephrine in the central nervous system. Klaus Scheidtmann and colleagues from Bad Aibling Neurological Hospital, Germany, investigated whether levodopa could enhance the efficacy of physiotherapy after hemiplegia.
53 primary stroke patients were assessed in a prospective, randomised study. For the first 3 weeks patients received single doses of 100 mg levodopa or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. Motor function was assessed every week by Rivermead motor assessment (RMA).
Motor recovery was substantially improved after 3 weeks of drug intervention in patients given levodopa (RMA improved by 6.4 points) compared with placebo (4.1), and the result was independent of initial degree of impairment. The advantage of the levodopa group was maintained 3 weeks after levodopa was stopped. At the end of the study the total RMA score gain for the levodopa group was 8.2 points compared with 5.7 in the placebo group.
Friedemann Müller (one of the investigators) comments: “A single dose of levodopa was well tolerated and, when given in combination with physiotherapy, was found to enhance motor recovery in patients with hemiplegia. This trend should be confirmed, and we need to establish long-term ceiling effects, which our short observation period did not allow us to judge. We should also ascertain to what extent the lesion size and amount of levodopa affect enhanced functional recovery. In view of its minimal side-effects, levodopa will be a possible add- on during stroke rehabilitation.”

 In 2009 there was this research:

New step forward for stroke patients

New research will determine whether an inexpensive drug called L-dopa, widely used in the treatment of Parkinson’s disease, could also help thousands of stroke patients regain mobility and independence.
The world’s first large scale study of this treatment, led by Professor Bipin Bhakta at the University of Leeds, will investigate whether L-dopa, when used with conventional physiotherapy and occupational therapy, increases the person’s ability to relearn essential day to day activities such as walking and dressing.
Professor Bhakta, head of the Academic Department of Rehabilitation Medicine in the Leeds Institute of Molecular Medicine explains: “If an existing and inexpensive drug can help augment the effects of conventional rehabilitation treatments this represents a major step forward in improving stroke recovery.”
He says existing scientific evidence shows that certain nerve pathways in the brain are important in how people learn movement skills.  L-dopa may work by enhancing the activity of some of these pathways and by combining the medication with routine rehabilitation treatments there may be an opportunity to increase the effect of our current treatments. 

 

So where is your doctor on this? Ask him/her.

Cognitive impairment in Khat users

Our brains are impaired enough already so make sure you lay off the khat.

Cognitive impairment in Khat users

A recently published study examines the cognitive effects of khat (Catha edulis) chewing. Colzato and colleagues (2011) recruited 20 khat users with 10.5 (6.5 SD) years of use, averaging 3.1 (1.8 SD) times per week. The average time spent chewing khat in each session was 5.8 hrs (1.7 SD) and all khat users met at least four criteria which define addiction under DSM-IV or ICD-10 criteria. Marijuana consumption in these individuals and the khat-free controls was about 2 joints per week, they consumed 6-8 drinks per week and had zero lifetime exposure to cocaine, amphetamines or ketamine. Subjects were also matched on IQ (using the Ravens Standard Matrices), age (~31 years), ethnicity/origin (all African) and sex (2 female in each group), although two male subjects from the khat-user group had to be excluded for excessive error rates in the switching task

nicotine and stroke rehab

Nicotine Holds Promise for Stronger Stroke Recovery

nicotine and stroke rehab

What you get with nicotine is the animals with stroke show better recovery and improvement. It speeds things up and you get to a higher level of rehabilitation.
It turns out that nicotine, in contrast to amphetamines, acts in a larger area of the brain and seems to act where the amphetamines don't - in the motor system. That's a real advantage, because one of the big problems in stroke is loss of motor functions.
 I have never smoked and don't plan on starting or using patches.

 Don't consider this an endorsement of nicotine being good for your recovery.
Ask your doctor for guidance on this.