Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.My back ground story is here:

Monday, June 21, 2021

Effectiveness of Rehabilitation Nursing versus Usual Therapist-Led Treatment in Patients with Acute Ischemic Stroke: A Randomized Non-Inferiority Trial

 Obviously neither one is effective since no one talks about getting to 100% recovery.  My definition of efficacy is 100% recovery, what is yours? Anything less than 100% recovery should be fireable for all involved.

Effectiveness of Rehabilitation Nursing versus Usual Therapist-Led Treatment in Patients with Acute Ischemic Stroke: A Randomized Non-Inferiority Trial


Authors Wang J, Zhang Y, Chen Y, Li M, Yang H, Chen J, Tang Q, Jin J

Received 15 February 2021

Accepted for publication 13 May 2021

Published 21 June 2021 Volume 2021:16 Pages 1173—1184


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Zhi-Ying Wu

Download Article [PDF] 

Jianmiao Wang,1 Yuping Zhang,1 Yuanyuan Chen,2 Mei Li,1 Hongyan Yang,2 Jinhua Chen,2 Qiaomin Tang,2 Jingfen Jin1,3

1Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Neurology Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Changxing Branch Hospital, The Second Affiliated Hospital of Zhejiang University School of Medicine, Huzhou, Zhejiang Province, People’s Republic of China

Correspondence: Jingfen Jin
The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, Zhejiang Province, 310009, People’s Republic of China
Fax +86-0571-87783778


To determine the effectiveness of rehabilitation nursing program interventions in patients with acute ischemic stroke.
Patients and Methods: 

An assessment-blinded randomized controlled trial was conducted at a tertiary referral hospital in China. Eligible patients were stratified according to their weighted corticospinal tract lesion load and then randomly assigned to an experimental group (n = 121) or a control group (n = 103). The experimental group received rehabilitation nursing from well-trained, qualified nurses (30 minutes per session, two sessions per day for seven consecutive days). The control group received therapist-led rehabilitation with the same timing and frequency. Comparative analysis of the primary outcomes was performed to determine non-inferiority with a predetermined non-inferiority margin. The primary outcomes were the Motor Assessment Scale, Fugl-Meyer Assessment, and the Action Research Arm Test assessed at baseline and after seven days of treatment. The secondary outcomes were the modified Barthel Index, the National Institutes of Health Stroke Scale, and the modified Rankin Scale, evaluated before and after the intervention and at 4 and 12 weeks of follow-up.

Two hundred participants completed the trial. In both groups, all outcomes improved significantly after seven days and at follow-ups. The rehabilitation nursing program was non-inferior to therapist-led treatment with lower 95% confidence limits beyond the margins for primary outcomes (P < 0.001).

Both treatments had comparable effects; however, no definite conclusion could be drawn. Adequately powered studies are required.

Keywords: rehabilitation, nursing, acute ischemic stroke, motor function


Stroke is the leading cause of mortality and disability worldwide; 87% of all deaths from stroke and 89% of all stroke-related disability-adjusted life-years occur in low- and middle-income countries (LMICs).1 In contrast to the global downward trend, the incidence is rising in LMICs, with approximately 2.4 million new stroke cases each year in China; more than one-third of acute ischemic stroke (AIS) patients die or become disabled within three months or one year.2 The high risk of disability and dysfunction may be related to the aging of the population.3 By 2050, one in six people in the world will be 65 years of age or older.4 COVID-19-related ischemic stroke leads to worse functional outcomes and higher mortality.5 Secondary stroke risk increased not only because of the disease characteristics of COVID-19 but also because of lack of physical activity due to isolation or restriction of access to treatments.6 Due to limited medical resources and isolation policies, access to services has been significantly reduced, and the burden of disability has increased further.

The functional limitations of the trunk and limbs associated with stroke reduce the ability to participate in activities of daily living (ADLs), requiring assistance with eating, drinking, moving, toileting, performing personal hygiene tasks, dressing, and grooming,7 which seriously affects the quality of life of stroke patients.8 The severity and variety of disorders in patients after stroke relate to the site and infarct size, and motor dysfunction is the principal problem. The leading causes are damage to the corticospinal tract (CST) and brain motor centers.9 The CST is the most critical motor control pathway that affects motor function recovery and outcome from a stroke. Motor function training in the acute stage (within the first two weeks10) can increase the structural integrity of the ipsilesional CST.11

After a stroke, rehabilitation is essential to help survivors achieve an optimal functional level and prevent or delay future functional decline.12 In the first days and weeks, the brain responds most quickly to the stimulus of motor training;13 In appropriate amounts, early training aids recovery and improves outcomes and quality of life. Early rehabilitation interventions in acute care settings are critical to optimizing the recovery potential in repair windows and prevent various complications secondary to the disability. Guidelines recommend providing early rehabilitation services for hospitalized stroke patients in an organized, multi-professional stroke care environment.10,14

Nevertheless, there are few practice guidelines or clinical pathways, and published guidelines do not guarantee effective implementation in practice.15 There are gaps between the best evidence and current practice that are not conducive to clinical intervention implementation or patient benefits. The consensus reached in the second stroke recovery and rehabilitation roundtable was to determine knowledge translation priorities and take specific actions to deal with the practice gaps.16

Inadequate resources for rehabilitation services are the main reason why clinical practices do not follow guidelines well. Many LMICs provide some rehabilitation care in acute settings, and transitional and community rehabilitation are rare.16 The proportion of stroke patients in LMICs receiving rehabilitation treatment is too small, and rehabilitation or treatment within seven days after stroke is also limited.17 Currently, there are about 10,000 rehabilitation physicians and 20,000 rehabilitation therapists in China, with an average of 1 to 2 per 100,000 people, much lower than the 40 to 70 per 100,000 in developed countries.18 According to the World Health Organization’s Rehabilitation 2030 report, the numbers of rehabilitation practitioners, are far below those of high-income countries, while data on rehabilitation nurses are not available.19 Access to related rehabilitation services and staffing are systemic issues that need to be prioritized, and it is recommended that solutions be implemented to address these issues in the context of local realities to improve the quality of life of stroke patients.16

In LMICs, localized measures to improve functional outcomes after stroke with low-cost, resource-saving physical rehabilitation interventions are possible.20 There is evidence that aerobic programs and rehabilitation assistants increase the intensity of rehabilitation.16 As part of a multidisciplinary team, nurses play critical roles in facilitating stroke recovery, and recognizing their valuable contributions is essential.21 Nurses provide rehabilitation services in nursing homes and community rehabilitation centers and should also provide rehabilitation services in the acute phase.22 Primary care nurses’ complex interventions increased the number of objectively measured step-counts and moderate-to-intense physical activity.23 Enrolling nurses in task-oriented training can create more opportunities for patients to practice meaningful functional tasks outside of their regular treatment sessions. When nurses incorporate rehabilitation goals into nurses’ daily care, they also improve patient independence.24 However, in current clinical practice, nurses pay more attention to maintaining safe care and preventing potential problems, including falls; there is limited practical nursing evidence in the vital areas, including mobility.25

There is no consensus on acute rehabilitation nursing guidelines or practice activities.26 Stroke nursing includes good limb placement, turning over, and out-of-bed mobilization education. Rehabilitation principles should be more integrated into practice. Because the establishment of acute rehabilitation nursing is best customized locally to match available resources.27 We developed a rehabilitation nursing program to improve motor function. Due to insufficient evidence for interventions, based on expert opinions and combined with feasibility study results, we considered factors that facilitate or hinder implementation. The main components of rehabilitation nursing interventions include physical therapy (PT), occupational therapy (OT), ADLs, following the principles of repetitive task-oriented training and patient-centered individualization implementation, as described in our protocol.28 Our research was motivated by the question of whether rehabilitation nursing interventions are effective, and if so, how effective are they compared to rehabilitation provided by therapists in current practice?

While standard treatments already exist, some therapies may be safer, more convenient, or less expensive with similar efficacy. An educational training program for nurses improved their knowledge and practice in clinical settings and improved ADLs and self-care abilities for stroke patients.29 The results of the cost-effectiveness analysis provide evidence that nursing interventions can save costs for ischemic patients.30 Patients hospitalized in the acute phase are more likely to have access to nurses; therefore, it is possible to conduct a comparative study of rehabilitation nursing interventions with therapies used in practice.

This trial aimed to identify an option with comparable efficacy rather than superior efficacy. Non-inferiority trials attempt to determine whether a new treatment is inferior to a reference treatment and define a predetermined non-inferiority margin (δ).31 For this reason, it makes sense to use a non-inferiority trial design when comparing the effects of nurse-led rehabilitation and therapist-led rehabilitation. Because multidisciplinary team early rehabilitation is the guideline-recommended treatment, it would be unethical to use a placebo or no-treatment control in the study.32 This study could not be designed as a three-arm trial that included a blank control.

Therefore, our objective was a non-inferiority comparison between a rehabilitation nursing intervention and a therapist-led treatment regarding motor function assessments (the primary outcomes). Sequence tests and secondary outcomes were assessed for superiority.

Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study

 I see zero use for this in recovery, nothing here is going to make a bit of difference in how survivors are treated. Or are you going to have different protocols for premies? Assuming of course that you patient is lucid enough to understand and answer?  How are you going to question a locked-in patient?

Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study

Originally published ;0:STROKEAHA.120.033797

Background and Purpose:

Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort.


A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors.


In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12–1.43; P<0.001), and further stratified was 1.42 (1.11–1.81; P=0.005) for early preterm (22–33 weeks) and 1.22 (1.06–1.40; P=0.004) for late preterm (34–36 weeks), compared with full-term (39–41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: adjusted hazard ratio, 1.42 [95% CI, 1.04–1.94]; any preterm: 1.15 [0.97–1.35]) and ischemic stroke (early preterm: adjusted hazard ratio, 1.33 [95% CI, 0.87–2.03]; any preterm: 1.31 [1.07–1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families.


In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.


The core/penumbra model: implications for acute stroke treatment and patient selection in 2021

WHOM is doing the specific followup to create protocols on this? NO PROTOCOLS, RESEARCH WAS WASTED. I see nothing here that identifies which of the the 5 causes of the neuronal cascade of death is being solved

in the first week saving billions of neurons.

The core/penumbra model: implications for acute stroke treatment and patient selection in 2021

First published: 15 May 2021


Despite major advances in prevention, ischaemic stroke remains one of the leading causes of death and disability worldwide. After centuries of nihilism and decades of failed neuroprotection trials, the discovery, initially in non-human primates and subsequently in man, that ischaemic brain tissue termed the ischaemic penumbra can be salvaged from infarction up to and perhaps beyond 24 h after stroke onset has underpinned the development of highly efficient reperfusion therapies(Really? You have statistics proving 100% recovery? Nothing on 100% recovery , then they are not efficient. The problem to be solved is 100% recovery, NOT REPERFUSION!), namely intravenous thrombolysis and endovascular thrombectomy, which have revolutionized the management of the acute stroke patient. Animal experiments have documented that how long the penumbra can survive depends not only on time elapsed since arterial occlusion (‘time is brain’), but also on how severely perfusion is reduced. Novel imaging techniques allowing the penumbra and the already irreversibly damaged core in the individual subject to be mapped have documented that the time course of core growth at the expense of the penumbra widely differs from patient to patient, and hence that individual physiology should be considered in addition to time since stroke onset for decision-making. This concept has been implemented to optimize patient selection in pivotal trials of reperfusion therapies beyond 3 h after stroke onset and is now routinely applied in clinical practice, using computed tomography or magnetic resonance imaging. The notion that, in order to be both efficient and harmless, treatment should be tailored to each patient's physiological characteristics represents a radical move towards precision medicine.


Structural Connectivity Remote From Lesions Correlates With Somatosensory Outcome Poststroke

 In layperson terms what does this mean and how do survivors use this to recover?

Structural Connectivity Remote From Lesions Correlates With Somatosensory Outcome Poststroke

Originally published ;0:STROKEAHA.120.031520

Background and Purpose:

Changes in connectivity of white matter fibers remote to a stroke lesion, suggestive of structural connectional diaschisis, may impact on clinical impairment and recovery after stroke. However, until recently, we have not had tract-specific techniques to map changes in white matter tracts in vivo in humans to enable investigation of potential mechanisms and clinical impact of such remote changes. Our aim was to identify and quantify white matter tracts that are affected remote from a stroke lesion and to investigate the associations between reductions in tract-specific connectivity and impaired touch discrimination function after stroke.


We applied fixel-based analysis to diffusion magnetic resonance imaging data from 37 patients with stroke (right lesion =16; left lesion =21) and 26 age-matched healthy adults. Three quantitative metrics were compared between groups: fiber density; fiber-bundle cross-section; and a combined measure of both (fiber-bundle cross-section) that reflects axonal structural connectivity.


Compared with healthy adults, patients with stroke showed significant common fiber-bundle cross-section and fiber density reductions in 4 regions remote from focal lesions that play roles in somatosensory and spatial information processing. Structural connectivity along the somatosensory fibers of the lesioned hemisphere was correlated with contralesional hand touch function. Touch function of the ipsilesional hand was associated with connectivity of the superior longitudinal fasciculus, and, for the right-lesion group, the corpus callosum.


Remote tract-specific reductions in axonal connectivity indicated by diffusion imaging measures are observed in the somatosensory network after stroke. These remote white matter connectivity reductions, indicative of structural connectional diaschisis, are associated with touch impairment in patients with stroke.


Clinical characteristics of fast and slow progressors of infarct growth in anterior circulation large vessel occlusion stroke

 Pretty much useless since all the other measurements of damages are in understandable figures.

In each  untreated minute,

1.9 million neurons die

14 billion synapses die

12 km (7.5 miles) of myelinated fibers die

brain ages 3.6 years each hour without treatment

Clinical characteristics of fast and slow progressors of infarct growth in anterior circulation large vessel occlusion stroke

First Published June 17, 2021 Research Article 

Fast and slow progressor phenotypes of infarct growth due to anterior circulation large vessel occlusion (ACLVO) remain poorly understood. We aimed to define clinical predictors of fast and slow progressors in a retrospective study of patients with ACLVO who underwent baseline advanced imaging within 24 hours of stroke onset. Fast progressors (ischemic core > 70 ml, < 6 hours after onset) and slow progressors (ischemic core ≤ 30 ml, 6 to 24 hours after onset) were identified amongst 185 patients. Clinical and laboratory variables were tested for association with fast or slow progressor status. In the early epoch, no significant differences were found between fast progressors and controls. In the delayed epoch, slow progressors had a median NIHSS of 14 versus 20 (p < 0.01) and MCA occlusion in 80% versus 63% (p < 0.05) relative to controls. In multivariate analyses, NIHSS (OR 0.83, 95% CI 0.73-0.95), hyperlipidemia (OR 4.24, 95% CI 1.01 – 19.3) and hemoglobin concentration (OR 0.75, 95% CI 0.57 – 0.99) were independently associated with slow progressor status. This study indicates that lower initial stroke symptom severity, a history of hyperlipidemia and mild anemia are associated with individual tolerance to ACLVO stroke.


Sunday, June 20, 2021

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS

 What the fuck good does prediction of non-recovery do? Do you tell your patients you have nothing that will get them 100% recovered? Or will you be like my doctor and know nothing and do nothing about stroke? And why are you talking about symptoms rather than an objective diagnosis? Symptoms can occur from multiple possibilities; see below:

See this example of nine reasons for a movement disability:


You can't tell me these all have the same solution, I'm not that stupid.
1. Penumbra damage to the motor cortex.
2. Dead brain in the motor cortex.
3. Penumbra damage in the pre-motor cortex.
4. Dead brain in the pre-motor cortex.
5. Penumbra damage in the executive control area.
6. Dead brain in the executive control area.
7. Penumbra damage in the white matter underlying any of these three.
8. Dead brain in the white matter underlying any of these three.
9. Spasticity preventing movement from occurring.

The latest here:

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS

and on behalf of the MaRISS Investigators*
Originally published 2021;52:1995–2004

Background and Purpose:

Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population.


This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase.


A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded (<1%).


A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup.


URL:; Unique identifier: NCT02072681.


Intracerebral hemorrhage correlates with 'significant' health care costs

Wrong focus. 'COSTS' not the disability or the lack of recovery? My God, who approves crapola research like this?

Intracerebral hemorrhage correlates with 'significant' health care costs

Total 1-year costs associated with intracerebral hemorrhage exceeded $120 million per year, according to results of a retrospective cohort study among adult patients in Ontario, Canada that were published in Neurology.

“While morbidity and mortality from intracerebral hemorrhage has been extensively studied, less is known about patient- and health care-associated costs and resource utilization,” the researchers wrote. “An understanding of health care costs, particularly with relation to patient outcomes, is a necessary step in optimization of resource utilization and health care delivery. Patients with intracranial hemorrhage (also including subarachnoid hemorrhage and traumatic hemorrhage) have significant associated in-hospital costs, often a result of prolonged ICU stay.”

Fernando and colleagues reported a median total 1-year cost of $26,886 associated with intracerebral hemorrhage.
Reference: Fernando SM, et al. Neurology. 2021;doi:10.1212/WNL.0000000000012355.

Shannon M. Fernando, MD, MSc, a resident in the departments of medicine and emergency medicine at the University of Ottawa, and colleagues aimed to determine the resources used by patients with intracerebral hemorrhage and the related costs in both the short and long term. They also examined the relationship between oral anticoagulation and health care costs.

The researchers collected data on outcomes through health administrative databases and used generalized linear models to determine factors related to total cost. They limited their analysis of oral anticoagulation use to patients aged 66 years and under. Total 1-year direct health care costs in 2020 U.S. dollars served as the primary outcome.

The study included 16,248 individuals with intracerebral hemorrhage (mean age, 71.2 years; 52.3% men). In this group, the 1-year mortality rate was 46% and 24.2% of patients required mechanical ventilation, according to the study results. Median hospital length of stay was 9 days (interquartile range [IQR], 4-20 days). Only 2,290 patients (14.1%) were discharged to home independently, according to the study results; 7,076 patients (34.1%) were discharged to long-term hospital rehabilitation centers and 876 patients (4.2%) were discharged to long-term care.

Fernando and colleagues reported a median total 1-year cost for intracerebral hemorrhage of $26,886 (IQR, $9,641-$62,907). Costs among patients who survived to discharge were much higher ($44,969; IQR, $20,264-$82,414) compared with costs for patients who died in the hospital ($7,268; IQR, $4,031-$14,966). These results were statistically significant, according to the researchers (P < .001). Among patients who survived to discharge, more than half ($26,250) of the $44,969 in total cost per patient was related to costs after hospital discharge, according to the study results.

In their analysis of oral anticoagulant use, Fernando and colleagues found that these agents correlated with higher total 1-year costs (cost ratio, 1.06; 95% CI, 1.01-1.11).

The researchers reported a median inpatient cost per patient of $10,120 (IQR, $5,356-$23,940). Among patients using these services, the median cost per patient was $23,702 (IQR, $6,476-$55,297) for continuing complex outpatient care, $13,835 (IQR, $2,099-$26,811) for long-term care, $23,969 (IQR, $17,096-$31,951) for rehabilitation and $1,294 (IQR, $344-$4,868) for home care, according to the study results.

Fernando and colleagues also examined predictors for 1-year costs. They found that comorbidity burden correlated with increased cost, “suggesting that comorbid patients likely have increased care needs, particularly if they survive to discharge.” A prior intracerebral hemorrhage did not correlate with higher costs among survivors, but prior ischemic stroke did, the researchers noted.

“Our work provides novel data from a complete population regarding the financial burden of [intracerebral hemorrhage], with particular implications for health service administration, and highlights the system-level cost of this devastating condition,” Fernando and colleagues wrote.


Cathodal Transcranial Direct Current Stimulation in Acute Ischemic Stroke: Pilot Randomized Controlled Trial

Now we need human testing which your doctors and stroke hospital will do nothing to initiate.

Cathodal Transcranial Direct Current Stimulation in Acute Ischemic Stroke: Pilot Randomized Controlled Trial

Originally published 2021;52:1951–1960

Background and Purpose:

In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy.


STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score.


Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC95%]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively).


C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and β=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.


Worrying and the Aging Brain

 Your doctor is responsible for preventing your worrying and anxiety. And the only way to do that is to have EXACT 100% RECOVERY PROTOCOLS. Because then you know you'll get back to your old life. You doctor has none? Then call the president and ask when competent people will be hired.  YOU are responsible for cleaning out all the dead wood in stroke, if they don't have a plan for getting to 100% recovery, they all need to be fired, starting with the board of directors.

Worrying and the Aging Brain

Over the past decade, scientists and clinicians have noted a significant association between common mental health conditions and accelerated brain aging—the changes to brain structure, physiology, and function that are thought to lead to later cognitive decline. Both depression and anxiety disorders, for example, are strongly correlated with the development of dementias including Alzheimer’s disease later in life, yet it has been unclear why. Neuroscientists and gerontologists around the globe have diligently worked to investigate which particular symptoms might contribute to age-related cognitive decline. New research from the University of Pittsburgh, using a machine learning model to predict a person’s “brain age,” suggests that excessive worrying and rumination may influence the speed of neurodegeneration and the memory and attention deficits that come along with it.

Understanding Brain Aging

As we age, our bodies change in many ways. Our skin becomes more wrinkled, our hair thins and loses its pigment, and our limbs and trunk just don’t work as well as they once used to. The brain is no different. As we get older, the brain shrinks in volume and its network of blood vessels  changes significantly. But not all people experience brain aging at the same rate, said Helmet Karim, Ph.D., an assistant professor of psychiatry and bioengineering at the University of Pittsburgh.

“People’s bodies age in different ways over time. Chronologically, you may be in your 20s or 30s but, if you are smoker, for example, your lungs and skin likely look much older than a person of the same age who doesn’t smoke,” he said. “We sometimes look at people, find out how old they are, and say, ‘Wow, they look great. They’ve aged really well.’ It’s the same concept with the brain. Show a radiologist a functional magnetic resonance imaging (fMRI) picture of an older person with good [brain] volume and healthy vasculature, and they will probably say the same thing.”

But brain aging isn’t just a matter of physical good looks. People with “older looking” brains tend to score more poorly on metrics of attention, memory, and executive function.

“Over time, the aging brain is measured by the decline in the ability to perform everyday tasks—to pay attention to details or to remember appointments,” said Darya Gaysina, Ph.D., senior lecturer in psychology at the University of Sussex. “As we age, we all experience decline in those abilities. But, for some people, this decline will be much faster than it is for others.”

Depression and the Aging Brain

Accelerated brain aging is likely the result of both biological and environmental factors, and it is, unfortunately, highly correlated with the development of neurodegenerative conditions such as dementia and Alzheimer’s disease. If we knew more about the underlying neurobiological mechanisms that caused this acceleration, we could not only better predict who is likely to develop such conditions later in life but also  identify neurobiological targets to help treat or even prevent age-related cognitive decline. That’s one of the reasons why Gaysina and colleagues were interested in looking at the link between brain aging and depression.

“Researchers have shown a link between depression and dementia in older adults, but it was not clear whether depression might lead to faster cognitive decline in individuals without dementia,” she said. “Our work suggests people who are diagnosed with clinical depression, as well as those who experience elevated depressive symptoms, are more likely to show a faster cognitive decline as they age. Specifically, we found people who experienced accumulated symptoms of depression across adulthood had worse memory function by midlife.”

Gaysina’s work suggests that excess inflammation, at least in part, is responsible for faster brain aging in people with depression, especially declining memory function. But there are likely other factors, too, and they may also help explain the strong association between anxiety disorders and neurodegeneration.

“There have, to date, been fewer studies conducted on anxiety than on depression,” Gaysina said. “But depression and anxiety often co-occur, with some estimates suggesting it co-occurs in up to 75 percent of cases. It is likely that findings for depression are also relevant for anxiety.”

Understanding Anxiety’s Effects

Carmen Andreescu, M.D., who has spent her career studying late-life anxiety, hopes to uncover what specific symptoms of anxiety might be responsible for accelerated brain aging. She has focused her research on negative thought processes, such as excessive worrying, which clinicians use to help diagnose general anxiety disorders.

“Worry is a very interesting concept,” she said. “It’s a mixture of thought processes and negative affect. It’s also very hard to treat in people with anxiety, even younger individuals. It’s a hardcore kind of pathology that keeps many people from getting better even when they get therapy or medications. Its chronicity has always made me think it may be powerful enough to affect the integrity of the brain—it  provides a kind of continuous stressful state that could have the power to brine the brain in stress hormones, leading to this faster aging.”

To test the idea, Andreescu used a machine learning model, developed and validated by Karim, to investigate potential associations between brain age and anxiety, depression, stress, and emotional regulation in adults using standard measures, including metrics that quantify how severe a worry is. The group scanned the brains of 78 people 50 years old and older and then ran the images through the machine learning model. They found a strong relationship between increased brain age and greater chronological age, male sex, greater worry, and greater rumination. They also found a correlation between brain age and a decreased ability to suppress negative thoughts.

“It was interesting to connect the symptoms with actual pathology and find this relationship between brain aging and both worry and rumination,” said Andreescu. “For every extra point on the worry scale, the brain was aging 1.3 months more. This scale goes up to 70—really severe worriers are between 50 and 70—so  you can age your brain quite a bit by worrying a lot. It’s a big concern.”

Karim added that the group was surprised to find that the ability to suppress negative thoughts had a somewhat protective effect.

“We often think of suppressing feelings as a negative tactic,” he said. “But we see in some studies of older adults that suppression of these worrying feelings, so you aren’t just ruminating over these thoughts over and over again, can reduce your overall emotionality. Cognitive reappraisal, which is often used in cognitive behavioral therapy [CBT], works in a similar way. It’s possible that finding ways to decrease these negative thoughts could help lessen this associated brain aging.”

Protecting Your Brain at Any Age

Andreescu and Karim hope to follow this research with a longitudinal study that follows excessive worriers for 10 years to see how these particular symptoms may change the brain in that time.

“We hope to understand the biological basis of how this kind of worrying actually impacts brain age,” said Karim. “We think it’s the stress, and the resulting biological effects of stress, but it’s something we need to follow to know for sure.”

In the meantime, both Andreescu and Gaysina say that people can take actions now that can protect their brains from the harmful effects of excessive aging.

“Anxiety can become a chronic condition early in life,” said Andreescu. “So, the most important thing is to start managing it early. You can address mental health symptoms with cognitive behavioral therapy, medications, or mindfulness strategies. You want to adopt a healthier lifestyle, eat right and exercise, because they can also help with anxiety symptoms. With every point on the worry scale aging your brain another month, it’s important to try to arrest these pathological processes as early as you can.”

Gaysina said the same approach can help people who are experiencing depressive symptoms, and even those who are already in an older age bracket can benefit from making these sorts of changes.

“It’s important to understand that it is not inevitable that people with depression will see a greater decline in their cognitive abilities,” she said. “As the United Kingdom says, ‘There is no health without mental health.’ We all need to make efforts to look after our mental health. It is never too late to start.”


How many trials are needed in kinematic analysis of reach-to-grasp?—A study of the drinking task in persons with stroke and non-disabled controls

Well, what about failures like me that can't even do 1 trial? And 15 years later still can't do it. Cure my spasticity and I'll tell you how many trials are needed. This is a case of extreme cherry picking of survivors that can do reach-to-grasp tasks.

How many trials are needed in kinematic analysis of reach-to-grasp?—A study of the drinking task in persons with stroke and non-disabled controls



Kinematic analysis of the 3D reach-to-grasp drinking task is recommended in stroke rehabilitation research. The number of trials required to reach performance stability, as an important aspect of reliability, has not been investigated for this task. Thus, the aims of this study were to determine the number of trials needed for the drinking task to reach within-session performance stability and to investigate trends in performance over a set of trials in non-disabled people and in a sample of individuals with chronic stroke. In addition, the between-sessions test–retest reliability in persons with stroke was established.


The drinking task was performed at least 10 times, following a standardized protocol, in 44 non-disabled and 8 post-stroke individuals. A marker-based motion capture system registered arm and trunk movements during 5 pre-defined phases of the drinking task. Intra class correlation statistics were used to determine the number of trials needed to reach performance stability as well as to establish test–retest reliability. Systematic within-session trends over multiple trials were analyzed with a paired t-test.


For most of the kinematic variables 2 to 3 trials were needed to reach good performance stability in both investigated groups. More trials were needed for movement times in reaching and returning phase, movement smoothness, time to peak velocity and inter-joint-coordination. A small but significant trend of improvement in movement time over multiple trials was demonstrated in the non-disabled group, but not in the stroke group. A mean of 3 trials was sufficient to reach good to excellent test–retest reliability for most of the kinematic variables in the stroke sample.


This is the first study that determines the number of trials needed for good performance stability (non-disabled and stroke) and test–retest reliability (stroke) for temporal, endpoint and angular metrics of the drinking task. For most kinematic variables, 3–5 trials are sufficient to reach good reliability. This knowledge can be used to guide future kinematic studies.


Analysis of multi-joint 3D kinematics is needed to understand the underlying mechanisms of the altered movement strategies commonly seen post stroke [1]. Unlike traditional clinical assessments, objective measures of movement quality allow differentiation between behavioral recovery and compensation in evaluation of treatment effects [2,3,4]. Here, the kinematic analysis can provide detailed and objective information about movement performance and movement quality during everyday activities, such as reach-to-grasp [5, 6].

Reach-to-grasp is frequently used in daily activities and its performance in non-disabled individuals is characterized by efficient spatiotemporal coordination of the arm and hand segments for transport and grasping [7]. Regaining arm- and hand function post-stroke is one of the highest priority goals in rehabilitation, and still about 65% of the patients with hemiparesis have impaired ability to reach, grasp and handle objects at 6 months after stroke onset [8]. Motor performance of reach-to-grasp tasks in the stroke population shows longer movement time, lower peak velocity, decreased elbow extension, greater arm abduction and trunk displacement, and decreased smoothness as compared to non-disabled controls [5, 9,10,11]. Among the reach-to-grasp tasks, drinking from a glass has, due to its ecological validity and ease of standardization, been recommended as a functional task for quantifying quality of movement in stroke rehabilitation research [12].

Another aspect that needs to be considered in performance of daily purposeful tasks is variability of movements. Variability is inherent in human movement control, i.e. different neuromotor processes are available to produce automatic movement strategies needed for achieving goals in daily life [13]. The concept of movement variability is defined as typical variations in motor performance when a task is repeatedly being executed [14], which is something that needs to be taken into account when conducting clinical research studies. Optimal movement variability is crucial for healthy motor control [13, 15]. A high level of automaticity and relatively constant variability is, however, expected when a well-known activity is repetitively performed [16].

Requests for standardization of kinematic analysis of upper extremity movements have been highlighted [11] and for research purposes several efforts have been made to agree on which tasks to study and which systems and metrics to use [5, 9,10,11,12]. Clinimetric properties, including reliability, validity and responsiveness, have been reported for some kinematic metrics [9, 11, 17, 18] although more studies are needed [19, 20]. One aspect of reliability that has been sparsely investigated is the performance stability of selected variables within a session of a series of trials. Most of the studies of reach-to-grasp tasks in stroke populations include 3–10 trials per task although in few studies up to 20 trials have been reported [5, 11]. A recent consensus on kinematic studies in stroke recommended at least 15 trials to be collected, both for 2D performance assays and 3D functional tasks [12].

Hence, the question of how many trials that are needed to reach performance stability of kinematic measures in goal-directed reach-to-grasp tasks remains. A previous study analyzing movement performance during fast pointing in non-disabled participants, demonstrated that 3 trials were required to reach good within-trial reliability for movement time and peak velocity, whereas up to 47 trials were required for trajectory metrics [21]. Another study in persons with subacute stroke, where also 3D motion capture was used, reported that 5 trials was sufficient to get reliable results for reaching kinematics [22].

To our knowledge, no studies have defined the number of trials needed to achieve performance stability, i.e. good reliability, in kinematic measures of goal-directed reach-to-grasp tasks, nor has this been investigated in people with disabilities. Thus, the primary aim of this study was to determine the number of trials needed to reach good performance stability of the kinematic variables during the drinking task in non-disabled people and in a sample of individuals with chronic stroke. Further, the performance stability over the set of multiple trials was investigated. In addition, the between-sessions test–retest reliability of selected kinematics in a sub-sample of individuals with stroke was established.