Ischemic Stroke Increases Heart Vulnerability to Ischemia-Reperfusion and Alters Myocardial Cardioprotective Pathways

What EXACTLY is your stroke doctor and hospital doing to ensure this problem is solved? Sitting on their asses sucking their thumbs, most likely? They need to solve this since it is most likely contributing to 30 day stroke deaths.

Ischemic Stroke Increases Heart Vulnerability to Ischemia-Reperfusion and Alters Myocardial Cardioprotective Pathways

Alexandre Meloux

,

Eve Rigal

,

Luc Rochette

,

Yves Cottin

,

Yannick Bejot

, and

Catherine Vergely

Originally published8 Oct 2018Stroke. 2018;49:2752–2760

Abstract

Visual Overview

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Background and Purpose—

For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo and how they influence cardiac vulnerability to ischemia-reperfusion injury.

Methods—

Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery. Stroke lesions were evaluated by microsphere counting, tissue staining, and assessment of neurological deficit 2 hours, 24 hours, and 7 days after surgery. Cardiac function was evaluated in vivo by echocardiography and ex vivo in isolated perfused hearts. Heart vulnerability to ischemia-reperfusion injury was investigated ex vivo at different times post-embolization and with varying degrees of myocardial ischemia. Left ventricles (LVs) were analyzed with Western blotting and quantitatve real-time polymerase chain reaction.

Results—

Our stroke model produced large cerebral infarcts with severe neurological deficit. Cardiac contractile dysfunction was observed with an early but persistent reduction of LV fractional shortening in vivo and of LV developed pressure ex vivo. Moreover, after 20 or 30 minutes of global cardiac ischemia, recovery of contractile function was poorer with impaired LV developed pressure and relaxation during reperfusion in both stroke groups. Following stroke, circulating levels of catecholamines and GDF15 (growth differentiation factor 15) increased. Cerebral embolization altered nitro-oxidative stress signaling and impaired the myocardial expression of ADRB1 (adrenoceptor β1) and cardioprotective Survivor Activating Factor Enhancement signaling pathways.

Conclusions—

Our findings indicate that stroke not only impairs cardiac contractility but also worsens myocardial vulnerability to ischemia. The underlying molecular mechanisms of stroke-induced myocardial alterations after cerebral embolization remain to be established, insofar as they may involve the sympathetic nervous system and nitro-oxidative stress.

Healthy Lifestyle Trumps Genes for Stroke Risk

I met all 4 of the healthy lifestyle factors and still had a stroke. 

Healthy Lifestyle Trumps Genes for Stroke Risk

Fewer strokes with good exercise and diet habits, despite high genetic risk

• by Kate Kneisel, Contributing Writer, MedPage Today October 26, 2018

Action Points

• Genetic and lifestyle factors were independently associated with risk of incident stroke.
• Note that the study suggests that adhering to a healthy lifestyle could attenuate the effect of genetics on stroke risk.

Individuals following a healthy lifestyle had lower stroke risk regardless of genetic risk factors compared to those with unhealthier habits such as smoking and poor diet, according to results of a prospective study of men and women in the UK Biobank database in Great Britain.
The population-based assessment of the independent effects of genetic and lifestyle factors found that the risk of stroke was 35% higher among those at high genetic risk compared with those at low genetic risk (hazard ratio 1.35, 95% CI1.21-1.50), according to Loes C.A. Rutten-Jacobs, German Center for Neurodegenerative diseases, Bonn, Germany, and colleagues.
Importantly, regardless of a person's level of genetic risk, having an unfavorable lifestyle that included 0 or 1 of 4 healthy lifestyle factors based on American Heart Association guidelines -- no current smoking, healthy diet, body mass index <30, and moderate physical activity two or more times weekly -- was associated with a 66% increased risk of stroke compared with having a favorable lifestyle that includes three or four healthy lifestyle factors (HR 1.66, CI 1.45-1.89), the group reported online in The BMJ.
Rutten-Jacobs and colleagues emphasized that while no firm conclusions can be drawn about cause and effect from an observational study, "it might be hypothesized that adhering to a healthy lifestyle could attenuate the effect of genetics on stroke risk. A previous study in coronary artery disease (CAD)... found a statistically significant interplay between genetic and lifestyle risk factors in CAD risk."
A high genetic risk combined with an unfavorable lifestyle profile was associated with a more than twofold increase in risk of stroke compared with a low genetic risk and a favorable lifestyle. Of lifestyle factors, the effect of smoking was strongest -- about twice as strong as effects of the other individual lifestyle scores.
Asked for his perspective, Gregg C. Fonarow, MD, of the David Geffen School of Medicine at UCLA in Los Angeles, said the findings reflect a significant body of research, which has linked both genetic and lifestyle factors with the risk of stroke.
"Importantly, irrespective of the level of underlying genetic risk, a healthy lifestyle was associated with lower stroke risk," Fonarow, who was not involved in the study, told MedPage Today via email. "Both men and women have higher risk of stroke with unhealthy lifestyles in this study; however the relative and absolute risks were higher in men compared to women."
Indeed, men with an unfavorable lifestyle had a higher relative risk of stroke than did women with an unfavorable lifestyle (82% versus 36% increased risk, respectively).
"These same lifestyle interventions [i.e. not smoking, regular physical activity, healthy diet, and avoiding diabetes] have been shown to be associated with lower risk of heart disease, thus supporting benefits in terms of both long-term heart and brain health," Fonarow added. "Additional studies in more diverse individuals in terms of race/ethnicity and region of the world may provide additional insights."
The group developed a weighted genetic risk score based on 90 stroke-related gene variants in 306,473 white men and women in the UK Biobank database and tested its association with incident stroke, and whether adherence to a healthy lifestyle influenced this association. Participants were 40 to 73 years old and had no history of stroke or heart attack.
Genetic risk was divided into thirds, and lifestyle was recorded as "favorable" (three or four healthy lifestyle factors), "intermediate" (two healthy lifestyle factors), or "unfavorable" (no or one healthy lifestyle factor).
During a median follow-up of 7.1 years, 2,077 incident strokes were noted, the group reported. "The association between genetic risk and incident stroke was unchanged after adjustment for lifestyle, and the association of lifestyle with incident stroke was essentially unchanged after adjustment for the genetic risk score."
Rutten-Jacobs and colleagues calculated hazard ratios for stroke in participants classified as having low or high genetic risk, associated with the following risk factors:

• Current smoking: 2.35 (95% CI 1.84-3.01) low risk; 1.87 (95% CI 1.48-2.37) high risk
• BMI ≥30: 1.43 (95% CI 1.20-1.71) low risk; 1.19 (95% CI 1.02-1.40) high risk
• Lack of regular moderate physical activity: 1.09 (95% CI 0.92-1.28) low risk; 1.09 (95% CI 0.94-1.26) high risk
• Unhealthy diet: 1.10 (95% CI 0.93-1.30) low risk; 1.21 (95% CI 1.05-1.40) high risk

These findings "highlight the potential of lifestyle measures to reduce risk of stroke across entire populations, even in those at high genetic risk of stroke," noted Rutten-Jacobs and co-authors.
The group acknowledged several limitations, such as the narrow range of lifestyle factors, and that the study population included only people of European descent, which limits the findings' generalizability.

This work was in part supported by the British Heart Foundation. HSM has been paid for delivering educational presentations for AstraZeneca.
LCAR-J was supported by a British Heart Foundation; CLS receives salary from UK Biobank and the Scottish funding Council; MD received funding from the European Union's Horizon 2020 research and innovation programme; HSM is supported by a National Institute for Health Research (NIHR) senior investigator award, and the Cambridge Universities NIHR Comprehensive Biomedical Research Centre.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 10.29.2018

• Primary Source

  The BMJ

  Source Reference: Loes CA Rutten-Jacobs LCA et al "Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants" BMJ 2018;363:k4168

Body Cooling May Not Help Patients with Severe Brain Injury

I was hopeful this would help since most hospitals would easily be able to do this in the ER. 

Body Cooling May Not Help Patients with Severe Brain Injury

Results run contrary to lab outcomes, which may reflect real-world limitations

• by Judy George, Contributing Writer, MedPage Today October 26, 2018

Action Points

• A large international randomized controlled trial failed to demonstrate an advantage for early prophylactic hypothermia in the treatment of severe traumatic brain injury (TBI).
• The primary endpoint of neurologic outcomes as well as secondary endpoints of mortality and time to death did not differ significantly between those receiving hypothermic treatment vs. normothermic controls; all other treatments in both groups were at the discretion of the treating physicians.

Cooling the brain as early as possible after severe traumatic brain injury (TBI) did not improve neurologic outcomes at 6 months, the POLAR randomized clinical trial found.
In a study of over 500 adults with TBI, the proportion of patients with favorable neurologic outcomes at 6 months was 48.8% after hypothermia, compared with 49.1% after normothermia, reported D. James Cooper, MD, of Monash University in Melbourne, Australia, and colleagues in JAMA.
"POLAR is the largest randomized trial done on this topic and the findings are very clear: cooling the brain as early as possible after head injury does not improve long-term patient outcomes and has important complications," Cooper said.
"The best temperature for doctors to target after a severe head injury in the future is the normal one, not the cool one," he told MedPage Today.
POLAR sought to answer a decades-old controversy about whether cooling the brain early and long after severe TBI improves long-term patient outcomes, as it does in many lab studies.
"A systematic review of these laboratory studies supported prophylactic hypothermia for neuroprotection," noted Peter Andrews, MD, of Western General Hospital in Edinburgh, Scotland, and co-authors in an accompanying editorial. "Even more compelling was the report that when these studies were stratified according to risk of bias, data from the higher-quality studies showed that hypothermia was effective when delivered immediately or soon after injury."
But the benefits of hypothermia failed in translation to clinical trials, with four large multicenter trials showing either no effect or harm, the editorial noted. And none of these trials delivered early hypothermia -- and therefore didn't test the preclinical intervention.
In POLAR (Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury), a multicenter trial in six countries, researchers randomized 511 patients with TBI to either hypothermic (n=266) or normothermic (n=245) treatment from 2010 to 2017. The average patient age was 34.5, and about 80% were men. The median Glasgow Coma Scale score of the group was 6. Most patients (70.6%) had diffuse brain injury, and the median time to randomization was 1.9 hours.
The researchers managed temperature in both groups for 7 days; all other care was at the discretion of the treating physician. The intervention protocol was to induce and maintain hypothermia for at least 72 hours at 33°C/91.4°F (or 35°C/95°F, if there were bleeding concerns) with a combination of cold intravenous fluids and surface cooling wraps. The intervention was started as early as possible regardless of intracranial pressure, either before arriving at the hospital or in the emergency department, and continued for up to 7 days, followed by a gradual rewarming.
Achieving the protocol target was more difficult than expected: 33% of patients received less than 48 hours of hypothermia, and 27% never reached the final target temperature of 33°C because of complications or physician decisions.
In the normothermic group, the researchers targeted 37°C (98.6°F), using surface-cooling wraps when required.
Favorable functional outcomes -- defined as a score of 5 to 8 on the Glasgow Outcome Scale–Extended at 6 months -- occurred in 48.8% of the hypothermia group and 49.1% of the normothermia group (absolute risk difference, -0.4 percentage points, 95% CI −9.4 to 8.7; RR 0.99, 95% CI 0.82-1.19). While some patients in the hypothermia group were rewarmed prematurely either because the clinicians believed that the injury was not as severe as first thought or the patients developed serious bleeding problems, favorable outcomes were no different between the protocol or as-treated groups.
There were no significant differences in secondary outcomes, including mortality at hospital discharge and at 6 months. The proportions of patients with adverse events for new or increased intracranial bleeding were 18.1% in the hypothermia group and 15.4% in the normothermia group. For pneumonia, they were 55.0% in the hypothermia group and 51.3% in the normothermia group.
The median time to reach 33°C in this study was greater than 10 hours. Real-world protocols require time to exclude undiagnosed injuries, Cooper and his group noted: this may be why hypothermia lab studies don't translate to trauma patients.
Poor protocol adherence -- with both the target temperature range and the duration of cooling -- was a limitation of the trial, Andrews and co-authors observed. The researchers increased the study's external validity by enrolling patients regardless of intracranial pressure, but one in three patients in the hypothermia group had the intervention for less than 48 hours and one in four patients didn't reach the target temperature.
"Yet, this may reflect the realities of utilizing prophylactic hypothermia for patients with severe TBI in clinical practice, and there was still no benefit noted in the per-protocol or as-treated analyses," the editorial pointed out. It also was not possible to blind clinicians or patients' families in this trial.
Despite these limitations, "whether hypothermia has any place in intensive care in selected patients with severe traumatic brain injury and dangerously high brain pressures will now be questioned even more intently than in the past," Cooper said.

The trial was supported by grants from the National Health and Medical Research Council of Australia; the Victorian Neurotrauma Initiative; the Teaching Hospital of Besançon, France; and the Health Research Board of Ireland Clinical Trial Network Program.
Cooper reported receiving consulting fees from Pressura Neuro to Monash University for an unrelated traumatic brain injury drug trial.
Andrews reported receiving speaker fees from BARD, manufacturer of a cooling device.

• Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 10.29.2018

• Primary Source

  JAMA

  Source Reference: Cooper DJ, et al "Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial" JAMA 2018; doi:10.1001/jama.2018.17075.

• Secondary Source

  JAMA

  Source Reference: Docherty A, et al "Hypothermia after traumatic brain injury" JAMA 2018; doi:10.1001/jama.2018.17121.

The End Comes as a Wave - death of neurons

How will our stroke researchers use this knowledge to come up with prevention protocols post-stroke? Or will nothing be done because we have NO stroke leadership and they are waiting for SOMEONE ELSE TO SOLVE THE PROBLEM?

Inquiring minds want to know specifically whom is going to solve this problem? Specific names, not just put in a 10 year goal that will never be accomplished. We need to start taking names and firing all the incompetent people in stroke.  My manager used to assign many of the most difficult programming problems to me since I would keep at it until the original cause was found and fixed. Whom is that person in stroke research? Every stroke doctor and stroke hospital should be able to immediately roll that persons name off their tongue.

The End Comes as a Wave

by Sophie Fessl September 26, 2018

Shutterstock[See also video, below story]

Death is a part of life, and while much of life is poorly understood, death is shrouded in mystery. What goes on in our brains before we die?
Neuroscientists in Germany and the US have recently shown that “brain tsunamis,” waves of cell depolarization – massive short-circuits of the neurons – sweep the cortex within ten minutes of cardiac arrest. These waves of spreading depolarization mark the beginning of the end, and trigger a gradual poisoning of neurons. They recorded brain tsunamis not just as people died but also after other critical events, such as a brain hemorrhage. Their findings could have immediate application in ERs and critical-care wards.
Measuring what happens in the brain immediately after a stroke or cardiac arrest is difficult, but Jens Dreier, at the Center for Stroke Research Berlin, and Jed Hartings, at the University of Cincinnati, saw an opportunity in their work in neurocritical care. Their centers monitor the brain activity of patients with certain conditions, such as traumatic brain injury or bleeding after an aneurysm. This neuromonitoring involves putting electrodes either directly onto the surface of the brain or deep into the cerebral cortex. Clinicians can then record electrical activity directly from the cortex.

Some patients suffering from such brain injuries did not respond to treatment. After family discussion and agreement, the doctors withdrew life-sustaining therapy while neuromonitoring continued as the patient died. What the neuroscientists observed was striking, says Jed Hartings.
“Previously, it was thought that the end occurs when the brain stops its electrical activity and goes silent,” he says. “But it doesn’t. We show that the brain remains in a viable state for several minutes after this flatline. And then the final brain tsunami occurs: A wave of depolarization sweeps through the cortex.”
This brain activity reflects what happens to the neurons as the heart stops pumping fresh oxygen to it, explains Jens Dreier. “After cardiac arrest, blood flow to the brain stops. Neurons and astrocytes detect that the oxygens levels drop, even before their own metabolism is affected. The neurons then switch off their function to get into an energy-saving mode: electrical activity stops, the neurons no longer send any signals. This is the flatline.” But while the neurons use less energy in this mode, they don’t use none--they still need some to maintain their internal metabolism.
Normally, ion pumps monitor and maintain a difference in charge between the inside and outside of neurons; this difference is essential for neurons to send their signals. But the pumps need energy, and this is where the system fails, Dreier says. “Eventually, there is no longer enough energy to keep the ion pump going. The ion gradients collapse: Ions from inside the neurons stream out, and those from the outside stream in.” As cells, and neurons in particular, have a carefully balanced chemistry, this change in the concentrations has dramatic consequences.
“A massive depolarization occurs as the ion gradients collapse completely, releasing a great amount of energy,” Dreier says. “The massive depolarization isn’t localized though, waves of depolarization spread into the neighboring regions. This is the brain tsunami, or spreading depolarization.”
First results in humans
Spreading depolarizations, for all their dramatic impact, are nothing new. In 1944, the Brazilian physiologist Aristides Leo first described seeing waves of suppressed function in the cortex of rats after he stimulated the cortex intensely, in what he called “spreading depression.” From the 1980s onwards, medics increasingly accepted that spreading depolarization was relevant to brain injuries. By the 1990s, researchers had proven in animals that brain tsunamis cause the death of brain tissue, but because spreading depolarization is so hard to record, it remained unobserved in humans until this century. Finally, in 2002, neuroscientists demonstrated spreading depolarization in the human brain. Since then, COSBID, a clinical research collaboration of which Dreier and Hartings are members, and others have studied spreading depolarizations in brain injuries in hospitals across Europe and the US.
Notably, spreading depolarization does not mark the onset of cell death, but instead starts the clock counting down to cell death. Leão already showed that spreading depolarization is – in principle – reversible. If blood flow isn’t restored after a certain time, neurons are unable to recover and will die – this is the commitment point. However, even if depolarization is reversed, the neurons don’t necessarily survive, says Dreier.
“After depolarization, there is complete chaos in the cells,” he says. “Calcium levels, for example, increase a thousand-fold. These changes are highly toxic to the neuron. However, when blood flow sets in again and energy is provided to the brain, some cells can re-polarize and may recover their function. But it is fiendish: Although the depolarization is reversed, the neuron might still die from apoptosis.”
The commitment point, the beginning of the end, is elusive. “As spreading depolarization is, in principle, reversible, the commitment point at which neurons start dying and at which there is no going back is hard to define,” Dreier says. “Actually, we can only define this point in retrospect. Death is a process that takes some time.”
For Dreier and others, the findings have a concrete call to action.
“We see that patients live longer after a cardiac arrest if some circulation remains. So resuscitation attempts are very important. Even if the heart doesn’t start pumping again immediately, as long as the blood flow is kept going, the brain is kept in a state in which it is able to survive for longer.”
Clues to hemorrhage mystery
Spreading depolarization could also explain the puzzling clinical course seen in patients with sub-arachnoid hemorrhage (aSAH), or bleeding in the space between the brain and the tissues covering it, another recent study by Dreier and Hartings suggests.
Patients with aneurysmal sub-arachnoid haemorrhage are likely to develop a series of complications about a week after the initial bleeding. “This condition has remained enigmatic, as the causes for delayed deterioration were unknown,” Hartings says. “Previously, not much focus was put on the brain damage that occurs soon after the aneurysm ruptures. This was considered too early to medically intervene. But we found that the aneurysm itself causes a significant amount of brain damage.”
Dreier and Hartings analyzed recordings from 11 patients with aSAH and found that spreading depolarizations occur frequently in the initial days after aSAH. “Just the bleeding in the subarachnoid space itself is a trigger for brain tsunamis in humans, causing brain damage,” Hartings says. “The spreading depolarizations signal that a brain infarct [stroke] is developing.” In these patients, clusters of spreading depolarizations occurred again and again. The spreading depolarizations lasted progressively longer and were a marker of neurons dying.
These results could also change treatment for aSAH, Hartings hopes. “Through neuromonitoring, spreading depolarizations can act as an early warning system for clinicians before brain damage is irreversible,” he says. “Clinicians could, for example, pay close attention to whether the brain receives enough blood flow and oxygen.”
The two papers advanced the field of spreading depolarization significantly, says Bill Shuttleworth, Regent’s Professor of Neurosciences at the University of New Mexico, who is part of the COSBID consortium but not involved in the studies. “Previously, the real impact of spreading depolarizations in humans was questioned, but these studies take the step to real relevance of spreading depolarization in the clinic.”
“Looking at the end of life, the researchers tied together death and spreading depolarization in a very controlled clinical setting with strong data. This is an amazing observation, finding other ways in which spreading depolarizations impact the brain,” Shuttleworth says. “And by looking at subarachnoid hemorrhages, the researchers found the first electrophysiological signature for the events causing brain damage.”
“The spreading depolarization shows that brain cells are dying, and gives a tremendously useful marker in the clinic for when something is really hurting the brain,” he says. This is not just a curiosity, but something actionable in intensive care.”

 Video: A recording of brain electrical activity, played back 44x normal rate, in a patient who experienced a traumatic head injury. The crackling sound is the normal activity of brain cells; the periods of silence are short-circuits of electrical activity caused by brain tsunamis, waves of depolarization that spread across injured areas of the brain, causing a local loss of function. The brain’s electrical activity recovers, but with each brain tsunami, damage to cells may worsen. Video posted to YouTube by Mayfield Brain & Spine 

Measuring Habitual Arm Use Post-stroke With a Bilateral Time-Constrained Reaching Task

So you measured something. What the hell use is that to getting survivors 100% recovered? That is the only goal in stroke research. At least it would be if I was in charge. 

Measuring Habitual Arm Use Post-stroke With a Bilateral Time-Constrained Reaching Task

Sujin Kim^1,2, Hyeshin Park^1,3, Cheol E. Han⁴, Carolee J. Winstein¹ and Nicolas Schweighofer^1*

• ¹Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, United States
• ²Physical Therapy, Jeonju University, Jeonju, South Korea
• ³Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States
• ⁴Department of Electronics and Information Engineering, Korea University, Sejong, South Korea

Background: Spontaneous use of the more-affected arm is a meaningful indicator of stroke recovery. The Bilateral Arm Reaching Test (BART) was previously developed to quantify arm use by measuring arm choice to targets projected over a horizontal hemi-workspace. In order to improve clinical validity, we constrained the available movement time, thereby promoting more spontaneous decision making when selecting between the more-affected and less affected arm during the BART.

Methods: Twenty-two individuals with mild to moderate hemiparesis were tested with the time-based BART in three time-constraint conditions: no-time constraint, medium, and fast conditions. Arm use was measured across three sessions with a 2-week interval in a spontaneous choice block, in which participants were instructed to use either the more-affected or the less-affected arm to reach targets. We tested the effect of time-constraint condition on the more-affected arm use, external validity of the BART with the Actual Amount of Use Test (AAUT), and test-retest reliability across the three test sessions.

Results: The fast condition in the time-based BART showed reduced use of the more-affected arm compared to the no-time constraint condition P < 0.0001) and the medium condition P = 0.0006; Tukey post hoc analysis after mixed-effect linear regression). In addition, the fast condition showed strong correlation with the AAUT r = 0.829, P < 0.001), and excellent test-retest reliability (ICC = 0.960, P < 0.0001).

Conclusion: The revised BART with a time-restricted fast condition provides an objective, accurate, and repeatable measure of spontaneous arm use in individuals with chronic stroke hemiparesis.

Introduction

Spontaneous use of the more-affected upper extremity post-stroke is often lower than would be expected from impairment levels (1, 2), with low use associated with a reduced quality of life (3). Besides the common therapy goal of improving motor performance of the more-affected arm/hand, an additional approach would be to influence the decision-making system (4), with the aim to improve use of the more-affected arm/hand.

The three instruments commonly used for measuring spontaneous arm/hand use in the natural environment are the Motor Activity Log [MAL; (5)], the Actual Amount of Use Test [AAUT; (6)], and accelerometers (7, 8). These instruments are not ideal, however: the MAL relies on self-reported ratings from memory; the AAUT cannot be administered repeatedly once participants recognize that they are being tested, thereby revealing its covert nature; and accelerometers only provide overall activity, and thus not a direct measure of functional arm use.

We previously developed a simple and objective assessment tool, the Bilateral Arm Reaching Test (BART) to address these limitations (1). With BART, arm use is measured in a spontaneous choice block, in which participants are instructed to choose either the more-affected or the less-affected arm to reach displayed targets on a table. (I would never use my affected arm to reach for anything, spasticity prevents opening the hand, so success would never occur. So first of all you need to develop a cure for spasticity. Follow the goddamned stroke strategy. ) Although arm use as assessed with BART showed good test-retest reliability, it was only moderately correlated with the AAUT (1). In seeking to improve BART, we sought a better way to capture real-world spontaneous arm use. We turned to previous research in decision-making (9–11). Contemporary decision models posit that choices between potentially rewarding actions are driven by a combination of a goal-oriented system and a habitual system. The goal-directed system is called “model-based” because individuals learn through experience, and then mentally simulate, models of the decision environment to prospectively evaluate the outcomes of possible actions. In contrast, the habitual system is “model-free,” because choice is performed via direct comparison of expected rewards for each potential action (12). Mental simulations in the goal-directed system is a time-consuming process. As a result, performing choices under time-pressure enhances expression of the time-insensitive habitual system (13). For this reason, we modified BART by adding a short time-constraint condition to the experimental paradigm.

The aim of this study was to accurately quantify arm/hand use post-stroke with the time-based BART system. We hypothesized that a reduction of available decision time would reduce affected arm use. In addition, we reasoned that affected arm use in the time-constrained condition would more strongly correlate with arm use as assessed by the covert AAUT than arm use without time constraint.

Much more at link.

Assessing the Relationship Between Motor Anticipation and Cortical Excitability in Subacute Stroke Patients With Movement-Related Potentials

What the fuck is the possible use of this research in getting survivors 100% recovered? Describes a problem, but too fucking lazy to even suggest a solution. 

Assessing the Relationship Between Motor Anticipation and Cortical Excitability in Subacute Stroke Patients With Movement-Related Potentials

Ling Chen^1,2, Yurong Mao¹, Minghui Ding¹, Le Li¹, Yan Leng¹, Jiangli Zhao¹, Zhiqin Xu¹, Dong Feng Huang^1,3* and Wai Leung Ambrose Lo^1*

• ¹Department of Rehabilitation Medicine, Guangdong Engineering and Technology Research Center for Rehabilitation Medicine and Translation, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
• ²Department of Acupuncture and Moxibustion, The Secondary Medical College, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
• ³Xinhua College of Sun Yat-sen University, Guangzhou, China

Background: Stroke survivors may lack the cognitive ability to anticipate the required control for palmar grasp execution. The cortical mechanisms involved in motor anticipation of palmar grasp movement and its association with post-stroke hand function remains unknown.

Aims: To investigate (Not come up with a solution to the problem)the cognitive anticipation process during a palmar grasp task in subacute stroke survivors and to compare with healthy individuals. The association between cortical excitability and hand function was also explored.

Methods: Twenty-five participants with hemiparesis within 1–6 months after first unilateral stroke were recruited. Twenty-five matched healthy individuals were recruited as control. Contingent negative variation (CNV) was measured using electroencephalography recordings (EEG). Event related potentials were elicited by cue triggered hand movement paradigm. CNV onset time and amplitude between pre-cue and before movement execution were recorded.

Results: The differences in CNV onset time and peak amplitude were statistically significant between the subacute stroke and control groups, with patients showing earlier onset time with increased amplitudes. However, there was no statistically significant difference in CNV onset time and peak amplitude between lesioned and non-lesioned hemisphere in the subacute stroke group. Low to moderate linear associations were observed between cortical excitability and hand function.

Conclusions: The earlier CNV onset time and higher peak amplitude observed in the subacute stroke group suggest increased brain computational demand during palmar grasp task. The lack of difference in CNV amplitude between the lesioned and non-lesioned hemisphere within the subacute stroke group may suggest that the non-lesioned hemisphere plays a role in the motor anticipatory process. The moderate correlations suggested that hand function may be associated with cortical processing of motor anticipation.

Introduction

Cognitive Process of Movement Anticipation in Stroke Patients

Stroke is among the leading causes of long-term disability worldwide (1). It is one of the most severe issues encountered by the aging population (2). Seventy-five percent of stroke survivors have motor dysfunction that affects body coordination and motor skill (3). Motion prediction is a key component of cognitive function and is a high-level function that affects motor control (4). Motor function recovery is often measured in terms of motor execution, with little consideration given to the high level cognitive processes that feeds into the actual motor response (5). To execute activities of daily living such as reach and grasp, the upper extremity must apply the correct force, move the precise range and accurately coordinate multiple limb segments (6–10). The cognitive ability to anticipate the required movement control is therefore fundamental to hand motor performance. Published literature indicates that stroke patients lack the anticipatory ability of upper limb movement that is associated with palmar grasp (11–13). The lack of ability to anticipate was evidenced in the suboptimal application of force by producing markedly increased grip forces during lifting, holding and moving a hand-held object in patients with acute stroke (14). Patients with chronic stroke demonstrated a slower response to adapt to the perturbing force and exhibited smaller aftereffects when the perturbing force was unexpectedly removed than healthy controls (11).

Discussion

The primary aim of this study was to investigate the difference in the cognitive anticipation process between the lesioned and non-lesioned hemisphere in subacute stroke survivors and to compared those with healthy individuals.(Useless for recovery) The association between the electrophysiological process and the functional level as measured by the ARAT in the stroke group was also investigated.

Many more pages at link.

APT Weighted MRI as an Effective Imaging Protocol to Predict Clinical Outcome After Acute Ischemic Stroke

Damn it all, stop with this prediction crapola. Survivors want 100% recovery, they need rehab protocols, NOT THIS SHIT.  GET THERE! A great stroke association president would ream these researchers out for not following the stroke strategy that leads to 100% recovery.  Just because we have NO strategy is no reason to do these useless prediction ones.

APT Weighted MRI as an Effective Imaging Protocol to Predict Clinical Outcome After Acute Ischemic Stroke

Guisen Lin¹, Caiyu Zhuang¹, Zhiwei Shen¹, Gang Xiao², Yanzi Chen¹, Yuanyu Shen¹, Xiaodan Zong¹ and Renhua Wu^1,3*

• ¹Department of Medical Imaging, The Second Affiliated Hospital, Medical College of Shantou University, Shantou, China
• ²Department of Mathematics and Statistics, Hanshan Normal University, Chaozhou, China
• ³Provincial Key Laboratory of Medical Molecular Imaging, Shantou, China

To explore the capability of the amide-proton-transfer weighted (APTW) magnetic resonance imaging (MRI) in the evaluation of clinical neurological deficit at the time of hospitalization and assessment of long-term daily functional outcome for patients with acute ischemic stroke (AIS). We recruited 55 AIS patients with brain MRI acquired within 24–48 h of symptom onset and followed up with their 90-day modified Rankin Scale (mRS) score. APT weighted MRI was performed for all the study subjects to measure APTW signal quantitatively in the acute ischemic area (APTW_ipsi) and the contralateral side (APTW_cont). Change of the APT signal between the acute ischemic region and the contralateral side (ΔAPTW) was calculated. Maximum APTW signal (APTW_max) and minimal APTW signal (APTW_min) were also acquired to demonstrate APTW signals heterogeneity (APTW_max−min). In addition, all the patients were divided into 2 groups according to their 90-day mRS score (good prognosis group with mRS score <2 and poor prognosis group with mRS score ≥2). In the meantime, ΔAPTW of these groups was compared. We found that ΔAPTW was in good correlation with National Institutes of Health Stroke Scale (NIHSS) score (R² = 0.578, p < 0.001) and 90-day mRS score (R² = 0.55, p < 0.001). There was significant difference of ΔAPTW between patients with good prognosis and patients with poor prognosis. Plus, APTW_max−min was significantly different between two groups. These results suggested that APT weighted MRI could be used as an effective tool to assess the stroke severity and prognosis for patients with AIS, with APTW signal heterogeneity as a possible biomarker.

Introduction

As a promising contrast mechanism, chemical exchange saturation transfer (CEST) has become an important tool in the field of molecular imaging (1). Recently, APTW MRI, one form of CEST technology, has been increasingly applied in capturing tissue acidosis as a research tool based on its capability to detect pH and mobile proteins content (2). APTW MRI has been used to assess the severity of tissue acidification in hyperacute and acute stroke (3, 4). For all these pre-clinical researches, the induced stroke studies were carried out under highly controlled environment and the animals were scanned during early stage of stroke within hours. Under this circumstance, the APTW imaging was called pH-weighted imaging since pH was the major factor to affect the APTW signal intensity, accounting for more than 90% (5). Clinical assessment using APTW imaging is considered promising given its ability to characterize pH of the stroke area within hours from the symptom onset. The enthusiasm of applying the APTW imaging to patients with none hyperacute stroke (within hours from symptom onset) might be decreased given the fact that many factors can affect the APTW signal (5). However, a considerable proportion of patients with stroke have delay in presentation to the hospital (6, 7). Applying of APTW imaging might be clinically useful given the large number of patients with relatively delayed presentation to the hospital. In this study, we would like to testify the capability of APTW MRI as a tool to assess stroke severity as well as to predict clinical outcome of patient of acute ischemic stroke (AIS) with symptom onset between 24 and 48 h by measuring the change of APTW signal intensity.

Machine learning can predict stroke treatment outcomes

No, No, No. This just allows our stroke medical 'professionals' to stop working on better recovery options.  This type of nocebo should never be allowed.  If you get a prediction, scream at your doctor; 'Where are the 100% recovery protocols?' And don't stop screaming until they answer.  We can't let lazy crapola like this stop stroke research.

Machine learning can predict stroke treatment outcomes

 By Erik L. Ridley, AuntMinnie staff writer

October 30, 2018 -- Making use of imaging features and demographic information, machine-learning algorithms predicted 90-day outcomes in patients with acute ischemic stroke, offering potential as an aid for treatment decisions, according to research published online October 24 in the American Journal of Roentgenology.

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A team of researchers led by Yuan Xie of Stanford University developed machine-learning models that could perform reasonably well in predicting patient outcomes based on analysis of stroke biomarkers at admission for acute ischemic stroke. Performance significantly improved, however, with the addition of patient information that's available 24 hours after treatment.
Timely and accurate outcome prediction plays an important role in making decisions on treatment and rehabilitation strategy for patients with acute ischemic stroke. Currently, this decision-making process involves assessment of biomarkers, including imaging features and demographic information, according to the researchers. They sought to use machine-learning methods to integrate these clinical and imaging variables in the acute setting to predict three-month modified Rankin scale (mRS) scores, a measure of disability, in these patients.
The researchers elected to use decision-tree learning, a form of supervised machine learning that is constructed by performing binary tests on a given feature. The initial binary test forks into two new tests, each asking a new question. These questions then form a diverging flowchart, with each end of the branch providing a prediction with a certain confidence level. Ultimately, all of the decisions combine to yield a prediction, according to the researchers.
In a retrospective study, they included 512 patients from a registry of patients with acute ischemic stroke at Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland. Using ground-truth 90-day modified Rankin scale scores in these patients, they trained two types of decision-tree machine-learning models, extreme gradient boosting (XGB) and gradient boosting (GBM), to predict mRS scores using CT angiography and demographic biomarkers available when patients were admitted and 24 hours afterward.
The researchers found that a patient's 90-day mRS score correlated significantly with five biomarkers:

• Scores on the National Institutes of Health Stroke Scale (NIHSS) 24 hours after treatment
• Patient age
• Scores on the Alberta Stroke Program Early CT (ASPECT)
• Presence of hyperdense middle cerebral artery sign (HMCAS) on CT
• The North American Symptomatic Carotid Endarterectomy Trial (NASCET) degree of cervical carotid stenosis

Area under the receiver operating characteristic curve for predicting 90-day outcomes in acute ischemic stroke patients
Model	At admission	With selected features & NIHSS score 24 hours after treatment
XGB machine-learning model	0.758	0.884
GBM machine-learning model	0.772	0.877

In other results, the researchers also found that the models could predict outcomes separately in patients with early recanalization and those with persistent arterial occlusion.
"Prediction of patient recovery based on recanalization status can also help physicians assess the risk and benefits associated with endovascular treatment decisions," the author wrote.
Future work should involve improving multinomial models to specifically predict the modified Rankin scale scores, as well as using image-based predictions to prognosticate recovery outcomes, the researchers noted.
"For larger datasets, other methods, including deep learning, may yield even better results," they wrote.

“It’s Lonely”: Patients’ Experiences of the Physical Environment at a Newly Built Stroke Unit

Well shit, you mean you didn't take into account research showing nature scenes even in a painting were helpful.  My God, the stupidity involved in not keeping up with stroke research.

“It’s Lonely”: Patients’ Experiences of the Physical Environment at a Newly Built Stroke Unit 

Show all authors

Anna Anåker, RN, PhD Student, Lena von Koch, PhD, Ann Heylighen, PhD, ...

First Published October 18, 2018 Research Article

https://doi.org/10.1177/1937586718806696

Article information

Abstract

Objective:

The aim of this study was to explore patients’ experiences of the physical environment at a newly built stroke unit.

Background:

For a person who survives a stroke, life can change dramatically. The physical environment is essential for patients’ health and well-being. To reduce infections, a majority of new healthcare facilities mainly have a single-room design. However, in the context of stroke care, knowledge of how patients experience the physical environment, particularly their experience of a single-room design, is scarce.

Method:

This study used a qualitative design. Patients (n = 16) participated in semistructured individual interviews. Data were collected in December 2015 and February 2017 in Sweden; interviews were transcribed verbatim and analyzed using content analysis.

Results:

Two main themes were identified: (i) incongruence exists between community and privacy and (ii) connectedness with the outside world provides distraction and a sense of normality. In single rooms, social support was absent and a sense of loneliness was expressed. Patients were positively distracted when they looked at nature or activities that went on outside their windows.

Conclusions:

The physical environment is significant for patients with stroke. This study highlights potential areas for architectural improvements in stroke units, primarily around designing communal areas with meeting places and providing opportunities to participate in the world outside the unit. A future challenge is to design stroke units that support both community and privacy. Exploring patients’ experiences could be a starting point when designing new healthcare environments and inform evidence-based design.

Keywords evidence-based design, healthcare facilities, nursing, rehabilitation, single-room design

Stroke affects a large number of people, and the subsequent rehabilitation and care are challenging. In Sweden, as in most high-income countries, almost all people with stroke are cared for at special stroke units (Riksstroke, 2015). There are evidence-based guidelines for the care provided at stroke units, such as early and individual-based mobilization, frequent and accurate assessment of health status, and well-developed teamwork (Ringelstein et al., 2013; Stroke Unit Trialists’ Collaboration [SUTC], 2013). However, despite the fact that studies in other fields show that the physical environment is important and can influence the patient’s health outcomes and how care is provided (Ulrich et al., 2008), little is known about the physical environment’s contribution to the quality of care at stroke units. In this study, we describe how patients experience the physical environment at a stroke unit that has been rebuilt according to a new single-room design. Such an investigation is important because the majority of new healthcare facilities are built with a predominantly single-room design (Joint Commission, 2018). Recently, a study showed that patients in a newly built stroke unit with a single-room design spend more time being inactive and alone compared to patients in an older multibed room design (Anåker, von Koch, Sjöstrand, Bernhardt, & Elf, 2017). However, how patients experience being cared for in single-room units remains unexplored.
As an important part of the rehabilitation process at stroke units, the physical environment has recently been highlighted as an important factor in stimulating both cognitive and social activities among patients (Janssen et al., 2014; White, Bartley, Janssen, Jordan, & Spratt, 2015). According to Harris, McBride, Ross, and Curtis (2002), the physical environment can be described as the ambient environment (e.g., lighting, noise levels, and air quality); architectural features (e.g., layout of hospital); the size and shape of rooms and placement of windows; and interior design features (e.g., furnishing and artwork). All dimensions are important for supporting care and helping patients return to health and well-being. In nursing, the concept of the environment has traditionally been referred to as all that surrounds the patient; there is constant interaction between the patient and the environment (Meleis, 2017).
Ulrich (1991) argued that to promote well-being, the physical environment should be designed to support patient care by providing a sense of control, access to social support, and access to positive distraction. Researchers have examined several areas in which the physical environment can impact patients’ health outcomes; it has been found that sound and light (Huisman, Morales, van Hoof, & Kort, 2012) as well as the ability to experience nature (Ulrich et al., 2008) can affect health and well-being. Research has also shown that high levels of attractiveness, in the form of colorful contemporary furnishings and artwork, for example, may reduce patients’ anxiety (Becker & Douglass, 2008). The physical environment can also provide opportunities for activities and social interactions, for example, by providing access to communal areas with books, games, and computers; having access to these opportunities for interaction can be an important prerequisite for recovery after a stroke (Janssen et al., 2014; White et al., 2015).
Based on the knowledge that the physical environment can contribute to health and well-being, the concept of evidence-based design has been established and is increasingly attracting attention. Evidence-based design incorporates research to achieve the best possible health outcomes for patients, staff, and visitors (Hamilton & Watkins, 2009; Ulrich, Berry, Quan, & Parish, 2010). To gain a better understanding of the importance of the physical environment, individual experiences of the environment need to be studied further. This need for research applies especially when the trend is to go exclusively to single rooms.

To gain a better understanding of the importance of the physical environment, individual experiences of the environment need to be studied further.

Around the world, new healthcare environments are built primarily using a single-room design (Joint Commission, 2018). Studies have shown that patients treated in single rooms have a lower incidence of both airborne and contact-related infections (Simon, Maben, Murrells, & Griffiths, 2016; Ulrich et al., 2008) and confusions (Caruso, Guardian, Tiengo, dos Santos, & Junior, 2014) than patients in multibed rooms. Reduced noise levels in single rooms improve communication between patients and staff (Ulrich et al., 2008). Studies have also shown that patients appreciate being cared for in single rooms because these rooms provide a personal sphere without disturbing elements (Maben et al., 2015; Persson, Anderberg, & Ekwall, 2015). However, the sense of loneliness and isolation that patients experience as a result of a single-room design compared with multibedded units is receiving more attention (Persson et al., 2015: Singh, Subhan, Krishnan, Edwards, & Okeke, 2016).
The present study focuses on patients who have suffered a stroke. Stroke can affect any neurological function, for example, it can cause visual impairment and memory loss, and it can impact a person’s daily life (Elf, Eriksson, Johansson, von Koch, & Ytterberg, 2016; Langhorne, Bernhardt, & Kwakkel, 2011). Shortly after a stroke, increased engagement in physical activities targeting mobility may result in reduced impairment (Veerbeek et al., 2014).
To live independently and manage their daily lives at home, all stroke patients should be treated in stroke units. A stroke unit is an organized and highly specialized unit that provides complete care for stroke patients and constitutes a geographically defined unit in the hospital (SUTC, 2013). A person who receives care in a stroke unit is less likely to have complications caused by immobility, such as venous thromboembolism or chest infections, compared to a patient who receives care in a general ward (Govan, Langhorne, & Weir, 2007). The care at stroke units focuses on acute medical interventions and early rehabilitation, which are provided by a multiprofessional team (Riksstroke, 2015). Stroke guidelines recommend starting rehabilitation early to regain functions such as the abilities to walk, talk, and read (Ringelstein et al., 2013; SUTC, 2013).
Research on patients at stroke units has focused mainly on aspects such as where patients spend their days as well as the types of activities and interactions they engage in (Bernhardt, Dewey, Thrift, & Donnan, 2004; West & Bernhardt, 2012). Recently, we had the opportunity to compare patients’ behavior in a stroke unit before and after the unit underwent reconstruction. The comparison showed that patients’ activities and interactions varied between the old and the new units and that these variations could be related to the difference in design. In the new stroke unit, the patients spent more time alone in their rooms, were less active, and had fewer interactions compared with the patients in the old unit. One explanation could be the transformation from mainly multibed rooms to single rooms (Anåker et al., 2017). Nevertheless, we need a deeper understanding of how the physical environment affects patients and the quality of care at stroke units (Campbell, Roland, & Buetow, 2000). A well-designed physical environment can be defined as an environment that can contribute to social, psychological, spiritual, physical, and behavioral care (Jonas & Chez, 2004). However, the physical environment’s design and its impact on health and care are rarely the focus of the studies conducted at stroke units.
In summary, a well-designed, stimulating, and attractive healthcare environment is a key factor in patient care. Observations of patients’ activities and interactions during stroke care are important; however, such studies do not reveal how patients experience an environment and what meaning they give to that environment. How patients experience the physical environment in stroke units in general, and stroke units with single-room designs in particular, remains unknown. The aim of this study was to explore patients’ experiences of the physical environment at a newly built stroke unit, and the knowledge generated by this investigation can inform the design of new stroke units.

In summary, a well-designed, stimulating, and attractive healthcare environment is a key factor in patient care.