SCO-spondin-derived peptide NX210 rescues neurons from cerebral ischemia/reperfusion injury through modulating the Integrin-β1 mediated PI3K/Akt pathway

 So human testing needed. Will never occur since we have NO leadership and NO strategy anywhere in stroke. You, your children and grandchildren are screwed until we get survivors in charge.

SCO-spondin-derived peptide NX210 rescues neurons from cerebral ischemia/reperfusion injury through modulating the Integrin-β1 mediated PI3K/Akt pathway

Author links open overlay panelLiyuYang^acJinZhu^acLiYang^bcYunhaoGan^acDiHu^acJingZhao^bc

YongZhao^ac

https://doi.org/10.1016/j.intimp.2022.109079Get rights and content

Highlights

•

NX210 increased viability and reduced cytotoxicity after OGD/R injury in primary cortical neurons.

•

NX210 reduced the infarct volume and decreased brain edema after MCAO/R injury in rats.

•

NX210 neuroprotective effects were exerted via an integrin-β1 Integrin-β1/PI3K/Akt pathway.

•

NX210 is a potential therapeutic agent against cerebral ischemia/reperfusion injury.

Abstract

Ischemic stroke is a common condition with high morbidity and mortality, causing irreversible neuronal damage and seriously affecting neurological function. There has been no ideal effective treatment so far. The NX210 peptide is derived from the thrombospondin type 1 repeat (TSR) sequence of SCO-spondin, and has been reported to exert various neurogenic properties. This study investigated whether NX210 had therapeutic effects and possible underlying mechanisms against cerebral ischemia/reperfusion (I/R). Therefore, primary embryonic rat cortical neurons and Sprague–Dawley (SD) rats that were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively, were treated with or without NX210. We found that NX210 reduced OGD/R-induced cell viability loss and cytotoxicity. NX210 decreased cerebral infarct volume and brain edema, ameliorated neurological dysfunction, attenuated oxidative stress damage, and diminished neuronal apoptosis in MCAO/R rats. Furthermore, western blot analysis shown that treatment with NX210 up-regulated the expression of Integrin-β1, phosphorylated-PI3K (p-PI3K) and phosphorylated-Akt (p-Akt). The Integrin-β1 specific inhibitor, ATN-161, was used to identify pathways involved. The anti-oxidation activities and anti-apoptosis of NX210 was reversed by treatment with ATN-161. Overall, our results indicated that NX210 prevents oxidative stress and neuronal apoptosis in cerebral I/R via upregulation of the Integrin-β1/PI3K/Akt signaling pathway. These results indicated that NX210 may be a promising therapeutic candidate for ischemic stroke.

Smart daily-used objects for hand rehabilitation after stroke

 With no pictures you can't replicate this at all.

Smart daily-used objects for hand rehabilitation after stroke

Quirien R.M. Hover, Armagan Karahanoglu, Kostas Nizamis, Juliet A.M. Haarman^*

^*Corresponding author for this work

• Human Media Interaction
• Digital Society Institute
• Systems Engineering & Multidisciplinary Design
• TechMed Centre
• Interaction Design

Research output: Contribution to conference › Poster › Academic

• Overview
• Fingerprint
• Activities (1)

Abstract

Objective: 

By designing interactive activities of daily living (ADL)-based smart objects for home hand rehabilitation for people with stroke, our objective is to provide a better understanding of how daily activities and objects can facilitate rehabilitation. This way we can bypass the need for intrinsic motivation and offer functional hand exercises at home, that are seamlessly integrated into ADL.

Design: 

We applied a pilot study following a research-through-design approach combined with a user-centred design to evaluate a handle used as add on to cooking utensils.

Setting: 

We applied this research within a focus group setting within a rehabilitation centre.

Participants:  

Two adult people with stroke (male, aged over 40) participated. They both had a mildly impaired hand function due to stroke.

Interventions:  

 

Not applicable.(What?)

Main Outcome Measures: 

 

Both participants interacted with the prototype handle and experienced via a “wizard of Oz” approach some of the future features of the prototype. Additionally, they were asked to evaluate the usability of the idea of using daily objects as means for rehabilitation at home and expressed their opinion about the future features of such devices.

Results: 

Both participants recognised the value of daily objects for home stroke hand rehabilitation. They mentioned that they would prefer objects that promote bi-manual activities (or a multitude of activities via a modular design) and the importance of monitoring their progress and even adding elements of competition between participants.

Conclusions: 

 

This pilot test showed that our idea for seamless home rehabilitation with the use of smart daily objects is promising. In this work, we will present the results of the follow-up studies that we carried out with more people with stroke, after implementing the suggestions of the participants.

Key Words: Stroke, hand, home rehabilitation, smart objects, activities of daily living

Original language	English
Publication status	Published - 26 Jul 2022
Event	Rehab Week 2022 - Rotterdam Ahoy, Rotterdam, Netherlands Duration: 25 Jul 2022 → 29 Jul 2022 https://www.rehabweek.org/

Conference

Conference	Rehab Week 2022
Country/Territory	Netherlands
City	Rotterdam
Period	25/07/22 → 29/07/22
Internet address	https://www.rehabweek.org/

Effects of Edaravone on Muscle Atrophy and Locomotor Function in Patients with Ischemic Stroke (a Randomized Controlled Pilot Study)

You'll have to ask your doctor why the hell edaravone is approved in Japan since 2001 but not the US.

Has your stroke hospital done anything with edaravone in the last decade?

 

• edaravone (12 posts to November 2011)

Effects of Edaravone on Muscle Atrophy and Locomotor Function in Patients with Ischemic Stroke (a Randomized Controlled Pilot Study)

Background and Objective: Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase.

Methods: This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30mg twice daily for 3 days (short-term group) or 10–14 days (long-term group).

The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke.

Results: Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups.

However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6 – 5.9% and 1.5 – 6.0% vs 8.3 – 5.2% and 5.7 – 6.4%; p< 0.01 and p < 0.05) 3 months after stroke onset. Additionally, the maximum walking speed over a distance of 10m was significantly greater in the long-term group (98 – 67 vs 54 – 55 cm/sec; p < 0.05).

Conclusion: Edaravone treatment for up to 14 days suppresses the progression of disuse muscle atrophy and improves leg locomotor function to a greater extent than shorter-term treatment in acute stroke patients. This suggests that the management of stroke may be improved with long-term edaravone therapy by providing myoprotective effects that ameliorate functional outcome in the chronic phase.

Robot-assisted upper limb training combined with Botulinum toxin injection in the treatment of upper limb spasticity: a randomised single-blinded controlled trial

 Does your doctor have enough functioning brain cells to apply this for stroke patients?

Robot-assisted upper limb training combined with Botulinum toxin injection in the treatment of upper limb spasticity: a randomised single-blinded controlled trial

Marialuisa Gandolfi^1*, Nicola Valè¹, Eleonora Kirilova Dimitrova¹, Stefano Mazzoleni², Elena Battini², Maria Donata Benedetti¹, Alberto Gajofatto¹, Francesco Ferraro³, Matteo Castelli⁴, Maruo Camin⁴, Mirko Filippetti¹, Carola De Paoli¹, Elena Chemello¹, Alessandro Picelli^1,5, Jessica Corradi¹, Andreas Waldner⁶, Leopold Saltuari^7,8 and Nicola Smania^1,5

• ¹Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
• ²The BioRobotics Institute, Scuola Superiore Sant' Anna, Polo Sant' Anna Valdera, Pontedera, Italy
• ³Section of Neuromotor Rehabilitation, Department of Neuroscience, ASST Carlo Poma, Mantova, Italy
• ⁴Centro di riabilitazione Franca Martini—ATSM ONLUS, Trento, Italy
• ⁵UOC Neurorehabilitation, AOUI Verona, Verona, Italy
• ⁶Department of Neurological Rehabilitation, Private Hospital Villa Melitta, Bolzano, Italy
• ⁷Research Department for Neurorehabilitation South Tyrol, Bolzano, Italy
• ⁸Department of Neurology, Hochzirl Hospital, Zirl, Austria

Background : Integration of robotics and upper limb rehabilitation in people with multiple sclerosis (PwMS) has rarely been investigated.

Objective: To compare the effects of robot-assisted hand training against non-robotic hand training on upper limb activity in PwMS. To compare the training effects on hand dexterity, muscle activity, and upper limb dysfunction as measured with the International Classification of Functioning.

Methods: This single-blind, randomized, controlled trial involved 44 PwMS (Expanded Disability Status Scale:1.5–8) and hand dexterity deficits. The experimental group (n = 23) received robot-assisted hand training; the control group (n = 21) received non-robotic hand training. Training protocols lasted for 5 weeks (50 min/session, 2 sessions/week). Before (T0), after (T1), and at 1 month follow-up (T2), a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Action Research Arm Test. Secondary outcomes: Nine Holes Peg Test; Fugl-Meyer Assessment Scale–upper extremity section; Motricity Index; Motor Activity Log; Multiple Sclerosis (MS) Quality of Life−54; Life Habits assessment—general short form and surface electromyography.

Results: There were no significant between-group differences in primary and secondary outcomes. Electromyography showed relevant changes providing evidence increased activity in the extensor carpi at T1 and T2.

Conclusion: The training effects on upper limb activity and function were comparable between the two groups. However, robot-assisted training demonstrated remarkable effects on upper limb use and muscle activity. https://clinicaltrials.gov NCT03561155.

Action observation for arm rehabilitation after stroke

 Even with limited help stroke survivors would gladly do the work. NOW WHERE ARE THE VIDEOS WE CAN WATCH?

Action observation for arm rehabilitation after stroke

uthors: 

Borges LRDM, Fernandes ABGS, Oliveira dos Passos J, Rego IAnanda Oliveira, Campos TF

Primary Review Group: 

Stroke Group

See the full Review on

the Cochrane Library

►

Review question
We sought to compare the effects of action observation on arm and hand function after stroke with an alternative intervention or no intervention. In addition, we observed the effects of this therapy on upper extremity performance, everyday activities, quality of life, and activation of brain areas.

Background
Individuals who survive a stroke often have difficulty moving their arms, which can lead to problems with everyday activities and reduced participation in daily situations. Action observation is a physical rehabilitation approach proposed for arm rehabilitation, in which the person with stroke observes a healthy individual performing a task, either on video or in person, followed or not by execution of the same task. This safe technique can be performed without expensive and complicated equipment and requires minimal therapist supervision. Trials show that action observation activates brain areas similar to those activated when performing the same action, and may favor movement recovery after stroke.

Trial characteristics
We identified 16 trials involving 574 individuals after stroke. Most used video sequences and action observation followed by some form of motor practice, using a range of activities, with task complexity increased over the course of training or when it was easy for the participant to carry out. The evidence is current to May 2021.

Key results
Trials tested whether the use of action observation compared with an alternative intervention or no intervention resulted in participants' improved ability to use their arms and hands, and found that action observation might have a small effect on arm function (11 trials) and a large effect on hand function (five trials). There is no evidence of benefit or detriment from this therapy on everyday activities and quality of life of stroke patients. It was not possible to evaluate the results of upper extremity performance and activation of brain areas.

Certainty of the evidence
The certainty of the evidence was low for arm function and hand function, and very low for everyday activities and quality of life.(But better than the nothing we are getting today) Participants could engage in this therapy safely, since adverse events were not significant in scale or magnitude. The certainty of the evidence for each outcome was limited due to the small number of study participants, low study quality, and poor reporting of study details.

Authors' conclusions: 

The effects of AO are small for arm function compared to any control group; for hand function the effects are large, but not clinically significant. For both, the certainty of evidence is low. There is no evidence of benefit or detriment from AO on ADL and quality of life of people with stroke; however, the certainty of evidence is very low. As such, our confidence in the effect estimate is limited because it will likely change with future research.

An Unexplored Role for MMP-7 (Matrix Metalloproteinase-7) in Promoting Gut Permeability After Ischemic Stroke

 WHOM is going to do the followup research? WHOM is the stroke leader ensuring this gets done?

An Unexplored Role for MMP-7 (Matrix Metalloproteinase-7) in Promoting Gut Permeability After Ischemic Stroke

Jonathan Larochelle

,

Changjun Yang

,

Lei Liu

and

Eduardo Candelario-Jalil

Originally published29 Jul 2022https://doi.org/10.1161/STROKEAHA.122.040144Stroke. 2022;0:10.1161/STROKEAHA.122.040144

Abstract

Poststroke infections are common complications of stroke and are highly associated with poor outcomes for patients. Stroke induces profound immunodepression coupled with alterations to autonomic signaling, which together render the body more susceptible to infection from without (nosocomial/community-acquired infection) and from within (commensal bacterial infection). Critical to the hypothesis of commensal infection is the phenomenon of poststroke gut permeability and gut dysbiosis. Few studies have provided adequate explanations for the mechanisms underlying the molecular alterations that produce a more permeable gut and perturbed gut microbiota after stroke. A dysregulation in the production of matrix MMP-7 (metalloproteinase-7) may play a critical role in the progression of gut permeability after stroke. By cleaving junctional and extracellular matrix proteins, MMP-7 is capable of compromising gut barrier integrity. Because of MMP-7’s unique abundance in the small intestine and its capacity to be induced in states of bacterial invasion and inflammation, along with its unique degradative capability, MMP-7 may be crucially important to the progression of gut permeability after ischemic stroke.

 

 

 

 

 

 

 

 

 

 

Footnotes

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

For Sources of Funding and Disclosures, see page XXX.

Correspondence to: Eduardo Candelario-Jalil, PhD, Department of Neuroscience, University of Florida, McKnight Brain Institute, 1149 SW Newell Dr, Gainesville, FL 32610. Email ecandelario@ufl.edu

At least 150 minutes of weekly physical activity cuts risk for death

 

Your doctor is responsible for getting you recovered enough to do this amount of exercise.

At least 150 minutes of weekly physical activity cuts risk for death

Healthy adults who reported long-term, guideline-recommended moderate or vigorous physical activity were less likely to die of any cause during decades of follow-up compared with those reporting no exercise, data show.

The 2018 Physical Activity Guidelines for Americans recommend a minimum of 150 to 300 minutes per week of moderate physical activity, 75 to 150 minutes per week of vigorous physical activity or an equivalent combination of both. However, it remains unclear whether higher levels of long-term levels of moderate or vigorous physical activity are, independently and jointly, associated with lower mortality, researchers wrote in Circulation.

Source: Adobe Stock

“The potential impact of physical activity on health is great, yet it remains unclear whether engaging in high levels of prolonged, vigorous or moderate intensity physical activity above the recommended levels provides any additional benefits or harmful effects on cardiovascular health,” Dong Hoon Lee, ScD, MS, a research associate in the department of nutrition at the Harvard T.H. Chan School of Public Health, said in a press release. “Our study leveraged repeated measures of self-reported physical activity over decades to examine the association between long-term physical activity during middle and late adulthood and mortality.”

Lee and colleagues analyzed data from 116,221 adults from the Nurses’ Health Study and the Health Professionals Follow-up Study, in which researchers assessed self-reported leisure-time physical activity via questionnaires, repeated up to 15 times during follow-up. The mean age of participants during follow-up was 66 years; mean BMI was 26 kg/m² and most participants were white. Participants were free of chronic diseases at baseline. Researchers estimated HRs for the association between long-term leisure-time physical activity intensity and all-cause and cause-specific mortality.

During 30 years of follow-up, 47,596 participants died.

Compared with participants who reported no vigorous physical activity, those who met long-term leisure-time vigorous physical activity guidelines of 79 to 149 minutes per week were 19% less likely to die of any cause (HR = 0.81; 95% CI, 0.76-0.87), 31% less likely to die of CVD (HR = 0.69; 95% CI, 0.6-0.78) and 15% less likely to die of non-CVD causes (HR = 0.85; 95% CI, 0.79-0.92), according to the researchers.

Similarly, compared with participants who reported no long-term leisure-time moderate physical activity, those who met guidelines of 150 to 299 minutes per week were at 19% to 25% lower risk for all-cause, CV and non-CVD mortality.

Compared with participants who did meet long-term leisure-time physical activity guidelines, those who reported two to four times above the recommended minimum of long-term leisure-time vigorous physical activity, defined as 150 to 299 minutes per week, or moderate physical activity, defined as 300 to 599 minutes per week, had 2% to 4% and 3% to 13% lower mortality, respectively.

The researchers noted that the findings support current physical activity guidelines.

“Our study provides evidence to guide individuals to choose the right amount and intensity of physical activity over their lifetime to maintain their overall health,” Lee said in the release. “Our findings support the current national physical activity guidelines and further suggest that the maximum benefits may be achieved by performing medium to high levels of either moderate or vigorous activity or a combination.”

Biomarkers Show Who Faces Near-Term Cognitive Decline

 What worthless crapola!  Instead your mentors and senior researchers should have asked for creation of protocols that prevent cognitive decline.

Biomarkers Show Who Faces Near-Term Cognitive Decline

Consistent findings emerge in four groups of cognitively normal adults

by Judy George, Deputy Managing Editor, MedPage Today August 1, 2022

Many cognitively normal people with positive amyloid and tau PET biomarkers appeared to be at imminent risk of cognitive decline, longitudinal data showed.

Across four independent cohorts, 33% to 83% of cognitively normal people positive for both amyloid and tau progressed to mild cognitive impairment within a mean of 2.00 to 2.72 years, compared with less than 20% in other groups (all P≤0.004), reported Cherie Strikwerda-Brown, PhD, of Douglas Mental Health University Institute in Montreal, at the 2022 Alzheimer's Association International Conference.

These numbers increased across all four cohorts for cognitively unimpaired people who were positive for amyloid, tau, and neurodegeneration, reaching a progression rate of 43% to 100%.

"Our findings have potential implications for clinical trials," Strikwerda-Brown told MedPage Today. "These biomarkers may be used to select individuals who are highly likely to develop symptomatic Alzheimer's disease to target preventive interventions."

The findings, published simultaneously in JAMA Neurology, supported the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework for Alzheimer's disease, which is based on biomarkers of amyloid, tau, and neurodegeneration.

This scheme is intended to differentiate Alzheimer's from other dementias. It classifies amyloid (A), tau (T), and neurodegeneration (N) measures as abnormal (+) or normal (−), resulting in eight possible clinical profiles.

"It's currently unclear whether A+T+ cognitively unimpaired individuals are destined to show clinical progression or can preserve their cognitive abilities over time," noted Rik Ossenkoppele, PhD, of Amsterdam University Medical Center in the Netherlands, who recently led another study about cognitively unimpaired people with Alzheimer's pathology.

"This study and our preprint show that the risk of progression to a symptomatic stage of Alzheimer's disease is substantially increased and nearly all A+T+ individuals show decline on cognitive tests assessing memory function and global cognition," Ossenkoppele told MedPage Today.

"Together, these studies support the NIA-AA viewpoint that Alzheimer's disease can be biologically defined and that considering A+T+ status just as a risk factor may be underestimating its malignancy," he added.

Strikwerda-Brown and colleagues looked at four population-based cohorts of older adults without cognitive impairment who had data collected from 2003 to 2021. The researchers included 128 individuals from the Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) cohort; 153 from the Harvard Aging Brain Study (HABS); 48 from the Australian Imaging, Biomarkers & Lifestyle (AIBL) study; and 251 from the Knight Alzheimer Disease Research Center (ADRC) cohort.

Mean ages ranged from 67 to 76 across the cohorts, and 55% to 74% of participants were women. Neurodegeneration was assessed by cortical thickness. The primary outcome was clinical progression to mild cognitive impairment after amyloid and tau PET. Median clinical follow-up after PET ranged from 1.94 to 3.66 years.

Many A+T+ participants who didn't progress to mild cognitive impairment showed longitudinal cognitive decline. Abnormalities in both amyloid and tau PET were associated with greater risk of near-term clinical progression than abnormal amyloid alone.

Study limitations included modest sample sizes in some biomarker groups. In addition, most participants were white; whether the findings apply to other populations is unknown.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

Strikwerda-Brown received grants from the Canadian Institutes of Health Research, Fonds de Recherche du Québec–Santé, and the Alzheimer's Society of Canada during the conduct of the study.

Ossenkoppele declared no competing interests.

Primary Source

Alzheimer's Association International Conference

Source Reference: Strikwerda-Brown C "Elevated tau-PET signal predicts near-term conversion to mild cognitive impairment in cognitively unimpaired older adults" AAIC 2022.

Secondary Source

JAMA Neurology

Source Reference: Strikwerda-Brown C, et al "Association of elevated amyloid and tau positron emission tomography signal with near-term development of Alzheimer disease symptoms in older adults without cognitive impairment" JAMA Neurol 2022; DOI: 10.1001/jamaneurol.2022.2379.

Recovery after stroke: the severely impaired are a distinct group

So what? The goal is still 100% recovery.

Recovery after stroke: the severely impaired are a distinct group

1. http://orcid.org/0000-0002-5927-1089Anna K Bonkhoff1,
2. http://orcid.org/0000-0003-0714-8545Tom Hope2,
3. Danilo Bzdok3,4,5,
4. Adrian G Guggisberg6,
5. Rachel L Hawe7,8,
6. Sean P Dukelow8,
7. François Chollet9,
8. David J Lin10,
9. Christian Grefkes11,12,
10. Howard Bowman13,14

1. Correspondence to Dr Anna K Bonkhoff, J. Philip Kistler Stroke Research Center, Boston, MA 02114, USA; abonkhoff@mgh.harvard.edu

Abstract

Introduction Stroke causes different levels of impairment and the degree of recovery varies greatly between patients. The majority of recovery studies are biased towards patients with mild-to-moderate impairments, challenging a unified recovery process framework. Our aim was to develop a statistical framework to analyse recovery patterns in patients with severe and non-severe initial impairment and concurrently investigate whether they recovered differently.

Methods We designed a Bayesian hierarchical model to estimate 3–6 months upper limb Fugl-Meyer (FM) scores after stroke. When focusing on the explanation of recovery patterns, we addressed confounds affecting previous recovery studies and considered patients with FM-initial scores <45 only. We systematically explored different FM-breakpoints between severe/non-severe patients (FM-initial=5–30). In model comparisons, we evaluated whether impairment-level-specific recovery patterns indeed existed. Finally, we estimated the out-of-sample prediction performance for patients across the entire initial impairment range.

Results Recovery data was assembled from eight patient cohorts (n=489). Data were best modelled by incorporating two subgroups (breakpoint: FM-initial=10). Both subgroups recovered a comparable constant amount, but with different proportional components: severely affected patients recovered more the smaller their impairment, while non-severely affected patients recovered more the larger their initial impairment. Prediction of 3–6 months outcomes could be done with an R²=63.5% (95% CI=51.4% to 75.5%).

Conclusions Our work highlights the benefit of simultaneously modelling recovery of severely-to-non-severely impaired patients and demonstrates both shared and distinct recovery patterns. Our findings provide evidence that the severe/non-severe subdivision in recovery modelling is not an artefact of previous confounds. The presented out-of-sample prediction performance may serve as benchmark to evaluate promising biomarkers of stroke recovery.(You blithering idiots need to solve stroke to 100% recovery, not just use biomarkers to predict failure to recover! I'd fire the lot of you!)

FDA places hold on phase 2/3 clinical trial of stroke therapy

What is your doctor's competence level on knowing about this research? NONE?

FDA places hold on phase 2/3 clinical trial of stroke therapy

Biopharmaceutical company DiaMedica Therapeutics Inc. announced that the FDA placed a clinical hold on its phase 2/3 ReMEDy2 trial of a synthetic protein therapy for treatment of acute ischemic stroke.

According to a press release, the hold was initiated following DiaMedica’s pausing of patient enrollment and submission of three serious adverse event reports to the FDA related to clinically significant, transient hypotension that occurred shortly after initiation of an IV dose of the therapeutic DM199. Blood pressure levels of the three patients recovered back to their baseline blood pressure within minutes after IV infusion was stopped, per the release.

Source: Adobe Stock.

“Patient safety is very important as we plan and conduct our clinical studies,” Kirsten Gruis, MD, chief medical officer of DiaMedica, stated in the release. “Patient blood pressure is easily and routinely monitored in stroke patients, which is why our study sites were able to quickly identify the issue and immediately stop the dosing of DM199, after which the patients then recovered within minutes and suffered no injuries.”

DiaMedica stated it believes the adverse events resulted from switching to an IV bag formulated from different materials in the ReMEDy2 trial compared with the IV bag used in the prior phase 2 ReMEDy1 trial.

As a result of the hold, DiaMedica may not enroll any additional patients in the ReMEDy2 trial until it provides the FDA with analysis of the events leading to or causing the hypotension, provides suggested protocol modifications to address the mitigation of these events, supplies a rationale and supporting data for the protocol modifications, and the FDA notifies DiaMedica that it may resume enrollment.

“While having to pause enrollment in the ReMEDy2 trial was not desirable, we remain confident about the future potential of DM199 and are committed to refining the dosing procedures and methods that will further enhance patient safety,” DiaMedica President and CEO Rick Pauls said in the release.

Non-invasive brain stimulation for improving gait, balance, and lower limbs motor function in stroke

I see nothing here that suggests they are solving the spasticity problem in walking.

Since 30% of survivors that have spasticity, they are screwed in walking recovery.

Non-invasive brain stimulation for improving gait, balance, and lower limbs motor function in stroke

• Jitka Veldema &
• Alireza Gharabaghi 

Journal of NeuroEngineering and Rehabilitation volume 19, Article number: 84 (2022) Cite this article

• 64 Accesses

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Abstract

Objectives

This systematic review and meta-analysis aim to summarize and analyze the available evidence of non-invasive brain stimulation/spinal cord stimulation on gait, balance and/or lower limb motor recovery in stroke patients.

Methods

The PubMed database was searched from its inception through to 31/03/2021 for randomized controlled trials investigating repetitive transcranial magnetic stimulation or transcranial/trans-spinal direct current/alternating current stimulation for improving gait, balance and/or lower limb motor function in stroke patients.

Results

Overall, 25 appropriate studies (including 657 stroke subjects) were found. The data indicates that non-invasive brain stimulation/spinal cord stimulation is effective in supporting recovery. However, the effects are inhomogeneous across studies: (1) transcranial/trans-spinal direct current/alternating current stimulation induce greater effects than repetitive transcranial magnetic stimulation, and (2) bilateral application of non-invasive brain stimulation is superior to unilateral stimulation.

Conclusions

The current evidence encourages further research and suggests that more individualized approaches are necessary for increasing effect sizes in stroke patients.

Introduction

Each year, approximately 795,000 people experience a new or recurrent stroke [1]. Walking and balance disturbances are common post-stroke complications, affecting about two-thirds of stroke survivors [2]. These deficits are associated with worsened quality of life, impeded community reintegration [3], and an increased risk of falling [4]. The ability to walk independently is the most common rehabilitation goal after stroke [5]. However, about 50% of stroke survivors suffer from an impaired walking ability 6 months after current standard of care [2]. Other interventions are therefore needed to improve recovery. Thus, the development of innovative therapeutical strategies for improving balance and walking ability is one of the top research priorities in stroke rehabilitation [6]. Non-invasive neuromodulation methods such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct/alternating current stimulation (tDCS/tACS) and trans-spinal direct current stimulation (tsDCS) can modulate neural processing and have thus the potential to counteract maladaptive neural plasticity after stroke and contribute to a better recovery [7, 8].

Neural background of walking and balance

Neuroimaging studies have shown that walking and balance are complex sensorimotor functions controlled by integrated cortical, subcortical, and spinal networks [9,10,11]. A single photon emission computed tomography study demonstrates bilateral activation within the primary sensorimotor area, supplementary motor area, basal ganglia as well as within the visual cortex, cerebellar vermis, and part of the left lower temporal lobe during walking [12]. Similarly, a positron emission tomography study shows a bilateral increase of cerebral blood flow within the primary sensory cortex, primary motor cortex and supplementary motor cortex as well as within the anterior part of the cerebellum during active and passive bipedal movement [13]. A recent meta-analysis indicates a key role of the brainstem, cerebellum, basal ganglia, thalamus, and several cortical regions during postural control [9]. Accordingly, another meta-analysis shows that the cerebellum, basal ganglia, thalamus, hippocampus, inferior parietal cortex, and frontal lobe regions are involved during balance tasks [14]. Importantly, the available data indicates that also a spinal network may be involved in postural balance and gait control [15]. E.g., multiple studies demonstrate that balance training induces suppression of H-reflexes [16]. Thus, it is conceivable that the application of non-invasive brain stimulation over several cortical regions as well as over the cerebellum, the brainstem and the spinal cord may be effective in the modulation of walking, balance and/or lower limbs motor function.

Stroke-induced changes of neural control during walking

Up to now, different neuroimaging techniques have been used to investigate the neural mechanism of walking disability and walking recovery in stroke patients. A large part of the available data demonstrates a stroke-induced disinhibition of the contralesional hemisphere with a shift of the between-hemispheric balance to the detriment of the affected hemisphere, as well as a correlation between normalization of neural processing and favorable motor recovery [17,18,19,20,21]. A diffusion tensor MRI demonstrates a between-hemispheric asymmetry in fractional anisotropy of the posterior limb of the internal capsule [18]. The shift of balance towards the non-lesioned hemisphere correlates with the amount of walking disability [18]. An optical imaging study shows a between-hemispheric imbalance of oxygenated hemoglobin level in the medial primary sensorimotor cortex that is greater in the unaffected hemisphere than in the affected hemisphere. A reduction of this asymmetry is associated with a favorable gait recovery [19]. A TMS study shows an interhemispheric asymmetry of corticomotor excitability of the legs to the detriment of the affected hemisphere, as well as a correlation between the reduction of this asymmetry and a favorable motor outcome [20]. Another TMS trial reveals increased connectivity between the contralesional hemisphere and the affected lower limb, which correlated with the amount of walking disability [18]. A diffusion-weighted MRI shows that the higher the anatomical connectivity between the ipsilesional M1 and the (a) cerebral peduncle, (b) thalamus, and (c) red nucleus, the better is the lower limb motor performance [21]. Furthermore, stroke-related disturbances of the spinal system were detected, as well as its relationship to gait disability. In fact, stroke patients show an increase of the H-reflex, in comparison to healthy subjects [22], and its normalization to be associated with a successful motor recovery of the walking ability [23].

More at link.

Cognitive reserve protects executive function in older adults

 

Since you probably used up all your cognitive reserve just surviving your stroke, Ask your doctor for EXACT SPECIFICS ON THE EXERCISES TO DO. AND HOW TO MEASURE YOUR COGNITIVE RESERVE TO MAKE SURE YOU HAVE ENOUGH TO PRESERVE EXECUTIVE FUNCTION.

I couldn't find a free version of Wide Range Achievement Test so ask your doctor for the test.

Cognitive reserve protects executive function in older adults

SAN DIEGO — Cognitive reserve acted as a protective factor that preserved executive function in older adults with benefits mitigated by depression level, according to a presentation at the Alzheimer’s Association International Conference.

“Cognitive reserve operates as a protective mechanism on cognitive performance,” Loredana Frau, of the school of psychology at Liverpool John Moores University in the U.K., said during her presentation.

Source: Adobe Stock.

Frau and colleagues sought to examine the relationship between cognitive reserve, depression and executive function in older adults over a 10-year period.

Their longitudinal study involved 416 individuals (290 cognitively stable [CUS], 97 cognitively unimpaired declining [CUD] and 29 with mild cognitive impairment [MCI]) from the Wisconsin Registry for Alzheimer’s Prevention dataset. Participants were screened for cognitive reserve via the Wide Range Achievement Test (WRAT-4), for depression by the Center for Epidemiologic Studies Depression Scale (CES-D), for executive functions by CFL, Digit Span and number sequencing tests. Screening for the APOE e4 gene was done through blood analysis. Hierarchical linear regression, controlling for age, gender, APOE and diagnosis (CUS, CUD, MCI) in model 1, cognitive reserve and depression in model 2 and CR-depression interaction in model 3 were performed. Multinomial logistic regression was utilized to predict conversion to CUD and MCI from a healthy baseline (CUS).

Results showed that, over the 10-year follow-up interval, cognitive reserve acted as a protective factor that preserved executive function; however, the beneficial effect of cognitive reserve on executive function was linked to mitigation of increasing symptoms of depression. In addition, data revealed that level of depression predicted a changeover from CUS to CUD, but depression and APOE e4 best predicted a conversion from CUS to MCI.

“These studies can be very important to analyze different proxies of cognitive reserve or motor disorders,” Frau stated in the presentation.

Social isolation, loneliness may drive risk for fatal or nonfatal MI, stroke

Your doctor needs to get you 100% recovered immediately before you lose the first two groups of friends that Aristotle describes.  DEMAND results or your doctor will use the craptastic saying; 'All strokes are different, all stroke recoveries are different'. You can't allow your doctor to hide and cower behind that useless saying.

Aristotle believes that there are three different kinds of friendship; that of utility, friendship of pleasure, and virtuous friendship. 

and that you will likely lose all of the first two post stroke?

Social isolation, loneliness may drive risk for fatal or nonfatal MI, stroke

Social isolation and loneliness are common and underrecognized determinants of CV and brain health, and more research is needed to understand causal pathways and interventions, according to a new scientific statement.

“Over 4 decades of research has clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” Crystal W. Cene, MD, MPH, FAHA, professor of clinical medicine and chief administrative officer for health equity, diversity and inclusion at the University of California San Diego Health and chair of the writing group for the American Heart Association scientific statement, said in a press release. “Given the prevalence of social disconnectedness across the U.S., the public health impact is quite significant.”

Data were derived from Cené CW, et al. J Am Heart Assoc. 2022;doi:10.1161/JAHA.122.026493.

Social isolation is defined as the objective state of having few or infrequent social contacts, whereas loneliness is perceived isolation that is distressing for the individual, the statement notes. The two terms, while related, are distinct, have different pathways and unique downstream effects on health.

Crystal W. Cene

“Individuals can lead a relatively isolated life and not feel lonely; conversely, individuals with many social contacts may still experience loneliness,” the researchers wrote. “Both social isolation and loneliness denote some degree of social disconnection.”

Data on some outcomes ‘less robust’

In a systematic scoping review, Cene and colleagues reviewed observational and intervention research examining the impact of social isolation and loneliness on CV and brain health, discussing proposed mechanisms for observed associations.

The researchers found that evidence is most consistent for a direct association between social isolation, loneliness, and CHD and stroke mortality. However, data on the association between social isolation and loneliness with HF, dementia and cognitive impairment are sparse and less robust.

“Even where associations were found, after adjusting for factors that are presumed to be on the causal pathway, the effect sizes are on the order of 1 to 1.5, which is comparable to recognized psychosocial factors, including depression and anxiety,” the researchers wrote.

The evidence is most consistent for an association among social isolation, loneliness and death from heart disease and stroke, with a 29% increase in risk for MI and/or CV death and a 32% increased risk for stroke and stroke death, according to the researchers.

“Social isolation and loneliness are also associated with worse prognosis in individuals who already have coronary heart disease or stroke,” Cené said in the release.

The researchers found that socially isolated adults with three or fewer social contacts per month may have a 40% increased risk for recurrent stroke or MI, as well as lower 5-year HF survival rate compared with those who have more social contacts.

More data needed on diverse groups

The statement also notes that the effects may be underestimated because of underrepresentation or loss to follow-up in longitudinal studies of individuals and groups who may be at higher risk for both social isolation and CVD, such as people from underrepresented racial and ethnic groups; those with multiple chronic conditions and those with lower levels of education, income, wealth or social status, such as immigrants or incarcerated people.

The researchers also noted that it is unclear whether social isolation or loneliness matters most for CV and brain health, as few studies examined both in the same sample.

“More research is needed to examine the associations among social isolation, loneliness, coronary heart disease, stroke, dementia and cognitive impairment, and to better understand the mechanisms by which social isolation and loneliness influence cardiovascular and brain health outcomes,” Cene said in the release.

Researchers also did not find any intervention studies that sought to reduce the adverse impact of social isolation or loneliness on CV or brain health outcomes.

“Overall, findings suggest an increased risk of worse outcomes among individuals with prevalent CHD and stroke in those who are also socially isolated or lonely; however, these studies do not suggest causality, and associations may be mediated by other factors that need to be further tested in intervention trials,” the researchers wrote.

The statement follows recent research suggesting that social isolation and loneliness increases CV risk. As Healio previously reported, social isolation and loneliness are independently associated with an 11% to 16% higher risk for CVD among older women, with overall CVD risk was highest for women who had high social isolation and high loneliness.