Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 493 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:

Tuesday, October 2, 2018

One-Quarter of People Leave Inpatient Stroke Rehabilitation with Physical Capacity for Community Ambulation

That is an appalling statistic. And you're paid for that 75% failure rate?

One-Quarter of People Leave Inpatient Stroke Rehabilitation with Physical Capacity for Community Ambulation


Background and Purpose

Ability to walk in the community is important for independence and participation in life roles, but is difficult for many people following stroke. The purpose of this study was to determine the proportion of people with stroke with the physical capacity to be independent community ambulators at discharge from a publicly funded inpatient rehabilitation setting.


Consecutive medical records were audited to collate walking outcome at discharge, and to clarify if people with stroke had potential to walk independently in the community as defined by 4 criteria: independence with stairs; ability to traverse slopes and inclines; walking speed of .8m/s or more; and walking distance 367 m or higher on 6-Minute Walk Test.


While 80% of the 124 persons with stroke could walk indoors, only 27% could perform 4 essential skills needed to walk independently in the community at discharge from hospital. The proportion that met each criterion was 52% for stairs, 39% for slopes and inclines, 58% for speed, and 40% for distance. For the overall sample, mean (standard deviation) walking speed was .90 (.33) m/s, and distance for 6-Minute Walk Test was 349.6 (146.5) m.

Discussion and Conclusion

A retrospective review found that three quarters of stroke survivors lacked physical capacity for 4 skills required to walk independently in the community at the time of discharge from a public inpatient rehabilitation. Our findings recommend that people with stroke have access to outpatient physical rehabilitation to optimize walking outcome.(What good does that do? There are NO protocols for walking rehab. You are all just 'winging it'. )

Key Words

walking environment
mobility limitation
activities of daily living

Source of Funding: This project was undertaken as a Capstone project at The University of Melbourne. This project was undertaken without funding support.

Presentations of this study: Preliminary data from this study was presented as poster at Austin Health Research week (13-17 October, 2014). Data have only been published in abstract format.

Ethics details: Approved by Human Research Ethics Committee at Austin Health in August 2014 (LNR/14/ Austin/392).

Acupuncture Confirmed To Speed Recovery From Stroke

Really? Impossible to have effects except as a placebo. Energy meridians have never been proven to exist.
No mechanism of action is possible.

Acupuncture Confirmed To Speed Recovery From Stroke

Science has confirmed the efficacy of acupuncture in helping stroke survivors to recover more quickly, with a trial showing improved functions that were disrupted by an acute ischemic stroke.
Millions of stroke survivors do not get treatment quickly enough and experience the full range of negative conditions. Patients who undergo extensive rehabilitation with stroke have a better chance of surviving the stroke, and a likelier to retain independence with better bodily functions. Rehabilitation programs for stroke survivors in China include acupuncture sessions, with electroacupuncture and scalp acupuncture being the two most commonly used methods.
Acupuncture use to treat stroke and associated problems is a divisive topic among experts as some studies indicate it is ineffective and others report it exerted limited positive effects on stroke patients during rehab. Such conflicting reports inspired Zhejiang Chinese Medical University researchers to conduct a high quality clinical study with significant statistical power, seeking to determine if acupuncture could improve neurological problems, motor dysfunctions, swallowing issues, and cognitive impairment caused by acute ischemic stroke.
A large group of hospitalized patients due to acute ischemic stroke and paralysis on one side of the body were recruited to conduct this study. These 250 patients received either standard rehabilitation treatment which involved 2 hour periods of physiotherapy and occupational therapy for 6 days each week for three weeks; or acupuncture treatment sessions for 30 minutes 6 days a weeks along with the conventional treatment.  Assessment of primary and secondary outcomes occurred at the beginning of the trial, first and third weeks of the trial, and again seven weeks after the trial.
Primary outcome was a neurological deficit, secondary outcomes were motor function of upper extremities, swallowing function, and cognitive function. Safety of acupuncture based on adverse reaction experienced by patients was also evaluated.
The group receiving acupuncture treatment were observed to display significantly better neurological functions, improved function of lower extremities, swallowing, and cognitive function, no improvements in upper extremities were noted and when taken into consideration overall motor function score did not show much improvement.
Upper extremities involve fine motor skills which are theorized to require higher level of recovery than that which is provided by acupuncture. Acupuncture is believed to improve stroke related neurological deficit through different aspects as it greatly improved swallowing functions. Adverse reaction did develop in a few cases in response to acupuncture which were mild and posed no danger to the patients which suggests the treatment is safe enough to be routinely used.
Based on their findings the researchers suggest that acupuncture could be considered to be a multi-effect treatment having shown it can assist recovery of different neuroprotective, microcirculatory, and metabolic systems that were affected by the stroke.
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Antioxidant Reduces Risk for 2nd Stroke, Heart Attack

Now YOU just need to find the protocol for this and train your doctor in its use.  Not the other way around. Has your doctor EVER  put ANY clinical research into practice? This is one of the few things I got from the NSA that was worth it.

Antioxidant Reduces Risk for 2nd Stroke, Heart Attack

Posted by Lynn Bronikowski Sep 27 2018
Healthcare professionals have long known that in the months after a heart attack or stroke, patients are more likely to have another attack or stroke.
Now a study published in the Journal of the American College of Cardiology explains what happens inside blood vessels to increase stroke and heart attack risk—and suggests a new way to treat it.
Researchers found that heart attacks in mice caused inflammatory cells and platelets to more easily stick to the inner lining of arteries throughout the body—particularly where there was already plaque, according to the study’s writeup. As a result, these sticky cells and platelets caused plaque to become unstable and contribute to blood clots that led to another stroke or heart attack.
But the study found treating mice that had experienced a stroke or heart attack with the powerful antioxidant apocynin cut plaque buildup in half and lowered inflammation to pre-attack levels.
"Knowing that newer forms of antioxidants such as apocynin can lower the risk of a second heart attack or stroke gives us a new treatment to explore and could one day help reduce heart attacks and strokes," said the study’s author, Jonathan R. Lindner, M.D., a professor of cardiovascular medicine at the OHSU School of Medicine.
Lindner penned the research paper with colleagues from OHSU, Scripps Research Institute and Bloodworks NW.
The researchers discovered the sticky cells and platelets by using unique forms of ultrasound imaging they developed to view molecules on the lining of blood vessels.
This research could help explain why the recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study, also known as the CANTOS clinical trial, found an anti-inflammatory drug already approved to treat juvenile arthritis also reduced the risk of a second heart attack in trial participants by 15 percent.
Lindner and his colleagues are further studying how the relative stickiness of remote arteries affects the risks for additional heart attacks and strokes and are also evaluating new therapies beyond antioxidants.
The study was supported by the National Institutes of Health and the Swiss National Science Foundation.

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Apocynin, a Low Molecular Oral Treatment for Neurodegenerative Disease

This may just become my go to supplement for Parkinsons and dementia prevention along with massive amounts of coffee. What does your doctor say? ANYTHING AT ALL?

Apocynin, a Low Molecular Oral Treatment for Neurodegenerative Disease


Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

1. Introduction

Ageing societies are facing an increasing prevalence of neurodegenerative diseases. Some relatively prevalent examples are Alzheimer's and Parkinson's disease and less prevalent are Huntington's and Lou Gehrig's disease (amyotrophic lateral sclerosis; ALS). All neurodegenerative diseases have in common that no effective treatment exists that can stop the progressive deterioration of neurological functions. Of note, none of the neuroprotective agents that have been tested in the clinic have an efficacy that goes beyond symptoms control.
In recent years the insight has been growing that inflammatory reactions from resident or infiltrated innate immune cells may have a significant impact on the pathogenesis of neurodegenerative disorders [1]. A recognized central player is the microglia, a glial cell that belongs to the myeloid lineage and is often indicated as the macrophage of the CNS. This intriguing new insight may imply that drugs with proven efficacy in the protection of peripheral organs against the cytotoxic function of innate immune cells, such as mononuclear or polymorphonuclear phagocytes (resp., MNCs and PMNs), might also be useful for the treatment of the neuroinflammatory component of neurodegenerative diseases. A major hurdle that drugs need to take is to cross the blood brain barrier and penetrate the CNS parenchyma where the neurodegenerative process takes place. In this review we will discuss preclinical studies highlighting the potential of apocynin, a small phenolic antioxidant, as treatment of neurodegenerative diseases.

2. Apocynin, a Pharmacologically Active Plant Phenol

Apocyin (4′-hydroxy-3′-methoxyacetophenone or acetovanillone) was identified as the biologically active substance in the roots of Picrorhiza kurroa Royle ex Benth, a perennial plant growing in the alpine Himalaya. Extracts from the roots are used in the Ayurvedic medical tradition of India and Sri Lanka for the preparation of ethnic medicines for the treatment of ailments of liver, heart, joints, and lungs. We have prepared a 95% ethanolic root extract under controlled conditions in the laboratory and subjected the preparation to an activity-guided purification using the oxidative burst of human polymorphonuclear/neutrophilic granulocytes (PMN) as an experimental test for acute inflammation [2].
The read-out assay we used was based on the generation of luminol-enhanced chemiluminescence by human PMN stimulated with zymosan opsonized in human serum. The essence of the assay is that the serum-opsonized yeast particles stimulate the PMN via surface-exposed receptors of immunoglobulins or complement factors. The activation signals relayed via these receptors lead to the emptying of cytoplasmic granules (degranulation) and the assembly of the phagocyte NADPH oxidase Nox2. The Nox2 enzyme complex is assembled from membrane-bound (gp91phox, p22phox) and cytoplasmic (p40phox, p47phox, p67phox, and Rac2) subunits [3]. The assembly process involves phosphorylation of subunits by specific kinases and formation of thiol-bridges. The assembled complex takes up electrons from NADPH and transfers these onto free molecular oxygen leading to formation of superoxide anion (O2 ; one electron reduction) and hydrogen peroxide (H2O2; two electron reduction). Both oxidants have cytotoxic activity as could be shown using red blood cells from different species [4]. The oxidative burst of PMN comprises a cascade of strongly reactive oxygen species, collectively indicated as ROS (Figure 1). By reaction of O2 with nitric oxide the strongly cytotoxic peroxynitrite is formed. In the presence of Fe2+ ions H2O2 is converted into highly reactive hydroxyl radicals (OH), which via peroxidation of membrane lipids affect the fluidity of cell membranes. Myeloperoxidase released by degranulation of the PMN catalyzes the reaction of H2O2 with halide molecules (Cl2, Br2, and J2) forming highly toxic hypohalides (OCl, OBr, and OJ). ROS are essential components of the intracellular killing of phagocytosed microbes, but when released into the extracellular milieu they are important mediators of the tissue destructive activity of activated PMNs [5, 6].
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Reactive oxygen species produced in the phagocyte oxidative burst. MPO: myeloperoxidase; NOS: nitric oxide (NO) synthase.
It can be envisaged that components of chemically complex plant extracts can interfere with the read-out assay at multiple levels and may also exert nonspecific effects such as killing of the PMN or scavenging of the oxyradicals. This implies that successful activity-guided purification needs to be well focused and carefully controlled for nonspecific effects to avoid false positive results. Notwithstanding these hurdles, we were able to demonstrate a highly specific activity of apocynin in the assay. Apocynin was found to be metabolically activated in an MPO-catalyzed reaction with H2O2 [7] forming a symmetrical dimer, diapocynin [8] (Figure 2). The observation that the reaction intermediate could be trapped with GSH led us to hypothesize that metabolically activated apocynin might block the formation of thiol bridges between the membrane-bound and cytosolic components that assemble functional Nox2. It was later found, however, that diapocynin directly inhibits Nox2 superoxide production and that this activity is independent of MPO [8]. An important finding with apocynin has been that it inhibits the oxidative burst of PMNs, without impeding the intracellular killing of bacteria. This implies that treatment with apocynin may prevent collateral damage to tissues infiltrated by activated PMN without impeding their bactericidal function.
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Inhibition of microglia Nox2 by metabolically activated apocynin. Receptor-mediated activation of microglia cells induces production of reactive oxygen species and release of myeloperoxidase (MPO). The MPO-catalyzed reaction of apocynin with H2O2 leads to production of a reactive intermediate that stabilizes by binding to free thiol groups, for example, GSH, or by dimerization. Dimeric apocynin (diapocynin) inhibits Nox2 activity.

3. Efficacy of Apocynin in AIMID Animal Models

The initial target disease in which we tested the clinical effect of apocynin was the WAG/Rij (RT-1u) rat model of collagen-induced arthritis (CIA), which is an accepted preclinical model of the autoimmune inflammatory disease (AIMID) rheumatoid arthritis (RA). In this model, PMNs have a clear pathogenic role [9], reflecting the situation in RA patients [6]. In the rat study we chose to administer apocynin at a dose range of 0,3 to 200 μg/mL drinking water, which was provided ad libitum. It was observed that already at the lowest dose of 0,3 μg/mL, corresponding to a daily oral dose of 6 μg, the arthritis was almost completely suppressed [10]. No effect of apocynin on serum levels of anti-collagen autoantibody or of IL-6, an important pathogenic cytokine in CIA and RA, was observed, suggesting high selectivity for the inflammatory component of the disease. Independent from us, Hougee et al. demonstrated in a mouse CIA model that orally administered apocynin restores the blocked production of cartilage proteoglycan in the arthritic joint [11]. An intriguing side effect of the treatment, illustrating the powerful anti-inflammatory effect of apocynin, was the dramatic suppression of the necrotizing skin lesions at the sites where the immunizing antigen/CFA formulation was injected [12].
Since its initial identification as potent anti-inflammatory agent in 1990, apocynin has become an established inhibitor of the oxidative burst in neutrophils as demonstrated in a wide range of in vivo models for immune-mediated inflammatory disorders affecting peripheral and central organs. Of particular importance for this review are the promising clinical effects observed in models of neurodegenerative disease, including ALS, Alzheimer, and Parkinson's disease. In these models the antioxidant activity of apocynin is not targeted to the neutrophil but to the “macrophage of the brain,” that is, microglia.

4. Microglia

The brain contains various cell types with the capacity to exert immune functions including astrocytes, microglia cells, and macrophages located in the meninges and perivascular spaces of brain arteries and capillaries [13]. For their immune tasks these cells are equipped with conserved receptors for pathogen-associated or damage-associated molecular patterns, which relay activation signals to the cells for inducing inflammatory effector mechanisms [14].
Microglia are innate immune cells ubiquitously distributed within the central nervous system where they are engaged in tight interactions with neurons, oligodendrocytes, and astrocytes. However, only microglia release MPO after stimulation, being a requisite for the metabolic activation of apocynin.
Microglia in the healthy CNS have a ramified resting phenotype. Opposite to earlier concepts, microglia in the healthy brain are not resting but are highly dynamic cells that carry out homeostatic surveillance of the extracellular environment by the extension and retraction of their protrusions and phagocytosis of tissue debris, which could otherwise cause inflammation [15]. Activated microglia are found in diseased CNS tissue, such as within demyelinated cortical grey matter lesions in the MS brain, surrounding amyloid plaques in Alzheimer brain and in the degenerating substantia nigra in Parkinson's disease [16, 17]. Although the diverse expression profiles of microglia appear to reflect a broad, continuous spectrum of activation states, two activation states at both ends of the spectrum can be recognized corresponding to the M1 and M2 state designated for macrophages [18]. “Classically activated” M1 microglia, for example, induced by LPS or IFNγ, have proinflammatory functions which are exerted by the secretion of proinflammatory cytokines such as TNF-α, IL-1β, and IL-12 and toxic substances such as reactive oxygen and nitrogen species. “Alternatively activated” M2 microglia, such as induced in a milieu containing high IL-4 or IL-13 levels, have anti-inflammatory and tissue regenerative activities, which are mediated by cytokines such as IL-4, IL-10, or TGF-β and repair factors such as insulin-like growth factor, arginase-1, or chitinase-like-1. Not only the cytokine milieu, but also the redox state of the microenvironment, which is directly related to NADPH oxidase activity, determines the functional differentiation of microglia towards an M1 or M2 phenotype [18].

5. Apocynin as a Potential Treatment of Neurodegenerative Disease

M1 microglia cells are the main resource of Nox2 in the brain. The expression by M1 microglia of activated Nox2 producing ROS is an essential component of microglia-mediated neurotoxicity. The broadly accepted notion that microglia-derived ROS are important mediators of neurodegenerative brain injury raises the question whether the favorable pharmacological profile and low toxicity of apocynin can be used for neuroprotective treatment. Microglia cells not only express Nox2 but also secrete MPO after activation and could thus potentially exert metabolic activation of apocynin. Several authors have reported on the beneficial effect of apocynin on (models of) acute neurological disorders, such as ischemia, intracerebral hemorrhage, and stroke (reviewed in [19]). What are the perspectives for apocynin in chronic neurodegenerative disorders?
In vitro studies using cultured microglia have implicated Nox2-derived ROS in the proliferation and functional polarization of microglia [20, 21]. A crucial finding has been that inhibition of Nox2 promotes alternative and anti-inflammatory microglia activation during neuroinflammation [22]. This implies that suppression of Nox2 with apocynin might restore a healthy balance between a proinflammatory M1 and an anti-inflammatory/proregenerative M2 phenotype of microglia. Others have shown that apocynin lowers the production of IL-1β, TNF-α, and nitric oxide by microglia, thus interrupting a self-perpetuating cycle of detrimental activity. While the exact neurotoxic mechanism of activated microglia in neurodegenerative disease is still uncertain, it is also of considerable interest that the release of the excitotoxin glutamate requires Nox2 activity and that this can be inhibited by apocynin [23]. Taken together, these data suggest a potentially beneficial role of apocynin in neurodegenerative disease. Indeed, promising effects of apocynin have been observed in mouse models of some major neurodegenerative diseases.
Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig Disease). Amyotrophic lateral sclerosis is a common adult-onset neurodegenerative disease affecting motor neurons. The disease leads to rapidly progressing motoric impairment and death usually within 5 years. While in the majority of patients the cause of the disease is unknown, in a subset of cases the disease has a genetic cause, namely, mutations in the superoxide dismutase-1 (SOD1) gene [24, 25]. The mutation enhances oxidative stress by dysregulated production of superoxide anion due to reduced dismutation to H2O2. Mutant SOD1 expressing astrocytes are linked to ALS pathology because of their reduced capacity to absorb glutamate [26] and/or by their release of neurotoxic factors [27]. Selective silencing of mutant SOD1 [28] or replacement of mutant by wild-type microglia [29] in the mutant SOD1 mouse model strongly point to a central pathogenic role of microglia. Harraz et al. have used oral apocynin to control progression of neurodegeneration in a SOD1 mutant mouse model and observed promising effects [30]; it was observed that administration of apocynin in the drinking water significantly prolonged survival and delayed the onset of motoric defects. This study shows that orally administered apocynin can build up a sufficiently high concentration within the CNS parenchyma for mitigating neurotoxic levels of ROS production. However, these promising data could not be reproduced in another study using the same mutant mouse strain [31].
Alzheimer Disease (AD). Alzheimer disease is an ageing-associated progressive neurological disorder leading to irreversible dementia. Neuropathological hallmarks of AD are senile plaques of misfolded and fibrillar amyloid-β aggregates and intraneuronal tangles of tau protein within the cerebral cortex [32]. Activated microglia cells were found clustered around senile plaques producing neurotoxic agents like ROS, NO, and TNF-α. Activation of microglia Nox2 by oligomeric and/or fibrillar amyloid-β [33, 34] and expression of activated Nox2 in Alzheimer brain [35] have been reported.
Lull et al. have tested apocynin at a daily oral dose of 10 mg/kg via the drinking water in a hAPP(751)SL transgenic mouse model of AD [36]. They observed in apocynin-treated mice a significant reduction of plaque size within cortex and hippocampus and a reduction of microglia numbers in the cortex, but not in the hippocampus. However, a behavioral feature of AD observed in this mouse model, that is, performance in the Morris water maze swim test, which tests spatial memory organized in the hippocampus, was not markedly improved by the treatment. The limited clinical effect of apocynin in the model might be due to the absence of clear neuroinflammation, while this is more prominent in AD patients, and because of the fact that plaque formation does not necessarily predict cognitive decline.
Parkinson's Disease (PD). The pathological hallmark of PD is a progressive degeneration of dopamine producing neurons in the substantia nigra (SN), a pigmented structure located in the bottom of the midbrain. Via the release of dopamine, the SN has a central role in the coordination of various neurological functions, including reward, addiction, and movement. The latter function is particularly disturbed in PD. To compensate for dopamine loss, a metabolically stable precursor of dopamine (L-DOPA) is given, which in a substantial number of patients causes typical involuntary movements known as hyperkinetic syndrome. While in the vast majority of (sporadic) PD patients the cause of the disease is not known, in a small fraction a genetic cause has been found, namely, mutations in several genes, including alpha-synuclein, parkin, leucine-rich repeat kinase 2, PTEN-induced putative kinase 1, and ATP13A2 [25]. The observation that users of heroin contaminated with MPTP developed PD symptoms [37] enabled generation of a clinically relevant animal PD model. After conversion of MPTP into MPP+ by monoamine oxidase B in astrocytes, MPP+ is concentrated in dopaminergic cells via uptake through the specific dopamine transporter, where it blocks complex I of the mitochondrial respiratory chain. The ensuing redox stress causes amongst others dysregulation of cellular Ca2+ leading to cell death. Just like in ALS and AD, neurodegeneration in PD is found to be associated with microglia Nox2 activation, which is thought to contribute significantly to the pathogenic process [38].
Using an in vitro system, Gao et al. demonstrated that ROS generated by microglia Nox2 enhances the sensitivity of dopaminergic neurons to MPP+ [39]. A beneficial effect of apocynin on neurotoxic effects mediated by microglia has been shown in a mouse model of PD [40].

6. The Effect of Apocynin in a Nonhuman Primate Parkinson's Disease Model

Repetitive injection of a low dose of MPTP in common marmosets, a small-bodied neotropical primate, elicits a neurological disease that at the level of clinical and neuropathological presentation closely approximates PD [41]. We have used this MPTP model in 5 marmoset twins to test whether oral apocynin is also effective in a higher species [35]. For oral administration, apocynin was dissolved in Arabic gum; one sibling of each twin was given apocynin containing gum and the other was given only the gum. Treatment with apocynin (100 mg/kg, TID) started one week before PD induction with MPTP (1 mg/kg, via subcutaneous injection for 8 days). Apocynin limited the typical body weight loss associated with the parkinsonian syndrome. Also the motor function in the apocynin treated monkeys was improved, indicating an anti-Parkinson efficacy of apocynin. Moreover, the number of surviving dopamine neurons was increased by apocynin, indicating a neuroprotective efficacy. Remarkably, apocynin has a similar molecular structure as homovanillic acid (HVA), a metabolite of dopamine. An explanation of the protective efficacy of apocynin in PD might also be related to the compensation of the reduced level of the natural available o-methoxycatechol HVA.

7. Perspective for Treatment of Human Patients

Apocynin is a potentially attractive oral prodrug because of its low general toxicity and the fact that its specific antioxidant action is elicited after metabolic activation by MPO releasing phagocytic cells. Safety data of apocynin are scarce, but those available show low toxicity and high stability (partly reviewed in [19]). The LD50 after oral dosing in mice has been estimated at 9 g/kg. In rats about 80% of intraperitoneally injected apocynin at 120 mg/kg was recovered in unchanged form in a urine sample collected 20 hours later. An intravenous dose of 420 mg/kg apocynin in mice caused minimal signs of toxicity [12].
To our knowledge, apocynin has not been tested in human neurodegenerative disease patients. However, Peters et al. have evaluated the therapeutic potential of inhaled apocynin on ozone-induced bronchial hyperresponsiveness to methacholine in asthmatic patients as a model of inflammatory lung disease [42]. The authors could exclude scavenging of ozone by apocynin and concluded that the effect was mitigating ROS production by PMNs and eosinophils that had infiltrated the lung upon ozone exposure.
The mouse studies discussed in this review show that low doses of apocynin administered via the oral route reach the CNS parenchyma in a sufficient concentration to inhibit the microglia oxidative burst and inhibit neurodegeneration. Taking the very low systemic toxicity and the highly specific mode of action of apocynin into account it would be an attractive perspective to test the therapeutic value in human neurodegenerative disease.

Half of women at risk of dementia, Parkinson's, stroke: study

Your doctor and hospital have one hell of a lot of work to do to come up with successful protocols that prevent dementia and Parkinsons post stroke. But they will do nothing, you're screwed.
Paris (AFP) - Nearly half of women and one in three men are at risk of developing stroke or degenerative neurological diseases such as dementia and Parkinson's during their lifetime, according to a study published Monday.
Dutch researchers considered all three conditions "in order to grasp how big the problem of incurable brain diseases in late life really is," said the study's senior author Arfan Ikram.
"We grouped these diseases together not only because they are common but also because there are indications that these often co-occur and might share some overlapping causes," Ikram, of the Erasmus MC University Medical Center Rotterdam in the Netherlands, told AFP.
This could mean there are also overlapping ways to delay or avoid getting the diseases, and the research found that some preventative strategies may cut the risk by between 20 and 50 percent.
For the study, published in the Journal of Neurology Neurosurgery and Psychiatry, researchers tracked more than 12,000 healthy people over the age of 45 from 1990 to 2016.
Over the 26 years, 5,291 people died. Nearly 1,500 were diagnosed with dementia -- 80 percent with Alzheimer's -- while 1,285 had a stroke and 263 developed Parkinson's.
The results indicated that the likelihood of women aged 45 years or older getting the diseases was 48 percent, while it was 36 percent for men.
The gender split is mostly due to the fact that men die earlier than women, Ikram said.

"Our study does not show some sort of protective effect for men," he said. "Instead it is merely due to fewer men surviving to old age."
Because they live longer, women have an increased risk of such diseases, and the study found women were twice as likely as men to develop both dementia and stroke.
While there are no cures for these diseases, a healthy lifestyle -- a good diet, not smoking or having diabetes -- can protect against stroke and help prevent the onset of dementia, Ikram said.
There are also indications that a healthy lifestyle can reduce the risk of Parkinson's, he added.
The cost of the three neurological diseases is believed to be more than two percent of the world's annual economic productivity (GDP), the researchers said in a statement.
However while the dangers of other illnesses such as breast cancer and heart diseases are well known, "the same can't be said of dementia, stroke and Parkinsonism", the statement said.
The researchers noted that as the study only included people of European ancestry with a relatively long life expectancy, it "might not be applicable to other ethnicities/populations".
Worldwide, about seven percent of people over 65 suffer from Alzheimer's or some form of dementia, a percentage that rises to 40 percent above the age of 85.
The number afflicted is expected to triple by 2050 to 152 million, according to the World Health Organization, posing a huge challenge to healthcare systems.

Installing motion sensor light one handed.

At my Mom's this past weekend, she needed a new light installed. I had to have my 89 year old Mom climb partway up the ladder to hold the light up while I screwed the electrical wires together. But success at last.

Broke your arm? Exercise the other one to strengthen it - Stroke?

Have you been told about this rehab recovery option post-stroke? More research needed since they were healthy volunteers.
If you have ever broken an arm and had to wear a cast or splint for a few weeks, you will be familiar with the alarming loss of muscle and uneasy feeling of weakness experienced after removing your cast.
Most people do not do much exercise while a broken arm is healing and can struggle with this loss of muscle, known as “atrophy,” and weakness for many weeks after the injury.
A new study published recently in the Journal of Applied Physiology, conducted in my lab by graduate student Justin Andrushko, suggests an effective strategy to offset muscle weakness might be to exercise the other arm.
We recruited a group of 16 college students to wear casts on their left wrists for four weeks. Half of these students exercised their right arm aggressively three days per week using a type of training known as “eccentric training” — which lengthens the muscle during contraction, and is quite effective for building muscle and enhancing strength.
Before and after the study period, we measured wrist strength in several different ways and quantified muscle volume using a Computed Tomography (CT) scan of the forearm. As expected, those students who did not train lost about 20 per cent of their strength and about three per cent of their muscle volume after four weeks.
Remarkably, the students who trained their opposite wrist completely preserved both the strength and muscle volume in the left, immobilized arm. This research has received a lot of attention.

Possible ‘mirror’ contractions

The phenomenon that creates the effect is known as “cross-education,” and has been documented for over a century, but the new study is one of just a handful to measure the effect when the opposite limb is immobilized.
We are the first to examine the effects using CT scans to measure muscle volume, and to measure the strength of multiple muscle groups in both arms (i.e. wrist flexors and extensors).
It turns out that the effect appears to be quite specific: training of the right wrist flexors preserved the left wrist flexors, but not the extensor muscles.
The loss of muscle after removing a cast from a broken limb can be alarming. (Shutterstock)
We do not fully understand what causes the effect. Most of the published work points towards changes in the nervous system relating to how the sides of the brain share information, or how they adapt together after training one arm. However, we are fascinated with the muscle size preservation effects.
Unfortunately, the study did not take detailed measures of anything inside the muscle. We suspect there could be some yet unknown connection between nervous system changes and the balance of muscle protein.
One theory is that there are small contractions, known as “mirror” contractions, under the cast while training the opposite side. We measured these contractions and they are very small — perhaps too small to preserve the muscle — but they are present. We need to do more research to understand the role of these small contractions in relation to prevention of atrophy.

Consider training the opposite limb

Although the results are exciting, we caution that the study was a controlled lab experiment involving young healthy volunteers without a real injury.
More work in clinical settings is needed before any changes to standard rehabilitation practices can be discussed.
There have been a few clinical studies already published — about wrist fracture and recovery from stroke and knee surgery — with promising results. The clinical studies seem more positive for fracture and stroke recovery and less so after knee surgeries.
Lab-controlled studies like the one we conducted are important to understand the underlying mechanisms of the effect, and to maximize its potential in future clinical work.
While more work in clinical settings is certainly needed, we can still recommend that if you ever experience a limb fracture, you might consider training your opposite limb. As with many types of exercise training, the risk of this approach is quite low and could have important benefits.

Removing faulty brain cells staves off dementia in mice

Can your doctors and hospital follow up this with research in humans? Or are they going to sit on their asses once again twiddling their thumbs?
Researchers say that when they swept away the senescent brain cells in mice, the outwards symptoms of their dementia vanished

Neurofibrillary tangles in the cerebellum of the brain of a person with Alzheimer’s disease.
Neurofibrillary tangles in the cerebellum of the brain of a person with Alzheimer’s disease. Photograph: George Musil/Getty Images
Purging “zombie cells” from the brain could stave off the effects of dementia, a groundbreaking study has found.
The research in mice is the first to show that so-called senescent cells, which enter a state of suspended animation as the body ages, contribute to neurodegeneration. Flushing out these cells was shown to prevent damage, potentially opening a new line of attack against Alzheimer’s and other forms of dementia.
Prof Lawrence Rajendran, deputy director of the Dementia Research Institute at King’s College London who was not involved in the study, described the findings as “exciting”.
“It is not only novel in its approach but also opens up new vistas for both diagnosis and therapy for neurodegenerative diseases, including Alzheimer’s,” he said.
Initially senescent cells were thought to be inert bystanders – useless, but harmless. However, in the past decade that picture has changed as evidence has emerged linking senescent cells to Parkinson’s disease, diabetes, arthritis, heart disease and ageing itself. The latest study adds dementia to this list.
Writing in the journal Nature, the researchers describe how mice with a genetic form of dementia accumulated senescent cells in regions of the brain that are involved in memory and cognition, such as the hippocampus. The mice had been genetically engineered to produce a faulty version of the brain protein tau, which was seen to build up in abnormal tangles as the mice lost the ability to learn and remember new information.

However, when the mice were treated by administering a genetically modified enzyme to sweep away senescent cells as they appeared, the outward symptoms of dementia vanished.
Darren Baker, a molecular biologist at the Mayo Clinic in Minnesota and senior author of the paper, said: “When senescent cells were removed, we found that the diseased animals retained the ability to form memories, eliminated signs of inflammation, did not develop [protein] tangles, and had maintained normal brain mass.”
People with the same mutation develop dementia early in life and show some of the hallmarks of Alzheimer’s disease. However, further work is needed to test whether the findings translate into patients. “We anticipate finding that senescent cells negatively impact brain health in humans, but those experiments will be difficult to design and perform,” said Baker.
The team also revealed the brain cells that became senescent were two forms of immune cell in the brain, called microglia and astrocytes, rather than neurons.
Baker said the team had not yet established why the senescent cells cause problems, although previous work has suggested they secrete inflammatory chemicals and cause other nearby cells to enter a semi-dormant state too.
Scientists are also uncertain what happens when senescent cells are removed from the brain – whether new brain cells would be generated or whether over time the brain’s cell content would gradually shrink.
Dr James Pickett, head of research at Alzheimer’s Society, said: “There hasn’t been a new dementia drug in 15 years so it’s exciting to see the results of this promising study in mice. However, there are several barriers to overcome before we can say if this is a safe, effective treatment in people. For example, we don’t know if this drug is actually able to enter the brain, and older people often have lots of harmless brain cells that look like the senescent ‘zombie’ cells this drug targets, so any treatment would have to be good at telling the two apart.”
Rosa Sancho, head of research at Alzheimer’s Research UK, said: “Researchers are continuing to build a clearer picture of the precise interplay between the immune system and the brain, and this new work adds another piece to this puzzle.”

Robotic arm rehabilitation in chronic stroke patients with aphasia may promote speech and language recovery

Novel idea, will your hospital implement this without your prodding? 

Robotic arm rehabilitation in chronic stroke patients with aphasia may promote speech and language recovery

  • 1New York University, United States
  • 2Weill Cornell Medicine, Cornell University, United States
  • 3Harvard Medical School, United States
  • 4Department of Mechanical Engineering,Massachusetts Institute of Technology, United States
  • 5Feinstein Institute for Medical Research, United States
Objective: This study aimed to determine the extent to which robotic arm rehabilitation for chronic stroke may promote recovery of speech and language function in individuals with aphasia.
Methods: We prospectively enrolled 17 individuals in a robotic arm rehabilitation study and evaluated their speech and language performance before and after a 12-week (36 session) arm treatment regimen. Performance changes were evaluated with paired t-tests comparing pre- and post-test measures. There was no speech therapy included in the treatment protocol.
Results: Overall, the individuals significantly improved on measures of motor speech production as well as overall aphasia severity from pre-test baseline to post-test.
Conclusions: This work indicates the importance of considering approaches to stroke rehabilitation across different domains of impairment, and warrants additional exploration of the possibility that robotic arm motor treatment may enhance rehabilitation for speech and language outcomes.
Keywords: Aphasia, stroke rehabilitation, apraxia of speech, motor control, Neurorehabilitation
Received: 29 Jan 2018; Accepted: 21 Sep 2018.
Edited by:
Nicola Smania, Università degli Studi di Verona, Italy
Reviewed by:
Kyrana Tsapkini, Johns Hopkins University, United States
Andrea Turolla, IRCCS Fondazione Ospedale San Camillo, Italy  
Copyright: © 2018 Buchwald, Falconer, Rykman, Cortes, Pascual-Leone, Thickbroom, Krebs, Gerber, Oromendia, Chang, Volpe and Edwards. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Adam Buchwald, New York University, New York City, United States,

Getting stroke survivors back on their feet

Have your doctor follow this up. You shouldn't have to request this followup but nothing will occur if you don't. I don't walk normally and never will until my spasticity is cured. But I can and have walked up to 17 miles a day in NYC.

Getting stroke survivors back on their feet

stroke survivors rehab: gait analysis stroke rehab
A USC study focuses on how to best improve the walking rehabilitation for patients who have suffered a stroke. (Photo/Shutterstock)
Every 40 seconds, someone in the United States has a stroke. And while it is the fifth leading cause of death in America, it’s much more disabling than it is fatal.
Physical therapy for stroke survivors can often mean treatment focused on correcting walking asymmetries (such as a limp) so that the individual can walk in an observationally normal way. But is this the best rehabilitation strategy?
That’s what James Finley aims to investigate in a new study supported by a $1.6 million grant from the National Institutes of Health. The study will examine the advantages and disadvantages associated with restoring symmetry in the walking patterns of survivors of stroke. Finley is an assistant professor and director of the Locomotor Control Laboratory at the USC Division of Biokinesiology and Physical Therapy.
Using a device to measure oxygen consumption, treadmills meant to elicit a stumble response and a motion capture system to record it all, Finley hopes to better understand how correcting gait asymmetries has an impact on energy efficiency and fall risk.
“One thing we would like to do is assess the individual and find the focus areas for how to rehabilitate them,” Finley said. “How can we help an individual reduce energetic costs so they can walk longer distances? Can we train people to have a walking pattern that would lower their risk of falling?”

New Treatment Approaches on the Horizon for Spastic Hemiparesis

I don't think that my spasticity is bad enough to even consider surgery. We need less drastic solutions. May have to look into hyaluronidase.

New Treatment Approaches on the Horizon for Spastic Hemiparesis


This article presents 2 recent articles that propose novel interventions for treating spastic hemiparesis by changing biological infrastructure. In 18 patients with unilateral spastic arm paralysis due to chronic cerebral injury greater than 5 years’ duration, Zheng et al transferred the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed. Over a follow-up period of 12 months, they found greater improvement in function and a reduction of spasticity compared to rehabilitation alone. Using functional magnetic resonance imaging, they also found evidence for physiological connectivity between the ipsilateral cerebral hemisphere and the paralyzed hand. In the second article, Raghavan et al examine the concept of stiffness, a common symptom in patients with spastic hemiparesis, as a physical change in the infrastructure of muscle. Raghavan’s non-neural hyaluronan hypothesis postulates that an accumulation of hyaluronan within spastic muscles promotes the development of muscle stiffness in patients with an upper motor neuron syndrome (UMNS). In a case series of 20 patients with spastic hemiparesis, Raghavan et al report that upper limb intramuscular injections of hyaluronidase increased passive and active joint movement and reduced muscle stiffness. Interventions that change biological infrastructure in UMNS is a paradigm on the horizon that bears watching.

Electrical Somatosensory Stimulation in Early Rehabilitation of Arm Paresis After Stroke: A Randomized Controlled Trial

You'll have to ask your doctor what is the ESS protocol and why isn't it being used for you?
First Published September 25, 2018 Research Article
Background. Arm paresis is present in 48% to 77% of acute stroke patients. Complete functional recovery is reported in only 12% to 34%. Although the arm recovery is most pronounced during the first 4 weeks poststroke, few studies examined the effect of upper extremity interventions during this period.  
Objective. To investigate the effect of electrical somatosensory stimulation (ESS) delivered during early stroke rehabilitation on the recovery of arm functioning.  
Methods. A total of 102 patients with arm paresis were randomized to a high-dose or a low-dose ESS group within 7 days poststroke according to our sample size estimation. The high-dose group received 1-hour ESS to the paretic arm daily during hospitalization immediately followed by minimum 15-minute task-oriented arm training that was considered a component of the usual rehabilitation. The low-dose group received a placebo ESS followed by identical training. Primary outcome—Box and Block Test (BBT); secondary outcomes—Fugl-Meyer Assessment (FMA), grip strength, pinch strength, perceptual threshold of touch, pain, and modified Rankin Scale (mRS); all recorded at baseline, postintervention and at 6 months poststroke.  
Results. There were no differences between the high-dose and the low-dose groups for any outcome measures at any time points. Improvements ⩾ minimal clinically important difference were observed for FMA, hand grip strength, and mRS in both groups.  
Conclusions. Providing the present ESS protocol prior to arm training was equally beneficial as arm training alone. These results are valid for patients with mild-to-moderate stroke and moderate arm impairments. We cannot exclude benefits in patients with other characteristics, in other time intervals poststroke or using a different ESS protocol. Trial Registration. (NCT02250365).