Deans' stroke musings
What this blog is for:
My back ground story is here:http://oc1dean.blogspot.com/2010/11/my-background-story_8.html
Wednesday, November 30, 2011
Or Drano? I would be worried about this, sloughing off chunks
Evidence-Based Review of Stroke Rehabilitation
From MIT Medialab; Hopefully this will spread to other countries, I would have a heyday.
For the past five years Farber has been battling not only her own disease but also the wall of resistance erected by those who believe that a patient can make about as much of a meaningful contribution to the process of scientific discovery as a laboratory rat.
What are the best ways to improve cognition after a stroke? How can stroke survivors and families be helped to cope with speech problems? Can exercise and fitness programmes help improve function and quality of life and avoid subsequent stroke?
Remarkably, there is little evidence to answer any of these questions, but following an exercise to identify what matters most to people who have had a stroke, or looked after someone affected, there is hope that research will address these areas.
A shortlist of 226 research questions has been whittled down to a top 10 by the people at the sharp end during an 18-month programme of consultation in Scotland.
Work was led by researchers at the Nursing, Midwifery & Allied Health Professions Research Unit (NMAHP), who run the Database of Research in Stroke (Doris). The team turned to the James Lind Alliance (JLA), which unites patients and carers with health professionals to identify and prioritise treatment research questions.
JLA priority-setting partnerships (PSPs) gather questions through surveys, newsletters and searching clinical guidelines for research gaps. Previous PSPs have tackled asthma and schizophrenia.
Doris had a tough challenge reaching participants because many had post-stroke communication problems and lived in the Highlands and islands. But Scotland has a network of support groups run by organisations such as CHSS [Chest, Heart and Stroke Scotland], The Stroke Association and Different Strokes. Alex Pollock, NMAHP research fellow, says: “We worked hard to capture diverse views: sat down with stroke club members with impairments, scribed for people unable to write, worked with communication partners for people unable to speak, extracted questions through discussions with people with cognitive impairments. We comforted people in tears, [who were] struggling to describe what mattered.”
His team devised an online presentation with recorded narration for people with visual problems. They also wrote an information sheet for people with aphasia, a language disorder affecting about one in three stroke survivors.
In total, 513 questions were gathered for possible research studies, half from stroke professionals and half from those with personal experience. Kathleen Frew is a CHSS community support worker who co-ordinates groups across west Scotland and cares for her husband, who had his first stroke 17 years ago. “In the NHS, you can’t access patients without complex permissions, while we have links with over 40 patient groups,” she says. Frew believes their input will revolutionise research: “Patients and carers always seek better condition management. Acute care is great, but you want evidence for later: what sort of physio, occupational therapy, communication support, really work?”
She recalls a stroke patient who was registered blind and told that returning to work was impossible. “He met a physiotherapist who put him on to the RNIB. They taught him strategies enabling his return to work. How many patients would benefit if we had evidence for the effectiveness of such interventions?”
Lester Firkins gave up his job in banking after losing his son to vCJD. He advises the Department of Health on research from a user perspective. He chaired the stroke PSP, and co-chairs the JLA. “The steering group put in such effort to reach people across NHS Scotland and it reaped rewards: people can tell when others truly want to hear their views,” he says.
So how have previous PSPs improved research to help people living with another condition, asthma? A collaboration between the universities of Southampton and Aberdeen is to develop a DVD teaching breathing exercises at home to people with asthma. It is funded by the government’s National Institute for Health Research (NIHR) which also funds the JLA.
Several charities have used the outcomes of past PSPs to inform their research. Asthma UK is co-ordinating research into the top concern identified by asthma patients – the side-effects of steroid treatments. It found that about a third of people with asthma do not take their steroid medicines as prescribed. Previous studies found that this often stemmed from concerns about their treatment. For many, such concerns are not alleviated by the available information, which is unsurprising if, as this study found, health professionals felt that side effects would be relatively infrequent, yet people with asthma reported them frequently.
The hope now is that the top 10 stroke priorities will be widely disseminated to potential funders.
• Sophie Petit-Zeman is a member of two JLA steering groups. View the top 10 stroke research priorities at lindalliance.org/top-tens.asp
Monday, November 28, 2011
The Time Use and Activity Levels of Inpatients in a Co-located Acute and Rehabilitation Stroke Unit: An Observational Study
Purpose: Stroke patients spend a large proportion of their day alone and inactive. In one rehabilitation unit, practice changes had been implemented over several years to improve patient activity levels and practice, yet measures of patient activity had not been recorded. The aim of this study was to obtain baseline measures of the time use and activity levels of inpatients in that co-located acute and rehabilitation stroke unit. Methods: A quantitative observational design was used. The behavior of 11 inpatients was mapped at 15-minute intervals over 4 days between 7 am and 7 pm. Observations were recorded across 7 categories, including physical activity, location and person(s) present, and 42 possible subcategories. Thirteen allied health and nursing professionals were trained to record these observations and interrater reliability was examined. Frequencies, cross-tabulations, and t tests were used for data analysis. Results: Stroke patients spent a large proportion of the day in their bedroom, engaged in solitary behavior and being inactive (76%, 44% and 62% of observed time, respectively). Patients spent 11% of their weekday with an allied health or nursing professional. Good interrater agreement was achieved between raters for 41 of the 42 observational categories. Conclusions: These data provide a baseline for comparison following implementation of more practice change. A trained team of health professionals was able to reliably collect data.
Mindful attention and neuroplasticity of the brain are the hottest discoveries in neuroscience; yet, many of the pioneering researchers of mindful attention and neuroplasticity are Buddhist followers. Nonetheless Paul, under the inspiration of the Holy Spirit, penned the words of Romans 12:2 close to 2000 years ago, saying “be transformed by the renewing of your mind” (New American Standard Bible). This transformation of the mind comes not through the Buddhist religion, but through focused attention on taking “every thought captive,” and challenging lie-based beliefs until neural connections to the truth of God’s Word, the Gospel and the Lord Himself brings about true transformation of the mind. Sadly, Christians, like the rest of society, have reserved these sacred truths for Sunday mornings and seem to consider them irrelevant for daily living. Neuroscience, however, not only validates these biblical teachings but shows that these commands impact each person’s daily life.
Weekly subcutaneous injection of the investigational lipid-lowering agent mipomersen (Genzyme) was associated with a 47% reduction in low-density lipoprotein (LDL) levels and similar large reductions in most other lipid parameters in a small phase 2 study in high-risk patients intolerant to statins.
The drug is, however, also associated with flulike symptoms, liver-enzyme increases, and intrahepatic fat accumulation, which may limit its use.
Mipomersen is an antisense oligonucleotide designed to inhibit the synthesis of apolipoprotein B (apoB), which is essential for the synthesis of all atherogenic lipoproteins.
In the current study, presented at last week's American Heart Association 2011 Scientific Sessions, 34 statin-intolerant patients at high risk of cardiovascular disease were randomized (2:1) to receive 26 weekly doses of 200-mg mipomersen (n=22) or placebo (n=12).
At the end of the study period, LDL levels had decreased from 242 mg/dL to 128 mg/dL in the treatment group—a reduction of 114 mg/dL. Presenting the data, Dr Erik Stroes (Academic Medical Center, Amsterdam, the Netherlands) said this would translate into a >50% reduction in events. All other atherogenic lipid parameters showed similar impressive reductions.Mean change in lipid parameters with mipomersen
| Lipid parameter || Mean change from baseline, % |
| LDL cholesterol || -47.3 |
| ApoB || -46.2 |
| Total cholesterol || -36.9 |
| Non-HDL cholesterol || -45.6 |
| Triglycerides || -27.0 |
| HDL cholesterol || +8.1 |
| Lp(a) || -27.1 |
| VLDL cholesterol || -27.1 |
Small LDL particles showed the greatest reductions, with more modest reductions in large LDL particles.
In terms of adverse events, 19 patients (90%) in the mipomersen group experienced flulike symptoms and 20 (95%) had injection-site reactions, although only four patients discontinued treatment.
Hepatic steatosis (fatty liver) occurred in 11 mipomersen patients (54%). Liver needle biopsies performed in two patients showed severe hepatic steatosis "with minimal inflammation and minimal to no fibrosis." Transaminase levels were raised to more than twice the upper limit of normal in 12 patients.
Stroes concluded that "future studies with mipomersen need further monitoring of long-term hepatic effects, but interim results suggest that liver fat stabilizes or improves with more than 12 months of continued dosing."
May have a role in very high-risk patients
Commenting on the study for heartwire, session cochair Dr Amit Khera (University of Texas Southwestern Medical Center, Dallas) described mipomersen as "exciting, as it is a completely novel agent," but added, "the challenge will be where and when to use it."
He said he thought it could have a role in patients with very high LDL who can't get to goal on statins and in those who can't tolerate statins.
Khera said the side effect of fatty liver was "potentially worrisome." He commented: "The consequences of this are not clear at the moment. Fatty liver can be accompanied by inflammation, in which case it is more serious. The presenter was trying to build a case that the fatty liver seen with this drug was the noninflammation, benign type, but this was a very short-term study in only a small number of patients. Larger studies are needed to give more information on this."
Even with all the side effects, Khera still believes the drug may find a niche. "If people are very high risk—ie, they have [familial hypercholesterolemia] FH and very high LDL levels—there certainly could be a role for a drug like this. I don't think that the fact it is an injection is a complete negative. Several new drugs for diabetes are injectable but are still being used. I think if the patient is at sufficient risk, they would tolerate an injection."
The other cochair, Dr Melvyn Rubenfire (University of Michigan, Ann Arbor), had similar opinions. He said he was impressed with the degree of LDL and apoB lowering and pointed out that it was the only drug—apart from niacin—that lowers lipoprotein (a). On the issue of hepatic steatosis, he noted that mipomersen mimics the heterozygote genetic condition of hypobetalipoproteinemia, in which patients have fatty livers, which "seems relatively innocent compared with the protective effect of the very low apoB and LDL and VLDL cholesterol." He added: "The mipomersen data on fatty liver by MRI that have been previously published [have found it to be] to be reversible when the drug is stopped. I've heard it said that the fat decreases over time while treatment is continued but have not seen published data."
Rubenfire pointed out that patients with FH often do not adequately respond to statins, even in combination with other lipid-lowering agents, and many will have cardiovascular events in middle age or even childhood if homozygous. "In these patients, the major treatment is LDL apheresis, which is very costly, has major complications, and fails to get many patients to target. Mipomersen will be a welcome drug for these very high-risk patients. As a lipidologist, I'm hopeful the safety data will be adequate to allow FDA approval with limited indications and careful monitoring postapproval."
Sunday, November 27, 2011
I don't know what to say here since nobody seems to know what to do.
Aspirin is not a good investment for healthy women who want to prevent heart attacks or stroke, Dutch researchers say.
They said 50 women would need to take the medication for 10 years for just one to be helped - assuming they are all at high risk to begin with.
“There are very few women who actually benefit,” the Daily Mail quoted Dr Jannick Dorresteijn of University Medical Center Utrecht in The Netherlands, as saying.
“If you don’t want to treat 49 patients for nothing to benefit one, you shouldn’t treat anyone with aspirin.”
The new study adds to a long-standing controversy over aspirin, one of the world’s most widely used drugs. Common side-effects include irritation of the stomach or bowel, heart burn and nausea.
Doctors agree it’s worth taking for people who’ve already had a heart attack or a stroke, but they are less certain when it comes to so-called primary prevention.
Friday, November 25, 2011
Summary The EMG patterns for 16 muscles involved in human walking are reported along with stride-to-stride and
inter-subject variability measures. These profiles and measures were developed for basic researchers and clinical investigators as a baseline reference of motor patterns and for use in the diagnosis of gait pathologies.
Evident from a comparison of these patterns were some fundamental aspects of the neuromuscular control and the mechanical
demands of walking. These comparisons can be summarized as follows:
(1) The distal support muscles (soleus, tibialis anterior, gastrocnemii) are the most active muscles, the more proximal muscles are
(2) The least variable EMG patterns, as quantified by the normalized inter-subject variability measures, are seen in the most distal
single joint muscles, the most variable are the more proximal muscles. The EMGs of the biarticulate muscles, both proximal and
distal, exhibit higher variability than the EMGs of the single joint muscles.
(3) The detailed patterns and levels of EMG activity demonstrate the different mechanical tasks of each muscle over the gait
Detailed position of electrodes. You'll have to look at the link.
It is considered useful for basic and clinical
researchers to have a profile of normal EMG
activity that can be used as a reference. Clinical
investigators require these normal patterns in order
to diagnose individual patients (Knutsson and
Richards 1979; Peat et al. 1976; Winter 1984a).
Basic researchers, interested in motor patterns,
require such profiles as a reference for discussions
of the role of various muscles during the gait
cycle, or as inputs for use in simulation models of
human gait. Thus the patterns as presented in
Figs. 3a, b, 4a and b will be useful. A rough
comparison can be made regarding the shapes of
the ensemble averages from other studies. The
only comparison for the erector spinae is with a
single subject (Thorstensson et al. 1982) and the
phasic patterns showing two bursts, one just after
heel contact of the ipsilateral limb and the second,
lesser burst after heel contact of the contralateral
limb. The phasic peaks of EMG activity of the
hamstrings, gastrocnemius, rectus femoris and
tibialis anterior agreed within 5% of the stride
period with inter-subject averages (10 subjects)
reported by Knutsson and Richards (1979). Similar
agreement was seen in the profiles obtained
from 20 subjects (Dubo et al. 1976) for tibialis
anterior, gastrocnemius, medial hamstrings and
vastus lateralis muscles.
From Table III it is valuable to note the
summary of CVs as calculated from these normalized
and unnormalized ensemble averages. The
normalization procedure reduced the variability to
about half (89-48.5%). Again, as was seen from
the range of EMG amplitudes presented in Table
II lower variability is seen in the more distal
muscles, especially the single joint ones: soleus,
tibialis anterior, extensor digitorum longus and
peroneus longus have an average CV (unnormalized)
of 59%. Conversely, the more proximal biarticulate
muscles: sartorius, biceps femoris, semitendinosus,
rectus femoris have an average CV
(unnormalized) of 112% which reinforces their
flexibility and adaptability compared with the
higher and more consistent support and power
Fig. 3. a: inter-subject ensemble average for 8 of the muscles
recorded. EMG profiles from each subject were unnormalized,
with amplitude reported in microvolts. Number of subjects
involved in each ensemble average is indicated along with the
CV. b: inter-subject ensemble average for second group of 8
generation roles of the distal single joint muscles.
The normalization technique is such that it
removes any amplitude differences between each
subject's EMG. Thus the resultant CV is a measure
of the dissimilarity in shape of each subject's
EMG over the stride period. If the shapes were
exactly the same for a given muscle, the CV after
normalization would be zero. With these normalized
CVs we again see that the single joint muscles
have the lowest variability and therefore a more
similar pattern. For example, the soleus intra-subject
CV was 31% and inter-subject CV was also
31%; conversely, the medial gastrocs had consistent
patterns within subjects (CV = 33%) but
somewhat dissimilar patterns between subjects
(CV = 61%). Similarly, the more proximal muscles
show greater differences in their inter-subject patterns.
Considerable discussion is possible when we
examine the detailed shape of the individual
muscle profiles as presented in Figs. 3 and 4.
However, general differences and similarities will
be noted. The weight-accepting muscles (tibialis
anterior, extensor digitorum longus, rectus femoris,
vastus lateralis, hamstrings, gluteus maximus and
medius) have their major peak in the first 15% of
stride. Erector spinae also peaks at 10%, to control
forward rotation of the trunk as it decelerates
during weight acceptance; a second peak is seen at
60% presumably for the same purpose when the
contralateral limb is accepting weight. The plantarflexors
(medial and lateral gastrocs, soleus and
peroneus longus) all have peaks at push-off (50%
of stride). Peroneus longus also has an initial peak
at flat foot to control foot inversion. The hip
extensors and knee flexors (gluteus maximus and
hamstrings) have increasing activity in late swing
to arrest the forward movement of the swinging
Fig. 4. a: inter-subject ensemble average for same 8 muscles as
in Fig. 3a except that each subject's mean EMG over the stride
was normalized to 100% prior to averaging. CV was reduced to
about half because the inter-subject amplitude differences have
been eliminated and resultant variability results only from
differences in the shape of the EMG profiles. CV is indicated
along with the mean EMG amplitude (in microvolts) from all
subject profiles that was calculated for this normalization
procedure, b: inter-subject normalized ensemble average for
same 8 muscles as in Fig. 3b.
410 D.A. WINTER, H.J. YACK
lower limb. Tibialis anterior and extensor digitorum
longus have similar patterns during both
stance and swing, the first peak during weight
acceptance (lowering of foot to the ground) and
the second early in swing to dorsiflex the foot for
toe clearance. The two adductors (longus and
magnus) have slightly different patterns. During
stance they both have a moderate but decreasing
activity probably as a co-contraction to stabilize
the hip joint against the action of the hip abductors.
They have major peaks in swing presumably
to control the lateral movement of the swinging
lower limb; adductor longus peaks at 70% stride
and magnus at 80% of stride. The adductor longus
peaks early in swing because of its additional role
of a hip flexor.
In patients with atrial fibrillation, a higher CHADS2 score is associated with increased risk for stroke or systemic embolism, bleeding, and death, even with optimal anticoagulation with warfarin or dabigatran, according to a subgroup analysis of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial .
Nicolas G. Bazan, MD, Ph.D, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health Sciences Center New Orleans, and David Stark, an MD/Ph.D student working in his lab, have discovered how a key chemical neurotransmitter that interacts with two receptors in the brain promotes either normal function or a disease process - determining whether brain cells live or die. The work is published and highlighted in the September 28, 2011 issue of the Journal of Neuroscience.
These findings reveal how receptor signaling takes place between receptors of synapses (gaps between neurons through which chemical or electrical signals pass permitting cells to "talk" to each other) and the mechanisms involved in initiating disease. The receptors, called NMDARs, are located both inside and outside of the synapses. Activation of the NMDRs inside (synaptic) allows the synapse to adjust response to signals and activation of the synaptic NMDRs is also required for survival of the cell. In contrast, activation of the receptors outside the synapse (extrasynaptic) leads to cell death.
The LSUHSC research team believed that activation of the extrasynaptic NMDRs promotes the pathological effects of cyclooxygenase 2 (COX-2), a protein known to contribute to inflammation associated with neurotoxicity. They found that activating the synaptic NMDRs greatly increased levels of COX-2, but not of the chemical (arachidonic acid) upon which COX-2 acts. Conversely, activating the extrasynaptic NMDRs increased the levels of arachidonic acid, but not COX-2. The researchers discovered, however, when synaptic and extrasynaptic NMDARs were sequentially activated, the levels of both COX-2 and arachidonic acid increased, as did neurotoxic inflammation.
"We have discovered a fascinating relationship regarding the "conversations" that occur between these two receptors in the brain," said Dr. Nicolas G. Bazan, Professor and Director, LSUHSC Neuroscience Center of Excellence.
"In this paper, we demonstrate how these signals affect cell functions and how they lead to diseases, including stroke, epilepsy and other neurodegenerative disorders. Targeting mechanisms that couple sequential synaptic then extrasynaptic NMDAR stimulations may lead to new anti-inflammatory/neuroprotective approaches."
The research was supported by grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, and the National Center for Complementary and Alternative Medicine.
"I have a very gifted and talented young MD/Ph.D student in my lab, David Stark, who has a National Institutes of Health award, performed exemplary experiments and co-authored the paper with me," said Dr. Bazan.
Identification Of Gene Critical For Cell Responses To Oxygen Deprivation May Have Implications For Heart Disease, Stroke And Cancer
Scientists at the Gladstone Institutes have identified a protein that kick-starts the response to low levels of oxygen, suggesting new lines of research relevant to a variety of potentially fatal disorders associated with diminished oxygen supply, including cancer, heart disease, stroke and other neurological conditions that affect millions of people worldwide.
In a paper published in Molecular Cell, the laboratory of Gladstone Associate Investigator Katerina Akassoglou, PhD, maps out the chain of events that take place during hypoxia. Hypoxia is a condition that can occur in people with diseases such as heart disease and stroke. It deprives tissues and organs of an adequate oxygen supply.
"This discovery provides a novel understanding of the steps by which cells normally respond to hypoxia, a fundamental biological process that is implicated in many medical conditions," said Dr. Akassoglou, whose research at Gladstone - a leading and independent biomedical-research organization - investigates the mechanisms of inflammation and tissue repair in the brain.
The paper details how Dr. Akassoglou's lab discovered the previously unknown biological function of a protein called p75NTR. When activated by hypoxia, p75NTR sets off the cascading series of events that results in increased blood-vessel production to replenish oxygen levels during disease.
Previous research had indicated that hypoxia triggers the activation of a protein called HIF1-alpha - an activation that ultimately leads to more blood vessels and an ensuing improvement in oxygen flow. There has been much interest among researchers in modifying levels of the HIF1-alpha protein to spur blood-vessel production in individuals with hypoxic conditions. But Dr. Akassoglou decided to take a different approach in her research.
By monitoring the responses of mice under hypoxic conditions, Dr. Akassoglou found that hypoxia first activated the p75NTR protein, which then activated HIF1-alpha and set everything in motion.
"What was most striking to us was what happened when we removed the gene that makes p75NTR," said Natacha Le Moan, PhD, a Gladstone postdoctoral fellow and the first author of the paper. "By effectively silencing p75NTR, the mice's response to hypoxia was impaired and blood-vessel production decreased."
"Now that we've shown that p75NTR spurs the activation of HIF1-alpha and the production of blood vessels during hypoxia, we can move forward with exploring potential therapies," said Dr. Akassoglou, who is also an associate professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. In addition, Dr. Akassoglou is also an associate adjunct professor of pharmacology at the University of California, San Diego.
"Dr. Akassoglou's trailblazing discovery could enable the development of pharmaceutical therapies for conditions that are caused or exacerbated by reduced oxygen levels," added Lennart Mucke, MD, who directs neurological research at Gladstone. "This is important news for those who suffer from hypoxia-related illnesses such as heart disease, stroke and certain types of cancer."
Thursday, November 24, 2011
Over the past decade, neuroscientists at the Duke University Center for Neuroengineering (DUCN) have developed the field of brain-machine interface (BMI) into one of the most exciting—and promising—areas of basic and applied research in modern neuroscience. By creating a way to link living brain tissue to a variety of artificial tools, BMIs have made it possible for non-human primates to use the electrical activity produced by hundreds of neurons, located in multiple regions of their brains, to directly control the movements of a variety of robotic devices, including prosthetic arms and legs.
As a result, BMI research raises the hope that in the not-too-distant future, patients suffering from a variety of neurological disorders that lead to devastating levels of paralysis may be able to recover their mobility by harnessing their own brain impulses to directly control sophisticated neuroprostheses.
The Walk Again Project, an international consortium of leading research centers around the world represents a new paradigm for scientific collaboration among the world’s academic institutions, bringing together a global network of scientific and technological experts, distributed among all the continents, to achieve a key humanitarian goal.
The project’s central goal is to develop and implement the first BMI capable of restoring full mobility to patients suffering from a severe degree of paralysis. This lofty goal will be achieved by building a neuroprosthetic device that uses a BMI as its core, allowing the patients to capture and use their own voluntary brain activity to control the movements of a full-body prosthetic device. This “wearable robot,” also known as an “exoskeleton,” will be designed to sustain and carry the patient’s body according to his or her mental will.
In addition to proposing to develop new technologies that aim at improving the quality of life of millions of people worldwide, the Walk Again Project also innovates by creating a complete new paradigm for global scientific collaboration among leading academic institutions worldwide. According to this model, a worldwide network of leading scientific and technological experts, distributed among all the continents, come together to participate in a major, non-profit effort to make a fellow human being walk again, based on their collective expertise. These world renowned scholars will contribute key intellectual assets as well as provide a base for continued fundraising capitalization of the project, setting clear goals to establish fundamental advances toward restoring full mobility for patients in need.