Rhythm's Imcivree scores 'transformative' FDA approval in brain damage-related obesity

 In case your stroke caused this problem, see highlighted text.

Rhythm's Imcivree scores 'transformative' FDA approval in brain damage-related obesity

Rhythm Pharmaceuticals is switching up the tempo for its melanocortin-4 receptor (MC4R) agonist Imcivree. After its initial approval more than five years ago to treat certain patients with genetic-driven obesity, the drug is moving into a different and broader realm with an FDA nod for acquired hypothalamic obesity (HO). 

Acquired HO, for which Imcivree is the first approved treatment, represents an “expanded thinking” on the weight-regulating MC4R pathway that Rhythm’s product targets, Chief Scientific Officer Alastair Garfield, Ph.D., explained in a recent interview with Fierce. 

Until now, all of Imcivree’s approved uses have centered around specific genetic causes. HO, on the other hand, is a result of a hypothalamic injury such as a tumor or stroke that impairs the MC4R pathway and causes weight gain and insatiable hunger (hyperphagia).

Imcivree scored its first FDA approval in 2020 to treat obesity due to genetically confirmed POMC, PCSK1 or LEPR deficiencies. Then, two years later, it added monogenic obesity due to Bardet-Biedl syndrome to its label.

Moving outside of its bread-and-butter of genetic diseases is “a bit of a watershed moment” for Rhythm, Garfield said, presenting a “step-change in market potential” for the drug. 

The company estimates there’s an acquired HO patient population of about 10,000 in the U.S, a figure picked up from literature, tumor registries and claims data, Rhythm said in a press release. As part of its launch in the indication, Rhythm is placing importance on educating physicians and patients who might have the condition. Garfield anticipates the drug’s reach in the indication will be “a bit of a growth story,” but, as for a global patient spread, he thinks the company can “find these patients wherever we go looking.” 

Imcivree’s FDA approval was supported by Rhythm’s phase 3 Transcend trial, which saw a mean 18.4% improvement in body mass index (BMI) changes for Imcivree-treated patients. The mean BMI change from baseline came out to a 15.8% reduction for those taking the treatment, compared with a 2.6% BMI increase in the placebo group, according to the company. 

“This is a transformative milestone for Rhythm and reinforces our commitment to bringing meaningful therapies to patients living with rare MC4R pathway diseases,” CEO David Meeker, M.D., said in the company’s release. 

Related

Rhythm eyes label expansion after Imcivree helps patients with brain damage-related obesity lose weight

The new label specifically allows Imcivree’s use to reduce excess body weight and maintain reductions over the long term in adults and pediatric patients aged 4 years and older with acquired HO. 

In a note to clients, Leerink analysts called the nod a “significant label expansion” that bolsters the company’s leadership position in the genetic obesity space. The approval brings Rhythm to a “major inflection point,” the analysts wrote, noting that the company has “successfully transitioned from an R&D-stage biotech to a commercial-stage company with durable revenue visibility.”

Imcivree is Rhythm’s sole commercial product and garnered $194.8 million in 2025 sales.

The FDA’s blessing in acquired HO marks a welcome reprieve from a trial fail Rhythm reported earlier this week, which ended its hopes of expanding into a different subset of genetic obesities. Still, considering how “pivotal” the MC4R pathway is to defining body weight, “I think there are many more places where we’re going to learn in time our approach is going to be the most effective,” Garfield said. The executive spoke with Fierce Pharma before the latest results dropped. 

Related

Rhythm's Imcivree loses tempo across 4 rare genetic obesities, delivering phase 3 flop

As it stands, a potential expansion into Prader-Willi syndrome is “front and center for us,” Garfield noted.  
 

Obesity lessons
 

Rhythm cracked into the obesity space in its small genetic corner before Eli Lilly and Novo Nordisk busted the market wide open with their popular GLP-1 products for general obesity. When Lilly and Novo’s drugs rose to widespread popularity a few years back, Rhythm ultimately learned a “very valuable lesson,” Garfield said.

“We were concerned we were going to be the proverbial damsel in distress,” Garfield said, painting a picture of the smaller pharma “tied to the railway tracks as these two juggernauts of Novo and Lilly came careening across us.” 

Instead, Rhythm came to find out that “a rising tide lifts all boats,” Garfield said, referring to how the GLP-1s have increased awareness and interest in obesity therapeutics. 

Of course, that increased awareness comes with further education to be done on the differences between hyperphagia and general obesity and battling the notion that all obesity is the same. But, with additional awareness and proof that the MC4R mechanism works in the “right” populations, Rhythm can “put a moat around our patient populations,” Garfield said. In the future, he expects obesity to become an "umbrella term" with well-defined subsets underneath the broader definition. 

Thinning, Leaky Brain Blood Vessels Seen in COVID-19

 You don't want this or the other findings on brain damage post COVID-19.  So get vaccinated and mask up.

Earlier has these reports:

1. The researchers observed that, in slices of hamster brain, SARS-CoV-2 blocks the functioning of receptors on pericytes, causing capillaries in the tissue to constrict. “It turns out this is a big effect,” says Attwell.

2. Evidence has also accumulated that SARS-CoV-2 can affect the brain by reducing blood flow to it — impairing neurons’ function and ultimately killing them.

3. A new study offers the first clear evidence that, in some people, the coronavirus invades brain cells, hijacking them to make copies of itself. The virus also seems to suck up all of the oxygen nearby, starving neighboring cells to death.

Thinning, Leaky Brain Blood Vessels Seen in COVID-19

High-resolution MRI shows injury and inflammation, but no direct viral attack

by Judy George, Senior Staff Writer, MedPage Today January 4, 2021

Microvascular brain injury was seen in COVID-19 patients who died, but no evidence of a direct viral attack on the brain was detected, a pathology report showed.

Damage caused by thinning and leaky brain blood vessels consistently appeared on high-resolution MRI, but there were no signs of SARS-CoV-2 infection in tissue samples, reported Avindra Nath, MD, clinical director of the National Institute of Neurological Disorders and Stroke (NINDS), and co-authors in a New England Journal of Medicine letter.

"We found there were many foci of small blood vessel damage from which there was leakage of blood products into the brain tissue," Nath said. "The cause of this was not clear but is most likely due to damage from the immune cells or lymphocytes. We found some lymphocytes attached to the endothelial cells in the blood vessels and in the perivascular regions," he told MedPage Today.

"The inflammatory response is key to the neuropathogenesis of this syndrome, since we were unable to find virus in the brain," Nath added. "The study potentially has important implications for long-term damage to several structures in the brain, particularly the olfactory bulb and the brainstem."

Other researchers have found SARS-CoV-2 RNA and protein in the brain and nasopharynx of patients who died with COVID-19, with highest levels of viral RNA found in the olfactory mucous membrane.

In this study, Nath and colleagues looked at brain tissue samples of COVID-19 patients -- 16 cases from the New York City chief medical examiner's office and three from the University of Iowa in Iowa City -- who died between March and July 2020. Their analysis included 11.7T MRI images of 13 patients at resolutions of 25 μm for the olfactory bulb and 100 μm for the brain, plus conventional histopathological brain exams of 18 patients.

Ages ranged from 5 to 73, with a median of 50. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly. Of 16 patients with available medical histories, one had delirium, five had mild respiratory symptoms, four had acute respiratory distress syndrome, two had pulmonary embolism, and symptoms were unknown in three.

Magnetic resonance microscopy showed punctate hyperintensities representing areas of microvascular injury and fibrinogen leakage in nine patients that correlated with histopathological exam, which showed thinning of the basal lamina of endothelial cells.

In contrast, punctate hypointensities in 10 patients corresponded to congested blood vessels with areas of fibrinogen leakage and "relatively intact vasculature," the researchers said. They also observed minimal perivascular inflammation but no vascular occlusion, consistent with other studies.

Perivascular-activated microglia, macrophage infiltrates, and hypertrophic astrocytes were seen in 13 patients. In eight patients, T cells were observed in perivascular spaces and in lumens adjacent to endothelial cells.

"We were completely surprised," Nath said. "Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with stroke and neuroinflammatory disease."

SARS-CoV-2 was not detected in brain tissue, but it's possible the virus was cleared by the time of death or viral copy numbers were below levels of detection by the assays used, the researchers noted.

So far, the findings suggest the damage was not caused by direct brain infection, Nath observed. With limited clinical information available in this study, no conclusions can be drawn about how these findings relate to neurologic features of COVID-19.

But studies are underway to "further characterize the inflammatory infiltrates and the pattern of neuronal injury in the autopsy material," Nath said. In addition, NINDS researchers are studying a cohort of COVID-19 patients with neurologic sequelae to determine whether they also have microvascular injury and whether inflammatory infiltrates are linked to persistent neurologic symptoms.

• 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

This study was supported by the NIH Intramural Research Program at NINDS.

The researchers had no disclosures.

Primary Source

New England Journal of Medicine

Source Reference: Lee MH, et al "Microvascular Injury in the Brains of Patients with COVID-19" N Engl J Med 2020; DOI: 10.1056/NEJMc2033369.

 

Unlocking the Key to COVID-19 and the Brain

You mean these people missed this earlier research explaining how the brain is damaged? 

Earlier has these reports:

1. The researchers observed that, in slices of hamster brain, SARS-CoV-2 blocks the functioning of receptors on pericytes, causing capillaries in the tissue to constrict. “It turns out this is a big effect,” says Attwell.

2. Evidence has also accumulated that SARS-CoV-2 can affect the brain by reducing blood flow to it — impairing neurons’ function and ultimately killing them.

3. A new study offers the first clear evidence that, in some people, the coronavirus invades brain cells, hijacking them to make copies of itself. The virus also seems to suck up all of the oxygen nearby, starving neighboring cells to death.

Unlocking the Key to COVID-19 and the Brain

What we know, and don't know, about SARS-CoV-2 and the nervous system

by Judy George, Senior Staff Writer, MedPage Today January 21, 2022

How can a respiratory pathogen like SARS-CoV-2 cause the nervous system to go haywire?

That's a question yet to be answered, observed Serena Spudich, MD, MA, of Yale University, and Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, in an essay in Science.

"Though COVID-19 is well known as a respiratory disease, neurological symptoms such as confusion, strokes, headaches, weakness, and nerve problems also occur in some patients around the time of the initial illness," Spudich told MedPage Today.

"Additionally, some people have difficulties with thinking, abnormal skin sensations, headaches, and other neurological symptoms for months after recovery from COVID-19," she continued. "Even patients with mild initial COVID-19 manifest a wide variety of persistent neurological and psychiatric symptoms, thus millions who have recovered from COVID-19 are at risk for these conditions."

The essay reviewed what's currently known about the effects of SARS-CoV-2 on the brain and what's still a mystery.

"Neurological complications are common, very diverse in presentation, and long lasting," Nath told MedPage Today. "They are largely immune-mediated, the brain endothelial cells being a major target."

"We do not have specific treatments for these illnesses, and the long-term consequences remain unknown," Nath noted. A concern is whether neurologic complications of COVID-19 could accelerate the process of neurodegenerative diseases, he added.

Clinical neurologic and psychiatric syndromes have emerged in studies of hospitalized COVID-19 patients, but little is known about their physiopathology. In their essay, Spudich and Nath discussed potential mechanisms for neurologic complications, including neuroinflammation, coagulopathy, neuronal injury, and possible viral infection in the central nervous system (CNS).

"Despite early speculation that SARS-CoV-2 may enter the CNS via migration through the nasal cavity and the olfactory pathway or trafficking across the blood-brain barrier, analysis of cerebrospinal fluid (CSF) from living patients with neuropsychiatric manifestations has almost uniformly failed to detect viral RNA by reverse transcription polymerase chain reaction," Spudich and Nath noted.

Instead, most evidence from CSF and brain tissue suggests that immune activation and inflammation within the CNS is the primary driver of neurologic disease in acute COVID-19, they said. Histopathological studies of brain tissue from patients who died with acute COVID-19 reveal only limited detection of SARS-CoV-2 nucleic acid or viral protein in the brain, consistent with findings in CSF from live patients, they noted.

What's also unknown is what drives the nervous system symptoms in long COVID. "Research is needed to understand whether longer-term neurologic and psychiatric symptoms that last in some people after recovery from acute COVID-19 -- nervous system long COVID -- relates to the persistence of immune and vascular abnormalities, or arises from other causes," Spudich said. "We also do not fully understand whether distinct SARS-CoV-2 variants or breakthrough cases after COVID-19 vaccination confer different risks for acute neurologic disorders or nervous system long COVID."

Since early in the pandemic, COVID-19 patients have described lingering symptoms after acute infection, including difficulty with memory and concentration, frequent headaches, alterations in skin sensation, autonomic dysfunction, and intractable fatigue. Many people with long COVID neurologic symptoms are under age 50 and were healthy and active prior to SARS-CoV-2 infection, Spudich and Nath noted. Most were never hospitalized for acute COVID-19 illness.

The COVID Mind Study at Yale is studying people with persistent post-COVID symptoms involving the nervous system with brain imaging, blood and spinal fluid assessments, and clinical tests. "Our multidisciplinary team applies state-of-the-art methods to look for signs of immune changes, vascular injury, and even ongoing presence of virus to reveal the underlying causes of nervous system long COVID, in order to develop targeted treatment," Spudich said.

"In the NIH intramural program, we are establishing a cohort of long COVID patients that will undergo deep phenotyping, and we are also in the process of starting a clinical trial using immunomodulatory drugs," Nath added.

"The COVID-19 pandemic has brought together patient groups, community members, clinicians, and investigators in an unprecedented manner to tackle the unexpected and emerging global neurological consequences of SARS-CoV-2," Spudich observed. "Discovery related to the effects of this viral infection in the nervous system may help to shed light on other infectious and immune-mediated disorders of the brain and nerves."

• 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

No disclosures were reported.

Primary Source

Science

Source Reference: Spudich S, Nath A "Nervous system consequences of COVID-19" Science 2022; DOI: 10.1126/science.abm2052.

 

Machine learning delivers insight into medication’s effects on stroke patients

Using this we could finally have accurate damage diagnoses which would mean stroke research trials could finally be repeated.  And rehab protocols could be rated for efficacy by  scanning the brain again to see where repair has occurred.

Machine learning delivers insight into medication’s effects on stroke patients

Researchers have used machine learning to identify how individual stroke patients might respond to different medications, based on the unique structure of their brain.
An experiment by University College London (UCL) found that applying computer intelligence to data from from people who had suffered a stroke allowed researchers to see what effect drugs had on brains with varying patterns of damage.
For the study, a machine learning algorithm was applied to CT and MRI scans of 1172 stroke patients and mapped the anatomical pattern of damage throughout the brain of each individual.
The researchers then simulated the effects of certain hypothetical drugs, to see if any reactions that would have been missed by conventional methods could be identified.
They found that the algorithm was particularly advantageous when looking at medication effects that reduced the size of lesions in patients’ brains.
Dr Parashkev Nachev, UCL Institute of Neurology and the study’s lead author, said: “Conventional statistical models will miss an effect even if the drug typically reduces the size of the lesion by half, or more, simply because the complexity of the brain’s functional anatomy – when left unaccounted for – introduces so much individual variability in measured clinical outcomes.”
“Yet saving 50% of the affected brain area is meaningful even if it doesn’t have a clear impact on behaviour. There’s no such thing as redundant brain.”
The researchers explained that the machine learning technique was so effective as it treated the stoke as a unique “fingerprint” in each patient, taking into account the presence or absence of damage throughout the brain accordingly.
Fellow author Tianbo Xu, of the UCL Institute of Neurology explained that stroke trials tend to use relatively few, crude variables, such as the size of the lesion, ignoring whether the lesion is centred on a critical area or at the edge of it.
He added, however, their algorithm learned the entire pattern of damage across the brain, “employing thousands of variables at high anatomical resolution.”
“We used well-established methods of machine learning, teaching the algorithm on subsets of data and then testing its performance on other subsets it had not seen.”
While the study only used data from stoke patients, the researchers aim to apply the technique more widely to clinical trials concerning the brain. They added that it could eventually be applied to other medical fields in order to offer patients more effective, tailored treatment.
Speaking to Digital Health News, Nachev said that machine learning will enable them to better predict the course of illness in each individual patient by taking into account not just one or two factors, “but the wide multiplicity that defines our individuality.”
He said such predictions will be extended to optimal treatment, optimal dose, and so on.
“Second, it will allow us to cast light on biological processes too complex to be modelled with the simple inferential techniques in current use,” Nachev added.
“Since in biology simplicity is the exception, not the rule, this will potentially unlock many new areas of understanding that were previously inaccessible.”
The exact role of machine learning and artificial intelligence in healthcare is yet to be determined, however its implications are widespread.
As well as improving the success of clinical trials, it is hoped that the technology will be capable of analysing large sets of human data and spot healthcare trends that could lead to better preventative healthcare.
“I think in time, machine learning will be seen not as an exotic luxury, but the principal way of making sense of biology, for it is far better equipped to deal with it than the simpler techniques of the past,” Nachev said.

Heart disease protein linked to brain damage

You had a stroke, have your doctor test you for this. You don't want early stage brain damage, your brain is damaged enough. 

Heart disease protein linked to brain damage

Radiological Society of North America News

Levels of a protein in the blood associated with heart disease are also linked to early–stage brain damage, according to a study appeared online in the journal Radiology.

A substance, or marker, in the blood indicative of subclinical heart disease and brain diseases like stroke and dementia could speed the initiation of treatments and lifestyle changes, potentially slowing or even reversing the disease's course.

One promising marker is N–terminal Pro–B–type natriuretic peptide (NT–proBNP), a protein released into the blood in response to cardiac wall stress. Blood serum levels of NT–proBNP rise when heart failure worsens and drop when it gets better. While previous studies have shown a link between heart disease and brain disease, less is known about the association between NT–proBNP and the entire spectrum of imaging markers of subclinical brain damage, like brain volume and white matter integrity.

Researchers from the Netherlands recently investigated this association in 2,397 community–dwelling middle–aged and elderly non–demented people without a clinical diagnosis of heart disease. The patients were drawn from the landmark Rotterdam Study, an ongoing, population–based study of more than 10,000 people from a suburb of Rotterdam, the Netherlands.

When the researchers compared serum levels of NT–proBNP with MRI findings, they discovered a clear association between higher NT–proBNP levels and brain damage.

"We found that higher serum levels of NT–proBNP were associated with smaller brain volumes, in particular with smaller gray matter volume, and with poorer organization of the brain's white matter," said Meike W. Vernooij, MD, PhD, the study's lead author and a neuroradiologist at Erasmus MC University Medical Center in Rotterdam.

The findings imply a close link between the heart and brain even in presumably healthy individuals, Dr. Vernooij said. There are several hypotheses to explain the link between cardiac dysfunction and subclinical brain damage, according to Dr. Vernooij. For instance, decreases in blood flow could lead to cerebral microvascular damage or problems in the function of the blood–brain barrier, a network of blood vessels that allow essential nutrients into the brain while blocking potentially harmful substances. Inflammatory factors associated with cardiac stress could also harm the barrier, leading to increased permeability and damage to the brain.

While NT–proBNP is currently used in a clinical setting to rule out heart failure, it is too early to say if it can play a similar role for subclinical brain damage, as the new study only looked at people at one point in time.

"We cannot rule out that the observed subclinical brain damage led to increased levels of NT–proBNP," Dr. Vernooij said. "However, from a biological perspective, and based on animal studies, it is more likely that cardiac dysfunction affects brain changes rather than vice versa."

Further research, including follow–up brain MRI studies and measurements of NT–proBNP, will be needed to clarify the relationship between cardiac dysfunction and subclinical brain disease, the researchers said

Inter-Rater Reliability of the Chedoke Arm and Hand Activity Inventory in an Acquired Brain Injury Population

You can check out the CAHAI here and see how subjective it is contrary to what the research here implies. Needing research on inter-rater reliability already means that the measurement used is wrong. You really need to start doing objective scans of brain damage and maybe then we could finally precisely map stroke protocols to damage rather than these crappy subjective measurements. 

Inter-Rater Reliability of the Chedoke Arm and Hand Activity Inventory in an Acquired Brain Injury Population

Authors:	Johnson, Denise
Advisor:	Harris, Jocelyn
Department:	Rehabilitation Science
Keywords:	Brain Injury;Reliability
Publication Date:	2016
Abstract:	Background: Motor impairments are common sequelae of Acquired Brain Injuries (ABI). An estimated 55-75% of ABI survivors have on-going limitations in UL function. Objective measures of UL function that have established validity and reliability in the ABI population are not readily available in the literature. The Chedoke Arm and Hand Inventory (CAHAI) is an assessment used with the stroke population. There are 4 versions of this assessment; a 13 item version and 3 shortened ones. The main purpose is to assess how much the affected UL contributes to a bilateral task. The CAHAI has strong reliability and validity in this population; however, it is unknown whether this measure can be used with other clinical populations such as ABI. Purpose: The purpose of this study was to estimate the inter-rater reliability of the Chedoke Arm and Hand Activity Inventory (CAHAI) when used with persons with ABI including 3 shortened versions of the measure.   Methods: This is an observational parameter estimation study.   Participants were recruited from an in-patient ABI rehabilitation program.   The administration of the CAHAI was video recorded for 6 persons with ABI.  The videos were assessed by 6 clinicians to estimate inter-rater reliability.  A Latin square design was used to balance the order raters evaluated the videos.   Analysis:  A repeated measures ANOVA was performed and the variance components were used to calculate an intra-class correlation coefficient (ICC) and standard error of measurement (SEM) with 95% confidence intervals (CI).   Results: Inter-rater reliability was high for all versions: CAHAI-7 ICC= 0.96 (95% CL: 0.89-0.99, SEM 2.65); CAHAI-8 ICC= 0.96 (95% CL: 0.90-0.99, SEM 2.72); CAHAI-9 ICC= 0.95 (95% CL: 0.85-0.99, SEM 3.49); CAHAI -13 ICC=0.96 (95%CL: 0.88-0.99, SEM 3.35).   Conclusions: These results suggest the CAHAI is highly reliability in the ABI population. The shortened versions may be particularly useful when time constraints or patient tolerance are an issue.
URI:	http://hdl.handle.net/11375/20633
Appears in Collections:	Open Access Dissertations and Theses

What does research reproducibility mean?

I'd be willing to bet that none of the clinical stroke research trials since forever are reproducible or replicable.  Because they don't have an objective starting point of exact description of the size and location of the dead/damaged areas.
Definitions from Retraction Watch
Here’s how the US National Science Foundation (NSF) defines “reproducibility,” according to the authors:

…reproducibility refers to the ability of a researcher to duplicate the results of a prior study using the same materials as were used by the original investigator. That is, a second researcher might use the same raw data to build the same analysis files and implement the same statistical analysis in an attempt to yield the same results…. Reproducibility is a minimum necessary condition for a finding to be believable and informative.

And here’s how the NSF defines “replicability,” the authors say:

…the ability of a researcher to duplicate the results of a prior study if the same procedures are followed but new data are collected.

What does research reproducibility mean?

1. Steven N. Goodman*,
2. Daniele Fanelli and
3. John P. A. Ioannidis

+ Author Affiliations

1. ↵*Corresponding author. Email: steve.goodman@stanford.edu

Science Translational Medicine  01 Jun 2016:
Vol. 8, Issue 341, pp. 341ps12
DOI: 10.1126/scitranslmed.aaf5027

• Article
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Abstract

The language and conceptual framework of “research reproducibility” are nonstandard and unsettled across the sciences. In this Perspective, we review an array of explicit and implicit definitions of reproducibility and related terminology, and discuss how to avoid potential misunderstandings when these terms are used as a surrogate for “truth.”

Locomotor Rehabilitation of Individuals With Chronic Stroke: Difference Between Responders and Nonresponders

You'll have to ask your doctor to get the walking protocol they were using because our fucking failures of stroke associations have no mechanism to collect and distribute research protocols. You would think that at a minimum they would collect such data. But no, they are too busy putting out stupid press releases.
http://www.archives-pmr.org/article/S0003-9993%2812%2901196-3/abstract

Mark G. Bowden, PhD, PT

,

Andrea L. Behrman, PhD, PT

,

Richard R. Neptune, PhD

,

Chris M. Gregory, PhD, PT

,

Steven A. Kautz, PhD

DOI: http://dx.doi.org/10.1016/j.apmr.2012.11.032

Article Info

Publication History

Published Online: December 06, 2012

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• Full Text
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Abstract

Objectives

To identify the clinical measures associated with improved walking speed after locomotor rehabilitation in individuals poststroke and how those who respond with clinically meaningful changes in walking speed differ from those with smaller speed increases.

Design

A single group pre-post intervention study. Participants were stratified on the basis of a walking speed change of greater than (responders) or less than (nonresponders) .16m/s. Paired sample t tests were run to assess changes in each group, and correlations were run between the change in each variable and change in walking speed.

Setting

Outpatient interdisciplinary rehabilitation research center.

Participants

Hemiparetic subjects (N=27) (17 left hemiparesis; 19 men; age: 58.74±12.97y; 22.70±16.38mo poststroke).

Intervention

A 12-week locomotor intervention incorporating training on a treadmill with body weight support and manual trainers accompanied by training overground walking.

Main Outcome Measures

Measures of motor control, balance, functional walking ability, and endurance were collected at pre- and postintervention assessments.

Results

Eighteen responders and 9 nonresponders differed by age (responders=63.6y, nonresponders=49.0y, P=.001) and the lower extremity Fugl-Meyer Assessment score (responders=24.7, nonresponders=19.9, P=.003). Responders demonstrated an average improvement of .27m/s in walking speed as well as significant gains in all variables except daily step activity and paretic step ratio. Conversely, nonresponders demonstrated statistically significant improvements only in walking speed and endurance. However, the walking speed increase of .10m/s was not clinically meaningful. Change in walking speed was negatively correlated with changes in motor control in the nonresponder group, implying that walking speed gains may have been accomplished via compensatory mechanisms.

Conclusions

This study is a step toward discerning the underlying factors contributing to improved walking performance. Did you look at the damage location at all? Or are you that stupid? And these people have PhDs?

What is so special about the human brain?

Lots of fascinating info on the brain in this TED talk.
What is so special about the human brain?
This part is interesting for those thinking that raw foods or a Paleo diet are so wonderful.
Gorillas and orangutans, for instance, afford about 30 billion neurons by spending eight and a half hours per day eating, and that seems to be about as much as they can do. Nine hours of feeding per day seems to be the practical limit for a primate.  We have 86 billion neurons.

Has your doctor told you how many neurons you killed off? Doesn't that sound like something useful to know?

Brain arteries

A selection of brain artery images for you to take to your doctor and demand to know where the exact area the artery plugged or broke. This will be the only way we will ever be able to objectively correlate artery break to damage in the brain. It hasn't occurred in the last 70 years, it's time to start screaming at our doctors now. We can't let them run a failing system for another 70 years.
From 
https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiWF5ReGIDJwZdxYJ0sacLI5FKb6t3GT_zHqVeZHKIgiF2jva-4d5L_B94Htq_kTzfpsyB1TKJ-GXIGpxaCZav0SoBGGlfh4Ryw6X_E9uQuL8bmwlmG5ePUQ_rsykZLjrWpT6ZssipICAQ/s1600/arteries_supplying_the_brain.jpg


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Multineurons is developing head-worn sensor & iPad app to monitor patients with brain disorders

We most certainly have brain disorders, so what is your doctor doing with this to determine your specific brain problems? Your doctor has to know specifically what damage has occurred. Or how will they come up with the correct stroke protocols to correct the problems and pass on the right prescriptions to the therapists? Because today they know absolutely nothing about your damage and are totally worthless in helping you recover. That statement should create dozens of flame wars in the comments.
http://medcitynews.com/2014/03/multineurons-developing-head-worn-sensor-monitor-patients-brain-disorders/?

Scientists catch brain damage in the act

Article here:
http://news.ubc.ca/2014/03/13/macvicar/
So they can see the damage occurring, Damn it figure out a way to stop the damage from occurring. Don't be so damn lazy and just stop and report on the problem.
Fix it!!!

Brain and nervous system damaged by low-level exposure to organophosphate pesticides

Your brain has been badly insulted stay away from this stuff.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=126485&CultureCode=en
Scientists have found that low-level exposure to organophosphates (OPs) produces lasting decrements in neurological and cognitive function. Memory and information processing speed are affected to a greater degree than other cognitive functions such as language.
The systematic review of the literature was carried out by researchers at UCL and the Open University. It is the first to attempt a quantitative evaluation of the data assimilated from 14 studies and more than 1,600 participants. The researchers used meta-analysis to obtain an overview of the literature and their findings are published in the journal Critical Reviews in Toxicology.
“Meta-analysis combines the results of several studies and moves the discussion away from individual pieces of research, towards an overview of a body of literature,” says lead author Dr Sarah Mackenzie Ross (UCL Clinical, Educational & Health Psychology).
“This is considered to be the method of choice in situations where research findings may be used to inform public policy,” explains Professor Chris McManus (UCL Clinical, Educational & Health Psychology), co-author of the study.
Dr Mackenzie Ross continues: “This is the first time anyone has analysed the literature concerning the neurotoxicity of organophosphate pesticides, using the statistical technique of meta-analysis.
“The analysis reveals that the majority of well-designed studies undertaken over the last 20 years find a significant association between low-level exposure to organophosphates and impaired cognitive function.”
Pesticides prevent millions of people from starving to death and from contracting disease, but they are also harmful to humans under certain circumstances. Derived from World War II nerve gas agents, organophosphate pesticides are the most widely used insecticides in the world. They are used extensively in agriculture, by the military and also for domestic purposes.
According to the World Health Organisation (WHO) organophosphate pesticides are one of the most hazardous pesticides to vertebrate animals, responsible for many cases of poisoning worldwide.
The toxic effects of high level poisoning are well established but the possibility that long-term low-level exposure to OPs in doses below that causing acute toxicity causes ill health is controversial.
“In the UK a number of occupational groups have expressed concern that their health has been affected by exposure to organophosphates,” explains Dr Virginia Harrison (Open University), co-author of the study. This includes sheep farmers, who between 1988 and 1991 were required to dip sheep yearly in pesticide formulations containing OPs. Between 1985 and 1998 more than 600 reports of ill health following exposure to sheep dip were received by a government adverse reaction surveillance scheme.
Other groups affected include:
(1)   Gulf War Veterans, who were exposed to pesticides on a daily basis during their tour of duty to protect them from pests such as sand flies, mosquitoes and fleas which carry infectious diseases
(2)   airline pilots and cabin crew, who can be exposed to organophosphates in engine oil.
The researchers hope their findings will be of interest to Government advisory committees and departments who are currently reviewing the neurotoxicity of low level exposure to OPs; as well as farmers, Gulf War veterans and aviation workers who believe their health has been affected by exposure to OPs.