Posts Tagged brain

[News] New noninvasive ultrasound neuromodulation technique for epilepsy treatment

Reviewed by Emily Henderson, B.Sc.May 15 2020

Epilepsy is a central nervous system disorder characterized by recurrent seizures resulting from excessive excitation or inadequate inhibition of neurons.

Ultrasound stimulation has recently emerged as a noninvasive method for modulating brain activity; however, its range and effectiveness for different neurological disorders, such as Parkinson’s Disease, Epilepsy and Depression, have not been fully elucidated.

Researchers from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences developed a noninvasive ultrasound neuromodulation technique, which could potentially modulate neuronal excitability without any harm in the brain.

Low-intensity pulsed ultrasound and ultrasound neuromodulation system were prepared for non-human primate model of epilepsy and human epileptic tissues experiments, respectively.

The results showed that ultrasound stimulation could exert an inhibitory influence on epileptiform discharges and improve behavioral seizures in a non-human primate epileptic model.

Ultrasound stimulation inhibited epileptiform activities with an efficiency exceeding 65% in biopsy specimens from epileptic patients in vitro.

The mechanism underlying the inhibition of neuronal excitability could be due to adjusting the balance of excitatory-inhibitory (E/I) synaptic inputs by the increased activity of local inhibitory neurons. In addition, the variation of temperature among these brain slices was less than 0.64°C during the experimental procedure.

The study demonstrated for the first time that low-intensity pulsed ultrasound improved electrophysiological activities and behavioral outcomes in a non-human primate model of epilepsy and suppressed epileptiform activities of neurons from human epileptic slices.

It provided evidence for the potential clinical use of non-invasive low-intensity pulsed ultrasound stimulation for epilepsy treatment.

Source: Chinese Academy of Sciences Headquarters

Journal reference: Lin, Z., et al. (2020) Non-invasive ultrasonic neuromodulation of neuronal excitability for treatment of epilepsy.

BiopsyBrainCentral Nervous SystemDepressionEpilepsyin vitroNervous SystemNeuromodulationNeuronsTheranosticsUltrasound

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[ARTICLE] Advances in brain imaging in multiple sclerosis – Full Text

Brain imaging is increasingly used to support clinicians in diagnosing multiple sclerosis (MS) and monitoring its progression. However, the role of magnetic resonance imaging (MRI) in MS goes far beyond its clinical application. Indeed, advanced imaging techniques have helped to detect different components of MS pathogenesis in vivo, which is now considered a heterogeneous process characterized by widespread damage of the central nervous system, rather than multifocal demyelination of white matter. Recently, MRI biomarkers more sensitive to disease activity than clinical disability outcome measures, have been used to monitor response to anti-inflammatory agents in patients with relapsing–remitting MS. Similarly, MRI markers of neurodegeneration exhibit the potential as primary and secondary outcomes in clinical trials for progressive phenotypes. This review will summarize recent advances in brain neuroimaging in MS from the research setting to clinical applications.


In the last decade, magnetic resonance imaging (MRI) has emerged as a fundamental imaging biomarker for multiple sclerosis (MS). Currently, MRI plays a key role in several aspects of the disease including diagnosis,1 prognosis2 and treatment response assessment.3

Over the last few years, developments in brain imaging acquisition and post-processing have advanced the field and have made tremendous contributions to our understanding of disease-specific pathogenetic mechanisms.4 This has improved the accuracy of MS diagnosis and differentiation from other inflammatory diseases of the central nervous system (CNS).5 Furthermore, promising imaging biomarkers are now used to reflect pathological processes occurring in progressive MS.6 This has culminated in the recent use of advanced imaging technique measures as outcomes in phase II and III MS clinical trials of disease-modifying and neuroprotective therapies.7

There is expanding scientific literature on brain imaging in MS. Therefore, we constrained our review to the clinical advances in human brain MRI achieved over the last 5 years in the MS field. Although positron emission tomography (PET)8 and optical coherence tomography (OCT)9 are currently emerging as key tools in the understanding of MS pathophysiology and in monitoring the disease, these neuroimaging techniques were not included in our search criteria.

The aim of this review was to describe advances in brain MRI imaging used to support the diagnosis of MS and to characterize the pathological mechanisms underlying clinical activity and progression. Finally, we intended also to present the recent impact of these advances on clinical trials in MS. For these purposes, the review was conducted using literature from Embase and PubMed using the following keywords: multiple sclerosis; magnetic resonance imaging; brain; pathogenesis; diagnosis; progression. As regards clinical trials, we focused on completed phase II and III trials in relapsing–remitting MS (RR-MS) or progressive MS using clinical trials databases, such as and

Recent advances in neuroimaging considering different brain locations are listed in Figure 1.


Figure 1. Advances in brain imaging in multiple sclerosis in different brain locations.
CVS, central vein sign; DGM, deep grey matter; DMD, disease-modifying drug; ihMT, inhomogeneous magnetization transfer; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; MWF, myelin water fraction; NODDI, neurite orientation dispersion and density imaging; PET, positron emission tomography; qMT, quantitative magnetization transfer; SEL, slowly expanding lesion; TSC, total sodium concentration.


Continue —-> Advances in brain imaging in multiple sclerosis – Rosa Cortese, Sara Collorone, Olga Ciccarelli, Ahmed T. Toosy, 2019

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[TED-Ed] Is marijuana bad for your brain? Anees Bahji. – Video Animation

In 1970, marijuana was classified as a schedule 1 drug in the United States: the strictest designation possible, meaning it was completely illegal and had no recognized medical uses. Today, marijuana’s therapeutic benefits are widely acknowledged, but a growing recognition for its medical value doesn’t answer the question: is recreational marijuana use bad for your brain? Anees Bahji investigates.

via Is marijuana bad for your brain? – Anees Bahji | TED-Ed

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[ARTICLE] Self-Support Biofeedback Training for Recovery From Motor Impairment After Stroke – Full Text


Unilateral arm paralysis is a common symptom of stroke. In stroke patients, we observed that self-guided biomechanical support by the nonparetic arm unexpectedly triggered electromyographic activity with normal muscle synergies in the paretic arm. The muscle activities on the paretic arm became similar to the muscle activities on the nonparetic arm with self-supported exercises that were quantified by the similarity index (SI). Electromyogram (EMG) signals and functional near-infrared spectroscopy (fNIRS) of the patients (n=54) showed that self-supported exercise can have an immediate effect of improving the muscle activities by 40–80% according to SI quantification, and the muscle activities became much more similar to the muscle activities of the age-matched healthy subjects. Using this self-supported exercise, we investigated whether the recruitment of a patient’s contralesional nervous system could reactivate their ipsilesional neural circuits and stimulate functional recovery. We proposed biofeedback training with self-supported exercise where the muscle activities were visualized to encourage the appropriate neural pathways for activating the muscles of the paretic arm. We developed the biofeedback system and tested the recovery speed with the patients (n=27) for 2 months. The clinical tests showed that self-support-based biofeedback training improved SI approximately by 40%, Stroke Impairment Assessment Set (SIAS) by 35%, and Functional Independence Measure (FIM) by 20%.


Stroke is the leading cause of long-term disability worldwide. Of more than 750,000 stroke victims in the United States each year [1], approximately two-thirds survive and require immediate rehabilitation to recover lost brain functions [2]. These stroke rehabilitation programs, of which direct and indirect costs were estimated to be 73.7 billion dollars in 2010 [3], aim to help survivors gain physical independence and better quality of life.

Stroke damage typically interrupts blood flow within one brain hemisphere, resulting in unilateral motor deficits, sensory deficits, or both. The preservation of long-term neural and synaptic plasticity is essential for the functional reorganization and recovery of neural pathways disrupted by stroke [4]–[5][6]. Stroke survivors typically require long-term, intensive rehabilitation training due to the length of time required for these recovery processes [7], [8]. The typical time course for partial recovery of arm movement after mild to moderate unilateral stroke damage is 2 to 6 months, depending on the severity of tissue damage and the latency of treatment initiation [9], [10]; however, patients with severe damage require additional months to years of rehabilitation. Given the economic burden on patients’ families and the medical system, novel rehabilitation methods that promote rapid and complete functional recovery are needed, along with a better understanding of the functional mechanisms and neural circuits that can participate in potential therapeutic processes. The identification of rehabilitation methods that can more effectively recover brain functions in the damaged hemisphere by re-engaging dormant motor functions should be a major global objective, from both economic and societal perspectives. Such an objective would require the interface of biology, medical research, and clinical practice [4].

Recently, candidate brain areas that become activated during stroke recovery have been identified in patients and animal models [7]. Brain imaging studies during stroke recovery suggest that the extent of functional motor recovery is associated with an increase in neuronal activity in the sensorimotor cortex of the ipsilesional hemisphere [10]–[11][12]. Other work has suggested that repetitive sensorimotor tasks may promote cortical reorganization and functional recovery in the ipsilesional area by increasing bilateral cortical activity to enhance neuroplasticity [13]. Activation in the contralesional hemisphere is also observed in the early stages of post-stroke patients. This activation has been explained by the emergence of communication in corticospinal projections that are silent in the healthy state [11], and it may also contribute to movement-related neural activity on the ipsilesional limb [14], [15]. Functional brain imaging studies show that activity of the contralesional hemisphere is increased early after stroke and gradually declines as recovery progresses [16]. The functional relevance of contralesional recruitment remains unclear [17], [18]. Some reported studies have linked high abnormal activity to a high inhibitory signaling drive onto the ipsilesional cortex [19], which may be a major contributor to motor impairment [6], [20]. Recent studies have also investigated the benefits of activating the contralesional and/or ipsilesional hemispheres in functional motor recovery using brain-computer interface (BCI) and transcranial magnetic stimulation (TMS) therapies [21], [22].

Current stroke rehabilitation approaches have largely focused on paretic limb rehabilitation interventions such as muscle strengthening and endurance training [23], forced-use therapy [24], constraint-induced exercise [25], robot therapy with biofeedback [26], nonparetic limb interventions (e.g., mirror-therapy [27], [28]), or bilateral/bimanual training [29], [30]. However, to date, none have clearly investigated how the use of a patient’s unaffected neural circuits in the healthy cortical hemisphere, or in the local peripheral circuit, affect the impaired limb in terms of functional rehabilitation of the bilateral cortical sensorimotor network [31].

In this study, we investigated a motor recovery approach for post-stroke unilateral arm impairment that combined sensory feedback, motor control, and motor intention. While observing a patient cohort with unilateral stroke damage and arm movement impairment, we found that a specific self-guided motion, which we termed self-supported exercise, surprisingly reactivated a healthy muscles pattern in the paretic arm. The key of the self-supported exercise is use of the nonparetic arm as a support to help move the paretic arm. First, we will show the observation of appropriate muscle recruitment and reduction of abnormal muscle synergies for post-stroke patients during the self-supported exercise, which are a common problem in stroke recovery [32]. Then, we conduct the experiments of functional imaging and electromyography recordings and characterized the neurobiology and physiology of this self-supported exercise. Based on this mechanism, we designed a rehabilitation program involving biofeedback-aided self-supported exercises that employ a patients’ self-initiated motor intention. The results of the comparative experiments between the feedback training cohorts and the control cohorts show that this method results in efficient recovery from post-stroke motion paralysis. Finally, we discuss the significance of our findings for the design of biologically-based stroke rehabilitation.[…]

via Self-Support Biofeedback Training for Recovery From Motor Impairment After Stroke – IEEE Journals & Magazine

FIGURE 2. - The four types of exercises.

FIGURE 2.The four types of exercises.




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[TED-Ed] The brain-changing benefits of exercise – Wendy Suzuki

What’s the most transformative thing that you can do for your brain today? Exercise! says neuroscientist Wendy Suzuki. Get inspired to go to the gym as Suzuki discusses the science of how working out boosts your mood and memory — and protects your brain against neurodegenerative diseases like Alzheimer’s.

via The brain-changing benefits of exercise – Wendy Suzuki | TED-Ed

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[Infographic] Music & The Brain


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[NEWS] Novel artificial intelligence algorithm helps detect brain tumor


A brain tumor is a mass of abnormal cells that grow in the brain. In 2016 alone, there were 330,000 incident cases of brain cancer and 227,000 related-deaths worldwide. Early detection is crucial to improve patient prognosis, and thanks to a team of researchers, they developed a new imaging technique and artificial intelligence algorithm that can help doctors accurately identify brain tumors.


Image Credit: create jobs 51 /

Image Credit: create jobs 51 /

Published in the journal Nature Medicine, the study reveals a new method that combines modern optical imaging and an artificial intelligence algorithm. The researchers at New York University studied the accuracy of machine learning in producing precise and real-time intraoperative diagnosis of brain tumors.

In the past, the only way to diagnose brain tumors is through hematoxylin and eosin staining of processed tissue in time. Plus, interpretation of the findings relies on pathologists who examine the specimen. The researchers hope the new method will provide a better and more accurate diagnosis, which can help initiate effective treatments right away.

In cancer treatment, the earlier cancer has been diagnosed, the earlier the oncologists can start the treatment. In most cases, early detection improves health outcomes. The researchers have found that their novel method of detection yielded a 94.6 percent accuracy, compared to 93.9 percent for pathology-based interpretation.

The imaging technique

The researchers used a new imaging technique called stimulated Raman histology (SRH), which can reveal tumor infiltration in human tissue. The technique collects scattered laser light and emphasizes features that are not usually seen in many body tissue images.

With the new images, the scientists processed and studied using an artificial intelligence algorithm. Within just two minutes and thirty seconds, the researchers came up with a brain tumor diagnosis. The fast detection of brain cancer can help not only in diagnosing the disease early but also in implementing a fast and effective treatment plan. With cancer caught early, treatments may be more effective in killing cancer cells.

The team also utilized the same technology to accurately identify and remove undetectable tumors that cannot be detected by conventional methods.

“As surgeons, we’re limited to acting on what we can see; this technology allows us to see what would otherwise be invisible, to improve speed and accuracy in the OR, and reduce the risk of misdiagnosis. With this imaging technology, cancer operations are safer and more effective than ever before,” Dr. Daniel A. Orringer, associate professor of Neurosurgery at NYU Grossman School of Medicine, said.

Study results

The study is a walkthrough of various ideas and efforts by the research team. First off, they built the artificial intelligence algorithm by training a deep convolutional neural network (CNN), containing more than 2.5 million samples from 415 patients. The method helped them group and classify tissue samples into 13 categories, representing the most common types of brain tumors, such as meningioma, metastatic tumors, malignant glioma, and lymphoma.

For validation, the researchers recruited 278 patients who are having brain tumor resection or epilepsy surgery at three university medical centers. The tumor samples from the brain were examined and biopsied. The researchers grouped the samples into two groups – control and experimental.

The team assigned the control group to be processed traditionally in a pathology laboratory. The process spans 20 to 30 minutes. On the other hand, the experimental group had been tested and studied intraoperatively, from getting images and processing the examination through CNN.

There were noted errors in both the experimental and control groups but were unique from each other. The new tool can help centers detect and diagnose brain tumors, particularly those without expert neuropathologists.

“SRH will revolutionize the field of neuropathology by improving decision-making during surgery and providing expert-level assessment in the hospitals where trained neuropathologists are not available,” Dr. Matija Snuderl, associate professor in the Department of Pathology at NYU Grossman School of Medicine, explained.

Journal references:

Patel, A., Fisher, J, Nichols, E., et al. (2019). Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology.

Hollon, T., Pandian, B, Orringer, D. (2019). Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks. Nature Medicine.


via Novel artificial intelligence algorithm helps detect brain tumor

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[WEB SITE] Why Your Brain Needs Exercise

Why Your Brain Needs Exercise

Credit: Bryan Christie Design

Why Your Brain Needs Exercise

The evolutionary history of humans explains why physical activity is important for brain health


  • It is by now well established that exercise has positive effects on the brain, especially as we age.
  • Less clear has been why physical activity affects the brain in the first place.
  • Key events in the evolutionary history of humans may have forged the link between exercise and brain function.
  • Cognitively challenging exercise may benefit the brain more than physical activity that makes fewer cognitive demands.


In the 1990s researchers announced a series of discoveries that would upend a bedrock tenet of neuroscience. For decades the mature brain was understood to be incapable of growing new neurons. Once an individual reached adulthood, the thinking went, the brain began losing neurons rather than gaining them. But evidence was building that the adult brain could, in fact, generate new neurons. In one particularly striking experiment with mice, scientists found that simply running on a wheel led to the birth of new neurons in the hippocampus, a brain structure that is associated with memory. Since then, other studies have established that exercise also has positive effects on the brains of humans, especially as we age, and that it may even help reduce the risk of Alzheimer’s disease and other neurodegenerative conditions. But the research raised a key question: Why does exercise affect the brain at all?

Physical activity improves the function of many organ systems in the body, but the effects are usually linked to better athletic performance. For example, when you walk or run, your muscles demand more oxygen, and over time your cardiovascular system responds by increasing the size of the heart and building new blood vessels. The cardiovascular changes are primarily a response to the physical challenges of exercise, which can enhance endurance. But what challenge elicits a response from the brain?

Answering this question requires that we rethink our views of exercise. People often consider walking and running to be activities that the body is able to perform on autopilot. But research carried out over the past decade by us and others would indicate that this folk wisdom is wrong. Instead exercise seems to be as much a cognitive activity as a physical one. In fact, this link between physical activity and brain health may trace back millions of years to the origin of hallmark traits of humankind. If we can better understand why and how exercise engages the brain, perhaps we can leverage the relevant physiological pathways to design novel exercise routines that will boost people’s cognition as they age—work that we have begun to undertake.


To explore why exercise benefits the brain, we need to first consider which aspects of brain structure and cognition seem most responsive to it. When researchers at the Salk Institute for Biological Studies in La Jolla, Calif., led by Fred Gage and Henriette Van Praag, showed in the 1990s that running increased the birth of new hippocampal neurons in mice, they noted that this process appeared to be tied to the production of a protein called brain-derived neurotrophic factor (BDNF). BDNF is produced throughout the body and in the brain, and it promotes both the growth and the survival of nascent neurons. The Salk group and others went on to demonstrate that exercise-induced neurogenesis is associated with improved performance on memory-related tasks in rodents. The results of these studies were striking because atrophy of the hippocampus is widely linked to memory difficulties during healthy human aging and occurs to a greater extent in individuals with neurodegenerative diseases such as Alzheimer’s. The findings in rodents provided an initial glimpse of how exercise could counter this decline.

Following up on this work in animals, researchers carried out a series of investigations that determined that in humans, just like in rodents, aerobic exercise leads to the production of BDNF and augments the structure—that is, the size and connectivity—of key areas of the brain, including the hippocampus. In a randomized trial conducted at the University of Illinois at Urbana-Champaign by Kirk Erickson and Arthur Kramer, 12 months of aerobic exercise led to an increase in BDNF levels, an increase in the size of the hippocampus and improvements in memory in older adults.

Other investigators have found associations between exercise and the hippocampus in a variety of observational studies. In our own study of more than 7,000 middle-aged to older adults in the U.K., published in 2019 in Brain Imaging and Behavior, we demonstrated that people who spent more time engaged in moderate to vigorous physical activity had larger hippocampal volumes. Although it is not yet possible to say whether these effects in humans are related to neurogenesis or other forms of brain plasticity, such as increasing connections among existing neurons, together the results clearly indicate that exercise can benefit the brain’s hippocampus and its cognitive functions.

Researchers have also documented clear links between aerobic exercise and benefits to other parts of the brain, including expansion of the prefrontal cortex, which sits just behind the forehead. Such augmentation of this region has been tied to sharper executive cognitive functions, which involve aspects of planning, decision-making and multitasking—abilities that, like memory, tend to decline with healthy aging and are further degraded in the presence of Alzheimer’s. Scientists suspect that increased connections between existing neurons, rather than the birth of new neurons, are responsible for the beneficial effects of exercise on the prefrontal cortex and other brain regions outside the hippocampus.


With mounting evidence that aerobic exercise can boost brain health, especially in older adults, the next step was to figure out exactly what cognitive challenges physical activity poses that trigger this adaptive response. We began to think that examining the evolutionary relation between the brain and the body might be a good place to start. Hominins (the group that includes modern humans and our close extinct relatives) split from the lineage leading to our closest living relatives, chimpanzees and bonobos, between six million and seven million years ago. In that time, hominins evolved a number of anatomical and behavioral adaptations that distinguish us from other primates. We think two of these evolutionary changes in particular bound exercise to brain function in ways that people can make use of today.

Graphic shows how increased production of the protein BDNF may promote neuron growth and survival in the adult brain.

Credit: Tami Tolpa


For more, visit —->  Why Your Brain Needs Exercise – Scientific American

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[BLOG POST] Exercise can help your brain injury, not just your muscles – #jumbledbrain

Having suffered a car accident, I had some serious injuries. These included my spine, nerves and my brain. I had foot drop, where when you raise your leg, you can not raise your foot from your ankle, leaving it to hang limply. That means you cannot put any weight on it and it will not offer any support or flexibility. On top of this, due tExerciseo a damaged nerve in my neck, and had weakness down my left side. However after 10 days, the hospital team got me walking with crutches, and sent me home.

I knew that I needed to do some exercise to help rebuild some of my strength. But what I didn’t know was how good exercise is for your brain as well.

We all know that the more you practise at something, the better you will get at it. Well, the brain is just the same. Every time you perform an action, you are creating the building blocks for a new pathway in your brain. Let me give you an example. I used to love painting and drawing. But following my  brain injury, I could barely write legibly. For me this was depressing, as my art was a part of who I was. My partner James, kept badgering me to keep trying although I felt he just didn’t understand. I couldn’t make my hand follow the instructions I gave it properly, leaving me frustrated.

Exercise doesn’t mean you have to hit the gym. Just practise a physical activity.

So many sheets of paper ended up in the bin. (I would like to apologise to the trees who were sacrificed  for my cause.) But in time my writing improved, and I found my artistic flair returning to me. Just by reminding the muscles in my hand and arm how to behave, I had begun to regain my skill. But it wasn’t because the muscles needed to be rebuilt, it was because my brain needed to create new pathways to replace those that were damaged. This is the same process as when you learn a skill for the first time, and why your mother always said “practise makes perfect.” The more we do an action, the more the brain prioritises building pathways which make a shortcut to that action.

Now I know you are saying “but Michelle drawing and writing isn’t exercise.” And yes you are right, but I wanted to share this example with you to help you see that although there is the physical muscles movements, there is much more that needs to happen and I think we can all agree agree creativity is something very much in your brain.

Think about how in sports there is a tactical element, spacial awareness, problem solving… the list goes on.

Think of your favourite teams and how some are better at the element of surprise than others. This is the players having to read the current situation and apply the tactics that they have been practising all whilst dealing with how their opponents are trying to stop them. Yes it helps to be the fastest and strongest person on the pitch, but if you can’t get your timing, accuracy and game plan right, you’re going to still struggle. And whilst you might take the feedback from your coach with, you can only get better at these things by going out there and trying again. Ths that’s why exercise can help your brain injury recovery for other parts of the brain too.

I’m now 5 years on from my accident, and most people wouldn’t notice my slight limp. For someone who struggled to walk for so long, that’s not bad. I still have nerve damage, and I may do for the rest of my life, but I can deal with it. I’d be frightened to go skiing again, but it doesn’t affect my everyday life much at all. Yes I get pain and tire much easier, but I can cope with that.

My brain is still trying to repair my cognitive skills. Bearing in mind I couldn’t read or write to start with, I think it’s fair to say it’s doing a pretty good job. I even set up this website all by myself even though I had no experience of doing this sort of thing before. (If you are thinking of starting a blog but aren’t sure where to start head over to Starting a blog following a brain injury is difficult, but it is achievable to get some ideas on how to get going.)

No matter what your fitness level, or sporting ability never underestimate the importance of exercise.

You don’t need to run like you’re Mo Farah, just find something you enjoy which you can fit into your busy schedule. Dance, yoga and swimming are all great options. As evidence is growing to show regular exercise can stave off dementia, your brain will thank you for it. We all have days when just getting out of bed is an achievement, so don’t feel any shame in taking it easy. But just remember your efforts will encourage enhancements in much more than just becoming physically stronger. Your mental health and general well being will benefit too. Exercise can help your brain injury recovery process and you might even discover a talent for something new that you never knew you had.

Other articles you may like:

What exercises have you found most beneficial following your brain injury?

via Exercise can help your brain injury, not just your muscles #jumbledbrain

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[WEB PAGE] Study reveals three effective treatments to stop epilepsy seizures


There are effective treatments to stop life-threatening epilepsy seizures when the initial treatment has failed, a sweeping new study reveals.

The study offers important answers about three such emergency drugs that are used to treat prolonged seizures, known as status epilepticus, even though physicians have had little understanding of the drugs’ effectiveness. Until now, there has been no clear indication of which is best or how much should be given.

The study found that the three drugs – intravenous levetiracetam, fosphenytoin, and valproate – were all about equally effective at stopping the potentially deadly seizures when the default choice, benzodiazepines, proved unable to do so. The results were so clear that the shocked researchers stopped their trial early.

When we planned the study, we didn’t even know if these drugs work 10%, 25% or 50% of the time. So the big, big takeaway is that each of these drugs works about 45 percent of the time. And this is an important finding because it tells us patients can get better. They don’t have to be placed on a on a ventilator [breathing machine].”

Jaideep Kapur, MBBS, PhD, investigator and the head of the University of Virginia Brain Institute

Effect on Clinical Practice

The study’s findings, published in the prestigious New England Journal of Medicine, both affirm existing clinical practices and suggest a major change.

Doctors can feel confident that their preferred drug of choice is as effective as the other options, Kapur noted, but they also should significantly increase how much levetiracetam they give when they choose it.

“Prior to this, people were using their best guess as to which drug to use and how much of it to use. And this puts those things to rest and tells you exactly how much of which to use, and what to expect,” said Kapur, of the UVA School of Medicine’s Department of Neurology.

The trial organizers tested the maximum safe dose of each of the drugs so there would be no question whether too little had been used to gauge the medicine’s effectiveness. In so doing, they gave twice as much levetiracetam as many doctors administer.

“When I started 25 years ago, there was not a single scientifically proven drug [for status epilepticus]. We didn’t know which drug to use, even for the first-line treatment, and how much of them to use,” Kapur said. “And 25 years later, we can treat more than 80% of the patients – 85% of the patients – using scientifically proven drugs. 85% of our patients will get better, will stop having seizures and start waking up. That is the effect of scientific research on improving care of patients, and this is real.”

About the Epilepsy Seizure Trial

The randomized, double-blinded trial looked at the effect of the drugs in 384 patients at 57 emergency departments in the United States between November 2015 and the end of October 2017.

The researchers originally planned to study 795 patients over five years, but the results were so clear that was deemed unnecessary. “Clinical trials are notorious for going over long and over budget, and we came in under budget,” Kapur said.

That was possible, he said, because of the participation of many top experts in both the United States and Europe. Participating sites included the University of Michigan, Medical University of South Carolina, UVA, Children’s National Medical Center in Washington, D.C., and many more.

“It was an amazingly accomplished group of people,” Kapur said. “We had the best experts from all over the United States and Europe. For me, it’s been a great joy working with the team as the leader of the Brain Institute. That’s the spirit I want to bring to UVA. That’s really what motivated me to start the Brain Institute: to fashion these teams within UVA, so that we can do really significant, societally impactful research.”

UVA Emergency Medicine physician Stephen Huff, MD, led the study at the UVA site, which enrolled seven subjects. Amy Fansler, Emily Gray and Lea Becker helped organize the study.

Kapur expressed his gratitute to all the patients who participated in the study. “President Ryan [UVA President Jim Ryan] has said we must be great and good,” Kapur said, “and this is the kind of good we want to do.”

Next Steps

The researchers are now looking more closely at the drugs’ effectiveness and dosing in children. That will offer important information on how best to treat the young patients, as the causes of status epilepticus in adults and children often differ.


via Study reveals three effective treatments to stop epilepsy seizures

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