Tag: stroke

Brains do Not Actually ‘Rewire’ Themselves, Scientists Argue

Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Contrary to the commonly-held view, the brain does not have the ability to rewire itself to compensate for conditions such as stroke, loss of sight or an amputation, say scientists in the journal eLife.

Professors Tamar Makin of Cambridge University and John Krakauer of Johns Hopkins University argue that the notion that the brain, in response to injury or deficit, can reorganise itself and repurpose particular regions for new functions, is fundamentally flawed – despite being commonly cited in scientific textbooks. Instead, they argue that what is occurring is merely the brain being trained to utilise already existing, but latent, abilities.

One of the most common examples given is where a person loses their sight – or is born blind – and the visual cortex, previously specialised in processing vision, is rewired to process sounds, allowing the individual to use a form of ‘echolocation’ to navigate a cluttered room. Another common example is of people who have had a stroke and are initially unable to move their limbs repurposing other areas of the brain to allow them to regain control.

Krakauer, Director of the Center for the Study of Motor Learning and Brain Repair at Johns Hopkins University, said: “The idea that our brain has an amazing ability to rewire and reorganise itself is an appealing one. It gives us hope and fascination, especially when we hear extraordinary stories of blind individuals developing almost superhuman echolocation abilities, for example, or stroke survivors miraculously regaining motor abilities they thought they’d lost.

“This idea goes beyond simple adaptation, or plasticity – it implies a wholesale repurposing of brain regions. But while these stories may well be true, the explanation of what is happening is, in fact, wrong.”

In their article, Makin and Krakauer look at a ten seminal studies that purport to show the brain’s ability to reorganise. They argue, however, that while the studies do indeed show the brain’s ability to adapt to change, it is not creating new functions in previously unrelated areas – instead it’s utilising latent capacities that have been present since birth.

For example, a 1980s study by Professor Michael Merzenich at University of California, San Francisco looked at what happens when a hand loses a finger. The hand has a particular representation in the brain, with each finger appearing to map onto a specific brain region. Remove the forefinger, and the area of the brain previously allocated to this finger is reallocated to processing signals from neighbouring fingers, argued Merzenich – in other words, the brain has rewired itself in response to changes in sensory input.

Not so, says Makin, whose own research provides an alternative explanation.

In a study published in 2022, Makin used a nerve blocker to temporarily mimic the effect of amputation of the forefinger in her subjects. She showed that even before amputation, signals from neighbouring fingers mapped onto the brain region ‘responsible’ for the forefinger — in other words, while this brain region may have been primarily responsible for process signals from the forefinger, it was not exclusively so. All that happens following amputation is that existing signals from the other fingers are ‘dialled up’ in this brain region.

Makin, from the Medical Research Council (MRC) Cognition and Brain Sciences Unit at the University of Cambridge, said: “The brain’s ability to adapt to injury isn’t about commandeering new brain regions for entirely different purposes. These regions don’t start processing entirely new types of information. Information about the other fingers was available in the examined brain area even before the amputation, it’s just that in the original studies, the researchers didn’t pay much notice to it because it was weaker than for the finger about to be amputated.”

Another compelling counterexample to the reorganisation argument is seen in a study of congenitally deaf cats, whose auditory cortex appears to be repurposed to process vision. But when they are fitted with a cochlear implant, this brain region immediately begins processing sound once again, suggesting that the brain had not, in fact, rewired.

Examining other studies, Makin and Krakauer found no compelling evidence that the visual cortex of individuals that were born blind or the uninjured cortex of stroke survivors ever developed a novel functional ability that did not otherwise exist.

Makin and Krakauer do not dismiss stories such as blind people navigating using hearing, or individuals who have experienced a stroke regain their motor functions. They argue instead that rather than completely repurposing regions for new tasks, the brain is enhancing or modifying its pre-existing architecture — and it is doing this through repetition and learning.

Understanding the true nature and limits of brain plasticity is crucial, both for setting realistic expectations for patients and for guiding clinical practitioners in their rehabilitative approaches, they argue.

Makin added: “This learning process is a testament to the brain’s remarkable – but constrained – capacity for plasticity. There are no shortcuts or fast tracks in this journey. The idea of quickly unlocking hidden brain potentials or tapping into vast unused reserves is more wishful thinking than reality. It’s a slow, incremental journey, demanding persistent effort and practice. Recognising this helps us appreciate the hard work behind every story of recovery and adapt our strategies accordingly.

“So many times, the brain’s ability to rewire has been described as ‘miraculous’ – but we’re scientists, we don’t believe in magic. These amazing behaviours that we see are rooted in hard work, repetition and training, not the magical reassignment of the brain’s resources.”

The original text of this story is licensed under a Creative Commons Licence.

Source: University of Cambridge

Converting Brain Immune Cells into Neurons Boosts Stroke Recovery in Mice

Source: CC0

Japanese researchers have turned microglia (brain immune cells) into neurons, successfully restoring brain function after stroke-like injury in mice. These findings, published in PNAS, suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans.

Recovery from stroke, where blood supply to neurons is disrupted by blockage or bleeding, is often poor, with patients suffering from severe physical disabilities and cognitive problems.

“When we get a cut or break a bone, our skin and bone cells can replicate to heal our body. But the neurons in our brain cannot easily regenerate, so the damage is often permanent,” says Professor Kinichi Nakashima, from Kyushu University’s Graduate School of Medical Sciences. “We therefore need to find new ways to replace lost neurons.”

One possible strategy is to convert other cells in the brain into neurons. Here, the researchers focused on microglia, the main immune cells in the central nervous system. Microglia are tasked with removing damaged or dead cells in the brain, so after a stroke, they move towards the site of injury and replicate quickly.

“Microglia are abundant and exactly in the place we need them, so they are an ideal target for conversion,” says first author Dr Takashi Irie, from Kyushu University Hospital.

In prior research, the team demonstrated that they could coax microglia to develop into neurons in the brains of healthy mice. Dr Irie and Professor Nakashima and colleagues, now showed that this strategy of replacing neurons also works in injured brains and contributes to brain recovery.

To conduct the study, the researchers caused a stroke-like injury in mice by temporarily blocking the right middle cerebral artery — a major blood vessel in the brain that is commonly associated with stroke in humans. A week later, the researchers examined the mice and found that they had difficulties in motor function and had a marked loss of neurons in a brain region known as the striatum. This part of the brain is involved in decision making, action planning and motor coordination.

The researchers then used a lentivirus to insert DNA into microglial cells at the site of the injury. The DNA held instructions for producing NeuroD1, a protein that induces neuronal conversion. Over the subsequent weeks, the infected cells began developing into neurons and the areas of the brain with neuron loss decreased. By eight weeks, the new induced neurons had successfully integrated into the brain’s circuits.

At only three weeks post-infection, the mice showed improved motor function in behavioural tests. These improvements were lost when the researchers removed the new induced neurons, providing strong evidence that the newly converted neurons directly contributed to recovery.

“These results are very promising. The next step is to test whether NeuroD1 is also effective at converting human microglia into neurons and confirm that our method of inserting genes into the microglial cells is safe,” says Professor Nakashima.

Furthermore, the treatment was conducted in mice in the acute phase after stroke, when microglia were migrating to and replicating at the site of injury. Therefore, the researchers also plan to see if recovery is also possible in mice at a later, chronic phase.

Source: Kyushu University

For Stroke Recovery, Deep Brain Stimulation may Aid Rehabilitation

Deep brain stimulation illustration. Credit: NIH

A first-in-human trial of deep brain stimulation (DBS) for post-stroke rehabilitation patients has shown that using DBS to target the dentate nucleus – which regulates fine-control of voluntary movements, cognition, language, and sensory functions in the brain – is safe and feasible.

The EDEN trial (Electrical Stimulation of the Dentate Nucleus for Upper Extremity Hemiparesis Due to Ischemic Stroke) also shows that the majority of participants (9 of 12) demonstrated improvements in both motor impairment and function. Importantly, the study found that participants with at least minimal preservation of distal motor function at enrolment showed gains that almost tripled their initial scores.

Published in Nature Medicine, these findings build on more than a decade of preclinical work led by principal investigators Andre Machado, MD, PhD, and Kenneth Baker, PhD, at Cleveland Clinic.

“These are reassuring for patients as the participants in the study had been disabled for more than a year and, in some cases, three years after stroke. This gives us a potential opportunity for much needed improvements in rehabilitation in the chronic phases of stroke recovery,” said Dr Machado, patented the DBS method in stroke recovery. “The quality-of-life implications for study participants who responded to therapy have been significant.”

“We saw patients in the study regain levels of function and independence they did not have before enrolling in the research,” Dr Machado said. “This was a smaller study and we look forward to expanding as we have begun the next phase.”

The completed EDEN trial enrolled 12 individuals with chronic, moderate-to-severe hemiparesis of the upper extremity as a result of a unilateral middle cerebral artery stroke 12-to-36 months prior. There were no major complications throughout the study. Nine of the 12 participants improved to a degree that is considered meaningful in stroke rehabilitation.

Source: Cleveland Clinic

IBD Patients Have an Increased risk of Ischaemic Stroke

Credit: American Heart Association

In a nationwide Swedish study of more than 85 000 patients with biopsy-confirmed inflammatory bowel disease (IBD), researchers saw an increased risk of stroke, especially ischaemic stroke, compared to the general population. The results are published in Neurology.

IBD is a chronic intestinal disease with a relapsing-remitting manner, including Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unclassified. Prior studies have suggested that IBD patients have a greater risk of thromboembolic events, but evidence for long-term risk of stroke remains scarce. A recent postmarketing safety study on tofacitinib, a new drug approved for IBD treatment, found an increased stroke risk.

The researchers, from Karolinska Institutet and Örebro University (Sweden), conducted a cohort study by linking a nationwide histopathology cohort (the ESPRESSO study) to national healthcare registers in Sweden to explore whether patients with a biopsy-confirmed IBD had an increased long-term risk of stroke compared to their IBD-free siblings or the general population.

During an average follow-up of 12 years, 3720 of IBD sufferers had a stroke (32.6/10 000 person years), compared with 15 599 of the IBD-free people (27.7/10 000 person-years). When accounting for other factors, such as heart disease, hypertension and obesity, they found that people with IBD were 13% more likely to have a stroke than those without IBD. The risk stayed elevated even 25 years after IBD diagnosis, equating to one additional stroke case per 93 IBD patients. The excess risk was mainly driven by ischaemic stroke rather than haemorrhagic stroke.

The risk for ischaemic stroke was significantly increased across all IBD subtypes (ie, CD, UC, and IBD-U). Sibling comparison analyses confirmed the main findings, suggesting the excess risk of stroke may be independent of familial factors.

Clinical implications

“Due to the excess risk of stroke in IBD patients, screening and management of traditional stroke risk factors in IBD patients could be more urgent to prevent fatal CVD complications”, says first author Jiangwei Sun, postdoc at the Department of Medical Epidemiology and Biostatistics.

“These findings highlight the need for clinical vigilance about the long-term excess risk of cerebrovascular events in IBD patients”, adds last author Jonas F Ludvigsson, professor at Karolinska Institutet and pediatrician at Örebro University Hospital.

Source: Karolinska Institutet

For Stroke Recovery, Physical Activity is Crucial

Photo by Kampus Production on Pexels

A University of Gothenburg study shows that after a stroke, physical activity can be pivotal to successful recovery. People who spend four hours a week exercising after their stroke achieve better functional recovery within six months than those who do not.

The study, published in JAMA Network Open, analysed data from 1500 stroke patients who were grouped according to their post-stroke patterns of physical activity.

The results show that increased or maintained physical activity, with four hours’ exercise weekly, doubled the patients’ chances of recovering well by six months after a stroke. Men and people with normal cognition kept up an active life relatively more often, with better recovery as a result.

Positive programming from exercise

The researchers have previously succeeded in demonstrating a clear inverse association between physical activity and the severity of stroke symptoms at the actual onset of the condition. These new findings highlight the importance of maintaining a healthy, active lifestyle after a stroke.

The first and corresponding author of the study, Dongni Buvarp, is a researcher in clinical neuroscience at Sahlgrenska Academy, University of Gothenburg. Besides her research internship, she is a resident doctor at an initial stage of specialist training at Sahlgrenska University Hospital.

“Physical activity reprograms both the brain and the body favourably after a stroke. Exercise improves the body’s recovery at the cellular level, boosts muscle strength and well-being, and reduces the risk of falls, depression, and cardiovascular disease. Regardless of how severe the stroke has been, those affected can derive benefits from exercising more,” she says.

Knowledge and support vital

“Being physically active is hugely important, especially after a stroke. That’s a message that health professionals, stroke victims and their loved ones should all know. Women and people with impaired cognition seem to become less active after stroke. The study results indicate that these groups need more support to get going with physical activity,” Buvarp says.

One weakness of the study is that, with a few exceptions, the researchers were unable to study the participants’ degree of activity before the stroke. The patients included were treated in Sweden in the period from 2014 to 2019.

Source: University of Gothenburg

Increasing Age Blunts the Strength of Certain Stroke Risk Factors

Photo by CDC on Unsplash

Hypertension and diabetes are known risk factors for stroke, but now a new study shows that the amount of risk may decrease as people age. The study is published in Neurology.

“High blood pressure and diabetes are two important risk factors for stroke that can be managed by medication, decreasing a person’s risk,” said study author George Howard, DrPH, of the University of Alabama at Birmingham School of Public Health. “Our findings show that their association with stroke risk may be substantially less at older ages, yet other risk factors do not change with age. These differences in risk factors imply that determining whether a person is at high risk for stroke may differ depending on their age.”

The study involved 28 235 people who had never had a stroke and were followed for 11 years. Risk factors included hypertension, diabetes, smoking, atrial fibrillation, heart disease and left ventricular hypertrophy. Because of the well-known higher stroke risk in Black people (comprising 41% of participants), race was also considered as part of the assessed risk factors, Howard added.

Researchers followed up with participants every six months, confirming strokes by reviewing medical records.

During the study, there were 1405 strokes over 276 074 person-years. Participants were divided into three age groups. The age ranges for those groups varied slightly depending on the data being analysed by researchers. In general, the younger group included participants ages 45–69, the middle group included people in their late 60s to 70s and the older group included people 74 and older.

Researchers found that people with diabetes in the younger age group were approximately twice as likely to have a stroke as people of similar age who did not have diabetes, while people with diabetes in the older age group had an approximately 30% higher risk of having a stroke than people of similar older age who did not have diabetes.

Researchers also found that people with high blood pressure in the younger age group had an 80% higher risk of having stroke than people of similar age without high blood pressure while that risk went down to 50% for people with high blood pressure in the older age group compared to people of similar age without high blood pressure.

With race/ethnicity as a risk factor, Black participants in the younger age group compared to White participants in that group, a difference which decreased in the older age group. For stroke risk factors such as smoking, atrial fibrillation and left ventricular hypertrophy, researchers did not find an age-related change in risk.

“It is important to note that our results do not suggest that treatment of high blood pressure and diabetes becomes unimportant in older age,” said Howard. “Such treatments are still very important for a person’s health. But it also may be wise for doctors to focus on managing risk factors such as atrial fibrillation, smoking and left ventricular hypertrophy as people age.”

Howard also noted that even where the impact of risk factors decreases with age, the total number of people with strokes at older ages may still be larger since overall risk of stroke increases with age. For example, in the younger age group for hypertension, researchers estimate that about 2.0% of normotensive people had a stroke, compared to 3.6% of hypertensive people. In the older age group, about 6.2% of normotensive people had a stroke, compared to 9.3% of hypertensive people.

A limitation of the research was that participants’ risk factors were assessed only once at the start of the study, and it’s possible they may have changed over time.

Source: American Academy of Neurology 

Study Reveals How Shingles Elevates the Risk of Stroke

MRI images of the brain
Photo by Anna Shvets on Pexels

Scientists investigating why people who have had shingles have an increased stroke risk now believe the answer lies within, exosomes, lipid vesicles called that shuttle proteins and genetic information between cells. Their study, published The Journal of Infectious Diseases, details the mechanisms behind the link between shingles and strokes.

“Most people know about the painful rash associated with shingles, but they may not know that the risk of stroke is elevated for a year after infection,” said the study’s lead author Andrew Bubak, PhD, assistant research professor in the Department of Neurology at the University of Colorado School of Medicine. “Importantly, the rash is often completely healed and individuals feel normal but nonetheless are walking around with this significant elevation in stroke risk.”

Herpes zoster (HZ) or shingles is caused by the varicella zoster virus which causes chicken pox. The virus lingers in the ganglionic neurons and can reactivate, causing excruciating pain. But researchers have found that shingles can also increase the risk of stroke especially for those under age 40 where the shingles vaccine is not typically recommended.

The risk is greatest in people with the rashes on their faces, perhaps due to the proximity to the brain.

To better understand how this works, Bubak and his team began looking more closely at exosomes.

“Exosomes carry pathogenic cargo that can cause thrombosis and inflammation distant from site of actual infection,” Bubak said. “That could ultimately lead to a stroke in patients.”

Researchers collected plasma samples from 13 patients with shingles and 10 without. The samples were taken at time of infection and at 3-month follow-ups for a subset of patients and exosomes were extracted from the plasma.

The researchers found prothrombotic exosomes which could cause blood clots in those with the infection. They also discovered proinflammatory exosomes that also pose risks for stroke at the 3-month follow-up.

Bubak said the findings suggest that in a subset of people with shingles, the virus may not return to latency or the circulating exosomes that induce a prolonged prothrombotic state may persist even after therapy is done and the rash is gone. He said using antiviral agents longer with the addition of antiplatelet and anti-inflammatory agents could help.

“As well as initiatives to increase HZ vaccine uptake to decrease stroke risk, particularly in individuals with known preexisting stroke risk factors,” said Bubak. “If these findings are confirmed with a larger longitudinal study, then this could change clinical practice.”

Most physicians are unaware of the connection between shingles (which has an effective vaccine) and stroke.

“But it’s really important and so easily mitigated,” Bubak said. “Send them home with antiplatelet agents.”

Source: University of Colorado Anschutz Medical Campus

Smartphone Video of Carotid Arteries Predicts Stroke Risk

Credit: American Heart Association

Narrowed arteries in the neck – a major risk factor for stroke – may be detected by analysing smartphone video that picks up the motion of blood flowing just beneath the skin, a small study shows.

The research, published Wednesday in the Journal of the American Heart Association, may be useful in developing a non-invasive, early screening tool for detecting blockages in the carotid arteries that can lead to strokes.

“Between 2% and 5% of strokes each year occur in people with no symptoms, so better and earlier detection of stroke risk is needed,” study author Dr. Hsien-Li Kao said in a news release. He is an interventional cardiologist at National Taiwan University Hospital in Taipei.

“This was an exciting ‘eureka’ moment for us,” he said. “Existing diagnostic methods – ultrasound, CT and MRI – require screening with specialised medical imaging equipment and personnel. Analysis of video recorded on a smartphone is non-invasive and easy to perform, so it may provide an opportunity to increase screening.”

The carotid arteries, found in the neck, can become blocked by a buildup of fatty deposits known as plaque. That condition – carotid artery stenosis – restricts blood flow to the brain and may lead to an ischemic stroke. Nearly 87% of all strokes in the US are this type of stroke.

The carotid artery is just below the skin’s surface. When velocity and blood flow patterns change, those changes are reflected in the motion of the overlying skin, Kao said. However, those differences cannot be detected by the naked eye.

In the study, researchers used motion magnification and pixel analysis to detect subtle changes in pulse characteristics on the skin’s surface captured in 30-second smartphone video recordings. An older-generation smartphone was used to make video clips of the necks of 202 Taiwanese adults, who were an average 68 years old when the study took place between 2016 and 2019. While recordings were being made, participants lay on their backs with their heads tilted back in a custom-made box that restricted movement.

Among participants, 54% had previously been diagnosed with a blockage of 50% or more in the carotid artery. The phone videos were 87% accurate in predicting who had a blockage in the artery. Narrowing in the arteries was confirmed using a Doppler ultrasound test.

Kao said further research could determine whether it is possible to take recordings and perform the motion analysis remotely, in conjunction with a downloadable app.

“More research is needed to determine whether video recorded on smartphones is a promising approach to help expedite and increase stroke screening,” he said. “Carotid artery stenosis is silent until a stroke happens. With this method, clinicians may be able to record a video of the patient’s neck with a smartphone, upload the videos for analysis and receive a report within five minutes. The early detection of carotid artery stenosis may improve patient outcomes.”

Source: American Heart Association

Falling Victim to Fraud Has a Lasting Impact on Men’s Blood Pressure

A new study published in the Journal of the American Geriatrics Society suggests that experiencing financial exploitation, fraudulent schemes, and scams may raise a person’s blood pressure, especially in later life. A key difference in the findings was that fraud victimisation was linked with elevated blood pressure in men, but not in women.

Instead of focusing on subjective measures of health after fraud vicitimisation, this study included objective measures of physical health, specifically, systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure. Chronic elevation of these measures are known to contribute to end organ damage including stroke, cardiovascular disease morbidity, and mortality. 

The study participants consisted of 1200 older adults from the Rush Memory and Aging Project. During up to 11 years of annual observations, participants were asked about fraud victimisation and underwent serial blood pressure measurements.

In men, blood pressure elevations were observed after they had been the victims of fraud. Those elevations, compounded over time, could indicate future poor health. The rise in blood pressure persisted for years after the fraud had taken place, especially in old age.

“These findings show that fraud victimisation has important public health consequences and underscore the need for efforts to prevent exploitation,” said lead author Melissa Lamar, PhD, of Rush University Medical Center.

Source: Wiley

Gout Flare-ups Linked to Increased MI and Stroke Risk

Photo by freestocks.org

The risk of myocardial infarction (MI) and strokes temporarily increases in the four months after a gout flare, suggests a study published in the journal JAMA.

The findings showed that gout patients who suffered from an MI or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the 61-120 days prior.

Gout is a common form of arthritis that is caused by high levels of uric acid, a chemical produced by breakdown of body tissues and present in certain foods and drinks.

At high levels, uric acid is deposited in and around joints as needle shaped urate crystals. Once released from their deposits, these crystals cause severe inflammation that manifest as joint pain, swelling, redness, and tenderness that often lasts for 1–2 weeks. These episodes, called gout flares, often recur. Inflammation is also a risk factor for heart attack and stroke.

While gout patients tend to have more cardiovascular risk factors, there have been no previous studies about whether gout flares are linked with an increased risk of MI and stroke.

To address this, the team used data from 62 574 patients with gout treated in the NHS. Of these, 10 475 experienced heart attack or stroke after the diagnosis of gout, while matched controls did not experience such events. They evaluated the association between heart attacks or strokes and recent gout flares and adjusted these results for possible confounding factors. They found that gout patients who suffered an MI or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the preceding 61–120 days.

They found a similar high rate of MI or stroke in the 0–60 and 61–120 days after gout flares compared with other time periods, when they used information from only patients who consulted for a gout flare and also experienced either MI or stroke. This further strengthened the finding that gout flares are associated with a transient increase in cardiovascular events following flares. The increased odds and rates persisted when people with pre-existing heart disease or stroke before their gout diagnosis were excluded, and when shorter exposure periods such as 0-15 and 16-30 days prior to MI or stroke, were considered.

Gout patients who died from a MI or stroke had over four times the odds of experiencing a gout flare in the preceding 0-60 days and over twice the odds of gout flare in the preceding 61-120 days.

The study’s lead author, Professor Abhishek at the University of Nottingham, said: “This is the first study of its kind to examine whether there is an association between recent gout flares and heart attacks and strokes.

“The results show that among patients with gout, patients who experienced a heart attack or stroke had significantly increased odds of a gout flare during the preceding 120-days compared with patients who did not experience such events. These findings suggest that gout flares are associated with a transient increase in cardiovascular events following flares.

“People with recurrent gout flares should be considered for long-term treatment with urate lowering treatments such as allopurinol. This is a reliable way of removing urate crystal deposits and providing freedom from gout flares. Patients should also be considered for concurrent treatment with anti-inflammatory medicines such as colchicine for the first few months because urate lowering treatments may trigger gout flares in the short term.

“People with gout should be encouraged to adopt a healthy lifestyle with appropriate treatment of conditions such as high blood pressure, high cholesterol, obesity and diabetes to minimise their background risk of heart attack and stroke.”

Source: University of Nottingham