Category: Neurology

Categories : Injury & Trauma NeurologyTags :

Study Reveals Unseen Changes in Motor Control After Spinal Cord Injury

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One of the study participants exerts force with their calf muscles while sensors measure electrical activity. (Photo: Ruoli Wang)

Even when people with incomplete spinal cord injuries can walk, everyday functions like standing, balancing or producing steady force may remain difficult. A new study shows why.

Using surface skin electrical sensors, a research team in Sweden identified previously unseen changes in motor coordination that result from incomplete spinal cord injuries (SCI). The study is the first to examine how individual motor units (nerve to muscle connections that create movement) work together in people with SCI.  

“Our study reveals, at the cellular level, how the central nervous system adapts to the injury to control movement,” says Ruoli Wang, associate professor in biomechanics at Promobilia MoveAbility Lab, KTH Royal Institute of Technology. She says the researchers’ approach was completely non-invasive.

The results were published in the Journal of NeuroEngineering and Rehabilitation.  

The study’s lead author, PhD student Zhihao Duan, says the researchers found the nervous system struggles to spread signals smoothly across muscles at low levels of exertion after the injury. And it appears to overcompensate at higher levels of exertion, sending “louder”, less refined signals.  

Effect on motor units

Muscles move through hundreds or thousands of motor units, each turning on and off precisely to create smooth force. Composed of a single motor neuron and its connecting muscle fibres, these motor units respond to shared signals from the nervous system, much like different sections of musicians led by an orchestra conductor. That shared input is what allows them to act in coordinated patterns. 

To explore how well these units coordinate under the control of the central nervous system, the team examined 25 people (including 10 control participants). They used high-density electromyography (HD-EMG) to measure electrical activity in the functionally similar calf muscles – soleus and gastrocnemius – while volunteers pushed lightly or moderately against a device.  

Duan says that at 20% effort, fewer of the motor units in the two calf muscles were working in a shared, coordinated way compared with people without injury. As a result, their movements were shaky and unstable. “They were much less being driven by the same coordinated signal from the nervous system.” he says. 

At a higher level of effort (50%) the SCI group showed stronger lowfrequency synchronization between the two muscles. The body loses flexibility and precision in control of the movement. “This could be a sign of the nervous system compensating by sending louder, less refined signals,” Duan says. 

Unique insights

“One interesting finding is that after spinal cord injury the nervous system becomes more rigid and less able to change its approach as the muscles work harder. A healthy nervous system on the other hand is able to adapt its strategy as force demands, to adjust the shared neural drive level,” Wang says. 

Although the study was limited by a small sample size and challenges in identifying enough motor units per muscle from the skin surface, Wang says the results offer unique insight into how SCI reshapes motor control.  

“This finding may open the door to a new rehabilitation biomarker, helping clinicians and researchers design new neurorehabilitation strategies to re-tune the spinal cord control and to restore coordinated neural input,” she says.  

David Callahan

Source: KTH Royal Institute of Technology

Categories : Mental Health NeurologyTags :

How Oestrogen in the Brain Impacts Stress and Trauma Response

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New research reveals how oestrogen levels in the brain influence vulnerability to stress-related memory problems, helping explain sex differences in PTSD risk.

Photo by Sherise Van Dyk on Unsplash

For some people, a single traumatic event like a shooting, a natural disaster or a violent assault, can leave an imprint that lingers long after the immediate danger has passed. Memories of that event may return with unusual intensity, shaping mood, behaviour, and mental health in ways that are difficult to predict. Others exposed to similar trauma recover without developing lasting memory problems or trauma-related symptoms.

Why those outcomes diverge is a central question in stress and trauma research. Clinicians have long observed that severe acute stress can permanently alter memory for some people but not others, and that women face roughly twice the lifetime risk of posttraumatic stress disorder (PTSD). Recent research from the University of Pennsylvania in collaboration with the University of California-Irvine suggests that part of the answer may lie in the brain’s biological state at the precise moment trauma occurs.

Elizabeth Heller, PhD, an associate professor of Pharmacology in the Perelman School of Medicine at the University of Pennsylvania, and her team in the Heller Lab, have now shed light on how the brain’s biological state at the time of stress, particularly its oestrogen levels, can shape vulnerability long after the acute stress has lifted. Heller helped uncover that oestrogen levels in the brain may play a surprising role in this vulnerability, and for both sexes. The study, published in Neuron, also provides new insight into why women are more likely than men to develop post-traumatic stress disorder (PTSD) and to face higher dementia risk later in life.

Unpacking oestrogen’s role in memory vulnerability

Oestrogen is widely known to support learning and memory. This study found that high levels of oestrogen in the hippocampus, a brain region critical for memory, help the brain’s cells change and adjust more easily. However, in the context of severe acute stress, this flexibility can increase vulnerability to stress-related memory problems.

Heller and the Penn team mapped how high levels of oestrogen interact with chromatin structure (the storage packaging up DNA inside cells) in the hippocampus to make some brains more susceptible to PTSD‑like memory changes.

The findings help explain why traumatic events such as natural disasters, mass violence, and assaults can cause long-term memory problems, and why women are roughly twice as likely as men to develop PTSD.

“A lot of what determines vulnerability is the state your brain is already in,” Heller explained. “If a traumatic event hits during a period when oestrogen is already unusually high, the resulting plasticity can amplify the impact in lasting ways, promoting vulnerability to stress. Even with these findings in hand, the word oestrogen can mislead readers into assuming the biology applies only to women. That assumption shaped public understanding for decades, but it doesn’t hold up against what this research, and years of foundational neuroscience, actually shows.

As Heller notes, oestrogen is a critical brain hormone in both sexes. It is produced locally in regions like the hippocampus where it helps regulate learning, mood, and responses to stress. Recognising that universality is essential to understanding what this study truly reveals.

“The striking thing is that oestrogen levels are actually high in both males and in females in some parts of the hormonal cycle. Thus, the effects of high oestrogen levels happen in both males and females,” Heller said. “We tend to treat oestrogen as a women’s health hormone, but the brain makes its own oestrogen, and it plays powerful roles in stress, memory, mood, and emotion across sexes.”

By Eric Horvath

Source: Penn Medicine

Categories : Neurology OphthalmologyTags :

Surprising Discovery in the Retina May Explain Low-light Vision

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Photoreceptor cells in the retina. Credit: Scientific Animations

A new Yale School of Medicine (YSM) study has uncovered surprising new details about how our eyes process what we see.

When we look at something, our visual system breaks down different aspects of the scene – such as colour, contrast, and motion – and processes those components separately. It’s called parallel visual processing and it’s what allows our brains to work out what we’re seeing so quickly.

This separation of information starts in the retina, and scientists have thought that separation is maintained as the information travels through the visual system. But in a study published in Neuron, researchers have found that information channels are more integrated than previously thought. This may help cells process weak visual signals, such as low-light conditions, the researchers say.

“We found that while different channels can deliver their own features, they’re also interconnected by underlying electrical circuitry,” says Yao Xue, PhD, a postdoctoral fellow in the department of ophthalmology and visual science at YSM and the study’s first author.

Untangling bipolar cell signals in the retina

The rods and cones in our retinas detect light and transmit signals to a type of neuron called bipolar cells. In these cells, visual components such as night, day, colour, shape, and contrast begin to separate into more than a dozen parallel channels.

But when researchers zoomed in on bipolar cell synapses, they found these information channels intermingle.

Neurons have two types of synapses: chemical and electrical. At chemical synapses, neurons release chemical messengers known as neurotransmitters that bind to the recipient cell. Electrical synapses, also known as gap junctions, facilitate communication with electric currents. Bipolar cells primarily communicate through chemical synapses.

The researchers found, however, that in the mouse and human retinas they studied, electric synapses were integrating most of those seemingly separate bipolar cell information channels. When the scientists electrically stimulated one bipolar cell, instead of seeing a localised release of neurotransmitters just within that cell’s channel, they observed cloud-like patterns of signalling – suggesting crosstalk among the different types of cells.

“When we stimulated one bipolar cell, many bipolar cells released neurotransmitters,” says Z. Jimmy Zhou, PhD, Professor of Ophthalmology and Visual Science and principal investigator.

“If the signal is already very weak and is divided into several channels, there isn’t much left for each channel to process. The integration is particularly useful for detecting low contrast signals or signals from very small objects.”

Seunghoon Lee, PhD Research Scientist of Ophthalmology and Visual Science

To their surprise, they also identified one type of bipolar cell, called BC6, that drove this signalling. These cells generated strong signals that travelled through the parallel channels in a hierarchical manner. “People had assumed that the different types of bipolar cells were more or less autonomous,” Zhou says. “But we found a driver among all these cell types that creates this network with a hierarchy.”

Having distinct parallel channels can help bipolar cells divide and conquer as they process different parts of a visual signal. The linkage of these channels through electrical synapses, on the other hand, could help the cells process weak visual signals, the researchers say.

“If the signal is already very weak and is divided into several channels, there isn’t much left for each channel to process,” says Seunghoon Lee, PhD, a research scientist in the department of ophthalmology and visual Science at YSM and co-corresponding author of the study. “The integration is particularly useful for detecting low contrast signals or signals from very small objects.”

“And the cells aren’t cooperating in a random way,” adds Xue. “There’s a commander within them – BC6 – that leads them in relaying signals to the downstream target.”

Recording from hard-to-reach cells

For the study, the researchers used several methods to study the synaptic circuitry of bipolar cells, including imaging to observe the cells’ activity and how they released and responded to neurotransmitters, as well as stimulating activity in bipolar cells and recording responses in recipient cells.

One challenge of studying signal transmission in bipolar cells is that they live in the middle of the retina. Previous studies have cut the retina into slices in order to access the cells, but that can disrupt the synaptic circuitry. In the new study, however, the researchers were able to apply the dual patch-clamp technique in fully intact mouse retinas. This method uses electrodes to stimulate activity in different types of bipolar cells and records the responses of recipient cells.

“No other lab in the world has been able to pull off these kinds of recordings systematically,” says Zhou. “It is a tour de force of Yao Xue’s PhD thesis work, pairing an innovative approach with exceptional electrophysiological skill.”

The team then repeated the experiment in human retinas, which they obtained from the department of pathology’s Legacy Tissue Donation Program. These are the first experiments of their kind in an intact human retina, the YSM researchers say.

Source: Yale School of Medicine

Categories : Mental Health NeurologyTags :

Two Major Symptoms of Schizophrenia Share a Single Explanation

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Our dopamine learning system helps us make choices, some as simple as whether to eat a green or red apple, says Arvind Kumar (pictured). He co-authored a new study showing what happens when this system breaks down, and how misalignment contributes to two symptoms of schizophrenia. (Photo: David Callahan)

Scientists have long known that dopamine helps the brain learn from rewards, but a new computational model shows how for people with schizophrenia this learning system can break down and simultaneously produce two very different symptoms – delusions and a loss of motivation.

Publishing in the Journal of Neuroscience, researchers at Stockholm’s KTH Royal Institute of Technology and University of Tokyo, Japan found that problems with motivation and the formation of delusional beliefs may both be linked to a single underlying problem: when an overactivated cortex disrupts the brain’s ability to link actions and consequences.

Arvind Kumar, associate professor in computational neuroscience at KTH, says the study offers a computational neuroscience model that attempts to unify several known roles of the brain’s dopamine system: learning from rewards, controlling motivation and building an internal picture of what’s going on.

Why a unified explanation?

A unified explanation would make it easier to study how these symptoms develop together and may guide future research into treatments, the lead author Kenji Morita says. “If the suggested root cause is validated, then mechanistically grounded therapies could be developed.”

The model in the study shows what happens when this internal cause-and-effect tracking system breaks down. The model suggests that two simultaneous learning processes in the cortico-basal ganglia-midbrain circuits need to align for a person to realize what is rewarding and why.

Deep within the brain, the striatum is a control center that enables the brain to learn which reward is which and selectively increase motivation for right one, such as food when hungry or water when thirsty.

The other dopamine alignment takes place in the cortex. This is the part that enables the brain to essentially follow what is happening. It enables the brain to assign credit correctly: for example, a smell of baked bread predicts food, or the sound of liquid predicts drink.

The researchers found that both reduced motivation and delusion‑like beliefs could arise when an overstimulated cortex disrupts alignment between these processes.

“It causes the brain’s learning system to mix up association between motivation and reward,” Kumar says, “leading to both low motivation and delusion‑like ideas, such as assigning the wrong reasons for things happening.”

“The brain needs to align motivation, reward identity and their causes together to make a suitable choice,” he says.

By David Callahan

Source: KTH Royal Institute of Technology

Categories : Gastrointestinal NeurologyTags :

The Gut’s Connection to Healing Traumatic Brain Injuries

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Houston Methodist researchers find antibiotics aid recovery from traumatic brain injury

Coup and contrecoup brain injury. Credit: Scientific Animations CC4.0

In a new study published in Nature Communications Biology, Houston Methodist researchers led by Sonia Villapol, PhD, found that short-term antibiotic treatment significantly reduced neuroinflammation and neurodegeneration following traumatic brain injury (TBI) by altering the gut microbiome in animal models. 

“We found that antibiotic treatment following TBI can reduce harmful gut bacteria, decrease lesion size and limit cell death,” said Villapol, an associate professor in the Department of Neurosurgery at Houston Methodist. “Our results support a gut–brain mechanism in which microbiome changes influence peripheral immunity and, in turn, neuroinflammation after TBI.”

Administering antibiotics cleans the gut of harmful bacteria, allowing beneficial bacteria to flourish. The study found that two helpful bacteria, Parasutterella excrementihominis and Lactobacillus johnsonii, are key to driving cell repair. According to Villapol, they could also be major regulators for peripheral inflammation in the body.

Notably, 70% of immune system regulation is generated by the gut microbiome. During gut imbalance, the bidirectional nature of the brain-gut axis can wreak havoc throughout the entire body. 

“Our brains are constantly sending signals to the rest of our bodies. Following a traumatic brain event, those signals can get scrambled and disrupt other organs, including our digestive system,” Villapol said. “If the gut stays out of balance, the brain may have a harder time healing.”

There are an estimated 4 million traumatic brain injuries a year in the U.S. Recent studies indicate that TBI-induced gut microbiome imbalance may even contribute to the development of neurodegenerative diseases like Parkinson’s, Alzheimer’s and dementia. 

Villapol’s lab is focused on investigating and developing new neuroprotective treatments to fight inflammation linked with neurodegenerative disease. “If we can break neuroinflammation in the acute or chronic stage, we can reduce the risk of developing Alzheimer’s or dementia,” said Villapol. 

The next phase of the research will focus on bioengineering Parasutterella excrementihominis and Lactobacillus johnsonii to further develop precision therapies to reduce neuroinflammation.

Source: Houston Methodist

Categories : NeurologyTags :

X-chromosomes: A New Lens on Autism’s Sex Bias

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Autism has a significant and enduring sex bias, with roughly four boys diagnosed for every girl. For many years, experts have believed this disparity arises primarily from diagnostic inequities because much of autism research – and the screening tools that grew out of it – has historically focused on boys, effectively setting a male standard for what autism “looks like.” As a result, girls and women are more likely to be overlooked, misdiagnosed, or diagnosed much later in life.

This disparity has also shaped the science around autism. When fewer females with the condition are identified, fewer are included in research studies, creating a feedback loop where scientific understanding of autism in females remains limited. Because of this underrepresentation of females, it has been difficult for scientists to disentangle how much of the sex bias in autism reflects social inequities versus underlying biological differences between the sexes. 

While the search for biological explanations has largely lagged behind, one leading theory, known as the “female protective effect,” proposes that females may be biologically buffered against developing autism in a way males aren’t. 

The idea can be traced back to studies showing that females diagnosed with autism tend to carry a higher number of genetic mutations or “hits” than males with the condition, meaning that they require a higher load of the same genetic mutations for autism to manifest. But, until now, there’s been little clarity on the exact biological mechanism behind this apparent resilience.

Now, a perspective from the lab of Whitehead Institute Member David Page, published March 30 in Nature Genetics, proposes a genetic explanation for the female protective effect and suggests that biological differences between males and females contribute to autism’s strong sex bias.

The work is one of many projects from the Page lab uncovering the biological underpinnings of sex bias in everything from heart health and autoimmune disease to certain cancers. 

“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page, who is also a professor of biology at Massachusetts Institute of Technology and an investigator at the Howard Hughes Medical Institute (HHMI).

The researchers propose that this protective effect extends beyond autism, and could help explain why 17 other congenital and developmental disorders predominately affect males. By characterizing the biological factors that make one sex more or less likely to develop certain health conditions, scientists see an opportunity to improve how these conditions are diagnosed and how people receive care.

“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page.

Page and Harvard-MIT MD-PhD student Maya Talukdar trace the female protective effect to the X chromosome. Talukdar is a graduate student in Page’s lab and the lead author of the perspective. 

Most females have two X chromosomes (XX) while most males have one X and one Y chromosome (XY). Sex chromosomes can dial up and down the expression of thousands of genes on the other 22 pairs of chromosomes in a cell, impacting cell function across the entire body. 

Historically, scientists believed that the second X chromosome in females is largely inactive. But, in recent years, research out of the Page lab has shown that the so-called “inactive X,” also called Xi, plays a crucial role in regulating gene expression on the active X chromosome, and the rest of the chromosomes.

In this perspective, the researchers point to a subset of genes that are expressed from both the active and inactive X chromosome — often known as genes that “escape” X chromosome inactivation. Many of these genes are dosage-sensitive regulators of key cellular processes. These processes influence thousands of other genes across the genome, including many linked to autism. 

Because females have an extra copy of these regulatory genes expressed from Xi, Page and Talukdar propose that they may be better able to buffer the effects of autism-associated mutations than males.

The female protective effect beyond autism

This mechanism, the researchers say, extends beyond autism to a range of congenital and developmental diseases with a male bias. 

“Many of the other congenital or developmental conditions we’re pointing to aren’t subject to diagnostic inequities in the way autism is,” says Talukdar. “This strengthens the idea that the female protective effect is emerging from genetic differences in males and females.”

One example is pyloric stenosis, which like autism, affects four boys for every girl. Infants with the condition experience severe vomiting due to thickening of the pyloric sphincter, the passage between the stomach and small intestine. As with autism, girls with pyloric stenosis appear to require more genetic “hits” in order to develop the condition.

The researchers’ new framework of looking at Xi to understand sex differences in disease could impact treatment and care not just for conditions that predominately affect males, but also for those that are more common in women, such as autoimmune diseases. 

“Our biology isn’t one-size-fits-all,” Talukdar says “Sex differences clearly play a huge role in health, and it’s so important that we understand them.”

By Shafaq Zia

Source: Whitehead Institute for Biomedical Research

Categories : Neurology Pain ManagementTags :

Pain Neurons Protect Nerve Health and Offer New Therapeutic Targets

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A healthy neuron. Credit: NIH

Researchers at Karolinska Institutet, have uncovered a previously unknown mechanism that helps pain sensing nerve cells stay healthy and respond to injury. The findings, published in Nature Communications, may improve understanding of chronic pain and nerve damage and maintenance of myelin integrity.

A new study shows that a molecule called RNase4, is produced by specialised pain-sensing neurons. It plays a key role in maintaining their normal function and influences both these neurons and the structure of nearby nerve fibres, positioning pain-sensing neurons not only as sensory transducers but also as sentinels of nerve integrity.

The researchers showed that RNase4 is expressed in unmyelinated sensory neurons, including neurons that innervate the auditory organ, and in the pain-sensing neurons that innervate the face, head, dura mater, and the rest of the body. By combining multiple experimental approaches on mice, they demonstrated that loss of RNase4 alters mechanical pain responses and disrupts the myelin structure surrounding neighbouring nerve fibres. They also found that RNase4 levels increase after nerve injury, both during the pain phase and the subsequent recovery period.

“Our results point to RNase4 as part of a regulatory pathway that supports nerve integrity. This molecule has not previously been linked to pain sensing neurons, so its presence and role came as a surprise,” says corresponding author Saida Hadjab, head of the Neurobiology of pain & Therapeutics laboratory at the Department of Neuroscience.

Chronic pain is often difficult to treat, partly because the underlying biology is still not fully understood. The findings suggest that pain sensing neurons may take on a more active role in maintaining the health of surrounding nerve tissue.

“This work has enabled us to identify a novel mechanism and position RNase4 as a regulator of afferent neuron integrity and local microenvironment. The localisation of RNase4 and its function in sensory neurons made it directly relevant to hearing dysfunction, headache, and chronic pain,” says Saida Hadjab.

RNase4 shows a comparable expression pattern in human pain-sensing neurons, supporting its potential relevance in humans. While further research is required to develop therapies targeting the RNase4 pathway, these findings provide a strong foundation for advancing the study of myelin integrity and long-lasting pain in humans.

Source: Karolinska Institutet

Categories : NeurologyTags :

The Most Common Recessive Neurodevelopmental Disorder Ever Discovered

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Photo by Anna Shvets

Researchers have identified and described a previously unknown recessive neurodevelopmental disorder (NDD) that appears to be the most prevalent ever discovered. The study, involving University of Bristol researchers and published in Nature Genetics, provides long-awaited answers for many families and may inform future drug development.

The condition is caused by changes in a small noncoding gene called RNU2-2. It is estimated to affect thousands of individuals and accounts for about ten percent of all recessive NDD cases with a known genetic cause.

The work was led by researchers from Icahn School of Medicine at Mount Sinai in New York in collaboration with colleagues from Stanford University and the University of Bristol. Clinical and scientific collaborators from other institutions in the UK, the Netherlands, Belgium, and Italy provided valuable contributions to this research.  

The team found that the disorder is caused by a near-complete absence of a molecule called U2-2 RNA, which is produced by the RNU2-2 gene. Children with the condition typically inherit one altered copy of the gene from each parent, although sometimes changes arise spontaneously by genetic mutation. While the parents are unaffected, the combined effect on both copies of the gene in their children leads to disrupted brain development in their child.

Symptoms of this disorder vary widely depending on the child’s specific genetic changes. Common features include low muscle tone, developmental delays, and limited speech. Some children have mild learning difficulties or autism traits, while others develop epilepsy, movement disorders, or trouble walking. Brain imaging may appear normal early on but can show changes over time. In the most severe cases, additional challenges may include feeding difficulties or respiratory problems. The wide range of symptoms reflects how the underlying U2-2 RNA deficiency affects each child differently.

“Our discovery gives families something they’ve often waited years for, a clear molecular explanation for their child’s condition,” said the study’s first author, Daniel Greene, Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine. “For many families, that clarity can be profoundly meaningful after a long and uncertain diagnostic journey. At the same time, it gives the research community a concrete biological target to guide future therapeutics.”

Using whole-genome sequencing data from the UK’s National Genomics Research Library, the team examined rare genetic variants in more than 41 000 non-coding genes, genes that produce functional RNA molecules that do not encode proteins. They analysed genetic data from 14,805 individuals with an NDD and 52,861 ‘controls’ without an NDD. Their statistical approach was specifically designed to detect dominant and recessive conditions. RNA sequencing of blood from patients and controls further revealed the immediate biological consequence of the disease-causing variants: the severe reduction of U2-2 RNA.

This discovery builds on two earlier landmark developments from the research group:

The new study expands this story by demonstrating that recessive variants in RNU2-2 cause a distinct and surprisingly prevalent disorder, now referred to as recessive ReNU2 syndrome. Notably, the researchers estimate that this recessive condition may be 60% as common as ReNU syndrome, which is unusual — the most prevalent NDDs are dominant rather than recessive.

Andrew Mumford, Emeritus Professor of Genomic Medicine at the University of Bristol, said: “This research completes a set of three landmark genetic discoveries from our team that have identified faults in two hitherto unsuspected genes as a common cause of what can sometimes be a devastating developmental disorder. This work will rapidly improve genetic diagnosis for families and children and lead to significant advancements in clinical care.”

The investigators are now enrolling families into the INDEED study at Mount Sinai to help deliver diagnoses and better understand the condition. Future work will focus on deepening the understanding of the biology behind the disorder and identifying paths toward future treatments.

“Our discovery will enable tens of thousands of families affected by this previously hidden genetic condition to receive closure through a genetic diagnosis. Parents will have the opportunity to connect with each other through the recently established ReNU2 Syndrome Foundation. Given the recessive inheritance pattern, diagnoses will provide critical information for family planning,” added Dr Ernest Turro, the study’s senior author.

“While a specific treatment for recessive ReNU2 syndrome is not yet available, understanding that the disorder stems from a loss of U2-2 RNA points to potential gene replacement strategies in the future,” he explains. “We are now enrolling families into the INDEED study to diagnose affected individuals, improve our understanding of the natural course of the condition, develop clinical management guidelines, and uncover precisely how U2-2 RNA loss disrupts neurodevelopment. We hope these steps will lay a strong foundation for future clinical trials.”

Paper

’Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder’ By D Greene et al. in Nature Genetics [open access]

Source: University of Bristol

Categories : Infection Control NeurologyTags :

Severe Infections May Raise Dementia Risk, Study Finds

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Finnish registry study finds that infections like cystitis and bacterial disease are linked to higher dementia risk independently of other coexisting conditions

Source: CC0

Severe infections increase the risk of dementia independently of other coexisting illnesses, according to a new study published March 24th in the open-access journal PLOS Medicine by Pyry Sipilä of the University of Helsinki, Finland, and colleagues.

Severe infections have been linked to an increased risk of dementia. However, it has been unclear whether this association is explained by other coexisting, non-infectious diseases that predispose people to both infections and dementia.

In the new study, researchers used nationwide Finnish health registry data covering more than 62 000 individuals aged 65 or older who were diagnosed with late-onset dementia between 2017 and 2020, along with more than 312 000 matched dementia-free controls. Taking a broad approach, they examined all hospital-treated diseases recorded during the previous twenty years, identifying 29 diseases that were robustly associated with increased dementia risk. Nearly half (47%) of dementia cases had at least one of the 29 identified diseases before their diagnosis.

Of those diseases, two were infections: cystitis (a urinary tract infection) and bacterial infection of an unspecified site. Among the non-infectious diseases, the strongest associations with dementia were seen for mental disorders due to brain damage or physical disease, Parkinson’s disease, and alcohol-related mental and behavioural disorders.

When the researchers then adjusted for all 27 non-infectious dementia-related diseases identified, the association between both infections and dementia remained largely intact. Less than one-seventh of the excess dementia risk among individuals with hospital-treated cystitis or bacterial infections was attributable to pre-existing conditions. The link between infections and dementia was even stronger for early-onset dementia (diagnosed before age 65), where five types of infection – including pneumonia and dental caries – were associated with elevated risk.

The study was limited by the lack of baseline cognitive assessments and clinical examination data before dementia diagnoses, as well as a lack of data on infection treatments.

“Overall, our findings support the possibility that severe infections increase dementia risk; however, intervention studies are required to establish whether preventing or effectively treating infections yields benefits for dementia prevention,” the authors say.

The authors add, “We found 27 diverse severe, hospital-treated diseases that were robustly associated with an increased risk of dementia. Two of these diseases were infections, namely urinary tract infections and unspecified bacterial infections.” 

“In our study, dementia-related infections occurred on average 5 to 6 years before dementia diagnosis. Given that the development of dementia often takes years or even decades, these findings suggest that severe infections might accelerate underlying cognitive decline. However, as these findings were observational, we cannot exclude the possibility that some unmeasured confounding factors might also have affected our findings. Thus, we cannot prove cause and effect.”

“Ideally, intervention trials should examine whether better infection prevention helps reduce dementia occurrence or delay the onset of this disease.”

Provided by PLOS

Categories : Neurology PaediatricsTags :

Intensive Therapy Approaches Benefit Infants and Toddlers with Cerebral Palsy

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Trial provides new evidence to guide early treatment decisions for families and clinicians

An infant participating in the Baby CHAMP study raises both hands while seated in a stroller. The NIH-funded trial led by the Fralin Biomedical Research Institute at VTC examines early therapies designed to improve arm and hand function in young children with cerebral palsy affecting one side of the body. Credit: Jennifer Murray

Infants and toddlers with unilateral cerebral palsy, which affects the brain’s control of muscles on one side of the body, show lasting improvements in hand and arm function when they receive early, high-dose therapy, according to a new multisite clinical trial led by Virginia Tech researchers at the Fralin Biomedical Research Institute at VTC.

The Baby CHAMP (Children with Hemiparesis Arm-and-Hand Movement Project) study directly compared three therapist-delivered interventions: two forms of constraint-induced movement therapy, which limit the stronger arm to encourage use of the weaker one when combined with therapy, and bimanual therapy, which promotes coordinated use of both hands.

The researchers found that children ages 6 to 24 months showed similar gains whether therapy involved full-time casting, a splint worn during sessions, or bimanual training without constraining the stronger arm.

Published in Pediatrics Open Science, the study addresses a long-standing gap in clinical evidence. 

“The brain in the first two years of life is remarkably plastic,” said Stephanie DeLuca, associate professor at the Fralin Biomedical Research Institute at VTC and co-principal investigator of the trial. “By delivering high-dose, play-based therapy early, we’re capitalizing on a window of opportunity when the nervous system is especially responsive to experience.” 

While both constraint-induced movement therapy and bimanual therapy are widely recommended for children older than 2 years with unilateral cerebral palsy, limited data have been available to guide treatment decisions for infants and toddlers. 

“This gives families and clinicians evidence-based options,” said Sharon Landesman Ramey, a Virginia Tech Distinguished Scholar, professor at the Fralin Biomedical Research Institute at VTC, and co-principal investigator of the Baby CHAMP trial. “The encouraging message is that early, intensive therapy works — and multiple approaches can help children build critical motor skills. Caregivers and families now have actionable evidence that can shape care during one of the most important periods of brain development.”

Unilateral cerebral palsy affects movement on one side of the body and can result in lifelong impairment of upper extremity function. Early intervention is considered critical because the brain is especially adaptable during the first two years of life.

DeLuca is director of the Fralin Biomedical Research Institute at VTC Neuromotor Research Clinic, which investigates novel treatments for children with a range of biomedical conditions and provides worldwide training for therapists to become certified in new evidence-based therapies. 

All children received three hours of therapy per day, five days a week, for four consecutive weeks, totaling 60 hours of structured intervention. Parents also supported additional guided home practice.

Fifty-eight children were enrolled in the randomized controlled trial, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Fifty-three completed treatment and end-of-therapy assessments, and 41 returned for evaluation six months later.

Across all three groups, children demonstrated significant improvements in the ability to use both hands, individually and together. Improvements were measured using standardized developmental assessments administered by evaluators who were unaware of each child’s treatment assignment.

Children also showed gains in fine motor skills in their less-affected arm. Improvements were most pronounced at the six-month follow-up, suggesting that benefits continued to build after formal therapy ended.

Researchers had hypothesized that bimanual therapy might lead to greater improvements in two-handed skills and that full-time casting might yield stronger gains in the affected arm. The data did not support those predictions. Instead, outcomes were broadly comparable across approaches.

The study also addressed concerns that constraining the stronger arm could impair its development. No evidence of harm was observed. In fact, children in the full-time cast group showed slightly greater gains in fine motor skills in their non-affected arm at six months compared with the bimanual group. 

“This is important to the field because many people have worried that the use of a constraint might slow the developmental process of the less-affected arm,” DeLuca said. “Our findings confirm that this did not occur and this therapy may even help promote improvements in skills on the less-affected arm and hand.”

Some parents reported their child showed short-term frustration wearing a cast or splint, and minor skin irritation occurred in a small number of children using casts, but no were caused by the therapy itself.

The trial was conducted in collaboration with researchers at Virginia Tech, The Ohio State University, and Nationwide Children’s Hospital. Therapists were centrally trained to deliver structured, play-based interventions grounded in motor learning principles, including repetition, reinforcement, and progressively challenging activities.

Longer-term studies will be needed to better understand how early therapy influences development across many dimensions of a child’s life.

Original study: 10.1542/pedsos.2025-000676

Source: Virginia Tech