New research shows attention lapses due to sleep deprivation coincide with a flushing of fluid from the brain — a process that normally occurs during sleep.
Anne Trafton | MIT News
Photo by Tim Gouw on Unsplash
Nearly everyone has experienced it: After a night of poor sleep, you don’t feel as alert as you should. Your brain might seem foggy, and your mind drifts off when you should be paying attention.
A new study from MIT reveals what happens inside the brain as these momentary failures of attention occur. The scientists found that during these lapses, a wave of cerebrospinal fluid (CSF) flows out of the brain – a process that typically occurs during sleep and helps to wash away waste products that have built up during the day. This flushing is believed to be necessary for maintaining a healthy, normally functioning brain.
When a person is sleep-deprived, it appears that their body attempts to catch up on this cleansing process by initiating pulses of CSF flow. However, this comes at a cost of dramatically impaired attention.
“If you don’t sleep, the CSF waves start to intrude into wakefulness where normally you wouldn’t see them. However, they come with an attentional tradeoff, where attention fails during the moments that you have this wave of fluid flow,” says Laura Lewis, the Athinoula A. Martinos Associate Professor of Electrical Engineering and Computer Science, a member of MIT’s Institute for Medical Engineering and Science and the Research Laboratory of Electronics, and an associate member of the Picower Institute for Learning and Memory.
Lewis is the senior author of the study, which appears today in Nature Neuroscience. MIT visiting graduate student Zinong Yang is the lead author of the paper.
Flushing the brain
Although sleep is a critical biological process, it’s not known exactly why it is so important. It appears to be essential for maintaining alertness, and it has been well-documented that sleep deprivation leads to impairments of attention and other cognitive functions.
During sleep, the cerebrospinal fluid that cushions the brain helps to remove waste that has built up during the day. In a 2019 study, Lewis and colleagues showed that CSF flow during sleep follows a rhythmic pattern in and out of the brain, and that these flows are linked to changes in brain waves during sleep.
That finding led Lewis to wonder what might happen to CSF flow after sleep deprivation. To explore that question, she and her colleagues recruited 26 volunteers who were tested twice — once following a night of sleep deprivation in the lab, and once when they were well-rested.
In the morning, the researchers monitored several different measures of brain and body function as the participants performed a task that is commonly used to evaluate the effects of sleep deprivation.
During the task, each participant wore an electroencephalogram (EEG) cap that could record brain waves while they were also in a functional magnetic resonance imaging (fMRI) scanner. The researchers used a modified version of fMRI that allowed them to measure not only blood oxygenation in the brain, but also the flow of CSF in and out of the brain. They also measured each subject’s heart rate, breathing rate, and pupil diameter.
The participants performed two attentional tasks while in the fMRI scanner, one visual and one auditory. For the visual task, they had to look at a screen that had a fixed cross. At random intervals, the cross would turn into a square, and the participants were told to press a button whenever they saw this happen. For the auditory task, they would hear a beep instead of seeing a visual transformation.
Sleep-deprived participants performed much worse than well-rested participants on these tasks, as expected. Their response times were slower, and for some of the stimuli, the participants never registered the change at all.
During these momentary lapses of attention, the researchers identified several physiological changes that occurred at the same time. Most significantly, they found a flux of CSF out of the brain just as those lapses occurred. After each lapse, CSF flowed back into the brain.
“The results are suggesting that at the moment that attention fails, this fluid is actually being expelled outward away from the brain. And when attention recovers, it’s drawn back in,” Lewis says.
The researchers hypothesise that when the brain is sleep-deprived, it begins to compensate for the loss of the cleansing that normally occurs during sleep, even though these pulses of CSF flow come with the cost of attention loss.
“One way to think about those events is because your brain is so in need of sleep, it tries its best to enter into a sleep-like state to restore some cognitive functions,” Yang says. “Your brain’s fluid system is trying to restore function by pushing the brain to iterate between high-attention and high-flow states.”
A unified circuit
The researchers also found several other physiological events linked to attentional lapses, including decreases in breathing and heart rate, along with constriction of the pupils. They found that pupil constriction began about 12 seconds before CSF flowed out of the brain, and pupils dilated again after the attentional lapse.
“What’s interesting is it seems like this isn’t just a phenomenon in the brain, it’s also a body-wide event. It suggests that there’s a tight coordination of these systems, where when your attention fails, you might feel it perceptually and psychologically, but it’s also reflecting an event that’s happening throughout the brain and body,” Lewis says.
This close linkage between disparate events may indicate that there is a single circuit that controls both attention and bodily functions such as fluid flow, heart rate, and arousal, according to the researchers.
“These results suggest to us that there’s a unified circuit that’s governing both what we think of as very high-level functions of the brain — our attention, our ability to perceive and respond to the world — and then also really basic fundamental physiological processes like fluid dynamics of the brain, brain-wide blood flow, and blood vessel constriction,” Lewis says.
In this study, the researchers did not explore what circuit might be controlling this switching, but one good candidate, they say, is the noradrenergic system. Recent research has shown that this system, which regulates many cognitive and bodily functions through the neurotransmitter norepinephrine, oscillates during normal sleep.
The research was funded by the National Institutes of Health, a National Defense Science and Engineering Graduate Research Fellowship, a NAWA Fellowship, a McKnight Scholar Award, a Sloan Fellowship, a Pew Biomedical Scholar Award, a One Mind Rising Star Award, and the Simons Collaboration on Plasticity in the Aging Brain.
This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.
Study reveals how targeting a cellular pathway could protect cancer patients from peripheral neuropathy
Photo by Tima Miroshnichenko on Pexels
Scientists at Wake Forest University School of Medicine, in collaboration with researchers at Weill Cornell Medicine, have made a breakthrough in understanding why many cancer patients develop nerve damage after chemotherapy. Their new study, published in Science Translational Medicine, reveals that a stress response inside certain immune cells can trigger this debilitating side effect. This discovery could open the door to new ways to prevent or treat nerve damage in cancer patients.
Chemotherapy-induced peripheral neuropathy is a common and often severe side effect of cancer treatment, especially with drugs like paclitaxel. It can cause tingling, numbness and pain in the hands and feet, sometimes forcing patients to stop life-saving treatment early. Up to half of all patients receiving chemotherapy may experience this condition, but until now, the exact cause has remained a mystery.
To better understand this nerve toxicity that could be painful, scientists used a well-established mouse model that closely reflects the nerve problems experienced by people undergoing cancer treatment. This model allowed researchers to observe how a specific immune cell pathway, known as IRE1α, contributes to triggering inflammation that led to neurotoxicity and pain. By blocking the IRE1α pathway in the immune cells of these mice, either through genetic techniques or with an IRE1a inhibitor, the team was able to prevent the development of nerve damage, pain and toxic inflammation.
The researchers also studied a group of patients from Atrium Health Wake Forest Baptist’s National Cancer Institute-designated Comprehensive Cancer Center. The patients were receiving chemotherapy for gynecological cancers, collecting blood samples before and after treatment to measure IRE1α activity in their immune cells. They found that patients with higher IRE1α activation were more likely to develop severe neuropathy due to chemotherapy, directly linking the mouse model findings to patient outcomes.
Key Findings
Chemotherapy activates a stress sensor (IRE1α) in immune cells, triggering inflammation and nerve damage.
Blocking this sensor in mice prevented nerve pain and damage, suggesting a new treatment target.
In patients, higher activation of this stress sensor in blood cells was linked to more severe nerve symptoms and also to the initiation of neuropathy symptoms.
“Our research shows that a stress response inside immune cells is a key contributor to chemotherapy-induced neuropathy that could be painful and debilitating. By targeting this pathway, we may be able to protect patients from one of the most challenging side effects of cancer treatment,” said E. Alfonso Romero-Sandoval, MD, PhD, professor of anaesthesiology at Wake Forest University School of Medicine and the study’s corresponding author. “Our study opens the opportunity to further explore if this pathway could be used to predict what patients will develop this condition and therefore could help clinicians implement patient-tailored treatments,” Romero-Sandoval said.
The discovery could lead to new drugs that block this pathway, helping patients stay on their cancer treatment without suffering from painful side effects.
According to Romero-Sandoval, who is a member of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, this is the first study to show that the IRE1α stress sensor in immune cells is directly linked to nerve damage from chemotherapy.
The team plans to conduct larger clinical studies to confirm these findings and test whether the IRE1α pathway could be used as a biomarker for disease progression and if drugs that block this stress sensor can safely prevent or reduce nerve damage in cancer patients. They also hope to explore whether this approach could help with other types of nerve pain. Interestingly, an IRE1a inhibitor is currently in clinical trials to improve anti-cancer effects of chemotherapy, including paclitaxel.
One of the most common antidepressants, sertraline, contributes to a modest improvement in core depression and anxiety symptoms, including low mood, within two weeks, finds a new analysis of a major clinical trial led by UCL researchers.
The study, published in Nature Mental Health, analysed the findings of the PANDA trial, which first published results in 2019 and found that sertraline may have an earlier impact on anxiety than depressive symptoms.* Researchers have now conducted a network analysis of the results, which is an innovative statistical method that allowed them to explore how specific symptoms respond to treatment.
The analysis revealed an improvement in symptoms such as low mood and suicidal thinking within two weeks of taking sertraline, while side effects of the drug led to symptoms such as low libido, low appetite, and tiredness. These side effects can also be symptoms of depression.
The researchers propose that the effect on all depressive symptoms put together in the initial analysis obscured the benefits of the antidepressants on some of the core depressive symptoms.
In the new analysis, the early improvements from sertraline were found to be on feelings of sadness, self-loathing, restlessness, and suicidal thoughts.
The PANDA trial was a randomised controlled trial testing the effects of sertraline on people with depressive symptoms, including a wide range of patients in England whose symptoms ranged from mild to moderate. In a paper published in The Lancet Psychiatry in 2019*, scientists reported that within six weeks, sertraline improved anxiety symptoms and people reported an overall improvement in their mental health, but depressive symptoms did not meaningfully improve until participants had been taking the drug for 12 weeks. The new analysis, using data from 571 participants of the trial (those who had complete data for each symptom), suggests that sertraline improves some core depressive symptoms more quickly than previously believed.
The somatic (physical) symptoms that worsened, including libido and poor sleep, can be seen as side effects of antidepressants, but they are also common symptoms of depression, which can complicate interpretation of treatment effects.
Lead author Dr Giulia Piazza (UCL Psychiatry and UCL Psychology & Language Sciences) said: “We have now painted a more complex picture of sertraline’s effects on the different symptoms of depression.
“Instead of thinking of depression and anxiety as each being a single, uniform condition, network analysis considers that they’re each a constellation of symptoms, that can appear in different combinations for different people. These symptoms influence each other over time; for example, poor sleep can lead to problems with concentration, which may then impact self-esteem.
“Our analysis was borne out of this theoretical approach, in order to gain deeper insights and add nuance to the results of the PANDA trial.”
The researchers found that sertraline contributed to improvements in anxiety symptoms and in the emotional symptoms of depression within two weeks, and a modest worsening of somatic symptoms. The effect on somatic symptoms plateaued after six weeks, while the improvements in emotional symptoms and anxiety continued to improve from six weeks to 12 weeks.
Dr Piazza added: “It appears that the adverse effects on somatic symptoms like poor sleep and libido may stabilise after six weeks, which is then counteracted by continued improvements in emotional symptoms, the core symptoms of depression.”
Antidepressants are the standard pharmaceutical treatment for both depression and generalised anxiety disorder. Sertraline is a selective serotonin reuptake inhibitor (SSRI), the most common class of antidepressants.
Co-author Professor Glyn Lewis (UCL Psychiatry), who led the PANDA trial, said: “Our findings provide robust evidence that continues to support the prescription of sertraline for people experiencing depressive and anxiety symptoms. These findings will help patients and clinicians to make more informed decisions about treatment.”
Co-senior author Professor Jean-Baptiste Pingault (UCL Psychology & Language Sciences) said: “We found that the beneficial effects of sertraline can be detected very early on, as soon as two weeks after people start taking the antidepressant.
“Beyond this study, our results highlight the importance of considering symptom-level effects when developing novel drugs and evaluating existing drugs in psychiatry, and how this can help us to understand how these drugs work and how they can help patients.”
In a new study using AI and machine learning, EPFL researchers have found that it’s not only what we eat, but how consistently we eat it that plays a crucial role in gut health. Many previous studies have shown that what we eat has an impact on our gut microbiota. Healthy diets rich in fruit, vegetables, fibre and nuts are strongly associated with increased microbial diversity and better stomach health.
But now, for the first time, EPFL research has shown that the regularity with which we eat a healthy diet is just as important for gut health as the amount of what we consume.
The importance of nutritional quality and regularity
In a new paper, just published in the journal Nature Communications, researchers in EPFL’s Digital Epidemiology Laboratory, part of both the Schools of Computer and Communication and Life Sciences, confirmed earlier research that certain types of foods, such as fruit and vegetables, contribute to a more diverse gut microbiota. Working with colleagues at the University of California, San Diego, they also made several striking new discoveries.
First, they found that it’s not just the consumption of fruit, vegetables and grains that create a healthy gut microbiota, but whether you eat them regularly or not. Whilst there’s always been a hunch that it’s important to eat good food regularly, encouraged by campaigns such as ‘five fruits and vegetables a day’, it has always been just that – a hunch.
“This research clearly shows that you cannot binge on vegetables on your healthy day and then eat in an unhealthy way for the rest of the week or month,” said Associate Professor Marcel Salathé, head of the Digital Epidemiology Lab and co-director of the EPFL AI Center. “In fact, our study suggests that irregular consumption of healthy foods undoes many of their beneficial effects on the gut microbiota. This is a real incentive for future studies to not just look at what people are eating but the patterns of what they are eating over time.”
Predicting diet from the microbiome
Second, the team was also able to show that a person’s gut bacteria and what they eat can predict each other with up to 85% accuracy. With just a simple stool sample — an increasingly common component of medical research — advanced machine learning techniques could predict a person’s diet using their microbiota and vice versa.
“For our collaborators in San Diego, who are some of the world’s leading experts in microbiome research, this was exciting,” explained Salathé. “Getting such data from a stool sample is relatively easy, but understanding someone’s diet is notoriously difficult, it’s data that’s been challenging to collect.”
The power of real-time data
The study was made possible by using detailed nutritional information from about 1000 participants who were part of the “Food & You” cohort.
High-resolution dietary data was collected via the AI-powered app MyFoodRepo, developed by the same EPFL lab, which allowed users to log their meals in real time by snapping photos or scanning barcodes. The app’s AI then analysed these entries for nutritional content, later verified by human reviewers.
“Historically, nutrition research has relied on food frequency questionnaires and 24-hour dietary recalls. In theory, you could ask somebody to write down everything they eat but in practice it’s just not done because it’s borderline impossible. Now, the AI is so good that we can do this data collection at a large scale,” said Rohan Singh, a Doctoral Assistant in the Digital Epidemiology Lab and lead author of the paper.
“Our study has been particularly interesting because when you look at lifestyle-oriented gastrointestinal disorders, they often develop gradually. Since nutrition is one of the big contributors to these diseases, analyses like ours may be able to assess what can be improved in a person’s diet. AI can then help nudge people to adjust their food intake accordingly,” he continued.
Looking ahead
Salathé believes the study’s findings suggest that current dietary guidelines may need to be updated to emphasize not just the types and quantities of food, but the regularity of healthy eating behaviors.
And, while this research project has ended, the MyFoodRepo app continues to be used by the Digital Epidemiology Lab team for other research. They are currently involved in a pilot project on nutrition and cognitive performance, studying potential links between the two.
Also, through the use of barcoded food data from the Food & You study, the researchers are investigating the link between food additives, like emulsifiers, found in ultra-processed foods, and the gut microbiota.
“There’s a strong hypothesis that some of these additives really may negatively impact your microbiota, and we have some early indications that this could indeed be the case. We’re still in the analysis stage but we are quite excited about early results,” said Salathé.
More generally, they are gratified that the MyFoodRepo app is now opening the door to important nutrition studies globally.
“From the outset, we knew we needed something extremely consumer friendly and easy to use, while still providing the data that we needed. We built it to serve our own research needs, but also in a way which others would find useful – and it’s now being used in many other nutrition studies globally,” Salathé concluded.
New Northwestern Medicine study provides answers and drug targets
Photo by Natanael Melchor on Unsplash
More than 50% of lung-transplant recipients experience a rejection of their new lung within five years of receiving it, yet the reason why this is such a prevalent complication has remained a medical mystery.
Now, a new Northwestern Medicine study has found that, following transplant and in chronic disease states, abnormal cells emerge and “conversations” between them drives the development of lung damage and transplant rejection.
These findings not only help answer why rejection occurs, but they also have spurred immediate exploration of new drugs to treat transplant rejection and other lung-scarring diseases.
“Chronic lung-transplant rejection has been a ‘black box.’ We knew it happened but did not exactly know why,” said corresponding author Dr Ankit Bharat, professor of thoracic surgery at Northwestern University Feinberg School of Medicine and executive director of the Northwestern Medicine Canning Thoracic Institute. “Our study provides the first comprehensive cellular and molecular roadmap of the disease.”
The study was published in JCI Insight.
Leading cause of death after the first year of transplantation
Surgeons perform approximately 3000 to 3500 lung transplants each year in the U.S., and more than 69 000 have been performed worldwide to date. Chronic lung allograft dysfunction (CLAD), which encompasses several manifestations of chronic lung rejection, remains the leading cause of death after the first year of transplantation. There currently are no effective treatments for CLAD once it develops, leaving patients with only one option: re-transplantation.
In the new study, after evaluating almost 1.6 million cells, scientists distinguished between abnormal cells from the donor lung versus cells from the recipient’s own immune system. They discovered the donor-derived structural cells and recipient’s immune cells talk to each other in harmful ways that perpetuate lung damage. The findings could lead to new drug targets and provide insights that could help patients with various lung-scarring diseases, not just transplant recipients.
Comparing rejection to other scarring lung diseases
The scientists discovered a rogue cell type (KRT17 and KRT5 cells) that drives lung scarring across multiple diseases, including idiopathic pulmonary fibrosis, interstitial lung disease, COPD, COVID-19 lung damage and transplant rejection. By integrating data from this array of scarring lung diseases, the scientists created the first comprehensive reference map showing which molecular features are shared across conditions and which are unique to each disease.
“By comparing chronic rejection to other scarring lung diseases, we identified both shared and unique features,” said Bharat, who also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This means treatments developed for one condition might help others. The benefits extend far beyond transplant patients.”
The scientists also identified previously unrecognised cell populations in rejected lungs. These include “exhausted” T cells that remain activated but dysfunctional, and “super-activated” macrophages that promote inflammation and scarring.
Lastly, the scientists developed new computational methods to analyse data from multiple studies together, overcoming technical barriers that previously prevented this kind of comprehensive analysis, Bharat said.
New drug targets identified
The scientists pinpointed specific genes and signaling pathways (like PDGF, GDF15 and TWEAK) that drive scarring, which allows them to identify potential targets for new drugs, Bharat said. Some existing medications, such as nintedanib, and pirfenidone, which are approved (in the US) for other lung diseases, might be repurposed for transplant rejection, he said.
“The findings have immediate translational potential,” Bharat said. “We’re already exploring therapeutic strategies based on these discoveries.”
Broad impact on pulmonary fibrosis
While addressing CLAD was the main focus of the paper, this research has major implications for understanding and treating all forms of pulmonary fibrosis, Bharat said.
“The molecular pathways and cell types we identified are relevant to conditions affecting hundreds of thousands of patients with various lung-scarring diseases, not just transplant recipients,” Bharat said. “This work essentially provides a ‘Rosetta Stone’ for understanding lung scarring regardless of the initial trigger.”
Cancer is one of the fastest-growing health challenges in South Africa, with over 100 000 new cases diagnosed annually, according to the National Cancer Registry. While most conversations focus on the physical and emotional impact, the financial strain of the disease often goes unspoken.
According to the South African Medical Journal, treatment costs for cancer can exceed R1 million per year, particularly when advanced therapies and prolonged care are required. This leaves many families facing difficult decisions that extend far beyond the hospital ward. With medical aid often falling short and with only 16% of South Africans covered by medical schemes, as reported by the Council for Medical Schemes the financial burden of cancer can be as devastating as the diagnosis itself.
“Medical aid alone often isn’t enough to cover the full cost of treatment, especially when it comes to critical illnesses like cancer,” says Matthew Green, Product Portfolio Manager at FNB Life. “We’ve seen firsthand how having the right insurance can make a real difference.”
The true impact of cancer is often measured in rands and cents: savings depleted, debt accumulated, and households forced to sacrifice essentials to pay for treatment. Myths about affordability and a lack of awareness mean that too many people enter this battle unprepared. The result is a financial shock that can be as devastating as the diagnosis itself. Beyond the direct medical expenses, families often face a range of additional costs from transport to and from treatment centres, specialised nutrition, home modifications, and caregiving support, to lost income due to time off work. Critical illness cover is designed to help bridge these financial gaps, providing a lump-sum payout that can be used not only for treatment, but also for these broader, often overlooked expenses that impact the entire household.
“Against this backdrop, insurers are under growing pressure to offer support that reflects the lived realities of ordinary South Africans. FNB Insure is among those stepping in to help close the gap – focusing on making financial protection more accessible, flexible, and relevant to everyday needs,” says Green.
Rather than positioning insurance cover as a luxury, the emphasis is on practical tools that help households navigate the rising costs of treatment and the economic strain that often follows a serious diagnosis. Whether it’s support during hospital stays, assistance with unexpected medical shortfalls, or a payout that enables immediate action after a diagnosis, the goal is to empower customers to focus on recovery – not financial survival.
This is evident from our customer feedback, where individuals have shared how timely access to cover helped them act quickly, avoid financial delays, and prioritise their health during some of life’s most difficult moments. “And its stories like this underline the importance of early financial planning and the role of accessible insurance in giving families space to focus on recovery rather than financial survival,” says Green.
With October marking Breast Cancer Awareness Month and November bringing the spotlight on men’s health through initiatives like Movember, FNB Insure is adding its voice to the broader call for awareness. “The message is clear: cancer doesn’t only affect health; it reshapes every aspect of life. Building resilience means preparing not just medically, but financially too,” concludes Green.
Research reveals Alzheimer’s disease-like DNA damage, hints at immune involvement
Photo by Hermes Rivera on Unsplash
Chronic traumatic encephalopathy (CTE), a neurodegenerative disease diagnosed after death, most often athletes of contact sports and military personnel, is not just caused by repeated head impact but also linked to DNA damage similar to that seen in Alzheimer’s disease, according to a new study led by researchers at Harvard Medical School, Boston Children’s Hospital, Mass General Brigham, and Boston University.
CTE is known to share characteristics with Alzheimer’s disease, namely the buildup of abnormal tau protein in the brain. CTE has also been associated with the development of dementia. The new research, published October 30 in Science, highlights the commonalities between CTE and Alzheimer’s at the genetic level and raises hopes that future treatments could target both diseases.
The findings also support recent work from study co-authors Jonathan Cherry and Ann McKee at Boston University in suggesting that immune system responses could help explain why only some people with repeated head impact go on to develop CTE.
“Our results suggest that CTE develops through some process in addition to head trauma,” said co-senior author Christopher A. Walsh, Professor of Pediatrics and Neurology and chief of the Division of Genetics and Genomics at Boston Children’s. “We suspect it involves immune activation in a way similar to Alzheimer’s disease, happening years after trauma.”
A new approach to studying CTE
The team used two types of single-cell genomic sequencing to identify somatic genetic mutations – non-inherited changes in DNA. This marked the first time scientists took such an approach to studying CTE.
Studying postmortem brain tissue samples, the researchers analysed hundreds of neurons from the prefrontal cortex of 15 individuals diagnosed with CTE after death and 4 individuals with repeated head impact but without CTE and compared them with 19 neurotypical controls and 7 individuals with Alzheimer’s.
The team found that neurons from individuals with postmortem CTE diagnoses had specific abnormal patterns of somatic genome damage that closely resemble those seen in Alzheimer’s. Individuals displaying signs of repeated head impact without postmortem CTE diagnoses didn’t have these changes.
“One of the most significant aspects of our work is the introduction of a new, single-cell genome approach to CTE,” said co-senior author Michael Miller, HMS assistant professor of pathology at Brigham and Women’s Hospital. “Our study provides further evidence that CTE is a bona fide neurodegenerative disease defined by its unique neuropathological features.”
The researchers also observed that the CTE brain samples showed signs of damage equivalent to more than 100 years of excess aging.
Clues to CTE’s origins
Repeated head impact most often occurs during contact sports such as American football, hockey, and rugby or during military service. CTE has been found postmortem in the brains of teenagers and young adults playing amateur sports as well as in older professional athletes.
Recent research in Nature from Cherry and McKee found that repeated head impact causes brain damage in young people even before tau deposition or symptoms indicative of CTE arise. That study also indicated that repeated head trauma induces immune activation in athletes’ brains, said Walsh, who is also an investigator of the Howard Hughes Medical Institute.
The October 30 paper adds to this growing evidence base by linking CTE with Alzheimer’s, which involves inflammation in microglial cells in the brain, despite the diseases’ differing risk factors, Walsh said.
The NHI Act is facing a slew of legal challenges from multiple organisations. For this special series, Spotlight combed through court papers, and spoke with legal experts to pin down what specific arguments litigants are betting on. In part one, we focused on the claim that the scheme is unaffordable and therefore unreasonable. Here, in part two, we discuss the argument that the NHI will unjustifiably compromise people’s right to access healthcare services.
Since the National Health Insurance (NHI) Act was signed into law by President Cyril Ramaphosa in May 2024, eight different groups have challenged it in court, with some filing multiple applications.
One core argument which appears in different ways across many of these submissions is that under the NHI, people will have access to fewer health services, or simply a reduced quality of care, than what they currently have.
If this was true then the NHI could be in violation of Section 27 of the country’s Constitution, according to which government has to do what it can to achieve the “progressive realisation” of the right to healthcare services (along with the right to food, water and social security). Courts have often interpreted this to mean that the government not only has to take active steps to advance people’s access to healthcare, but also that it should avoid doing things that might limit their existing rights.
Sasha Stevenson, who heads the public interest law clinic SECTION27, explained that the Constitution uses the phrase “progressive realisation” because of a “recognition that not everything can be perfect straight away, so the government needs to take steps to move toward full realisation of certain socioeconomic rights”. She added: “What that means logically is that you can’t move backwards.”
There is however some wiggle room, said Stevenson. This is because the Constitution only expects the government to take “reasonable” steps that are “within its available resources”, she said.
Thus, if the government was cash-strapped and able to show that it simply couldn’t afford to maintain its current levels of health expenditure without seriously compromising other core rights, then it may be able to take steps backward without violating the Constitution. Stevenson argued that, at its core, the key idea is simply that the state must fully justify what it is doing.
To show that the NHI Act violates Section 27 of the Constitution, litigants will need to prove that it not only limits people’s right to healthcare, but that the government hasn’t provided good enough reasons for why it is doing this.
But why are litigants arguing that the NHI would limit people’s right to healthcare in the first place? Let’s start with medical scheme members.
Cutting out medical schemes
Section 33 of the NHI Act states that once the scheme is fully implemented, medical schemes will only be allowed to cover top-up health services that aren’t covered by the NHI. In addition, the Act requires “mandatory prepayment”, meaning people will have to pay to be covered by the NHI, whether or not they want to join.
Thus, unless someone was able to afford both the mandatory prepayment for the NHI, and complimentary cover from their medical schemes, they would have to switch to relying solely on the NHI for their medical coverage.
This is an issue for the Board of Healthcare Funders (BHF), which represents the medical insurance industry, and was one of the first groups to challenge the NHI in court.
“When you look at what medical scheme members are entitled to now versus to what they’re entitled to under an NHI scheme, it’s a regressive process,” Neil Kirby, who heads the healthcare and life science practice area at Werksmans Attorneys, which represents BHF, told Spotlight.
“You probably would be entitled to less under an NHI scheme than you would under the current regime,” he said.
Of course, at present we don’t yet know exactly what health services the NHI will cover, as the package of benefits has not yet been detailed. It thus may be difficult for courts to assess this claim.
When asked about this, Kirby said: “The current assessment by various economic experts is that if one were to price the value of the current basket of prescribed minimum benefits [the services which medical schemes have to cover]… and spread that cost over the entire population covered by NHI, the NHI would be entirely unaffordable.”
As a result, he said: “There would have to be some degree of compromise in respect of the benefits to be provided under NHI in order for the state to afford to purchase those benefits”. In other words, they’d need to offer less than what medical schemes currently cover.
In response to this, the National Health Department’s NHI lead, Dr Nicholas Crisp, denied that people’s coverage would be compromised under the NHI. In a conversation with Spotlight, he argued that the NHI would not need to incur the same total payment obligations as medical schemes in order to cover a comprehensive package of health services. This is given that it could purchase services more efficiently, he said.
ANC President Cyril Ramaphosa, with Minister of Health, Dr Joe Phaahla and his deputy Dr Sibongiseni Dhlomo, during the signing into law of the National Health Insurance Bill. (Photo: @MYANC/Twitter)
Crisp justified this on several grounds. One is that private health providers are currently accused of overservicing clients, which he argues could be rectified under the NHI.
For instance, Crisp pointed to the Competition Commission’s Health Market Inquiry report, which found that private health facilities are reimbursed for each consultation, operation or other service that they provide. The report found that this “creates an incentive for providers to over-service patients, to over-invest in generously remunerated services, and under-invest in poorly remunerated services [even if they have a positive impact on patient outcomes]”.
Under the NHI scheme, a different reimbursement model would be used to cover health providers both at private and public health facilities. For instance, in the primary healthcare sector, the NHI would rely on capitation. This means that health providers would be provided a fixed fee for each patient, rather than for each individual service, removing the incentive to overservice, and thus overcharge.
Crisp also argued that the government is able to procure medicines and other health services at lower prices than the private sector partly by buying in bulk. Additionally, he noted that billions of rands are reportedly lost in fraud, waste and abuse within the private health sector, due for instance to fraudulent medical claims.
According to Crisp, the NHI fund would be able to save on all of these unnecessary costs.
Pushing back on this view, Professor Alex van den Heever, from the Wits school of governance, told Spotlight that there was no reason to think the state could purchase cover more efficiently than the private medical schemes.
In the public sector, he said that “whether you have a [national] monopoly like Eskom, or a public monopoly in a province like the Gauteng Department of Health, they hardly spend their money efficiently”. Van den Heever added: “For Tembisa hospital to lose R2 billion and not get a cent back in terms of actual products is an indication of the risk.”
He was referring to a damning report by the Special Investigating Unit which confirmed large-scale looting to the tune of around R2 billion meant for patient care at Tembisa Hospital in Gauteng’s East Rand. Their investigation zoomed in on nine criminal syndicates, with three of them pocketing nearly R1.7 billion. The SIU found that R122 million in kickbacks were paid to at least 15 current and former health department officials.
“So you have to have some real evidence that [the state would] be able to procure services more efficiently, and there’s no evidence. All the historical evidence suggests they’d do worse,” Van den Heever said.
Does the state have good reasons?
If litigants are able to show that the NHI was regressive for people on medical schemes in the sense that it diminished their rights, the courts might still decide that the government had provided a good enough justification for why these limitations are reasonable.
But according to Van den Heever, the government has thus far categorically failed to do this.
“From the green paper to the white paper to the [NHI] bill, there is not a single technical document that provides a clear rationale for Section 33 [the restriction on medical schemes],” said Van den Heever. Overall, the very question about what specific problems the NHI is trying to solve and how it would do this remain elusive.
He added that one public health professor had submitted court papers in support of NHI which argued that the existence of the private health sector undermines the public sector, for instance by hoarding doctors and specialists. Yet according to Van den Heever, “no technical report has ever been produced” which provides evidence for that claim.
Additionally, he noted that doctor shortages at public facilities are evidently not driven by private sector hoarding but by financial constraints emanating from mismanagement and corruption. This prevents public hospitals from hiring people who are available for work. (Previous Spotlight reporting has also suggested that the shortage of doctors in the public sector is driven by a lack of funding, rather than a lack of doctors.)
Similarly, the Hospital Association of South Africa (HASA) argued in court papers that the NHI Act’s restrictions on medical schemes serves “no rational, reasonable or economic purpose”.
The association also argued that there are no examples of health systems that impose these restrictions, aside from a few provinces in Canada, and thus Section 33 of the NHI Act is clearly “not a requirement for a successful national health system aimed at [universal health coverage]”.
Defending the restriction on medical schemes, Crisp said that if two different streams of health financing are allowed to continue, then so will inequity. He also stated that single-payer health systems funded by the state are not unusual, even if their exact form differs across countries.
Limiting the rights of public sector users
In addition to the arguments that the NHI Act will unjustly restrict the rights of medical scheme members, some have also argued that it will be regressive for public sector users.
One organisation making this argument is the Treatment Action Campaign (TAC). It has applied to be a friend of the court in the dispute between the South African Medical Association (SAMA) and the government. The TAC argued that the governance provisions within the NHI are so weak that they threaten the entire health system, including for those relying on government health facilities.
Stevenson, whose organisation SECTION27 is represents the TAC, said that checks and balances within the governance of the NHI fund are deficient, leaving it vulnerable to corruption and mismanagement.
Van den Heever, who is serving as an expert in the SAMA case, seconded this concern. He also said that the NHI ultimately centralises the management and purchasing of healthcare services under national institutions. This introduces inefficiencies that will compromise patient care at government facilities, he argued.
“Healthcare is [a sector] where the purchasing and management [should be] decentralised,” he said, largely because different communities have different health needs.
Even in the United Kingdom, said Van den Heever, the responsibility for the National Health Service, which provides the majority of medical services, is devolved across England, Wales, Scotland and northern Ireland, with semi-autonomous trusts, boards and hospitals in each country having a major say in operational decisions.
Van den Heever argued that not only would the centralisation of health under NHI be highly undesirable, but the actual transition to this system from one in which provinces are responsible for healthcare would be enormously disruptive, impacting patient care.
Asylum seekers compromised by NHI
An additional argument concerns the rights of asylum seekers and undocumented people, a central concern for SAMA and the TAC.
Stevenson explained that under our current system, all people, including asylum seekers and undocumented migrants, have the right to free primary healthcare services in the public sector. Just like ordinary citizens, asylum seekers also have the right to access public hospitals on a means-tested basis (meaning your level of subsidisation is determined by what you can afford).
In addition, pregnant and lactating women, as well as children under six, are entitled to all services regardless of documentation status, and the government is compelled to screen, test and treat anyone with HIV.
Under the NHI Act, all of these rights are compromised for asylum seekers and undocumented migrants. This is because Section 4 of the NHI Act states that these groups are only covered for emergency care and for services related to notifiable conditions. The country’s list of notifiable conditions includes diseases like cholera and pulmonary TB, but excludes HIV, diabetes and many other common diseases.
Stevenson argued that this not only compromises the rights of individual asylum seekers, but makes for terrible public health policy.
“It essentially means dropping part of our population off the HIV programme,” she said.
“It would also mean we’re waiting more and more for emergencies, because people can access care [at the point of emergency] but not at a primary healthcare level. So you can’t go and get yourself checked for diabetes… But when your foot is gangrenous [a symptom of untreated diabetes] and needs amputation then you’re in an emergency situation.”
Overall, the Act in its current form constitutes a clear regression for asylum seekers, said Stevenson, and the government has provided no comprehensive justification for why it is excluding this group. If the government wanted to justify the exclusion of migrants on the basis that it is too costly to cover them under the NHI then they “have to show the numbers”, Stevenson said.
Thus far, they haven’t done so.
“There has been no assessment of the so-called burden of migrants in the health sector, let alone how many people fit into which category or how much money is spent on services for people,” said Stevenson, “Instead, there has just been this persistent scapegoating, and these broad statements about the burden.”
Court documents submitted by SAMA have made similar allegations.
“There is no reliable study which shows the extension of the NHI to foreigners will have a significant effect on the affordability of the NHI,” it argued, noting that in fact the converse may be true, as the contributions of foreigners to the economy may outweigh the costs of providing them healthcare.
Asked about this, Crisp said that they were aware of the issue, and that while it was a complicated matter, the state would ultimately have to ensure healthcare for all people, in line with its domestic laws and international agreements.
Disclosure: SECTION27 is mentioned in this article. Spotlight is published by SECTION27, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council and subject to the South African Press Code.
An international panel of leading experts on women’s mental health is recommending that postpartum psychosis be recognised as a distinct category of mental illness and classified accordingly within standardised medical coding systems.
The recommendation, published in Biological Psychiatry, follows a comprehensive review of the scientific literature on the illness.
Postpartum psychosis is an acute and severe psychiatric illness that sets in within weeks after delivery. Most women with postpartum psychosis experience severe mood symptoms, including mania, mixed episodes, or depression with psychotic features. Impaired cognition, irritability, and agitation are also common.
The condition is considered a psychiatric emergency and, in most cases, requires hospitalisation of the mother. If left untreated, postpartum psychosis is associated with high risks of suicide and infanticide. However, if it is detected and treated in time, patients respond well to treatment and most women return to their previous functioning.
Despite being one of the most distinct clinical phenotypes in psychiatry, postpartum psychosis is not recognized in the Diagnostic and Statistical Manual (DSM-5) or the International Classification of Disease (ICD), which are used to code diseases and medical conditions for treatment and billing purposes.
The panel, in close collaboration with patient advocacy organisations and key interested partners, recommended classifying postpartum psychosis as a distinct category within the bipolar disorders chapter of the DSM and ICD.
“Postpartum psychosis is the most severe perinatal mental health problem, and yet one that is often misdiagnosed and mismanaged, with severe consequences for women, and their children and families. A proper nosological classification of this disorder is an essential step towards its correct identification and treatment”.Professor Paola Dazzan, Professor of Neurobiology of Psychosis, Vice Dean (International) at King’s IoPPN and a member of the research panel
Due to the risks to the patient and the infant, the rapid escalation of severity, and its severe and sudden course, it is imperative that postpartum psychosis is recognized, diagnosed, and treated as early as possible. To facilitate such care, the panel recommends DSM-5 and ICD-10 include the following criteria for a diagnosis of postpartum psychosis:
The onset of at least one of the following states within 12 weeks of childbirth, lasting at least one week and present most of the day, nearly every day, or any duration if hospitalisation is necessary:
Mania/mixed state
Delusions
Hallucinations
Disorganised speech or formal thought disorder
Disorganised, confusional, or catatonic behaviour
Depression with psychotic features
The episode is associated with an unequivocal change in functioning that is uncharacteristic of the postpartum period.
The disturbance in mood and the change in functioning are observable by others.
The episode is sufficiently severe enough to cause marked impairment in social functioning and in the care of the baby or to necessitate hospitalization to prevent harm to the patient, baby, or others.
“We have been working with the American Psychiatric Association and the DSM steering committee since 2020 to find a solution that will facilitate diagnostic accuracy and the provision of timely and evidence-based treatment to improve the quality of treatment and outcomes for women with postpartum psychosis and to prevent the tragic outcomes of suicide and infanticide. We are committed to continue this work,” concludes Dr Veerle Bergink, Director of the Women’s Mental Health Center at Mount Sinai and first author of the paper.
Imagine knowing in your 20s or 30s that you carry a gene which will cause your mind and body to slowly unravel. Huntington’s disease is inherited, relentless and fatal, and there is no cure. Families live with the certainty of decline stretching across generations.
Now, a new treatment is being widely reported as a breakthrough.
Last week, gene therapy company uniQure announced that a one-time brain infusion appeared to slow the disease in a small clinical study.
If confirmed, this would not only be a landmark for Huntington’s disease but potentially the first time a gene therapy has shown promise in any adult-onset neurodegenerative disorder.
But the results, which were announced in a press release, are early, unreviewed and based on external comparisons. So, while these findings offer families hope after decades of failure, we need to remain cautious.
Symptoms usually start in mid-life. They include involuntary movements, depression, irritability and progressive decline in thinking and memory. People lose the ability to work, manage money, live independently and eventually care for themselves. Most die ten to 20 years after onset.
The disease is caused by an expanded stretch of certain DNA repeats (CAG) in the huntingtin gene. The number of repeats strongly influences when symptoms begin, with longer expansions usually linked to earlier onset.
Looking for a treatment
The gene that causes Huntington’s disease was identified in 1993, 32 years ago. Soon afterwards, mouse studies showed that switching off the mutant huntingtin protein even after symptoms had begun could reverse signs and improve behaviour.
This suggested lowering the toxic protein might slow or even partly reverse the disease. Yet for three decades, every attempt to develop a therapy for people has failed to show convincing clinical benefit. Trials of huntingtin-lowering drugs and other approaches did not slow progression.
What is the new treatment?
The one-time gene therapy, called AMT-130, involves brain surgery guided by MRI. Surgeons infuse an engineered virus directly into the caudate and putamen brain regions, which are heavily affected in Huntington’s.
The virus carries a short genetic “microRNA” designed to reduce production of the affected huntingtin protein.
By delivering it straight into the brain, the treatment bypasses the blood–brain barrier. This natural wall usually prevents medicines from entering the central nervous system. That barrier helps explain why so many brain-targeted drugs have failed.
What did they find?
Some 29 patients received treatment, with 12 in each group (one low-dose, and one high-dose) followed for three years. According to uniQure, those given the higher dose declined much slower than expected.
The study compared how much participants’ movement, thinking and daily function declined, compared to a matched external group from a global Huntington’s registry (meaning they weren’t part of the study). The company claimed those given the higher dose had a 75% slowing in their decline.
On a functional scale focused on independence, the company reported a 60% slowing in decline for the higher dose group.
Other tests of movement and thinking also favoured treatment. Nerve-cell damage in spinal fluid was lower for study participants than would be expected for untreated patients.
Why should we be cautious?
These findings are an early snapshot of results reported by the company, not yet peer-reviewed. The study compared treated patients to an external matched control group, not people randomised to placebo at the same time. This design can introduce bias. The numbers are also small – only 12 patients at the three-year mark – so we can’t draw solid conclusions.
The company reports the therapy was generally well tolerated, with no new serious adverse events related to the drug since late 2022. Most problems were related to the neurosurgical infusion itself, and resolved. But in a disease that already causes such severe symptoms, it is often hard to know what counts as a side effect.
The company uniQure has said it plans to seek regulatory approval in 2026 on the basis of this dataset.
Regulators will face difficult decisions: whether to allow access sooner before all the questions and uncertainties are addressed – based on the needs of a community with no effective options – and wait for further data while people are being treated, or to insist on larger trials that confirm results before approval.
What does it mean?
If upheld, these results represent the first convincing signs that a gene-targeted therapy can slow Huntington’s disease. They may also be the first evidence of benefit from a gene therapy in any adult-onset neurodegenerative disorder. That would be a milestone after decades of failure.
But these results do not prove success. Only larger, longer and fully peer-reviewed studies will show whether this treatment truly changes lives. Even if approved, a complex neurosurgical gene therapy may not be easily accessible to all patients.
The company has said the drug’s price would be similar to other gene therapies – which can cost over A$3 million per patient – and will have the added cost of brain surgery.
The takeaway
For families who carry this gene, the hope is profound. But caution is just as important.
We may be witnessing the first credible step toward slowing an inherited adult-onset neurodegenerative disease, or just an early signal that may not hold up.
Ultimately, only time and rigorous science will show whether this treatment delivers the benefits so urgently needed.
