Coup and contrecoup brain injury. Credit: Scientific Animations CC4.0
Recent research has indicated that acoustic stimulation of the brain may ease persistent symptoms in individuals who experienced mild traumatic brain injury in the past.
The study, which appears in Annals of Clinical and Translational Neurology, included 106 military service members, veterans, or their spouses with persistent symptoms after mild traumatic brain injury sustained three months to 10 years ago. Participants were randomised 1:1 to receive either 10 sessions of engineered tones linked to brainwaves (intervention), or random engineered tones not linked to brainwaves (sham control). All participants rested comfortably in the dark in a ‘zero-gravity’ chair, eyes closed and listening to the computer-generated tones via earbud-style headphones. The primary outcome was change in symptom scores, with secondary outcomes of heart rate variability and self-reported measures of sleep, mood, and anxiety.
Among all study participants, symptom scores clinically and statistically improved compared with baseline, with benefits largely sustained at three months and six months; however, there were no significant differences between the intervention and control groups. Similar patterns were observed for secondary outcomes.
The results indicate that although acoustic stimulation is associated with marked improvement in postconcussive symptoms, listening to acoustic stimulation based on brain electrical activity, as it was delivered in this study, may not improve symptoms, brain function, or heart rate variability more than randomly generated, computer engineered acoustic stimulation.
“Postconcussive symptoms have proven very difficult to treat, and the degree of improvement seen in this study is virtually unheard of, though further research is needed to identify what elements are key to its success,” said corresponding author Michael J. Roy, MD, MPH, of Uniformed Services University and the Walter Reed National Military Medical Center, in Bethesda.
Posttraumatic stress disorder (PTSD) is a debilitating condition that arises after experiencing traumatic events. While many people experience trauma, only about 25–35% of them develop PTSD. Understanding the factors that make certain individuals more susceptible is crucial for both prevention and treatment.
A new study led by Carmen Sandi and Simone Astori at EPFL now reveals how the development of PTSD is influenced by glucocorticoids, which are stress hormones such as cortisol. The work, which is published in Biological Psychiatry, provides significant insights into the behavioural and biological traits associated with PTSD vulnerability.
“There are considerable differences in the levels of glucocorticoids that individuals release to the bloodstream when stressed,” says Carmen Sandi. “Low glucocorticoid levels are frequently observed in PTSD patients following trauma exposure and were initially suspected to be a consequence of trauma exposure.”
She continues: “The possibility that this could be a trait constituting a pre-existing PTSD risk factor has been an outstanding open question for many years, but tackling it has been challenging due to the difficulties of both collecting biological measures before trauma exposure, and having access to relevant animal models in which the causal role of these traits can be investigated.”
To explore how a reduced hormonal response to stress might be linked to PTSD symptoms, the researchers used a genetically selected rat model that mimics people with blunted responses to cortisol. To do this, the team used MRI scans to measure the volume of different brain regions, trained rats to associate a cue with fear, recorded their sleep patterns, and measured their brain activity.
By combining these methods, the researchers discovered that a blunted responsiveness to glucocorticoids led to a “correlated multi-trait response” that includes impaired fear extinction (in males), reduced hippocampal volume, and rapid-eye movement sleep disturbances.
To explain the terms: Fear extinction is a process by which a conditioned fear response diminishes over time; problems with fear extinction are a hallmark of PTSD. Rapid-eye movement is crucial for memory consolidation, and disturbances in this type of sleep pattern have long been associated with PTSD.
But the study didn’t end there: the researchers treated the rats with the equivalent of human cognitive and behavioral therapy to reduce their learned fears. After that, they gave the rats corticosterone. As a result, both excessive fear and disturbances in rapid-eye movement sleep receded. Not only that, but the increased levels of the stress-related neurotransmitter norepinephrine in the brain also returned to normal.
“Our study provides causal evidence of a direct implication of low glucocorticoid responsiveness in the development of PTSD symptomatology following exposure to traumatic experiences, i.e., impaired fear extinction,” says Carmen Sandi. “In addition, it shows that low glucocorticoids are causally implicated in the determination of other risk factors and symptoms that were until now only independently related to PTSD.”
Silvia Monari, the study’s first author, adds: “In a nutshell, we present mechanistic evidence – previously missing – that having low glucocorticoids such as cortisol in humans is a condition for causally predisposed individuals to present all to-date vulnerability factors for developing PTSD, and causally involved in deficits to extinguish traumatic memories.”
Researchers at the Institute of Basic Science (IBS) in South Korea have developed a novel approach to healing muscle injury by employing an ‘injectable tissue prosthesis’ in the form of conductive hydrogels and combining it with a robot-assisted rehabilitation system. They describe their research in a recent publication in the journal Nature.
A large wound such as a shark bite, with the loss of muscle and nerve in the wound cavity, results in a complete loss of motor/sensor function in the leg. If left untreated, such severe muscle damage would result in permanent loss of function and disability.
Traditional rehabilitation methods for these kinds of muscle injuries have long sought an efficient closed-loop gait rehabilitation system that merges lightweight exoskeletons and wearable/implantable devices. Such assistive prosthetic system is required to aid the patients through the process of recovering sensory and motor functions linked to nerve and muscle damage.
Unfortunately, the mechanical properties and rigid nature of existing electronic materials render them incompatible with soft tissues. This leads to friction and potential inflammation, stalling patient rehabilitation.
To overcome these limitations, the IBS researchers turned to a material commonly used as a wrinkle-smoothing filler, called hyaluronic acid. Using this substance, an injectable hydrogel was developed for ’tissue prostheses’, which can temporarily fill the gap of the missing muscle/nerve tissues while it regenerates. The injectable nature of this material gives it a significant advantage over traditional bioelectronic devices, which are unsuitable for narrow, deep, or small areas, and necessitate invasive surgeries.
Thanks to its highly ’tissue-like’ properties, this hydrogel seamlessly interfaces with biological tissues and can be easily administered to hard-to-reach body areas without surgery. The reversible and irreversible crosslinks within the hydrogel adapt to high shear stress during injection, ensuring excellent mechanical stability. This hydrogel also incorporates gold nanoparticles, which gives it decent electrical properties. Its conductive nature allows for the effective transmission of electrophysiological signals between the two ends of injured tissues. In addition, the hydrogel is biodegradable, removing the need for additional surgery.
With mechanical properties akin to natural tissues, exceptional tissue adhesion, and injectable characteristics, researchers believe this material offers a novel approach to rehabilitation.
Next, the researchers put this novel idea to the test in rodent models. To simulate volumetric muscle loss injury, a large chunk of muscle has been removed from the hind legs of these animals. By injecting the hydrogel and implanting the two kinds of stretchable tissue-interfacing devices for electrical sensing and stimulation, the researchers were able to improve the gait in the ‘injured’ rodents. The hydrogel prosthetics were combined with robot assistance, guided by muscle electromyography signals. Together, the two helped enhance the animal’s gait without nerve stimulation. Furthermore, muscle tissue regeneration was effectively improved over the long term after the conductive hydrogel was used to fill muscle damage.
The injectable conductive hydrogel developed in this study excels in electrophysiological signal recording and stimulation performance, offering the potential to expand its applications. It presents a fresh approach to the field of bioelectronic devices and holds promise as a soft tissue prosthesis for rehabilitation support.
Emphasizing the significance of the research, Professor SHIN Mikyung notes, “We’ve created an injectable, mechanically tough, and electrically conductive soft tissue prosthesis ideal for addressing severe muscle damage requiring neuromusculoskeletal rehabilitation. The development of this injectable hydrogel, utilizing a novel cross-linking method, is a notable achievement. We believe it will be applicable not only in muscles and peripheral nerves but also in various organs like the brain and heart.”
Professor SON Donghee added, “In this study, the closed-loop gait rehabilitation system entailing tough injectable hydrogel and stretchable and self-healing sensors could significantly enhance the rehabilitation prospects for patients with neurological and musculoskeletal challenges. It could also play a vital role in precise diagnosis and treatment across various organs in the human body.”
The research team is currently pursuing further studies to develop new materials for nerve and muscle tissue regeneration that can be implanted in a minimally invasive manner. They are also exploring the potential for recovery in various tissue damages through the injection of the conductive hydrogel, eliminating the need for open surgery.
Injuries of the knee’s anterior cruciate ligament (ACL) are typically thought to be caused by acute traumatic events, such as sudden twists. Published in the Journal of Orthopaedic Research, new work analysing an animal model of ACLs suggests that such injuries can also occur as a result of chronic overuse, specifically due to a reduced ability to repair microtraumas associated with overuse. Importantly, the team said, females also are less able to heal from these microtraumas than males, which may explain why females are two to eight times more likely to tear their ACL ligaments than males.
“ACL tears are one of the most common injuries, affecting more than 200 000 people in the US each year, and women are known to be particularly susceptible,” said principal investigator Spencer Szczesny, associate professor of biomedical engineering and of orthopaedics and rehabilitation at Penn State. “While recent research suggests that chronic overuse can lead to ACL injuries, until now, no one had investigated the differential biological response of female and male ACLs to applied force.”
In the Penn State-led study, researchers placed ACLs from deceased male and female rabbits in a custom-made bioreactor that simulated the conditions of a living animal but allowed direct observation and measurement of the tissue. Next, they applied repetitive forces to the ACLs that mimicked those that would naturally occur during activities such as standing, walking and trotting and measured the expression of genes related to healing.
In male samples, the team found that low and moderate applied forces, such as those that would occur during standing or walking, resulted in increased expression of anabolic genes, which are related to building molecules needed for healing. By contrast, larger applied forces, such as those that would occur with repetitive trotting, decreased expression of these anabolic genes. For female samples, however, the amount of force applied did not influence the level of anabolic gene expression.
“It didn’t matter whether there was low, medium or high activity for females,” said Lauren Paschall, graduate student in biomedical engineering at Penn State and first author on the paper. “Female ACLs exposed to chronic use just didn’t heal as well as male ACLs, which may explain why women are predisposed to injuries. This supports the hypothesis that noncontact ACL injuries are attributed to microtraumas associated with chronic overuse that predispose the ACL to injury.”
According to the researchers, one explanation for the sex differences the team observed could be due to the higher amounts of oestrogen in females.
“Some studies have found that the overall effect of oestrogen on ACL injury is negative,” Paschall said. “Specifically, studies have shown that human women are more likely to tear their ACLs during the preovulatory phase, when oestrogen levels are high, than during the postovulatory phase, when oestrogen levels are low.”
She said the team plans to further investigate the role of oestrogen on ACL injury.
Szczesny noted that although the team’s study was not in humans, the findings may suggest that providing additional recovery time for women following injuries could be advantageous.
“Ultimately, this work could also help to identify targets for therapeutics to prevent ACL injuries in women,” he said.
In a study on the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with crash risk among older adult drivers, researchers found that those with ADHD are at a significantly elevated crash risk compared with those without ADHD. Outcomes included hard-braking events, and self-reported traffic ticket events, and vehicular crashes. Until now research on ADHD and driving safety was largely limited to children and young adults, and few studies assessed the association of ADHD with crash risk among older adults. The results are published online in JAMA Network Open.
The research, from Columbia University Mailman School of Public Health, found that older adult drivers were more than twice as likely as their counterparts without ADHD to report being involved in traffic ticket events (22 versus 10 per million miles driven), and vehicular crashes (27 versus 13.5 per million miles driven).
“Our findings suggest that effective interventions to improve the diagnosis and clinical management of ADHD among older adults are warranted to promote safe mobility and healthy aging,” observed first author Yuxin Liu, MPH, at the Columbia Mailman School of Public Health.
ADHD is a chronic neurodevelopmental condition with symptoms such as inattentiveness, impulsivity, and hyperactivity. Although ADHD is commonly considered a childhood disorder, it can persist into adulthood and affect daily life performances of older adults. In the US, the reported prevalence of ADHD is 9% to 13% in children younger than 17 years and 8% in adults 18 to 44 years of age. The reported prevalence of ADHD in adults has increased in recent years due to improved diagnosis. In general, the prevalence of ADHD decreases with advancing age.
Study participants were active drivers aged 65 to 79 years of age enrolled during 2015 and 2017 in the Longitudinal Research on Aging Drivers (LongROAD) project who were followed for up to 44 months through in-vehicle data recording devices and annual assessments. The data analysis was performed between July 2022 and August 2023.
Of the 2832 drivers studied, 75 (2.6 %) had ADHD. The prevalence of ADHD was 7.2% among older adults with anxiety or depression. With adjustment for demographic characteristics and comorbidities, ADHD was associated with a 7% increased risk of hard-braking events, a 102% increased risk of self-reported traffic ticket events, and a 74% increased risk of self-reported vehicular crashes.
The researchers collected data from primary care clinics and residential communities in five U.S. sites in Ann Arbor, Michigan; Baltimore, Maryland; Cooperstown, New York; Denver, Colorado; and San Diego, California between July 2015 and March 2019. Participants were active drivers aged 65 to 79 years enrolled in the LongROAD project who were followed through in-vehicle data recording devices and annual assessments.
“Our study makes two notable contributions to research on healthy and safe aging,” said Guohua Li, MD, DrPH, professor of epidemiology at Columbia Mailman School of Public Health, and senior author. “The research fills a gap in epidemiologic data on ADHD among older adults and provides compelling evidence that older adult drivers with ADHD have a much higher crash risk than their counterparts without ADHD.”
Dr. Li and colleagues launched the LongROAD Project in 2014 to understand and meet the safe mobility needs of older adult drivers. A 2016 study by Li and colleagues in the Journal of the American Geriatrics Society showed that health worsens when older adults stop driving. Early this year, the research team reported in a study published in Artificial Intelligence in Medicine that driving data captured by in-vehicle recording devices are valid and reliable digital markers for predicting mild cognitive impairment and dementia.
“There are 48 million older adult drivers in the United States. As population aging continues, this number is expected to reach 63 million in 2030. Data from the landmark LongROAD project will enable us to examine the role of medical, behavioural, environmental, and technological factors in driving safety during the process of aging.” said Li, who is also professor of anaesthesiology at Columbia Vagelos College of Physicians and Surgeons, and founding director of the Columbia Center for Injury Science and Prevention.
Reporting of gun crime in South Africa is wildly inaccurate, work by the South African Medical Research Council (SAMRC) suggests. This is because the official death notification form does not distinguish between gun deaths from accidents and gun deaths from homicide.
The SAMRC has called on the government to update the country’s official death notification form. In a September 2023 South African Medical Journal (SAMJ) editorial, researchers and scientists Pam Groenewald, Richard Matzopoulos, Estevão Afonso and Debbie Bradshaw, say the form does not comply with international standards. While the World Health Organisation recommends reporting manner of death on the medical certificate for cause of death, South Africa’s form does not allow this, they say.
As a result, South Africa does not have accurate information on injury statistics, says Groenewald, a specialist scientist at SAMRC.
“Given that South Africa has got a really high injury burden, this is really not acceptable,” she said.
The SAMRC has pointed out that accurate, timely mortality data for natural and non-natural deaths is especially important after the Covid pandemic.
In a press release, the SAMRC said natural deaths had spiked during Covid waves, while injuries had fallen during government-imposed lockdowns and alcohol sales bans. “Of particular concern is the significant impact of alcohol bans on injury-related deaths,” the council said.
The release also said the statistics are necessary to develop and monitor programs to reduce injuries and violence, and track Sustainable Development Goals of road traffic injury reduction, gender equality and reducing violence-related death rates.
South Africa’s official mortality statistics overestimate accidental injuries and underestimate homicides, transport and suicide deaths, according to a research report also published in the September 2023 SAMJ.
In official death notification form data from Stats SA for 2017, nearly 99% of firearm deaths were classified as accidental and only 1% as homicide. But the SAMRC’s National Cause-of-Death Validation Project (NCoDV) found more than 88% of firearm deaths were homicide, and its Injury Mortality Survey (IMS) found more than 93%.
Similar differences occurred for suicides. Only 0.3% of firearm deaths were recorded as suicide in the 2017 Stats SA data, but they were recorded as 7% in NCoDV and IMS data.
The research report says NCoDV and IMS provide more detailed and consistent data on causes of injury than the death notification form, but they are costly and time-consuming, and not feasible for routine surveillance.
“It costs a lot of money, when we could be getting this data in with every death certificate that gets completed,” Groenewald says.
She says the SAMRC has been asking for an updated death certificate form since 2012.
No annual mortality report since 2018
Also, Stats SA has not published an updated mortality report since the pandemic. The last official report was released in 2021 for the year 2018.
“We’ve got no cause-of-death data at all, not just injuries, nothing. We haven’t seen a death certificate from during the Covid period; we don’t know what doctors have reported,” she said. “It’s mind boggling.”
Felicia Sithole, deputy director of media relations for Stats SA, said in a statement that the Mortality and Causes of Death report had been delayed by a backlog of processing death notification forms as a result of the Covid lockdown, and because of Census 2022 work.
Sithole said Stats SA is committed to publishing the 2019 and 2020 Mortality and Causes of Death reports by the end of March 2024.
“Stats SA fully comprehends the importance of the Mortality and Causes of Death release, especially during the Covid-19 pandemic, and acknowledges that our data must conform to international standards,” she said.
The SAMRC report also calls for the dormant National Forensic Pathology Services Committee to be reactivated. This would help improve data quality, the report says. The committee, established in 2014, has been inactive since 2018/9.
Foster Mohale, a media officer for the Department of Health, said the Minister of Health is in the process of appointing a new National Forensic Pathology Services Committee.
The Department of Home Affairs had not responded to requests for comment at the time of publication.
A pair of postgraduate students have developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury. The two researchers combined functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques to tackle one of the most complex issues in critical care. They describe the new technology in the Journal of Neurology.
Whether it is the result of a stroke, cardiac arrest or traumatic brain injury, lives can forever be changed by a serious brain injury. But the potential of a good recovery is highly uncertain.
The University of Western Ontario researchers, Matthew Kolisnyk and Karnig Kazazian, are PhD candidates at Schulich School of Medicine & Dentistry in the lab of neuroscientist Adrian Owen.
“For years we’ve lacked the tools and techniques to know who is going to survive a serious brain injury,” said Owen.
An interdisciplinary team of researchers from Western, in collaboration with neurologists at London Health Sciences Centre and Lawson Health Research Institute sought to find a solution to this problem. They were led by Loretta Norton, a psychology professor at King’s University College at Western, who was one of the first researchers in the world to measure brain activity in the ICU.
The team measured brain activity in 25 patients at one of London’s two ICUs in the first few days after a serious brain injury and tested whether it could predict who would survive and who would not.
“We previously found that information about the potential for recovery in these patients was captured in the way different brain regions communicate with each other,” said Norton. “Intact communication between brain regions is an important factor for regaining consciousness.”
The breakthrough occurred when the team realized they could combine this imaging technique with an application of AI known as machine learning. They found they could predict patients who would recover with an accuracy of 80 per cent, which is higher than the current standard of care.
“Modern artificial intelligence has shown incredible predictive capabilities. Combining this with our existing imaging techniques was enough to better predict who will recover from their injuries,” said Kolisnyk.
While encouraging, the researchers say the prediction was not perfect and needs further research and testing.
“Given that these models learn best when they have lots of data, we hope our findings will lead to further collaborations with ICUs across Canada,” said Kazazian.
A study of twins who fought in World War II showed that concussion early in life is tied to having lower scores on tests of thinking and memory skills decades later as well as having more rapid decline in those scores than twins who did not have a concussion, or traumatic brain injury (TBI). The study is published in Neurology®, the medical journal of the American Academy of Neurology.
“These findings indicate that even people with traumatic brain injuries in earlier life who appear to have fully recovered from them may still be at increased risk of cognitive problems and dementia later in life,” said study author Marianne Chanti-Ketterl, PhD, MSPH, of Duke University in Durham, North Carolina. “Among identical twins, who share the same genes and many of the same exposures early in life, we found that the twin who had a concussion had lower test scores and faster decline than their twin who had never had a concussion.”
The study involved 8662 men who were World War II veterans. The participants took a test of thinking skills at the start of the study when they were an average age of 67 and then again up to three more times over 12 years. Scores for the test can range from zero to 50. The average score for all participants at the beginning of the study was 32.5 points.
A total of 25% of the participants had experienced a concussion in their life.
Twins who had experienced a concussion were more likely to have lower test scores at age 70, especially if they had a concussion where they lost consciousness or were older than 24 when they had their concussion. Those twins with traumatic brain injury with loss of consciousness, more than one traumatic brain injury and who had their injuries after age 24 were more likely to have faster cognitive decline than those with no history of traumatic brain injury.
For example, a twin who experienced a traumatic brain injury after age 24 scored 0.59 points lower at age 70 than his twin with no traumatic brain injury, and his thinking skills declined faster, by 0.05 points per year.
These results took into account other factors that could affect thinking skills, such as high blood pressure, alcohol use, smoking status and education.
“Although these effect sizes are modest, the contribution of TBI on late life cognition, in addition to numerous other factors with a detrimental effect on cognition, may be enough to trigger an evaluation for cognitive impairment,” Chanti-Ketterl said. “With the trend we are seeing with increased emergency room visits due to sports or recreation activity injuries, combined with the estimated half million members of the military who suffered a TBI between 2000 and 2020, the potential long-term impact of TBI cannot be overlooked. These results may help us identify people who may benefit from early interventions that may slow cognitive decline or potentially delay or prevent dementia.”
A limitation of the study was that traumatic brain injuries were reported by the participants, so not all injuries may have been remembered or reported accurately.
In the ensuing court battle between Discovery Health and the Road Accident Fund (RAF) over reimbursements to be paid on motor vehicle claims, medical schemes members had always sought clarity or a position from the Council for Medical Schemes regarding this. In normative terms, the CMS is not obliged to release commentary on matters remote to its mandate, however, as a responsible regulator, it became a necessary act to clear any anomality.
Medical scheme members usually do not always have the full understating of the arrangements between RAF and medical schemes. At best, members sometimes have difficulty engaging with their scheme’s rules or RAF due to language barrier or be it of a technical nature of the matter.
In terms of the Medical Schemes Act 131 of 1998 (the “MSA”), Medical Schemes undertake liability in return for a contribution by among others granting assistance in defraying expenditure incurred in connection with the rendering of any relevant health services.
MSA further obliges medical schemes to pay for Prescribed Minimum Benefits (PMB), which include any emergency medical condition, under which motor vehicle claims could fall, in full. Unless a claim is specifically excluded in terms of the schemes’ rules and/or does not meet the criteria in terms of the definition of relevant healthcare, the medical scheme must still pay.
Most medical schemes provide for the handling of motor vehicle claims in their rules, wherein members of medical aid can claim compensation from the Road Accident Fund (the “RAF”) for such claims and any future healthcare services which may arise due to such motor vehicle accident.
It is also common cause that where RAF is responsible for claims, which a medical scheme has paid in terms of its rules and the MSA, that the RAF should refund to such medical scheme the amounts paid. Members of medical schemes who would have claimed directly from the RAF and received compensation for such claims, must also pay such amounts back to the medical scheme. This is commonly known as subrogation.
Should a member not receive any compensation from the RAF even after claiming, the scheme remains liable for the costs of the treatment subject to the registered scheme rules and must not be required to repay/refund such funds to the scheme.
The scheme may, however, attempt to recover such amounts paid from the RAF for the benefit of its members.
Subrogation allows medical schemes to minimise losses as a result of these claims and keep members’ contributions reasonable, by holding responsible parties accountable. It also prevents members from being “overcompensated” or unjustifiably enriched for the loss since they should not receive double compensation from both the medical scheme claim payout and the recovery from the RAF.
It must be emphasized that the financial risk associated with health interventions for which the need is uncertain is equitably shared within the covered population through a risk pool managed by medical schemes under the Medical Schemes Act. Therefore, CMS cannot condone a situation where members of medical schemes are forced to be out of pocket due to the non-payment of medical costs by RAF where these have since been paid out by medical schemes.
In line with our mandate under Section 7 of the Medical Schemes Act, it is not in the members interest if medical schemes are required to claw back payment made on behalf of members due to non-payment of these costs by RAF.
Moreover, the non-recovery of these costs by medical schemes negatively and unfairly withdraws from the entire risk pool that is aimed at benefitting the whole membership.
The World Health Organization (WHO) defines pooling as “…accumulation and management of revenues in such a way as to ensure that the risk of having to pay for healthcare is borne by all members within the pool, not by each contributor individually…” (WHO, 2000).
By implication, the refusal to refund medical schemes by RAF leads to the unfair deterioration of the entire risk pool funds.
Within this background, CMS believes that the refusal to refund medical schemes by RAF is not in line with the provisions of the Medical Schemes Act and it is not in the interest of beneficiaries of medical schemes.
DISCLAIMER: COUNCIL FOR MEDICAL SCHEMES. 2023
This document has been prepared by the author(s) from the Council for Medical Schemes Legal Services Unit and Benefits Management Unit. The views and information expressed in this article are for information purposes only. CMS cannot be held liable for any incorrectness of statements and statistical errors. Recommendations and conclusions are based on the author(s) research outcomes/findings and does not necessarily espouse or state as a CMS policy stance. The information is subject to change without notice. Companies and individuals wishing to use the information must reference the CMS in company reports, news reports, interviews, panel discussions etc.
A new study suggests that depression after traumatic brain injury (TBI) could be a clinically distinct disorder rather than traditional major depressive disorder. The findings, which are published in Science Translational Medicine, hold important implications for patient treatment.
“Our findings help explain how the physical trauma to specific brain circuits can lead to development of depression. If we’re right, it means that we should be treating depression after TBI like a distinct disease,” said corresponding author Shan Siddiqi, MD, from Brigham and Women’s Hospital,. “Many clinicians have suspected that this is a clinically distinct disorder with a unique pattern of symptoms and unique treatment response, including poor response to conventional antidepressants – but until now, we didn’t have clear physiological evidence to prove this.”
Siddiqi, who led the study, was motivated by a patient he shared with David Brody, MD, PhD, a co-author on the study and a neurologist at Uniformed Services University. The two started a small clinical trial that used personalised brain mapping to target brain stimulation as a treatment for TBI patients with depression. In the process, they noticed a specific pattern of abnormalities in these patients’ brain maps.
The current study included 273 adults with TBI, usually from sports injuries, military injuries, or car accidents. People in this group were compared to other groups who did not have a TBI or depression, people with depression without TBI, and people with posttraumatic stress disorder. Study participants went through a resting-state functional connectivity MRI, a brain scan that looks at how oxygen is moving in the brain. These scans gave information about oxygenation in up to 200 000 points in the brain at about 1000 different points in time, leading to about 200 million data points in each person. Based on this information, a machine learning algorithm was used to generate an individualised map of each person’s brain.
The location of the brain circuit involved in depression was the same among people with TBI as people without TBI, but the nature of the abnormalities was different. Connectivity in this circuit was decreased in depression without TBI and was increased in TBI-associated depression. This implies that TBI-associated depression may be a different disease process, leading the study authors to propose a new name: “TBI affective syndrome.”
“I’ve always suspected it isn’t the same as regular major depressive disorder or other mental health conditions that are not related to traumatic brain injury,” said Brody. “There’s still a lot we don’t understand, but we’re starting to make progress.”
With so much data, the researchers were not able to do detailed assessments of each patient beyond brain mapping. To overcome this limitation, investigators would like to assess participants’ behaviour in a more sophisticated way and potentially define different kinds of TBI-associated neuropsychiatric syndromes.
Siddiqi and Brody are also using this approach to develop personalized treatments. Originally, they set out to design a new treatment in which they used this brain mapping technology to target a specific brain region for people with TBI and depression, using transcranial magnetic stimulation (TMS). They enrolled 15 people in the pilot and saw success with the treatment. Since then, they have received funding to replicate the study in a multicentre military trial.
“We hope our discovery guides a precision medicine approach to managing depression and mild TBI, and perhaps even intervene in neuro-vulnerable trauma survivors before the onset of chronic symptoms,” said Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine, and co-author on the study.
