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More years of ice hockey play tied to higher CTE risk
new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.
This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”
Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.
The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Football data
CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.
“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”
From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.
The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.
For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.
Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.
Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”
The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
Consistent findings
Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.
“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”
Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).
Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.
In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.
The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.
Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.
Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
‘Skewed’ population?
Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.
Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.
He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.
“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”
As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.
He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”
The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.
This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”
Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.
The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Football data
CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.
“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”
From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.
The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.
For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.
Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.
Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”
The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
Consistent findings
Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.
“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”
Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).
Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.
In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.
The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.
Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.
Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
‘Skewed’ population?
Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.
Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.
He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.
“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”
As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.
He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”
The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. Early results from a study that examined donor brains showed that each additional year of ice hockey play increased the risk for CTE by 23%.
This information should be on the “radar” of all clinicians, said coinvestigator Jesse Mez, MD, associate professor of neurology at Boston University. “When they’re talking to kids and families and parents about playing contact sports, they should discuss the benefits as well as the risks so all that information can be taken into consideration.”
Dr. Mez noted that clinicians should also consider the amount of hockey played when assessing patients for thinking and memory trouble later in life. “CTE could be in the differential diagnosis,” he said.
The study findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Football data
CTE is a neurodegenerative disease associated with repetitive hits to the head. In previous research, the investigators showed that the more that athletes play American football, the more likely they are to develop CTE.
“Hockey, like football, involves repetitive head impacts as part of the game,” said Dr. Mez. “So we hypothesized that we would see a similar type of dose-response relationship in hockey.”
From two brain banks – the Veterans Affairs–Boston University–Concussion Legacy Foundation and the Framingham Heart Study – the researchers accessed 74 consecutive brains from donors who had played ice hockey. They collected information about hockey play during “pretty comprehensive” interviews with next of kin, Dr. Mez reported.
The study participants ranged in age from 13 to 91 years. The cause of death varied; most died with end-stage dementia and neurodegenerative disease, but some died of cardiovascular disease, and others from accidents.
For 9% of the individuals, the highest level of play was a youth league; 34% had reached the high school level, 30% reached the juniors/college level, and 26% played professionally. In addition, 46% played another contact sport – including 43% who played American football.
Primary outcomes included evidence of CTE from stage 0 (no CTE) to stage IV and severity of CTE, which was defined by the amount of neurofibrillary tangle (NFT) burden in 11 brain regions. For this burden, the score ranged from 0 (absent) to 3 (severe) in each region for a total range of 0-33.
Dr. Mez noted that, in CTE, tau protein accumulates abnormally. “It typically begins in the cortex in the frontal lobe and then spreads to other parts of the brain, including to the medial temporal structures, and is widespread by stage IV.”
The researchers estimated the association of duration of ice hockey play in years with each neuropathologic outcome and adjusted for age at death and duration of football play.
Consistent findings
Results showed that, of the 74 donors, 40 (54%) had CTE. Each additional year of hockey play corresponded to increased chances for having CTE (odds ratio, 1.23; 95% confidence interval, 11%-36%; P < .01). This increase in risk is similar to that which was found with football players, Dr. Mez noted. This was somewhat surprising, as hockey involves fewer “hits” than football.
“Hits are not as quintessential to the game of hockey as they are in football, where contacts occur with nearly every play,” he said. “In football, you have several hundred impacts over the course of a season.”
Researchers also found a 15% increase in odds for increasing one CTE stage (95% CI, 8%-22%; P < .01), and a .03 standard deviation increase in cumulative NFT burden (95% CI, 0.01-0.05; P < .01).
Dr. Mez noted that the fact that the results were consistent across different outcomes “improves the validity” of the findings.
In a sensitivity analysis that excluded participants who also played football, estimates “were pretty similar” to those in the full analysis, said Dr. Mez.
The investigators have not yet examined the effect of level of hockey play, such as professionally or at the college level, on CTE risk. However, in football players, they found that level of play is another “valuable predictor of CTE pathology,” Dr. Mez said, adding that level of play, position played, and years of play “are all probably contributing” to CTE risk.
Asking about years of play is useful in a clinical setting. “It’s very easy for a clinician to ask patients how many years of hockey they played,” said Dr. Mez.
Overall, the new results are important, as “millions of individuals” play contact sports, whether that is hockey, football, or European soccer, he added. “And for all sports, there seems to be this relationship between more play and risk of this disease.”
‘Skewed’ population?
Commenting on the findings, Frank Conidi, MD, director, Florida Center for Health and Sports Neurology, Port St. Lucie, said he was surprised the investigators found a 23% per year increase in risk for CTE among hockey players.
Dr. Conidi has played hockey himself and works with the Florida Panthers of the National Hockey League. In his practice, he treats retired professional football players who have neurodegenerative disorders. From his experience, the number of repetitive direct head impacts in football is significantly higher than in hockey. “Most of the forces seen in hockey are from hits to the body, where the force is transferred to the head,” said Dr. Conidi, who was not involved with the research.
He noted differences in the way hockey is played around the world. In European countries, for example, the ice surface is relatively large and the emphasis tends to be more on skill than hitting.
“It would have been interesting to have the study group analyze the data based on where the athlete grew up,” he said. Dr. Conidi would also like to know when the participants played hockey. “The game is vastly different now than it was in the 1970s, ‘80s, and early ‘90s, when there was more fighting, less protective gear, and more hitting in general.”
As is the case for most studies of CTE in athletes, the study population is “skewed” because the participants likely had neurocognitive and other problems that led to their decision to donate their brain, said Dr. Conidi.
He also doesn’t believe the study should be the sole factor in a decision to continue or stop playing hockey. “We are still in the infancy stages of understanding the effects of high-impact sports on athletes’ brains.”
The study received funding from the National Institute of Neurological Diseases and Stroke and the National Institute on Aging. Dr. Mez and Dr. Conidi have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Concussion increases risk of mental health issues in children
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
FROM JAMA NETWORK OPEN
MRI is key to diagnosing CTE in living patients?
, new research suggests.
“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.
The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
A new way to diagnose?
CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.
There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).
The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.
The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.
Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).
From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
More atrophy
Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.
The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).
Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.
The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.
The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.
Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.
“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.
Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).
Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
An important first step
The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).
When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).
Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”
He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.
While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.
“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
‘Not unexpected’
Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”
Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.
The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.
Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.
Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
Overstated conclusion?
Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.
“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”
A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”
The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”
Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.
A version of this article first appeared on Medscape.com.
, new research suggests.
“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.
The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
A new way to diagnose?
CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.
There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).
The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.
The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.
Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).
From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
More atrophy
Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.
The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).
Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.
The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.
The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.
Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.
“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.
Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).
Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
An important first step
The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).
When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).
Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”
He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.
While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.
“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
‘Not unexpected’
Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”
Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.
The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.
Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.
Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
Overstated conclusion?
Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.
“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”
A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”
The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”
Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.
A version of this article first appeared on Medscape.com.
, new research suggests.
“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.
The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
A new way to diagnose?
CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.
There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).
The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.
The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.
Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).
From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
More atrophy
Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.
The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).
Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.
The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.
The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.
Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.
“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.
Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).
Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
An important first step
The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).
When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).
Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”
He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.
While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.
“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
‘Not unexpected’
Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”
Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.
The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.
Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.
Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
Overstated conclusion?
Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.
“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”
A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”
The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”
Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.
A version of this article first appeared on Medscape.com.
Posttraumatic epilepsy is common, even after ‘mild’ TBI
, new research suggests.
Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.
“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.
Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”
The findings were published online Dec. 29 in JAMA Network Open.
Novel study
Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.
To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.
The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.
The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.
The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
Confirmatory data
Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.
Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.
The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).
This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.
Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.
“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.
The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.
“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
Universal screening?
The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.
Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.
Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.
What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.
The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.
The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.
A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.
The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.
A version of this article first appeared on Medscape.com.
, new research suggests.
Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.
“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.
Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”
The findings were published online Dec. 29 in JAMA Network Open.
Novel study
Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.
To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.
The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.
The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.
The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
Confirmatory data
Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.
Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.
The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).
This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.
Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.
“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.
The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.
“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
Universal screening?
The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.
Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.
Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.
What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.
The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.
The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.
A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.
The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.
A version of this article first appeared on Medscape.com.
, new research suggests.
Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.
“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.
Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”
The findings were published online Dec. 29 in JAMA Network Open.
Novel study
Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.
To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.
The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.
The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.
The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
Confirmatory data
Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.
Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.
The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).
This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.
Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.
“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.
The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.
“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
Universal screening?
The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.
Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.
Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.
What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.
The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.
The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.
A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.
The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.
A version of this article first appeared on Medscape.com.
Adolescents who exercised after a concussion recovered faster in RCT
After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.
The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.
Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”
“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.
The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.
For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.
“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.
The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.
A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).
Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.
More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.
The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.
The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.
After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.
The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.
Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”
“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.
The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.
For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.
“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.
The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.
A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).
Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.
More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.
The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.
The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.
After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.
The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.
Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”
“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.
The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.
For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.
“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.
The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.
A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).
Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.
More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.
The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.
The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.
FROM THE LANCET CHILD & ADOLESCENT HEALTH
FDA clears first mobile rapid test for concussion
, the company has announced.
Eye-Sync is a virtual reality eye-tracking platform that provides objective measurements to aid in the assessment of concussion. It’s the first mobile, rapid test for concussion that has been cleared by the FDA, the company said.
As reported by this news organization, Eye-Sync received breakthrough designation from the FDA for this indication in March 2019.
The FDA initially cleared the Eye-Sync platform for recording, viewing, and analyzing eye movements to help clinicians identify visual tracking impairment.
The Eye-Sync technology uses a series of 60-second eye tracking assessments, neurocognitive batteries, symptom inventories, and standardized patient inventories to identify the type and severity of impairment after concussion.
“The platform generates customizable and interpretive reports that support clinical decision making and offers visual and vestibular therapies to remedy deficits and monitor improvement over time,” the company said.
In support of the application for use in concussion, SyncThink enrolled 1,655 children and adults into a clinical study that collected comprehensive patient and concussion-related data for over 12 months.
The company used these data to develop proprietary algorithms and deep learning models to identify a positive or negative indication of concussion.
The study showed that Eye-Sinc had sensitivity greater than 82% and specificity greater than 93%, “thereby providing clinicians with significant and actionable data when evaluating individuals with concussion,” the company said in a news release.
“The outcome of this study very clearly shows the effectiveness of our technology at detecting concussion and definitively demonstrates the clinical utility of Eye-Sinc,” SyncThink Chief Clinical Officer Scott Anderson said in the release.
“It also shows that the future of concussion diagnosis is no longer purely symptom-based but that of a technology driven multi-modal approach,” Mr. Anderson said.
A version of this article first appeared on Medscape.com.
, the company has announced.
Eye-Sync is a virtual reality eye-tracking platform that provides objective measurements to aid in the assessment of concussion. It’s the first mobile, rapid test for concussion that has been cleared by the FDA, the company said.
As reported by this news organization, Eye-Sync received breakthrough designation from the FDA for this indication in March 2019.
The FDA initially cleared the Eye-Sync platform for recording, viewing, and analyzing eye movements to help clinicians identify visual tracking impairment.
The Eye-Sync technology uses a series of 60-second eye tracking assessments, neurocognitive batteries, symptom inventories, and standardized patient inventories to identify the type and severity of impairment after concussion.
“The platform generates customizable and interpretive reports that support clinical decision making and offers visual and vestibular therapies to remedy deficits and monitor improvement over time,” the company said.
In support of the application for use in concussion, SyncThink enrolled 1,655 children and adults into a clinical study that collected comprehensive patient and concussion-related data for over 12 months.
The company used these data to develop proprietary algorithms and deep learning models to identify a positive or negative indication of concussion.
The study showed that Eye-Sinc had sensitivity greater than 82% and specificity greater than 93%, “thereby providing clinicians with significant and actionable data when evaluating individuals with concussion,” the company said in a news release.
“The outcome of this study very clearly shows the effectiveness of our technology at detecting concussion and definitively demonstrates the clinical utility of Eye-Sinc,” SyncThink Chief Clinical Officer Scott Anderson said in the release.
“It also shows that the future of concussion diagnosis is no longer purely symptom-based but that of a technology driven multi-modal approach,” Mr. Anderson said.
A version of this article first appeared on Medscape.com.
, the company has announced.
Eye-Sync is a virtual reality eye-tracking platform that provides objective measurements to aid in the assessment of concussion. It’s the first mobile, rapid test for concussion that has been cleared by the FDA, the company said.
As reported by this news organization, Eye-Sync received breakthrough designation from the FDA for this indication in March 2019.
The FDA initially cleared the Eye-Sync platform for recording, viewing, and analyzing eye movements to help clinicians identify visual tracking impairment.
The Eye-Sync technology uses a series of 60-second eye tracking assessments, neurocognitive batteries, symptom inventories, and standardized patient inventories to identify the type and severity of impairment after concussion.
“The platform generates customizable and interpretive reports that support clinical decision making and offers visual and vestibular therapies to remedy deficits and monitor improvement over time,” the company said.
In support of the application for use in concussion, SyncThink enrolled 1,655 children and adults into a clinical study that collected comprehensive patient and concussion-related data for over 12 months.
The company used these data to develop proprietary algorithms and deep learning models to identify a positive or negative indication of concussion.
The study showed that Eye-Sinc had sensitivity greater than 82% and specificity greater than 93%, “thereby providing clinicians with significant and actionable data when evaluating individuals with concussion,” the company said in a news release.
“The outcome of this study very clearly shows the effectiveness of our technology at detecting concussion and definitively demonstrates the clinical utility of Eye-Sinc,” SyncThink Chief Clinical Officer Scott Anderson said in the release.
“It also shows that the future of concussion diagnosis is no longer purely symptom-based but that of a technology driven multi-modal approach,” Mr. Anderson said.
A version of this article first appeared on Medscape.com.
Young Black and White athletes differ in how they recover from concussions
, according to a new study on racial differences in concussion recovery.
“The findings from this study provide novel evidence that the recovery experience following sport-related concussion likely differs between Black and White athletes, and understanding these differences may serve to provide better and more personalized intervention and management strategies,” wrote lead author Aaron M. Yengo-Kahn, MD, of Vanderbilt University Medical Center in Nashville, Tenn. The study was published in the Journal of Neurosurgery: Pediatrics.
To assess how postconcussion experiences and recovery time differ among young White and Black athletes, the researchers launched a retrospective cohort study of youths between the ages of 12 and 23 from the middle Tennessee, northern Alabama, and southern Kentucky regions who had been treated for sport-related concussion. Using data from the Vanderbilt Sports Concussion Center’s outcome registry, they examined the records of 247 student-athletes, 211 of whom were White and 36 of whom were Black.
The majority of the athletes were male – 58% of the White group and 78% of the Black group – and their average age across groups was roughly 16 years. Thirty-three percent of the Black athletes were on public insurance, compared with just 6% of the White athletes, and 41% of the Black athletes lived in low–median income areas while 55% of the White athletes lived in areas with a high median income. Approximately 90% of each group played contact sports.
The median time to symptom resolution was 21 days (interquartile range, 10.5-61.0) for White athletes but just 12.3 days (IQR, 6.8-28.0) for Black athletes. Multivariable regression confirmed that Black athletes reached asymptomatic status sooner than White athletes (hazard ratio, 1.497; 95% confidence interval, 1.014-2.209; P = .042). “The observed shorter symptom resolution among the Black athletes may be explained by a complex interplay among race, concussion knowledge, attitudes toward sport-related concussion, reporting behavior, and sociodemographic disparities,” the authors noted.
The median time until returning to school post injury was 2 school days (IQR, 0-5) for White athletes and 0 school days (IQR, 0-2) for Black athletes. After multivariable analysis, being Black was indeed associated with returning to school sooner, compared with being White (HR, 1.522; 95% CI, 1.02-2,27; P = .040). Being Black was also associated with being less likely to a report a change in daily activity post concussion (odds ratio, 0.368; 95% CI, 0.136-0.996; P = .049).
Adding race to research
To make headway toward understanding race’s impact on concussion research, the authors proposed three immediate steps: Work directly with schools instead of clinics or emergency departments, match the diversity of study cohorts with the racial makeup of the surrounding community, and consider race as a covariate during study design.
“In our work with concussions, there is very little reported on race or racism or how racism affects how patients are navigating these spaces,” said coauthor Jessica Wallace, PhD, of the department of health science at the University of Alabama in Tuscaloosa, Ala., in an interview. “But we have so many athletes at the youth level, adolescent level, even the collegiate level; it’s such a diverse array of patients. We need to have data representative of all of our groups so that we know where we need to be intentional about reducing disparities and closing gaps.”
Dr. Wallace, who recently authored a study on the underreporting of concussions among Black and White high school athletes, emphasized the need for concussion research to be a true collaboration across disciplines.
“I approach this work from this public health and athletic training lens, whereas a lot of my collaborators are in neurosurgery and neurology,” she said. “Moving forward, we as a scientific clinical community have to do interdisciplinary work and be very intentional about how we go about closing these gaps. We have to recognize that there are differences in knowledge and in care, and they’re unacceptable, and we have to work collaboratively in providing resources to communities equitably to decrease them.”
The authors acknowledged their study’s limitations, including the retrospective nature of the study, using zip codes to determine median household income, and an unbalanced number of White and Black athletes. They did add, however, that the ratio of participants “generally aligns with census data in the surrounding metropolitan and county areas.” That said, they also surmised that the scarcity of Black athletes could indicate a deeper disparity in health care system usage and asked future researchers to “consider enrolling athletes directly from schools rather than from within the concussion clinic only.”
Dr. Yengo-Kahn disclosed holding a compensated position on the scientific advisory board of BlinkTBI, but the authors noted that the company had no role in the study and its products were not used. No other conflicts of interest were reported.
, according to a new study on racial differences in concussion recovery.
“The findings from this study provide novel evidence that the recovery experience following sport-related concussion likely differs between Black and White athletes, and understanding these differences may serve to provide better and more personalized intervention and management strategies,” wrote lead author Aaron M. Yengo-Kahn, MD, of Vanderbilt University Medical Center in Nashville, Tenn. The study was published in the Journal of Neurosurgery: Pediatrics.
To assess how postconcussion experiences and recovery time differ among young White and Black athletes, the researchers launched a retrospective cohort study of youths between the ages of 12 and 23 from the middle Tennessee, northern Alabama, and southern Kentucky regions who had been treated for sport-related concussion. Using data from the Vanderbilt Sports Concussion Center’s outcome registry, they examined the records of 247 student-athletes, 211 of whom were White and 36 of whom were Black.
The majority of the athletes were male – 58% of the White group and 78% of the Black group – and their average age across groups was roughly 16 years. Thirty-three percent of the Black athletes were on public insurance, compared with just 6% of the White athletes, and 41% of the Black athletes lived in low–median income areas while 55% of the White athletes lived in areas with a high median income. Approximately 90% of each group played contact sports.
The median time to symptom resolution was 21 days (interquartile range, 10.5-61.0) for White athletes but just 12.3 days (IQR, 6.8-28.0) for Black athletes. Multivariable regression confirmed that Black athletes reached asymptomatic status sooner than White athletes (hazard ratio, 1.497; 95% confidence interval, 1.014-2.209; P = .042). “The observed shorter symptom resolution among the Black athletes may be explained by a complex interplay among race, concussion knowledge, attitudes toward sport-related concussion, reporting behavior, and sociodemographic disparities,” the authors noted.
The median time until returning to school post injury was 2 school days (IQR, 0-5) for White athletes and 0 school days (IQR, 0-2) for Black athletes. After multivariable analysis, being Black was indeed associated with returning to school sooner, compared with being White (HR, 1.522; 95% CI, 1.02-2,27; P = .040). Being Black was also associated with being less likely to a report a change in daily activity post concussion (odds ratio, 0.368; 95% CI, 0.136-0.996; P = .049).
Adding race to research
To make headway toward understanding race’s impact on concussion research, the authors proposed three immediate steps: Work directly with schools instead of clinics or emergency departments, match the diversity of study cohorts with the racial makeup of the surrounding community, and consider race as a covariate during study design.
“In our work with concussions, there is very little reported on race or racism or how racism affects how patients are navigating these spaces,” said coauthor Jessica Wallace, PhD, of the department of health science at the University of Alabama in Tuscaloosa, Ala., in an interview. “But we have so many athletes at the youth level, adolescent level, even the collegiate level; it’s such a diverse array of patients. We need to have data representative of all of our groups so that we know where we need to be intentional about reducing disparities and closing gaps.”
Dr. Wallace, who recently authored a study on the underreporting of concussions among Black and White high school athletes, emphasized the need for concussion research to be a true collaboration across disciplines.
“I approach this work from this public health and athletic training lens, whereas a lot of my collaborators are in neurosurgery and neurology,” she said. “Moving forward, we as a scientific clinical community have to do interdisciplinary work and be very intentional about how we go about closing these gaps. We have to recognize that there are differences in knowledge and in care, and they’re unacceptable, and we have to work collaboratively in providing resources to communities equitably to decrease them.”
The authors acknowledged their study’s limitations, including the retrospective nature of the study, using zip codes to determine median household income, and an unbalanced number of White and Black athletes. They did add, however, that the ratio of participants “generally aligns with census data in the surrounding metropolitan and county areas.” That said, they also surmised that the scarcity of Black athletes could indicate a deeper disparity in health care system usage and asked future researchers to “consider enrolling athletes directly from schools rather than from within the concussion clinic only.”
Dr. Yengo-Kahn disclosed holding a compensated position on the scientific advisory board of BlinkTBI, but the authors noted that the company had no role in the study and its products were not used. No other conflicts of interest were reported.
, according to a new study on racial differences in concussion recovery.
“The findings from this study provide novel evidence that the recovery experience following sport-related concussion likely differs between Black and White athletes, and understanding these differences may serve to provide better and more personalized intervention and management strategies,” wrote lead author Aaron M. Yengo-Kahn, MD, of Vanderbilt University Medical Center in Nashville, Tenn. The study was published in the Journal of Neurosurgery: Pediatrics.
To assess how postconcussion experiences and recovery time differ among young White and Black athletes, the researchers launched a retrospective cohort study of youths between the ages of 12 and 23 from the middle Tennessee, northern Alabama, and southern Kentucky regions who had been treated for sport-related concussion. Using data from the Vanderbilt Sports Concussion Center’s outcome registry, they examined the records of 247 student-athletes, 211 of whom were White and 36 of whom were Black.
The majority of the athletes were male – 58% of the White group and 78% of the Black group – and their average age across groups was roughly 16 years. Thirty-three percent of the Black athletes were on public insurance, compared with just 6% of the White athletes, and 41% of the Black athletes lived in low–median income areas while 55% of the White athletes lived in areas with a high median income. Approximately 90% of each group played contact sports.
The median time to symptom resolution was 21 days (interquartile range, 10.5-61.0) for White athletes but just 12.3 days (IQR, 6.8-28.0) for Black athletes. Multivariable regression confirmed that Black athletes reached asymptomatic status sooner than White athletes (hazard ratio, 1.497; 95% confidence interval, 1.014-2.209; P = .042). “The observed shorter symptom resolution among the Black athletes may be explained by a complex interplay among race, concussion knowledge, attitudes toward sport-related concussion, reporting behavior, and sociodemographic disparities,” the authors noted.
The median time until returning to school post injury was 2 school days (IQR, 0-5) for White athletes and 0 school days (IQR, 0-2) for Black athletes. After multivariable analysis, being Black was indeed associated with returning to school sooner, compared with being White (HR, 1.522; 95% CI, 1.02-2,27; P = .040). Being Black was also associated with being less likely to a report a change in daily activity post concussion (odds ratio, 0.368; 95% CI, 0.136-0.996; P = .049).
Adding race to research
To make headway toward understanding race’s impact on concussion research, the authors proposed three immediate steps: Work directly with schools instead of clinics or emergency departments, match the diversity of study cohorts with the racial makeup of the surrounding community, and consider race as a covariate during study design.
“In our work with concussions, there is very little reported on race or racism or how racism affects how patients are navigating these spaces,” said coauthor Jessica Wallace, PhD, of the department of health science at the University of Alabama in Tuscaloosa, Ala., in an interview. “But we have so many athletes at the youth level, adolescent level, even the collegiate level; it’s such a diverse array of patients. We need to have data representative of all of our groups so that we know where we need to be intentional about reducing disparities and closing gaps.”
Dr. Wallace, who recently authored a study on the underreporting of concussions among Black and White high school athletes, emphasized the need for concussion research to be a true collaboration across disciplines.
“I approach this work from this public health and athletic training lens, whereas a lot of my collaborators are in neurosurgery and neurology,” she said. “Moving forward, we as a scientific clinical community have to do interdisciplinary work and be very intentional about how we go about closing these gaps. We have to recognize that there are differences in knowledge and in care, and they’re unacceptable, and we have to work collaboratively in providing resources to communities equitably to decrease them.”
The authors acknowledged their study’s limitations, including the retrospective nature of the study, using zip codes to determine median household income, and an unbalanced number of White and Black athletes. They did add, however, that the ratio of participants “generally aligns with census data in the surrounding metropolitan and county areas.” That said, they also surmised that the scarcity of Black athletes could indicate a deeper disparity in health care system usage and asked future researchers to “consider enrolling athletes directly from schools rather than from within the concussion clinic only.”
Dr. Yengo-Kahn disclosed holding a compensated position on the scientific advisory board of BlinkTBI, but the authors noted that the company had no role in the study and its products were not used. No other conflicts of interest were reported.
FROM THE JOURNAL OF NEUROSURGERY: PEDIATRICS
Gray hair goes away and squids go to space
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Many comatose TBI patients recover consciousness during rehab
according to a study of 3 decades of TBI survivors.
“Caution is warranted in consideration of withdrawing or withholding life-sustaining therapies in patients with severe TBI and DoC,” wrote Robert G. Kowalski, MBBCh, MS, of the department of neurology at the University of Colorado at Denver, Aurora, and colleagues. The study was published in JAMA Neurology.
To determine the likelihood of returning to consciousness in the weeks that follow a serious brain injury, along with any notable contributing factors, the researchers launched a retrospective analysis of 17,470 patients with moderate to severe TBI. All participants had been enrolled in the Traumatic Brain Injury Model Systems database from January 1989 to June 2019 after being admitted to any 1 of 23 inpatient rehabilitation centers. The cohort had a median age of 39 (interquartile range, 25-56), with 74% being male and 66% being white. Their median duration of acute hospital care was 16 days (IQR, 9-26).
Unconsciousness was defined by the researchers as not being able to follow commands or having a Glasgow Coma Scale motor score in the ED of lower than 6 or a Disability Rating Scale motor score greater than 0. Of the overall cohort, 7,547 (57%) patients initially lost consciousness and 2,058 (12%) remained unconscious as they were admitted to rehab. Of that subgroup, 1,674 (82%) recovered consciousness during rehab. The 414 patients who still had a DoC at completion of rehab had a longer median stay (37 days; IQR, 22-65), compared with the patients who recovered consciousness (19 days; IQR, 12-30; P < .001). After multivariable analysis, the factors most associated with recovery of consciousness were the absence of intraventricular hemorrhage (adjusted odds ratio, 0.678; 95% confidence interval, 0.532-0.863; P = .002) and the absence of intracranial mass effect (aOR, 0.759; 95% CI, 0.595-0.968; P = .03).
Though all patients experienced an improvement in functional status during rehabilitation, patients with DoC had an increase in median Functional Independence Measure total score from 19 to 71 while patients without DoC increased from 54 to 96 (change in total score, +43 versus +37; P = .002). After multivariate analysis, younger age and male sex were both associated with better functional outcomes during rehab and at discharge.
When it comes to TBI patients, don’t give up hope
The choice to withdraw care in TBI patients is a complicated and daunting one, and this study is further evidence that physicians should delay that decision in many scenarios, wrote Jennifer A. Kim, MD, PhD, and Kevin N. Sheth, MD, of Yale University, New Haven, Conn., in an accompanying editorial.
“By showing that a large proportion of patients with persistent DoC recover during acute rehabilitation, this article further challenges our potential toward overly nihilistic notions of who may or may not ultimately recover consciousness long term,” they added.
That said, they also recognized the questions that still persist: What are the reasons for late-stage withdrawal of lifesaving therapy? What is the recovery rate of all hospitalized patients with TBI, not just those in rehabilitation facilities? And is it possible to detect covert consciousness using MRI and electroencephalography, which this study did not include?
“Defining both good and poor prognostic risk factors is critical to portending recovery,” they wrote, emphasizing the need for physicians to rely on scientifically based predictions when making such important assessments.
Patience is a virtue for TBI specialists
“A lot of people write notes on hospital charts, ‘poor prognosis.’ You don’t know, that early in the game, in the acute care setting, how TBI patients are going to do,” said Jamie S. Ullman, MD, of the department of neurosurgery at Hofstra University, Hempstead, N.Y., in an interview. “It’s over the long term that we really have to judge that.”
“Of course, there may be some characteristics that patients might have that may portend for a worse outcome, like brain stem damage,” she added. “But in general, there is plenty of literature to suggest that not only can even the worst-looking patients have some kind of functional outcome but that it takes 18 months or more to actually realize an outcome from a traumatic brain injury.”
She emphasized that each patient with TBI is unique; beyond their current status, you have to consider the significance of their injury, the thoughts of their families or partner, and their own previously stated wishes and willingness to tolerate disability. Nonetheless, this study is another step toward distilling the “nihilistic thinking” that can lead physicians to expect the worst regarding patients who may still have a path toward a functional life.
“As traumatic brain injury specialists,” she said, “we need to see what we can do to give patients as good a chance as possible at a recovery.”
The authors acknowledged their study’s limitations, including an inability to account for 3 decades of variations in treatment regimens and its limited generalizability because of the cohort being composed of only TBI survivors admitted to inpatient rehab. In addition, they noted a possible referential bias for the study’s mostly young TBI patients in rehab facilities, another reason why these findings “may not be directly applicable to the overall population of patients with moderate or severe TBI.”
The study was funded by grants from the National Institute on Disability, Independent Living, and Rehabilitation Research; the Department of Health & Human Services; and the Veterans Health Administration Central Office VA TBI Model Systems Program of Research. The authors reported several potential conflicts of interest, including receiving grants and support from various government agencies and pharmaceutical companies.
according to a study of 3 decades of TBI survivors.
“Caution is warranted in consideration of withdrawing or withholding life-sustaining therapies in patients with severe TBI and DoC,” wrote Robert G. Kowalski, MBBCh, MS, of the department of neurology at the University of Colorado at Denver, Aurora, and colleagues. The study was published in JAMA Neurology.
To determine the likelihood of returning to consciousness in the weeks that follow a serious brain injury, along with any notable contributing factors, the researchers launched a retrospective analysis of 17,470 patients with moderate to severe TBI. All participants had been enrolled in the Traumatic Brain Injury Model Systems database from January 1989 to June 2019 after being admitted to any 1 of 23 inpatient rehabilitation centers. The cohort had a median age of 39 (interquartile range, 25-56), with 74% being male and 66% being white. Their median duration of acute hospital care was 16 days (IQR, 9-26).
Unconsciousness was defined by the researchers as not being able to follow commands or having a Glasgow Coma Scale motor score in the ED of lower than 6 or a Disability Rating Scale motor score greater than 0. Of the overall cohort, 7,547 (57%) patients initially lost consciousness and 2,058 (12%) remained unconscious as they were admitted to rehab. Of that subgroup, 1,674 (82%) recovered consciousness during rehab. The 414 patients who still had a DoC at completion of rehab had a longer median stay (37 days; IQR, 22-65), compared with the patients who recovered consciousness (19 days; IQR, 12-30; P < .001). After multivariable analysis, the factors most associated with recovery of consciousness were the absence of intraventricular hemorrhage (adjusted odds ratio, 0.678; 95% confidence interval, 0.532-0.863; P = .002) and the absence of intracranial mass effect (aOR, 0.759; 95% CI, 0.595-0.968; P = .03).
Though all patients experienced an improvement in functional status during rehabilitation, patients with DoC had an increase in median Functional Independence Measure total score from 19 to 71 while patients without DoC increased from 54 to 96 (change in total score, +43 versus +37; P = .002). After multivariate analysis, younger age and male sex were both associated with better functional outcomes during rehab and at discharge.
When it comes to TBI patients, don’t give up hope
The choice to withdraw care in TBI patients is a complicated and daunting one, and this study is further evidence that physicians should delay that decision in many scenarios, wrote Jennifer A. Kim, MD, PhD, and Kevin N. Sheth, MD, of Yale University, New Haven, Conn., in an accompanying editorial.
“By showing that a large proportion of patients with persistent DoC recover during acute rehabilitation, this article further challenges our potential toward overly nihilistic notions of who may or may not ultimately recover consciousness long term,” they added.
That said, they also recognized the questions that still persist: What are the reasons for late-stage withdrawal of lifesaving therapy? What is the recovery rate of all hospitalized patients with TBI, not just those in rehabilitation facilities? And is it possible to detect covert consciousness using MRI and electroencephalography, which this study did not include?
“Defining both good and poor prognostic risk factors is critical to portending recovery,” they wrote, emphasizing the need for physicians to rely on scientifically based predictions when making such important assessments.
Patience is a virtue for TBI specialists
“A lot of people write notes on hospital charts, ‘poor prognosis.’ You don’t know, that early in the game, in the acute care setting, how TBI patients are going to do,” said Jamie S. Ullman, MD, of the department of neurosurgery at Hofstra University, Hempstead, N.Y., in an interview. “It’s over the long term that we really have to judge that.”
“Of course, there may be some characteristics that patients might have that may portend for a worse outcome, like brain stem damage,” she added. “But in general, there is plenty of literature to suggest that not only can even the worst-looking patients have some kind of functional outcome but that it takes 18 months or more to actually realize an outcome from a traumatic brain injury.”
She emphasized that each patient with TBI is unique; beyond their current status, you have to consider the significance of their injury, the thoughts of their families or partner, and their own previously stated wishes and willingness to tolerate disability. Nonetheless, this study is another step toward distilling the “nihilistic thinking” that can lead physicians to expect the worst regarding patients who may still have a path toward a functional life.
“As traumatic brain injury specialists,” she said, “we need to see what we can do to give patients as good a chance as possible at a recovery.”
The authors acknowledged their study’s limitations, including an inability to account for 3 decades of variations in treatment regimens and its limited generalizability because of the cohort being composed of only TBI survivors admitted to inpatient rehab. In addition, they noted a possible referential bias for the study’s mostly young TBI patients in rehab facilities, another reason why these findings “may not be directly applicable to the overall population of patients with moderate or severe TBI.”
The study was funded by grants from the National Institute on Disability, Independent Living, and Rehabilitation Research; the Department of Health & Human Services; and the Veterans Health Administration Central Office VA TBI Model Systems Program of Research. The authors reported several potential conflicts of interest, including receiving grants and support from various government agencies and pharmaceutical companies.
according to a study of 3 decades of TBI survivors.
“Caution is warranted in consideration of withdrawing or withholding life-sustaining therapies in patients with severe TBI and DoC,” wrote Robert G. Kowalski, MBBCh, MS, of the department of neurology at the University of Colorado at Denver, Aurora, and colleagues. The study was published in JAMA Neurology.
To determine the likelihood of returning to consciousness in the weeks that follow a serious brain injury, along with any notable contributing factors, the researchers launched a retrospective analysis of 17,470 patients with moderate to severe TBI. All participants had been enrolled in the Traumatic Brain Injury Model Systems database from January 1989 to June 2019 after being admitted to any 1 of 23 inpatient rehabilitation centers. The cohort had a median age of 39 (interquartile range, 25-56), with 74% being male and 66% being white. Their median duration of acute hospital care was 16 days (IQR, 9-26).
Unconsciousness was defined by the researchers as not being able to follow commands or having a Glasgow Coma Scale motor score in the ED of lower than 6 or a Disability Rating Scale motor score greater than 0. Of the overall cohort, 7,547 (57%) patients initially lost consciousness and 2,058 (12%) remained unconscious as they were admitted to rehab. Of that subgroup, 1,674 (82%) recovered consciousness during rehab. The 414 patients who still had a DoC at completion of rehab had a longer median stay (37 days; IQR, 22-65), compared with the patients who recovered consciousness (19 days; IQR, 12-30; P < .001). After multivariable analysis, the factors most associated with recovery of consciousness were the absence of intraventricular hemorrhage (adjusted odds ratio, 0.678; 95% confidence interval, 0.532-0.863; P = .002) and the absence of intracranial mass effect (aOR, 0.759; 95% CI, 0.595-0.968; P = .03).
Though all patients experienced an improvement in functional status during rehabilitation, patients with DoC had an increase in median Functional Independence Measure total score from 19 to 71 while patients without DoC increased from 54 to 96 (change in total score, +43 versus +37; P = .002). After multivariate analysis, younger age and male sex were both associated with better functional outcomes during rehab and at discharge.
When it comes to TBI patients, don’t give up hope
The choice to withdraw care in TBI patients is a complicated and daunting one, and this study is further evidence that physicians should delay that decision in many scenarios, wrote Jennifer A. Kim, MD, PhD, and Kevin N. Sheth, MD, of Yale University, New Haven, Conn., in an accompanying editorial.
“By showing that a large proportion of patients with persistent DoC recover during acute rehabilitation, this article further challenges our potential toward overly nihilistic notions of who may or may not ultimately recover consciousness long term,” they added.
That said, they also recognized the questions that still persist: What are the reasons for late-stage withdrawal of lifesaving therapy? What is the recovery rate of all hospitalized patients with TBI, not just those in rehabilitation facilities? And is it possible to detect covert consciousness using MRI and electroencephalography, which this study did not include?
“Defining both good and poor prognostic risk factors is critical to portending recovery,” they wrote, emphasizing the need for physicians to rely on scientifically based predictions when making such important assessments.
Patience is a virtue for TBI specialists
“A lot of people write notes on hospital charts, ‘poor prognosis.’ You don’t know, that early in the game, in the acute care setting, how TBI patients are going to do,” said Jamie S. Ullman, MD, of the department of neurosurgery at Hofstra University, Hempstead, N.Y., in an interview. “It’s over the long term that we really have to judge that.”
“Of course, there may be some characteristics that patients might have that may portend for a worse outcome, like brain stem damage,” she added. “But in general, there is plenty of literature to suggest that not only can even the worst-looking patients have some kind of functional outcome but that it takes 18 months or more to actually realize an outcome from a traumatic brain injury.”
She emphasized that each patient with TBI is unique; beyond their current status, you have to consider the significance of their injury, the thoughts of their families or partner, and their own previously stated wishes and willingness to tolerate disability. Nonetheless, this study is another step toward distilling the “nihilistic thinking” that can lead physicians to expect the worst regarding patients who may still have a path toward a functional life.
“As traumatic brain injury specialists,” she said, “we need to see what we can do to give patients as good a chance as possible at a recovery.”
The authors acknowledged their study’s limitations, including an inability to account for 3 decades of variations in treatment regimens and its limited generalizability because of the cohort being composed of only TBI survivors admitted to inpatient rehab. In addition, they noted a possible referential bias for the study’s mostly young TBI patients in rehab facilities, another reason why these findings “may not be directly applicable to the overall population of patients with moderate or severe TBI.”
The study was funded by grants from the National Institute on Disability, Independent Living, and Rehabilitation Research; the Department of Health & Human Services; and the Veterans Health Administration Central Office VA TBI Model Systems Program of Research. The authors reported several potential conflicts of interest, including receiving grants and support from various government agencies and pharmaceutical companies.
FROM JAMA NEUROLOGY
A new biomarker of traumatic brain injury?
, new research suggests. “Reliable detection of this biomarker at very early time points may allow for prompt TBI detection and therefore intervention,” said study investigator Rachel Elizabeth Thomas, MD, PhD, a neurology resident at the University of Pennsylvania, Philadelphia, while presenting study findings at the American Academy of Neurology’s 2021 annual meeting.
“The level reflects the degree of severity and provides some degree of prognostic information,” she added.
A specific marker of acute injury?
Von Willebrand factor is a glycoprotein released in the endothelium in response to local trauma. It plays a part in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased expression of the factor is associated with vascular and neurodegenerative dementia.
The researchers examined whether von Willebrand factor is a biomarker of mild, repetitive TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing bouts.
Eligible participants were between the ages of 18 and 35 years. They had a score of greater than or equal to 1 on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ-3), had competed in at least three 3-minute bouts, and had withstood 25 or more blows to the head.
The investigators compared the plasma levels of von Willebrand factor of the boxers with those of 42 patients who presented to the University of Pennsylvania Trauma Center with TBI and with those of 23 uninjured control persons.
There was no significant difference in plasma levels of von Willebrand factor between boxers before the bout (13.15 µg/mL) and the control persons (6.16 µg/mL). Among the boxers, levels of von Willebrand factor increased by a factor of 1.8 within 30 minutes after bouts, compared with the levels among the control persons. The mean post-bout von Willebrand factor level was 25.09 µg/mL.
“Von Willebrand factor may be more specific for acute injuries, given that it does not seem to stay chronically elevated,” said Dr. Thomas.
In addition, the researchers found a significant positive correlation (r = 0.51; P = .03) between the fold change in plasma von Willebrand factor levels and the number of blows to the head that the athletes sustained.
They also found a significant positive correlation between fold change in von Willebrand factor and RPQ-3 score (r = 0.69; P = .002). These objective and subjective data suggest that levels of von Willebrand factor reflect injury severity, said Dr. Thomas.
Among patients hospitalized with TBI, levels of von Willebrand factor were significantly higher than among control persons (73.2 µg/mL vs. 40.8 µg/mL; P < .0009). The investigators found a linear correlation between plasma von Willebrand factor level and RPQ-3 score (r = 0.24) that was not statistically significant.
Levels of von Willebrand factor among patients hospitalized with TBI were higher on average and demonstrated a greater degree of variability than the levels among boxers immediately after a bout.
“This is not unexpected, given that this group represents a more heterogeneous population with varied forms of acute blunt injury, as compared to the boxers, who have undergone relatively repetitive, milder trauma,” Dr. Thomas said.
The traditional biomarkers of neurotrauma reflect neuronal and glial injury, whereas von Willebrand factor is an indicator of vascular trauma.
“Although on its own, von Willebrand factor is not specific to intracranial vascular injury, paired together with markers such as neurofilament light, GFAP [glial fibrillary acidic protein], and tau, it could be utilized to identify TBI-associated microvascular injury and thus delineate between specific TBI endophenotypes,” said Dr. Thomas. It could distinguish, for example, predominantly neuronal injury from predominantly vascular injury.
Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the investigators intend to pair measurements of plasma von Willebrand factor with advanced imaging techniques to evaluate cerebral blood flow or cerebrovascular reactivity. Such a study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
Point-of-care test?
Commenting on the findings, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the department of neurology at the University of Miami, said von Willebrand factor’s likely utility would be as a marker of injury in patients with mild TBI or sports-related concussion.
Imaging and clinical exams do not always reveal these injuries, Dr. O’Phelan added. “Having a biomarker that you can easily test in the blood would be extremely helpful,” she said.
The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or the battlefield for early detection of mild TBI, she added.
The fact that the test for von Willebrand factor has already been developed is an advantage, said Dr. O’Phelan. The normal and abnormal values of the test are clearly understood. “I do think that they will still need to calibrate it for head injury, because that’s not usually what the test is used for,” said Dr. O’Phelan.
One of the study’s strengths is that the investigators compared patients with TBI with control persons who had exercised, she added, because such a comparison helps clarify the biomarker’s relationship to the injury. Another strength is the application of the test to injuries of various types and of different degrees of severity.
But the biomarker will need to be tested in a larger population, said Dr. O’Phelan. In addition, there is a need to identify the right patient population for this test, as well as the best time frame for its application and potential factors that could confound the test results.
“I do worry a little bit about using early biomarkers for prognosis, particularly in severe TBI, because there’s so many variables that go into outcome,” said Dr. O’Phelan. This test likely would be administered in the first hours after injury, but many factors might affect patients’ outcomes, she added.
One influential factor is age. “If you have a von Willebrand factor of whatever number, that might have different importance in a 30-year-old than in an 80-year-old,” said Dr. O’Phelan. “We need to understand how to interpret those findings better.”
The study was supported by the National Institute for Neurological Disorders and Stroke, the U.S. Department of Defense, and the Pennsylvania Department of Health. Dr. Thomas and Dr. O’Phelan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. “Reliable detection of this biomarker at very early time points may allow for prompt TBI detection and therefore intervention,” said study investigator Rachel Elizabeth Thomas, MD, PhD, a neurology resident at the University of Pennsylvania, Philadelphia, while presenting study findings at the American Academy of Neurology’s 2021 annual meeting.
“The level reflects the degree of severity and provides some degree of prognostic information,” she added.
A specific marker of acute injury?
Von Willebrand factor is a glycoprotein released in the endothelium in response to local trauma. It plays a part in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased expression of the factor is associated with vascular and neurodegenerative dementia.
The researchers examined whether von Willebrand factor is a biomarker of mild, repetitive TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing bouts.
Eligible participants were between the ages of 18 and 35 years. They had a score of greater than or equal to 1 on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ-3), had competed in at least three 3-minute bouts, and had withstood 25 or more blows to the head.
The investigators compared the plasma levels of von Willebrand factor of the boxers with those of 42 patients who presented to the University of Pennsylvania Trauma Center with TBI and with those of 23 uninjured control persons.
There was no significant difference in plasma levels of von Willebrand factor between boxers before the bout (13.15 µg/mL) and the control persons (6.16 µg/mL). Among the boxers, levels of von Willebrand factor increased by a factor of 1.8 within 30 minutes after bouts, compared with the levels among the control persons. The mean post-bout von Willebrand factor level was 25.09 µg/mL.
“Von Willebrand factor may be more specific for acute injuries, given that it does not seem to stay chronically elevated,” said Dr. Thomas.
In addition, the researchers found a significant positive correlation (r = 0.51; P = .03) between the fold change in plasma von Willebrand factor levels and the number of blows to the head that the athletes sustained.
They also found a significant positive correlation between fold change in von Willebrand factor and RPQ-3 score (r = 0.69; P = .002). These objective and subjective data suggest that levels of von Willebrand factor reflect injury severity, said Dr. Thomas.
Among patients hospitalized with TBI, levels of von Willebrand factor were significantly higher than among control persons (73.2 µg/mL vs. 40.8 µg/mL; P < .0009). The investigators found a linear correlation between plasma von Willebrand factor level and RPQ-3 score (r = 0.24) that was not statistically significant.
Levels of von Willebrand factor among patients hospitalized with TBI were higher on average and demonstrated a greater degree of variability than the levels among boxers immediately after a bout.
“This is not unexpected, given that this group represents a more heterogeneous population with varied forms of acute blunt injury, as compared to the boxers, who have undergone relatively repetitive, milder trauma,” Dr. Thomas said.
The traditional biomarkers of neurotrauma reflect neuronal and glial injury, whereas von Willebrand factor is an indicator of vascular trauma.
“Although on its own, von Willebrand factor is not specific to intracranial vascular injury, paired together with markers such as neurofilament light, GFAP [glial fibrillary acidic protein], and tau, it could be utilized to identify TBI-associated microvascular injury and thus delineate between specific TBI endophenotypes,” said Dr. Thomas. It could distinguish, for example, predominantly neuronal injury from predominantly vascular injury.
Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the investigators intend to pair measurements of plasma von Willebrand factor with advanced imaging techniques to evaluate cerebral blood flow or cerebrovascular reactivity. Such a study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
Point-of-care test?
Commenting on the findings, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the department of neurology at the University of Miami, said von Willebrand factor’s likely utility would be as a marker of injury in patients with mild TBI or sports-related concussion.
Imaging and clinical exams do not always reveal these injuries, Dr. O’Phelan added. “Having a biomarker that you can easily test in the blood would be extremely helpful,” she said.
The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or the battlefield for early detection of mild TBI, she added.
The fact that the test for von Willebrand factor has already been developed is an advantage, said Dr. O’Phelan. The normal and abnormal values of the test are clearly understood. “I do think that they will still need to calibrate it for head injury, because that’s not usually what the test is used for,” said Dr. O’Phelan.
One of the study’s strengths is that the investigators compared patients with TBI with control persons who had exercised, she added, because such a comparison helps clarify the biomarker’s relationship to the injury. Another strength is the application of the test to injuries of various types and of different degrees of severity.
But the biomarker will need to be tested in a larger population, said Dr. O’Phelan. In addition, there is a need to identify the right patient population for this test, as well as the best time frame for its application and potential factors that could confound the test results.
“I do worry a little bit about using early biomarkers for prognosis, particularly in severe TBI, because there’s so many variables that go into outcome,” said Dr. O’Phelan. This test likely would be administered in the first hours after injury, but many factors might affect patients’ outcomes, she added.
One influential factor is age. “If you have a von Willebrand factor of whatever number, that might have different importance in a 30-year-old than in an 80-year-old,” said Dr. O’Phelan. “We need to understand how to interpret those findings better.”
The study was supported by the National Institute for Neurological Disorders and Stroke, the U.S. Department of Defense, and the Pennsylvania Department of Health. Dr. Thomas and Dr. O’Phelan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. “Reliable detection of this biomarker at very early time points may allow for prompt TBI detection and therefore intervention,” said study investigator Rachel Elizabeth Thomas, MD, PhD, a neurology resident at the University of Pennsylvania, Philadelphia, while presenting study findings at the American Academy of Neurology’s 2021 annual meeting.
“The level reflects the degree of severity and provides some degree of prognostic information,” she added.
A specific marker of acute injury?
Von Willebrand factor is a glycoprotein released in the endothelium in response to local trauma. It plays a part in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased expression of the factor is associated with vascular and neurodegenerative dementia.
The researchers examined whether von Willebrand factor is a biomarker of mild, repetitive TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing bouts.
Eligible participants were between the ages of 18 and 35 years. They had a score of greater than or equal to 1 on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ-3), had competed in at least three 3-minute bouts, and had withstood 25 or more blows to the head.
The investigators compared the plasma levels of von Willebrand factor of the boxers with those of 42 patients who presented to the University of Pennsylvania Trauma Center with TBI and with those of 23 uninjured control persons.
There was no significant difference in plasma levels of von Willebrand factor between boxers before the bout (13.15 µg/mL) and the control persons (6.16 µg/mL). Among the boxers, levels of von Willebrand factor increased by a factor of 1.8 within 30 minutes after bouts, compared with the levels among the control persons. The mean post-bout von Willebrand factor level was 25.09 µg/mL.
“Von Willebrand factor may be more specific for acute injuries, given that it does not seem to stay chronically elevated,” said Dr. Thomas.
In addition, the researchers found a significant positive correlation (r = 0.51; P = .03) between the fold change in plasma von Willebrand factor levels and the number of blows to the head that the athletes sustained.
They also found a significant positive correlation between fold change in von Willebrand factor and RPQ-3 score (r = 0.69; P = .002). These objective and subjective data suggest that levels of von Willebrand factor reflect injury severity, said Dr. Thomas.
Among patients hospitalized with TBI, levels of von Willebrand factor were significantly higher than among control persons (73.2 µg/mL vs. 40.8 µg/mL; P < .0009). The investigators found a linear correlation between plasma von Willebrand factor level and RPQ-3 score (r = 0.24) that was not statistically significant.
Levels of von Willebrand factor among patients hospitalized with TBI were higher on average and demonstrated a greater degree of variability than the levels among boxers immediately after a bout.
“This is not unexpected, given that this group represents a more heterogeneous population with varied forms of acute blunt injury, as compared to the boxers, who have undergone relatively repetitive, milder trauma,” Dr. Thomas said.
The traditional biomarkers of neurotrauma reflect neuronal and glial injury, whereas von Willebrand factor is an indicator of vascular trauma.
“Although on its own, von Willebrand factor is not specific to intracranial vascular injury, paired together with markers such as neurofilament light, GFAP [glial fibrillary acidic protein], and tau, it could be utilized to identify TBI-associated microvascular injury and thus delineate between specific TBI endophenotypes,” said Dr. Thomas. It could distinguish, for example, predominantly neuronal injury from predominantly vascular injury.
Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the investigators intend to pair measurements of plasma von Willebrand factor with advanced imaging techniques to evaluate cerebral blood flow or cerebrovascular reactivity. Such a study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
Point-of-care test?
Commenting on the findings, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the department of neurology at the University of Miami, said von Willebrand factor’s likely utility would be as a marker of injury in patients with mild TBI or sports-related concussion.
Imaging and clinical exams do not always reveal these injuries, Dr. O’Phelan added. “Having a biomarker that you can easily test in the blood would be extremely helpful,” she said.
The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or the battlefield for early detection of mild TBI, she added.
The fact that the test for von Willebrand factor has already been developed is an advantage, said Dr. O’Phelan. The normal and abnormal values of the test are clearly understood. “I do think that they will still need to calibrate it for head injury, because that’s not usually what the test is used for,” said Dr. O’Phelan.
One of the study’s strengths is that the investigators compared patients with TBI with control persons who had exercised, she added, because such a comparison helps clarify the biomarker’s relationship to the injury. Another strength is the application of the test to injuries of various types and of different degrees of severity.
But the biomarker will need to be tested in a larger population, said Dr. O’Phelan. In addition, there is a need to identify the right patient population for this test, as well as the best time frame for its application and potential factors that could confound the test results.
“I do worry a little bit about using early biomarkers for prognosis, particularly in severe TBI, because there’s so many variables that go into outcome,” said Dr. O’Phelan. This test likely would be administered in the first hours after injury, but many factors might affect patients’ outcomes, she added.
One influential factor is age. “If you have a von Willebrand factor of whatever number, that might have different importance in a 30-year-old than in an 80-year-old,” said Dr. O’Phelan. “We need to understand how to interpret those findings better.”
The study was supported by the National Institute for Neurological Disorders and Stroke, the U.S. Department of Defense, and the Pennsylvania Department of Health. Dr. Thomas and Dr. O’Phelan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAN 2021