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Oral contraceptive use associated with smaller hypothalamic and pituitary volumes
CHICAGO – Women taking oral contraceptives had, on average, a hypothalamus that was 6% smaller than those who didn’t, in a small study that used magnetic resonance imaging. Pituitary volume was also smaller.
Though the sample size was relatively small, 50 women in total, it’s the only study to date that looks at the relationship between hypothalamic volume and oral contraceptive (OC) use, and the largest examining pituitary volume, according to Ke Xun (Kevin) Chen, MD, who presented the findings at the annual meeting of the Radiological Society of North America.
Using MRI, Dr. Chen and his colleagues found that hypothalamic volume was significantly smaller in women taking oral contraceptives than those who were naturally cycling (b value = –64.1; P = .006). The pituitary gland also was significantly smaller in those taking OCs (b = –92.8; P = .007).
“I was quite surprised [at the finding], because the magnitude of the effect is not small,” especially in the context of changes in volume of other brain structures, senior author Michael L. Lipton, MD, PhD, said in an interview. In Alzheimer’s disease, for example, a volume loss of 4% annually can be expected.
However, “it’s not shocking to me in a negative way at all. I can’t tell you what it means in terms of how it’s going to affect people,” since this is a cross-sectional study that only detected a correlation and can’t say anything about a causative relationship, he added. “We don’t even know that [OCs] cause this effect. ... It’s plausible that this is just a plasticity-related change that’s simply showing us the effect of the drug.
“We’re going to be much more careful to consider oral contraceptive use as a covariate in future research studies; that’s for sure,” he said.
Although OCs have been available since their 1960 Food and Drug Administration approval, and their effects in some areas of physiology and health have been well studied, there’s still not much known about how oral contraceptives affect brain function, said Dr. Lipton, professor of neuroradiology and psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Montefiore medical system, New York.
The spark for this study came from one of Dr. Lipton’s main areas of research – sex differences in susceptibility to and recovery from traumatic brain injury. “Women are more likely to exhibit changes in their brain [after injury] – and changes in their brain function – than men,” he said.
In the present study, “we went at this trying to understand the effect to which the hormone effect might be doing something in regular, healthy people that we need to consider as part of the bigger picture,” he said.
Dr. Lipton, Dr. Chen (then a radiology resident at Albert Einstein College of Medicine), and their coauthors constructed the study to look for differences in brain structure between women who were experiencing natural menstrual cycles and those who were taking exogenous hormones, to begin to learn how oral contraceptive use might modify risk and susceptibility for neurologic disease and injury.
It had already been established that global brain volume didn’t differ between naturally cycling women and those using OCs. However, some studies had shown differences in volume of some specific brain regions, and one study had shown smaller pituitary volume in OC users, according to the presentation by Dr. Chen, who is now a radiology fellow at Brigham and Women’s Hospital, Boston. Accurately measuring hypothalamic volume represents a technical challenge, and the effect of OCs on the structure’s volume hadn’t previously been studied.
Sex hormones, said Dr. Lipton, have known trophic effects on brain tissue and ovarian sex hormones cross the blood brain barrier, so the idea that there would be some plasticity in the brains of those taking OCs wasn’t completely surprising, especially since there are hormone receptors that lie within the central nervous system. However, he said he was “very surprised” by the effect size seen in the study.
The study included 21 healthy women taking combined oral contraceptives, and 29 naturally cycling women. Participants’ mean age was 23 years for the OC users, and 21 for the naturally cycling women. Body mass index and smoking history didn’t differ between groups. Women on OCs were significantly more likely to use alcohol and to drink more frequently than those not taking OCs (P = .001). Participants were included only if they were taking a combined estrogen-progestin pill; those on noncyclical contraceptives such as implants and hormone-emitting intrauterine devices were excluded, as were naturally cycling women with very long or irregular menstrual cycles.
After multivariable statistical analysis, the only two significant predictors of hypothalamic volume were total intracranial volume and OC use. For pituitary volume, body mass index and OC use remained significant.
In addition to the MRI scans, participants also completed neurobehavioral testing to assess mood and cognition. An exploratory analysis showed no correlation between hypothalamic volume and the cognitive testing battery results, which included assessments for verbal learning and memory, executive function, and working memory.
However, a moderate positive association was seen between hypothalamic volume and anger scores (r = 0.34; P = .02). The investigators found a “strong positive correlation of hypothalamic volume with depression,” said Dr. Chen (r = 0.25; P = .09).
The investigators found no menstrual cycle-related changes in hypothalamic and pituitary volume among naturally cycling women.
Hypothalamic volume was obtained using manual segmentation of the MRIs; a combined automated-manual approach was used to obtain pituitary volume. Reliability was tested by having 5 raters each assess volumes for a randomly selected subset of the scans; inter-rater reliability fell between 0.78 and 0.86, values considered to indicate “good” reliability.
In addition to the small sample size, Dr. Chen acknowledged several limitations to the study. These included the lack of accounting for details of OC use including duration, exact type of OC, and whether women were taking the placebo phase of their pill packs at the time of scanning. Additionally, women who were naturally cycling were not asked about prior history of OC use.
Also, women’s menstrual phase was estimated from the self-reported date of the last menstrual period, rather than obtained by direct measurement via serum hormone levels.
Dr. Lipton’s perspective adds a strong note of caution to avoid overinterpretation from the study. Dr. Chen and Dr. Lipton agreed, however, that OC use should be accounted for when brain structure and function are studied in female participants.
Dr. Chen, Dr. Lipton, and their coauthors reported that they had no conflicts of interest. The authors reported no outside sources of funding.
SOURCE: Chen K et al. RSNA 2019. Presentation SSM-1904.
CHICAGO – Women taking oral contraceptives had, on average, a hypothalamus that was 6% smaller than those who didn’t, in a small study that used magnetic resonance imaging. Pituitary volume was also smaller.
Though the sample size was relatively small, 50 women in total, it’s the only study to date that looks at the relationship between hypothalamic volume and oral contraceptive (OC) use, and the largest examining pituitary volume, according to Ke Xun (Kevin) Chen, MD, who presented the findings at the annual meeting of the Radiological Society of North America.
Using MRI, Dr. Chen and his colleagues found that hypothalamic volume was significantly smaller in women taking oral contraceptives than those who were naturally cycling (b value = –64.1; P = .006). The pituitary gland also was significantly smaller in those taking OCs (b = –92.8; P = .007).
“I was quite surprised [at the finding], because the magnitude of the effect is not small,” especially in the context of changes in volume of other brain structures, senior author Michael L. Lipton, MD, PhD, said in an interview. In Alzheimer’s disease, for example, a volume loss of 4% annually can be expected.
However, “it’s not shocking to me in a negative way at all. I can’t tell you what it means in terms of how it’s going to affect people,” since this is a cross-sectional study that only detected a correlation and can’t say anything about a causative relationship, he added. “We don’t even know that [OCs] cause this effect. ... It’s plausible that this is just a plasticity-related change that’s simply showing us the effect of the drug.
“We’re going to be much more careful to consider oral contraceptive use as a covariate in future research studies; that’s for sure,” he said.
Although OCs have been available since their 1960 Food and Drug Administration approval, and their effects in some areas of physiology and health have been well studied, there’s still not much known about how oral contraceptives affect brain function, said Dr. Lipton, professor of neuroradiology and psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Montefiore medical system, New York.
The spark for this study came from one of Dr. Lipton’s main areas of research – sex differences in susceptibility to and recovery from traumatic brain injury. “Women are more likely to exhibit changes in their brain [after injury] – and changes in their brain function – than men,” he said.
In the present study, “we went at this trying to understand the effect to which the hormone effect might be doing something in regular, healthy people that we need to consider as part of the bigger picture,” he said.
Dr. Lipton, Dr. Chen (then a radiology resident at Albert Einstein College of Medicine), and their coauthors constructed the study to look for differences in brain structure between women who were experiencing natural menstrual cycles and those who were taking exogenous hormones, to begin to learn how oral contraceptive use might modify risk and susceptibility for neurologic disease and injury.
It had already been established that global brain volume didn’t differ between naturally cycling women and those using OCs. However, some studies had shown differences in volume of some specific brain regions, and one study had shown smaller pituitary volume in OC users, according to the presentation by Dr. Chen, who is now a radiology fellow at Brigham and Women’s Hospital, Boston. Accurately measuring hypothalamic volume represents a technical challenge, and the effect of OCs on the structure’s volume hadn’t previously been studied.
Sex hormones, said Dr. Lipton, have known trophic effects on brain tissue and ovarian sex hormones cross the blood brain barrier, so the idea that there would be some plasticity in the brains of those taking OCs wasn’t completely surprising, especially since there are hormone receptors that lie within the central nervous system. However, he said he was “very surprised” by the effect size seen in the study.
The study included 21 healthy women taking combined oral contraceptives, and 29 naturally cycling women. Participants’ mean age was 23 years for the OC users, and 21 for the naturally cycling women. Body mass index and smoking history didn’t differ between groups. Women on OCs were significantly more likely to use alcohol and to drink more frequently than those not taking OCs (P = .001). Participants were included only if they were taking a combined estrogen-progestin pill; those on noncyclical contraceptives such as implants and hormone-emitting intrauterine devices were excluded, as were naturally cycling women with very long or irregular menstrual cycles.
After multivariable statistical analysis, the only two significant predictors of hypothalamic volume were total intracranial volume and OC use. For pituitary volume, body mass index and OC use remained significant.
In addition to the MRI scans, participants also completed neurobehavioral testing to assess mood and cognition. An exploratory analysis showed no correlation between hypothalamic volume and the cognitive testing battery results, which included assessments for verbal learning and memory, executive function, and working memory.
However, a moderate positive association was seen between hypothalamic volume and anger scores (r = 0.34; P = .02). The investigators found a “strong positive correlation of hypothalamic volume with depression,” said Dr. Chen (r = 0.25; P = .09).
The investigators found no menstrual cycle-related changes in hypothalamic and pituitary volume among naturally cycling women.
Hypothalamic volume was obtained using manual segmentation of the MRIs; a combined automated-manual approach was used to obtain pituitary volume. Reliability was tested by having 5 raters each assess volumes for a randomly selected subset of the scans; inter-rater reliability fell between 0.78 and 0.86, values considered to indicate “good” reliability.
In addition to the small sample size, Dr. Chen acknowledged several limitations to the study. These included the lack of accounting for details of OC use including duration, exact type of OC, and whether women were taking the placebo phase of their pill packs at the time of scanning. Additionally, women who were naturally cycling were not asked about prior history of OC use.
Also, women’s menstrual phase was estimated from the self-reported date of the last menstrual period, rather than obtained by direct measurement via serum hormone levels.
Dr. Lipton’s perspective adds a strong note of caution to avoid overinterpretation from the study. Dr. Chen and Dr. Lipton agreed, however, that OC use should be accounted for when brain structure and function are studied in female participants.
Dr. Chen, Dr. Lipton, and their coauthors reported that they had no conflicts of interest. The authors reported no outside sources of funding.
SOURCE: Chen K et al. RSNA 2019. Presentation SSM-1904.
CHICAGO – Women taking oral contraceptives had, on average, a hypothalamus that was 6% smaller than those who didn’t, in a small study that used magnetic resonance imaging. Pituitary volume was also smaller.
Though the sample size was relatively small, 50 women in total, it’s the only study to date that looks at the relationship between hypothalamic volume and oral contraceptive (OC) use, and the largest examining pituitary volume, according to Ke Xun (Kevin) Chen, MD, who presented the findings at the annual meeting of the Radiological Society of North America.
Using MRI, Dr. Chen and his colleagues found that hypothalamic volume was significantly smaller in women taking oral contraceptives than those who were naturally cycling (b value = –64.1; P = .006). The pituitary gland also was significantly smaller in those taking OCs (b = –92.8; P = .007).
“I was quite surprised [at the finding], because the magnitude of the effect is not small,” especially in the context of changes in volume of other brain structures, senior author Michael L. Lipton, MD, PhD, said in an interview. In Alzheimer’s disease, for example, a volume loss of 4% annually can be expected.
However, “it’s not shocking to me in a negative way at all. I can’t tell you what it means in terms of how it’s going to affect people,” since this is a cross-sectional study that only detected a correlation and can’t say anything about a causative relationship, he added. “We don’t even know that [OCs] cause this effect. ... It’s plausible that this is just a plasticity-related change that’s simply showing us the effect of the drug.
“We’re going to be much more careful to consider oral contraceptive use as a covariate in future research studies; that’s for sure,” he said.
Although OCs have been available since their 1960 Food and Drug Administration approval, and their effects in some areas of physiology and health have been well studied, there’s still not much known about how oral contraceptives affect brain function, said Dr. Lipton, professor of neuroradiology and psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Montefiore medical system, New York.
The spark for this study came from one of Dr. Lipton’s main areas of research – sex differences in susceptibility to and recovery from traumatic brain injury. “Women are more likely to exhibit changes in their brain [after injury] – and changes in their brain function – than men,” he said.
In the present study, “we went at this trying to understand the effect to which the hormone effect might be doing something in regular, healthy people that we need to consider as part of the bigger picture,” he said.
Dr. Lipton, Dr. Chen (then a radiology resident at Albert Einstein College of Medicine), and their coauthors constructed the study to look for differences in brain structure between women who were experiencing natural menstrual cycles and those who were taking exogenous hormones, to begin to learn how oral contraceptive use might modify risk and susceptibility for neurologic disease and injury.
It had already been established that global brain volume didn’t differ between naturally cycling women and those using OCs. However, some studies had shown differences in volume of some specific brain regions, and one study had shown smaller pituitary volume in OC users, according to the presentation by Dr. Chen, who is now a radiology fellow at Brigham and Women’s Hospital, Boston. Accurately measuring hypothalamic volume represents a technical challenge, and the effect of OCs on the structure’s volume hadn’t previously been studied.
Sex hormones, said Dr. Lipton, have known trophic effects on brain tissue and ovarian sex hormones cross the blood brain barrier, so the idea that there would be some plasticity in the brains of those taking OCs wasn’t completely surprising, especially since there are hormone receptors that lie within the central nervous system. However, he said he was “very surprised” by the effect size seen in the study.
The study included 21 healthy women taking combined oral contraceptives, and 29 naturally cycling women. Participants’ mean age was 23 years for the OC users, and 21 for the naturally cycling women. Body mass index and smoking history didn’t differ between groups. Women on OCs were significantly more likely to use alcohol and to drink more frequently than those not taking OCs (P = .001). Participants were included only if they were taking a combined estrogen-progestin pill; those on noncyclical contraceptives such as implants and hormone-emitting intrauterine devices were excluded, as were naturally cycling women with very long or irregular menstrual cycles.
After multivariable statistical analysis, the only two significant predictors of hypothalamic volume were total intracranial volume and OC use. For pituitary volume, body mass index and OC use remained significant.
In addition to the MRI scans, participants also completed neurobehavioral testing to assess mood and cognition. An exploratory analysis showed no correlation between hypothalamic volume and the cognitive testing battery results, which included assessments for verbal learning and memory, executive function, and working memory.
However, a moderate positive association was seen between hypothalamic volume and anger scores (r = 0.34; P = .02). The investigators found a “strong positive correlation of hypothalamic volume with depression,” said Dr. Chen (r = 0.25; P = .09).
The investigators found no menstrual cycle-related changes in hypothalamic and pituitary volume among naturally cycling women.
Hypothalamic volume was obtained using manual segmentation of the MRIs; a combined automated-manual approach was used to obtain pituitary volume. Reliability was tested by having 5 raters each assess volumes for a randomly selected subset of the scans; inter-rater reliability fell between 0.78 and 0.86, values considered to indicate “good” reliability.
In addition to the small sample size, Dr. Chen acknowledged several limitations to the study. These included the lack of accounting for details of OC use including duration, exact type of OC, and whether women were taking the placebo phase of their pill packs at the time of scanning. Additionally, women who were naturally cycling were not asked about prior history of OC use.
Also, women’s menstrual phase was estimated from the self-reported date of the last menstrual period, rather than obtained by direct measurement via serum hormone levels.
Dr. Lipton’s perspective adds a strong note of caution to avoid overinterpretation from the study. Dr. Chen and Dr. Lipton agreed, however, that OC use should be accounted for when brain structure and function are studied in female participants.
Dr. Chen, Dr. Lipton, and their coauthors reported that they had no conflicts of interest. The authors reported no outside sources of funding.
SOURCE: Chen K et al. RSNA 2019. Presentation SSM-1904.
REPORTING FROM RSNA 2019
DoD Explores Virtual Health for Traumatic Brain Injury
NATIONAL HARBOR, MD – As it moves to expand the use of virtual health offerings, the US Department of Defense (DoD) Regional Health Command Europe piloted a virtual health (telehealth) program to treat service members with traumatic brain injury (TBI). Ronald Keen, FNP-C, and Steve Cain, PA, reported on the DoD use of virtual health at the 2019 AMSUS annual meeting in Maryland.
The study, conducted between October 2016 and May 2018, included 15 patients stationed in 4 countries, including Poland, Turkey, and Egypt and 67 total health care encounters. Patients were limited to service members in the direct care system or those who were in remote areas where gaps in care existed in the Tricare Network. The virtual health program was centered at Landstuhl Regional Medical Center in Germany and sought to determine whether virtual health was feasible to treat TBI and whether it would increase patient satisfaction. The multidisciplinary program brought together specialists in 7 different disciplines, including sleep medicine, optometry, behavioral health, and occupational therapy.
According to Keen, the results of the 15-patient pilot were promising. He conservatively estimated a savings of $3,700, and more important, the program saved 322 hours of on-duty time. Health care providers used the program an average 2.8 times, and patients used the system 1.6 times on average. Currently the DoD is requiring active permission from patients to receive a telehealth visit.
NATIONAL HARBOR, MD – As it moves to expand the use of virtual health offerings, the US Department of Defense (DoD) Regional Health Command Europe piloted a virtual health (telehealth) program to treat service members with traumatic brain injury (TBI). Ronald Keen, FNP-C, and Steve Cain, PA, reported on the DoD use of virtual health at the 2019 AMSUS annual meeting in Maryland.
The study, conducted between October 2016 and May 2018, included 15 patients stationed in 4 countries, including Poland, Turkey, and Egypt and 67 total health care encounters. Patients were limited to service members in the direct care system or those who were in remote areas where gaps in care existed in the Tricare Network. The virtual health program was centered at Landstuhl Regional Medical Center in Germany and sought to determine whether virtual health was feasible to treat TBI and whether it would increase patient satisfaction. The multidisciplinary program brought together specialists in 7 different disciplines, including sleep medicine, optometry, behavioral health, and occupational therapy.
According to Keen, the results of the 15-patient pilot were promising. He conservatively estimated a savings of $3,700, and more important, the program saved 322 hours of on-duty time. Health care providers used the program an average 2.8 times, and patients used the system 1.6 times on average. Currently the DoD is requiring active permission from patients to receive a telehealth visit.
NATIONAL HARBOR, MD – As it moves to expand the use of virtual health offerings, the US Department of Defense (DoD) Regional Health Command Europe piloted a virtual health (telehealth) program to treat service members with traumatic brain injury (TBI). Ronald Keen, FNP-C, and Steve Cain, PA, reported on the DoD use of virtual health at the 2019 AMSUS annual meeting in Maryland.
The study, conducted between October 2016 and May 2018, included 15 patients stationed in 4 countries, including Poland, Turkey, and Egypt and 67 total health care encounters. Patients were limited to service members in the direct care system or those who were in remote areas where gaps in care existed in the Tricare Network. The virtual health program was centered at Landstuhl Regional Medical Center in Germany and sought to determine whether virtual health was feasible to treat TBI and whether it would increase patient satisfaction. The multidisciplinary program brought together specialists in 7 different disciplines, including sleep medicine, optometry, behavioral health, and occupational therapy.
According to Keen, the results of the 15-patient pilot were promising. He conservatively estimated a savings of $3,700, and more important, the program saved 322 hours of on-duty time. Health care providers used the program an average 2.8 times, and patients used the system 1.6 times on average. Currently the DoD is requiring active permission from patients to receive a telehealth visit.
Children may develop prolonged headache after concussion
CHARLOTTE, N.C. – , according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.
“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
Few studies have examined prolonged pediatric postconcussion headache
The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.
Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.
The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.
Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
Healthy behaviors increased after concussion
Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.
Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).
Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.
In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.
After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
Long-term outcomes
Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.
The investigators did not report any study funding or disclosures.
SOURCE: Barissi M et al. CNS 2019, Abstract 95.
CHARLOTTE, N.C. – , according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.
“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
Few studies have examined prolonged pediatric postconcussion headache
The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.
Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.
The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.
Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
Healthy behaviors increased after concussion
Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.
Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).
Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.
In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.
After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
Long-term outcomes
Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.
The investigators did not report any study funding or disclosures.
SOURCE: Barissi M et al. CNS 2019, Abstract 95.
CHARLOTTE, N.C. – , according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.
“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
Few studies have examined prolonged pediatric postconcussion headache
The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.
Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.
The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.
Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
Healthy behaviors increased after concussion
Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.
Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).
Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.
In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.
After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
Long-term outcomes
Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.
The investigators did not report any study funding or disclosures.
SOURCE: Barissi M et al. CNS 2019, Abstract 95.
REPORTING FROM CNS 2019
Microbleeds After Brain Injury Predict Worse Disability
Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.
The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.
Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.
In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.
The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.
One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.
The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.
The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”
The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.
Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.
Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.
The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.
Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.
In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.
The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.
One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.
The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.
The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”
The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.
Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.
Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.
The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.
Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.
In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.
The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.
One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.
The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.
The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”
The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.
Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.
Soccer pros may face increased risk of death from neurodegenerative disease
, findings from a retrospective epidemiologic analysis suggest.
Former professional soccer players included in the analysis also received more dementia-related medication prescriptions than did controls, Daniel F. Mackay, PhD, of the Institute of Health and Wellbeing at the University of Glasgow (Scotland) and his colleagues reported online Oct. 21 in The New England Journal of Medicine.
Overall mortality during a median follow-up of 18 years from study entry at the age of 40 years was 15.4% among 7,676 former players, and 16.5% among 23,028 controls matched based on age, sex, and degree of social deprivation. All-cause mortality was lower among players versus controls before age 70 years, and was higher thereafter, and the mortality rates associated with ischemic heart disease and lung cancer were lower among the players (hazard ratios, 0.80 and 0.53, respectively), the investigators found.
Mortality rates from stroke or cerebrovascular disease were similar in the players and controls (HR, 0.88), they noted.
However, mortality with neurodegenerative disease listed as the primary cause was 1.7% in players versus 0.5% in controls (HR adjusted for competing risks of death, 3.45), they said. The estimated risk of death with neurodegenerative disease was highest among those with Alzheimer’s disease and lowest for those with Parkinson’s disease (HRs, 5.07 and 2.15, respectively).
Dementia-related medications also were prescribed more frequently for players vs. controls (odds ratio, 4.90).
A subgroup analysis showed no significant difference between goalkeepers and outfielders with respect to mortality with neurodegenerative disease listed as a factor (HR, 0.73), but dementia-related medications were prescribed less often to goalkeepers (OR, 0.41).
Concerns about the risk of neurodegenerative diseases among participants in contact sports have been raised, in part because of the recognition of pathologic changes of chronic traumatic encephalopathy among participants across a range of such sports, the investigators explained, noting that data regarding the risk of neurodegenerative disease among former professional soccer players are limited.
The findings of the current study, in terms of lower all-cause mortality up to the age of 70 years, are similar to those in previous studies involving elite athletes across a range of sports, and “may reflect higher levels of physical activity and lower levels of obesity and smoking in elite athletes than in the general population,” they noted.
“In contrast, mortality from neurodegenerative disease was higher among former soccer players, a finding consistent with studies involving former players in the U.S. National Football League,” they added, concluding that the findings, which “may be valuable to inform the management of risks in the sport,” require confirmation in prospective studies.
This study was supported by the Football Association and Professional Footballers’ Association, and by an NHS Research Scotland Career Researcher Fellowship. Dr. Mackay reported having no relevant financial disclosures.
SOURCE: Mackay D et al. N Engl J Med. 2019 Oct 21. doi: 10.1056/NEJMoa1908483.
The good news from the study by Mackay et al. is that mortality from common nonneurologic diseases is lower among former elite soccer players vs. controls; the bad news is that mortality from neurodegenerative diseases is higher and prescriptions for dementia-related medications more common, Robert A. Stern, PhD, wrote in an editorial.
The findings add to existing evidence that repetitive head impact in contact sports may increase the risk of neurodegenerative disease and dementia, but “should not engender undue fear and panic among soccer players, parents, and coaches,” as the findings cannot be generalized to recreational, amateur, or collegiate-level soccer, Dr. Stern said.
The findings should, however, lead to research and awareness of potential consequences of heading the ball in amateur soccer, he argued, noting that “perhaps ... there is already adequate evidence that repeated blows to the brain from heading in professional soccer is an occupational risk that needs to be addressed.”
Dr. Stern is with the Boston University Chronic Traumatic Encephalopathy Center, Boston University. He disclosed financial relationships (receipt of grants, personal fees, and/or other relationships outside the submitted work) with the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Concussion Legacy Foundation, Biogen, Eli Lilly, Psychological Assessment Resources, and King Devick Technologies.
The good news from the study by Mackay et al. is that mortality from common nonneurologic diseases is lower among former elite soccer players vs. controls; the bad news is that mortality from neurodegenerative diseases is higher and prescriptions for dementia-related medications more common, Robert A. Stern, PhD, wrote in an editorial.
The findings add to existing evidence that repetitive head impact in contact sports may increase the risk of neurodegenerative disease and dementia, but “should not engender undue fear and panic among soccer players, parents, and coaches,” as the findings cannot be generalized to recreational, amateur, or collegiate-level soccer, Dr. Stern said.
The findings should, however, lead to research and awareness of potential consequences of heading the ball in amateur soccer, he argued, noting that “perhaps ... there is already adequate evidence that repeated blows to the brain from heading in professional soccer is an occupational risk that needs to be addressed.”
Dr. Stern is with the Boston University Chronic Traumatic Encephalopathy Center, Boston University. He disclosed financial relationships (receipt of grants, personal fees, and/or other relationships outside the submitted work) with the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Concussion Legacy Foundation, Biogen, Eli Lilly, Psychological Assessment Resources, and King Devick Technologies.
The good news from the study by Mackay et al. is that mortality from common nonneurologic diseases is lower among former elite soccer players vs. controls; the bad news is that mortality from neurodegenerative diseases is higher and prescriptions for dementia-related medications more common, Robert A. Stern, PhD, wrote in an editorial.
The findings add to existing evidence that repetitive head impact in contact sports may increase the risk of neurodegenerative disease and dementia, but “should not engender undue fear and panic among soccer players, parents, and coaches,” as the findings cannot be generalized to recreational, amateur, or collegiate-level soccer, Dr. Stern said.
The findings should, however, lead to research and awareness of potential consequences of heading the ball in amateur soccer, he argued, noting that “perhaps ... there is already adequate evidence that repeated blows to the brain from heading in professional soccer is an occupational risk that needs to be addressed.”
Dr. Stern is with the Boston University Chronic Traumatic Encephalopathy Center, Boston University. He disclosed financial relationships (receipt of grants, personal fees, and/or other relationships outside the submitted work) with the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Concussion Legacy Foundation, Biogen, Eli Lilly, Psychological Assessment Resources, and King Devick Technologies.
, findings from a retrospective epidemiologic analysis suggest.
Former professional soccer players included in the analysis also received more dementia-related medication prescriptions than did controls, Daniel F. Mackay, PhD, of the Institute of Health and Wellbeing at the University of Glasgow (Scotland) and his colleagues reported online Oct. 21 in The New England Journal of Medicine.
Overall mortality during a median follow-up of 18 years from study entry at the age of 40 years was 15.4% among 7,676 former players, and 16.5% among 23,028 controls matched based on age, sex, and degree of social deprivation. All-cause mortality was lower among players versus controls before age 70 years, and was higher thereafter, and the mortality rates associated with ischemic heart disease and lung cancer were lower among the players (hazard ratios, 0.80 and 0.53, respectively), the investigators found.
Mortality rates from stroke or cerebrovascular disease were similar in the players and controls (HR, 0.88), they noted.
However, mortality with neurodegenerative disease listed as the primary cause was 1.7% in players versus 0.5% in controls (HR adjusted for competing risks of death, 3.45), they said. The estimated risk of death with neurodegenerative disease was highest among those with Alzheimer’s disease and lowest for those with Parkinson’s disease (HRs, 5.07 and 2.15, respectively).
Dementia-related medications also were prescribed more frequently for players vs. controls (odds ratio, 4.90).
A subgroup analysis showed no significant difference between goalkeepers and outfielders with respect to mortality with neurodegenerative disease listed as a factor (HR, 0.73), but dementia-related medications were prescribed less often to goalkeepers (OR, 0.41).
Concerns about the risk of neurodegenerative diseases among participants in contact sports have been raised, in part because of the recognition of pathologic changes of chronic traumatic encephalopathy among participants across a range of such sports, the investigators explained, noting that data regarding the risk of neurodegenerative disease among former professional soccer players are limited.
The findings of the current study, in terms of lower all-cause mortality up to the age of 70 years, are similar to those in previous studies involving elite athletes across a range of sports, and “may reflect higher levels of physical activity and lower levels of obesity and smoking in elite athletes than in the general population,” they noted.
“In contrast, mortality from neurodegenerative disease was higher among former soccer players, a finding consistent with studies involving former players in the U.S. National Football League,” they added, concluding that the findings, which “may be valuable to inform the management of risks in the sport,” require confirmation in prospective studies.
This study was supported by the Football Association and Professional Footballers’ Association, and by an NHS Research Scotland Career Researcher Fellowship. Dr. Mackay reported having no relevant financial disclosures.
SOURCE: Mackay D et al. N Engl J Med. 2019 Oct 21. doi: 10.1056/NEJMoa1908483.
, findings from a retrospective epidemiologic analysis suggest.
Former professional soccer players included in the analysis also received more dementia-related medication prescriptions than did controls, Daniel F. Mackay, PhD, of the Institute of Health and Wellbeing at the University of Glasgow (Scotland) and his colleagues reported online Oct. 21 in The New England Journal of Medicine.
Overall mortality during a median follow-up of 18 years from study entry at the age of 40 years was 15.4% among 7,676 former players, and 16.5% among 23,028 controls matched based on age, sex, and degree of social deprivation. All-cause mortality was lower among players versus controls before age 70 years, and was higher thereafter, and the mortality rates associated with ischemic heart disease and lung cancer were lower among the players (hazard ratios, 0.80 and 0.53, respectively), the investigators found.
Mortality rates from stroke or cerebrovascular disease were similar in the players and controls (HR, 0.88), they noted.
However, mortality with neurodegenerative disease listed as the primary cause was 1.7% in players versus 0.5% in controls (HR adjusted for competing risks of death, 3.45), they said. The estimated risk of death with neurodegenerative disease was highest among those with Alzheimer’s disease and lowest for those with Parkinson’s disease (HRs, 5.07 and 2.15, respectively).
Dementia-related medications also were prescribed more frequently for players vs. controls (odds ratio, 4.90).
A subgroup analysis showed no significant difference between goalkeepers and outfielders with respect to mortality with neurodegenerative disease listed as a factor (HR, 0.73), but dementia-related medications were prescribed less often to goalkeepers (OR, 0.41).
Concerns about the risk of neurodegenerative diseases among participants in contact sports have been raised, in part because of the recognition of pathologic changes of chronic traumatic encephalopathy among participants across a range of such sports, the investigators explained, noting that data regarding the risk of neurodegenerative disease among former professional soccer players are limited.
The findings of the current study, in terms of lower all-cause mortality up to the age of 70 years, are similar to those in previous studies involving elite athletes across a range of sports, and “may reflect higher levels of physical activity and lower levels of obesity and smoking in elite athletes than in the general population,” they noted.
“In contrast, mortality from neurodegenerative disease was higher among former soccer players, a finding consistent with studies involving former players in the U.S. National Football League,” they added, concluding that the findings, which “may be valuable to inform the management of risks in the sport,” require confirmation in prospective studies.
This study was supported by the Football Association and Professional Footballers’ Association, and by an NHS Research Scotland Career Researcher Fellowship. Dr. Mackay reported having no relevant financial disclosures.
SOURCE: Mackay D et al. N Engl J Med. 2019 Oct 21. doi: 10.1056/NEJMoa1908483.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Concussion effects may linger on MRI 1 year after athletes resume play
Among athletes with concussion, the effects of the injury on brain physiology may persist when they return to play and 1 year later.
MRI measures from 24 athletes with concussion significantly differed from those of controls at various time points and changed over time, according to a study published in Neurology. “Different aspects of brain physiology have different patterns of long-term recovery,” the researchers wrote.
While guidelines for safe return to play mainly rely on the resolution of symptoms, “the findings in this study indicate that more research is needed ... to better understand optimal recovery time from a biological standpoint,” wrote first author Nathan W. Churchill, PhD, a researcher at St. Michael’s Hospital in Toronto, and colleagues.
The study provides “evidence of incomplete or ongoing recovery” when athletes return to play, which could entail “a potential risk for long-term sequelae, given the evidence of worse outcomes if a second concussion occurs before recovery is complete,” according to the investigators. In addition,
To examine whether concussion-related brain changes dissipate by 1 year after athletes receive medical clearance to return to play, Dr. Churchill and colleagues analyzed MRI data from 24 college athletes with concussion and 122 control athletes without concussion.
Athletes with concussion were scanned within 1 week of the injury, at return to play a median of 27 days after the concussion, and 1 year after return to play. Control athletes were scanned before the start of the season. Participants’ sports included volleyball, hockey, soccer, football, rugby, basketball, lacrosse, and water polo. The participants had a mean age of about 20 years, and about half were women.
Athletes with concussion had elevated mean diffusivity within 1 week of injury, at return to play, and 1 year later, compared with controls. In athletes with concussion, cerebral blood flow was elevated soon after concussion, normal at return to play, and decreased 1 year later, relative to controls. Global functional connectivity increased and white matter fractional anisotropy decreased near the time of injury and at return to play, but these measures did not significantly differ from those of controls at 1 year.
The study did not capture MRI changes between return to play and 1 year later. In addition, MRI changes might be influenced by a lack of training before resuming play, as well as by exertion and subconcussive impacts after returning to play, the authors noted.
The Canadian Institutes of Health Research, the Canadian Institute for Military and Veterans Health Research, and Siemens Healthineers Canada supported the study. Siemens makes the MRI equipment used in the study. Dr. Churchill and colleagues had no relevant disclosures.
SOURCE: Churchill NW et al. Neurology. 2019 Oct 16. doi: 10.1212/WNL.0000000000008523.
Among athletes with concussion, the effects of the injury on brain physiology may persist when they return to play and 1 year later.
MRI measures from 24 athletes with concussion significantly differed from those of controls at various time points and changed over time, according to a study published in Neurology. “Different aspects of brain physiology have different patterns of long-term recovery,” the researchers wrote.
While guidelines for safe return to play mainly rely on the resolution of symptoms, “the findings in this study indicate that more research is needed ... to better understand optimal recovery time from a biological standpoint,” wrote first author Nathan W. Churchill, PhD, a researcher at St. Michael’s Hospital in Toronto, and colleagues.
The study provides “evidence of incomplete or ongoing recovery” when athletes return to play, which could entail “a potential risk for long-term sequelae, given the evidence of worse outcomes if a second concussion occurs before recovery is complete,” according to the investigators. In addition,
To examine whether concussion-related brain changes dissipate by 1 year after athletes receive medical clearance to return to play, Dr. Churchill and colleagues analyzed MRI data from 24 college athletes with concussion and 122 control athletes without concussion.
Athletes with concussion were scanned within 1 week of the injury, at return to play a median of 27 days after the concussion, and 1 year after return to play. Control athletes were scanned before the start of the season. Participants’ sports included volleyball, hockey, soccer, football, rugby, basketball, lacrosse, and water polo. The participants had a mean age of about 20 years, and about half were women.
Athletes with concussion had elevated mean diffusivity within 1 week of injury, at return to play, and 1 year later, compared with controls. In athletes with concussion, cerebral blood flow was elevated soon after concussion, normal at return to play, and decreased 1 year later, relative to controls. Global functional connectivity increased and white matter fractional anisotropy decreased near the time of injury and at return to play, but these measures did not significantly differ from those of controls at 1 year.
The study did not capture MRI changes between return to play and 1 year later. In addition, MRI changes might be influenced by a lack of training before resuming play, as well as by exertion and subconcussive impacts after returning to play, the authors noted.
The Canadian Institutes of Health Research, the Canadian Institute for Military and Veterans Health Research, and Siemens Healthineers Canada supported the study. Siemens makes the MRI equipment used in the study. Dr. Churchill and colleagues had no relevant disclosures.
SOURCE: Churchill NW et al. Neurology. 2019 Oct 16. doi: 10.1212/WNL.0000000000008523.
Among athletes with concussion, the effects of the injury on brain physiology may persist when they return to play and 1 year later.
MRI measures from 24 athletes with concussion significantly differed from those of controls at various time points and changed over time, according to a study published in Neurology. “Different aspects of brain physiology have different patterns of long-term recovery,” the researchers wrote.
While guidelines for safe return to play mainly rely on the resolution of symptoms, “the findings in this study indicate that more research is needed ... to better understand optimal recovery time from a biological standpoint,” wrote first author Nathan W. Churchill, PhD, a researcher at St. Michael’s Hospital in Toronto, and colleagues.
The study provides “evidence of incomplete or ongoing recovery” when athletes return to play, which could entail “a potential risk for long-term sequelae, given the evidence of worse outcomes if a second concussion occurs before recovery is complete,” according to the investigators. In addition,
To examine whether concussion-related brain changes dissipate by 1 year after athletes receive medical clearance to return to play, Dr. Churchill and colleagues analyzed MRI data from 24 college athletes with concussion and 122 control athletes without concussion.
Athletes with concussion were scanned within 1 week of the injury, at return to play a median of 27 days after the concussion, and 1 year after return to play. Control athletes were scanned before the start of the season. Participants’ sports included volleyball, hockey, soccer, football, rugby, basketball, lacrosse, and water polo. The participants had a mean age of about 20 years, and about half were women.
Athletes with concussion had elevated mean diffusivity within 1 week of injury, at return to play, and 1 year later, compared with controls. In athletes with concussion, cerebral blood flow was elevated soon after concussion, normal at return to play, and decreased 1 year later, relative to controls. Global functional connectivity increased and white matter fractional anisotropy decreased near the time of injury and at return to play, but these measures did not significantly differ from those of controls at 1 year.
The study did not capture MRI changes between return to play and 1 year later. In addition, MRI changes might be influenced by a lack of training before resuming play, as well as by exertion and subconcussive impacts after returning to play, the authors noted.
The Canadian Institutes of Health Research, the Canadian Institute for Military and Veterans Health Research, and Siemens Healthineers Canada supported the study. Siemens makes the MRI equipment used in the study. Dr. Churchill and colleagues had no relevant disclosures.
SOURCE: Churchill NW et al. Neurology. 2019 Oct 16. doi: 10.1212/WNL.0000000000008523.
FROM NEUROLOGY
Key clinical point: Among athletes with concussion, the effects of the injury on brain physiology may persist when they return to play and 1 year later.
Major finding: Athletes with concussion had elevated mean diffusivity within 1 week of injury, at return to play, and 1 year later, compared with controls. In athletes with concussion, cerebral blood flow was elevated soon after concussion, normal at return to play, and decreased 1 year later. Global functional connectivity increased and white matter fractional anisotropy decreased near the time of injury and at return to play, but these measures did not significantly differ from those of controls at 1 year.
Study details: An observational study of 24 college athletes with concussion.
Disclosures: The study was supported by the Canadian Institutes of Health Research, the Canadian Institute for Military and Veterans Health Research, and Siemens Healthineers Canada. Siemens makes the MRI equipment used in the study. The researchers had no relevant disclosures.
Source: Churchill NW et al. Neurology. 2019 Oct 16. doi: 10.1212/WNL.0000000000008523.
Urine Reveals Biomarker for Potential TBI
Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”
Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.
A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”
They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.
The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”
Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”
Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.
A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”
They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.
The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”
Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”
Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.
A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”
They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.
The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”
‘Fast MRI’ may be option in TBI screening for children
“Fast MRI,” which allows scans to be taken quickly without sedation, is a “reasonable alternative” to screen certain younger children for traumatic brain injury, a new study found.
The fast MRI option has “the potential to eliminate ionizing radiation exposure for thousands of children each year,” the study authors wrote in Pediatrics. “The ability to complete imaging in about 6 minutes, without the need for anesthesia or sedation, suggests that fast MRI is appropriate even in acute settings, where patient throughput is a priority.”
Daniel M. Lindberg, MD, of the University of Colorado at Denver, Aurora, and associates wrote that children make between 600,000 and 1.6 million ED visits in the United States each year for evaluation of possible traumatic brain injury (TBI). While the incidence of clinically significant injury from TBI is low, 20%-70% of these children are exposed to potentially dangerous radiation as they undergo CT.
The new study focuses on fast MRI. Unlike traditional MRI, it doesn’t require children to remain motionless – typically with the help of sedation – to be scanned.
The researchers performed fast MRI in 223 children aged younger than 6 years (median age, 12.6 months; interquartile range, 4.7-32.6) who sought emergency care at a level 1 pediatric trauma center from 2015 to 2018. They had all had CT scans performed.
CT identified TBI in 111 (50%) of the subjects, while fast MRI identified it in 103 (sensitivity, 92.8%; 95% confidence interval, 86.3-96.8). Fast MRI missed six participants with isolated skull fractures and two with subarachnoid hemorrhage; CT missed five participants with subdural hematomas, parenchymal contusions, and subarachnoid hemorrhage.
While the researchers hoped for a higher sensitivity level, they wrote that “we feel that the benefit of avoiding radiation exposure outweighs the concern for missed injury.”
In a commentary, Brett Burstein, MDCM, PhD, MPH, and Christine Saint-Martin, MDCM, MSc, of Montreal Children’s Hospital and McGill University Health Center, also in Montreal, wrote that the study is “well conducted.”
However, they noted that “the reported feasibility reflects a highly selected cohort of stable patients in whom fast MRI is already likely to succeed. Feasibility results in a more generalizable population of head-injured children cannot be extrapolated.”
And, they added, “fast MRI was unavailable for 65 of 299 consenting, eligible patients because of lack of overnight staffing. Although not included among the outcome definitions of imaging time, this would be an important ‘feasibility’ consideration in most centers.”
Dr. Burstein and Dr. Saint-Martin wrote that “centers migrating toward this modality for neuroimaging children with head injuries should still use clinical judgment and highly sensitive, validated clinical decision rules when determining the need for any neuroimaging for head-injured children.”
The study was funded by the Colorado Traumatic Brain Injury Trust Fund (MindSource) and the Colorado Clinical and Translational Sciences Institute. The study and commentary authors reported no relevant financial disclosures.
SOURCES: Lindberg DM et al. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-0419; Burstein B, Saint-Martin C. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-2387.
“Fast MRI,” which allows scans to be taken quickly without sedation, is a “reasonable alternative” to screen certain younger children for traumatic brain injury, a new study found.
The fast MRI option has “the potential to eliminate ionizing radiation exposure for thousands of children each year,” the study authors wrote in Pediatrics. “The ability to complete imaging in about 6 minutes, without the need for anesthesia or sedation, suggests that fast MRI is appropriate even in acute settings, where patient throughput is a priority.”
Daniel M. Lindberg, MD, of the University of Colorado at Denver, Aurora, and associates wrote that children make between 600,000 and 1.6 million ED visits in the United States each year for evaluation of possible traumatic brain injury (TBI). While the incidence of clinically significant injury from TBI is low, 20%-70% of these children are exposed to potentially dangerous radiation as they undergo CT.
The new study focuses on fast MRI. Unlike traditional MRI, it doesn’t require children to remain motionless – typically with the help of sedation – to be scanned.
The researchers performed fast MRI in 223 children aged younger than 6 years (median age, 12.6 months; interquartile range, 4.7-32.6) who sought emergency care at a level 1 pediatric trauma center from 2015 to 2018. They had all had CT scans performed.
CT identified TBI in 111 (50%) of the subjects, while fast MRI identified it in 103 (sensitivity, 92.8%; 95% confidence interval, 86.3-96.8). Fast MRI missed six participants with isolated skull fractures and two with subarachnoid hemorrhage; CT missed five participants with subdural hematomas, parenchymal contusions, and subarachnoid hemorrhage.
While the researchers hoped for a higher sensitivity level, they wrote that “we feel that the benefit of avoiding radiation exposure outweighs the concern for missed injury.”
In a commentary, Brett Burstein, MDCM, PhD, MPH, and Christine Saint-Martin, MDCM, MSc, of Montreal Children’s Hospital and McGill University Health Center, also in Montreal, wrote that the study is “well conducted.”
However, they noted that “the reported feasibility reflects a highly selected cohort of stable patients in whom fast MRI is already likely to succeed. Feasibility results in a more generalizable population of head-injured children cannot be extrapolated.”
And, they added, “fast MRI was unavailable for 65 of 299 consenting, eligible patients because of lack of overnight staffing. Although not included among the outcome definitions of imaging time, this would be an important ‘feasibility’ consideration in most centers.”
Dr. Burstein and Dr. Saint-Martin wrote that “centers migrating toward this modality for neuroimaging children with head injuries should still use clinical judgment and highly sensitive, validated clinical decision rules when determining the need for any neuroimaging for head-injured children.”
The study was funded by the Colorado Traumatic Brain Injury Trust Fund (MindSource) and the Colorado Clinical and Translational Sciences Institute. The study and commentary authors reported no relevant financial disclosures.
SOURCES: Lindberg DM et al. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-0419; Burstein B, Saint-Martin C. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-2387.
“Fast MRI,” which allows scans to be taken quickly without sedation, is a “reasonable alternative” to screen certain younger children for traumatic brain injury, a new study found.
The fast MRI option has “the potential to eliminate ionizing radiation exposure for thousands of children each year,” the study authors wrote in Pediatrics. “The ability to complete imaging in about 6 minutes, without the need for anesthesia or sedation, suggests that fast MRI is appropriate even in acute settings, where patient throughput is a priority.”
Daniel M. Lindberg, MD, of the University of Colorado at Denver, Aurora, and associates wrote that children make between 600,000 and 1.6 million ED visits in the United States each year for evaluation of possible traumatic brain injury (TBI). While the incidence of clinically significant injury from TBI is low, 20%-70% of these children are exposed to potentially dangerous radiation as they undergo CT.
The new study focuses on fast MRI. Unlike traditional MRI, it doesn’t require children to remain motionless – typically with the help of sedation – to be scanned.
The researchers performed fast MRI in 223 children aged younger than 6 years (median age, 12.6 months; interquartile range, 4.7-32.6) who sought emergency care at a level 1 pediatric trauma center from 2015 to 2018. They had all had CT scans performed.
CT identified TBI in 111 (50%) of the subjects, while fast MRI identified it in 103 (sensitivity, 92.8%; 95% confidence interval, 86.3-96.8). Fast MRI missed six participants with isolated skull fractures and two with subarachnoid hemorrhage; CT missed five participants with subdural hematomas, parenchymal contusions, and subarachnoid hemorrhage.
While the researchers hoped for a higher sensitivity level, they wrote that “we feel that the benefit of avoiding radiation exposure outweighs the concern for missed injury.”
In a commentary, Brett Burstein, MDCM, PhD, MPH, and Christine Saint-Martin, MDCM, MSc, of Montreal Children’s Hospital and McGill University Health Center, also in Montreal, wrote that the study is “well conducted.”
However, they noted that “the reported feasibility reflects a highly selected cohort of stable patients in whom fast MRI is already likely to succeed. Feasibility results in a more generalizable population of head-injured children cannot be extrapolated.”
And, they added, “fast MRI was unavailable for 65 of 299 consenting, eligible patients because of lack of overnight staffing. Although not included among the outcome definitions of imaging time, this would be an important ‘feasibility’ consideration in most centers.”
Dr. Burstein and Dr. Saint-Martin wrote that “centers migrating toward this modality for neuroimaging children with head injuries should still use clinical judgment and highly sensitive, validated clinical decision rules when determining the need for any neuroimaging for head-injured children.”
The study was funded by the Colorado Traumatic Brain Injury Trust Fund (MindSource) and the Colorado Clinical and Translational Sciences Institute. The study and commentary authors reported no relevant financial disclosures.
SOURCES: Lindberg DM et al. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-0419; Burstein B, Saint-Martin C. Pediatrics. 2019 Sep 18. doi: 10.1542/peds.2019-2387.
FROM PEDIATRICS
Hyperphosphorylated tau visible in TBI survivors decades after brain injury
Brain deposits of hyperphosphorylated tau are detectable in traumatic brain injury (TBI) patients 18-51 years after a single moderate to severe incident occurred, researchers reported Sept. 4 in Science Translational Medicine.
Imaging with the tau-specific PET radioligand flortaucipir showed that the protein was most apparent in the right occipital cortex, and was associated with changes in cognitive scores, tau and beta amyloid in cerebrospinal fluid (CSF), and white matter density, Nikos Gorgoraptis, PhD, of Imperial College London and his colleagues wrote.
“The ability to detect tau pathology in vivo after TBI has major potential implications for diagnosis and prognostication of clinical outcomes after TBI,” the researchers explained. “It is also likely to assist in patient selection and stratification for future treatment trials targeting tau.”
The cohort study comprised 21 subjects (median age, 49 years) who had experienced a single moderate to severe TBI a median of 32 years (range, 18-51 years) before enrollment. A control group comprised 11 noninjured adults who were matched for age and other demographic factors. Everyone underwent a PET scan with flortaucipir, brain MRI, CSF sampling, apolipoprotein E genotyping, and neuropsychological testing.
TBI subjects were grouped according to recovery status: good and disabled. Overall, they showed impairments on multiple cognitive domains (processing speed, executive function, motivation, inhibition, and verbal and visual memory), compared with controls. These findings were largely driven by the disabled group.
Eight TBI subjects had elevated tau binding greater than 2,000 voxels above the threshold of detection (equivalent to 16 cm3 of brain volume), and seven had an increase of 249-1,999 voxels above threshold. Tau binding in the remainder was similar to that in controls. Recovery status didn’t correlate with the tau-binding strength.
Overall, the tau-binding signal appeared most strongly in the right lateral occipital cortex, regardless of functional recovery status.
In TBI subjects, CSF total tau correlated significantly with flortaucipir uptake in cortical gray matter, but not white matter. CSF phosphorylated tau correlated with uptake in white matter, but not gray matter.
The investigators also examined fractional anisotropy, a measure of fiber density, axonal diameter, and myelination in white matter. In TBI subjects, there was more flortaucipir uptake in areas of decreased fractional anisotropy, including association, commissural, and projection tracts.
“Correlations were observed in the genu and body of the corpus callosum, as well as in several association tracts within the ipsilateral (right) hemisphere, including the cingulum bundle, inferior longitudinal fasciculus, uncinate fasciculus, and anterior thalamic radiation, but not in the contralateral hemisphere. Higher cortical flortaucipir [signal] was associated with reduced tissue density in remote white matter regions including the corpus callosum and right prefrontal white matter. The same analysis for gray matter density did not show an association.”
The increased tau signal in TBI subjects “is in keeping with a causative role for traumatic axonal injury in the pathophysiology of posttraumatic tau pathology,” the authors said. “Mechanical forces exerted at the time of head injury are thought to disrupt axonal organization, producing damage to microtubule structure and associated axonal tau. This damage may lead to hyperphosphorylation of tau, misfolding, and neurofibrillary tangle formation, which eventually causes neurodegeneration. Mechanical forces are maximal in points of geometric inflection such as the base of cortical sulci, where tau pathology is seen in chronic traumatic encephalopathy.”
These patterns suggest that tau imaging could provide valuable diagnostic information about the type of posttraumatic neurodegeneration, they said.
The work was supported by the Medical Research Council and UK Dementia Research Institute. None of the authors declared having any competing interests related to the current study. Some authors reported financial ties to pharmaceutical companies.
SOURCE: Gorgoraptis N et al. Sci Transl Med. 2019;11:eaaw1993. doi: 10.1126/scitranslmed.aaw1993.
Brain deposits of hyperphosphorylated tau are detectable in traumatic brain injury (TBI) patients 18-51 years after a single moderate to severe incident occurred, researchers reported Sept. 4 in Science Translational Medicine.
Imaging with the tau-specific PET radioligand flortaucipir showed that the protein was most apparent in the right occipital cortex, and was associated with changes in cognitive scores, tau and beta amyloid in cerebrospinal fluid (CSF), and white matter density, Nikos Gorgoraptis, PhD, of Imperial College London and his colleagues wrote.
“The ability to detect tau pathology in vivo after TBI has major potential implications for diagnosis and prognostication of clinical outcomes after TBI,” the researchers explained. “It is also likely to assist in patient selection and stratification for future treatment trials targeting tau.”
The cohort study comprised 21 subjects (median age, 49 years) who had experienced a single moderate to severe TBI a median of 32 years (range, 18-51 years) before enrollment. A control group comprised 11 noninjured adults who were matched for age and other demographic factors. Everyone underwent a PET scan with flortaucipir, brain MRI, CSF sampling, apolipoprotein E genotyping, and neuropsychological testing.
TBI subjects were grouped according to recovery status: good and disabled. Overall, they showed impairments on multiple cognitive domains (processing speed, executive function, motivation, inhibition, and verbal and visual memory), compared with controls. These findings were largely driven by the disabled group.
Eight TBI subjects had elevated tau binding greater than 2,000 voxels above the threshold of detection (equivalent to 16 cm3 of brain volume), and seven had an increase of 249-1,999 voxels above threshold. Tau binding in the remainder was similar to that in controls. Recovery status didn’t correlate with the tau-binding strength.
Overall, the tau-binding signal appeared most strongly in the right lateral occipital cortex, regardless of functional recovery status.
In TBI subjects, CSF total tau correlated significantly with flortaucipir uptake in cortical gray matter, but not white matter. CSF phosphorylated tau correlated with uptake in white matter, but not gray matter.
The investigators also examined fractional anisotropy, a measure of fiber density, axonal diameter, and myelination in white matter. In TBI subjects, there was more flortaucipir uptake in areas of decreased fractional anisotropy, including association, commissural, and projection tracts.
“Correlations were observed in the genu and body of the corpus callosum, as well as in several association tracts within the ipsilateral (right) hemisphere, including the cingulum bundle, inferior longitudinal fasciculus, uncinate fasciculus, and anterior thalamic radiation, but not in the contralateral hemisphere. Higher cortical flortaucipir [signal] was associated with reduced tissue density in remote white matter regions including the corpus callosum and right prefrontal white matter. The same analysis for gray matter density did not show an association.”
The increased tau signal in TBI subjects “is in keeping with a causative role for traumatic axonal injury in the pathophysiology of posttraumatic tau pathology,” the authors said. “Mechanical forces exerted at the time of head injury are thought to disrupt axonal organization, producing damage to microtubule structure and associated axonal tau. This damage may lead to hyperphosphorylation of tau, misfolding, and neurofibrillary tangle formation, which eventually causes neurodegeneration. Mechanical forces are maximal in points of geometric inflection such as the base of cortical sulci, where tau pathology is seen in chronic traumatic encephalopathy.”
These patterns suggest that tau imaging could provide valuable diagnostic information about the type of posttraumatic neurodegeneration, they said.
The work was supported by the Medical Research Council and UK Dementia Research Institute. None of the authors declared having any competing interests related to the current study. Some authors reported financial ties to pharmaceutical companies.
SOURCE: Gorgoraptis N et al. Sci Transl Med. 2019;11:eaaw1993. doi: 10.1126/scitranslmed.aaw1993.
Brain deposits of hyperphosphorylated tau are detectable in traumatic brain injury (TBI) patients 18-51 years after a single moderate to severe incident occurred, researchers reported Sept. 4 in Science Translational Medicine.
Imaging with the tau-specific PET radioligand flortaucipir showed that the protein was most apparent in the right occipital cortex, and was associated with changes in cognitive scores, tau and beta amyloid in cerebrospinal fluid (CSF), and white matter density, Nikos Gorgoraptis, PhD, of Imperial College London and his colleagues wrote.
“The ability to detect tau pathology in vivo after TBI has major potential implications for diagnosis and prognostication of clinical outcomes after TBI,” the researchers explained. “It is also likely to assist in patient selection and stratification for future treatment trials targeting tau.”
The cohort study comprised 21 subjects (median age, 49 years) who had experienced a single moderate to severe TBI a median of 32 years (range, 18-51 years) before enrollment. A control group comprised 11 noninjured adults who were matched for age and other demographic factors. Everyone underwent a PET scan with flortaucipir, brain MRI, CSF sampling, apolipoprotein E genotyping, and neuropsychological testing.
TBI subjects were grouped according to recovery status: good and disabled. Overall, they showed impairments on multiple cognitive domains (processing speed, executive function, motivation, inhibition, and verbal and visual memory), compared with controls. These findings were largely driven by the disabled group.
Eight TBI subjects had elevated tau binding greater than 2,000 voxels above the threshold of detection (equivalent to 16 cm3 of brain volume), and seven had an increase of 249-1,999 voxels above threshold. Tau binding in the remainder was similar to that in controls. Recovery status didn’t correlate with the tau-binding strength.
Overall, the tau-binding signal appeared most strongly in the right lateral occipital cortex, regardless of functional recovery status.
In TBI subjects, CSF total tau correlated significantly with flortaucipir uptake in cortical gray matter, but not white matter. CSF phosphorylated tau correlated with uptake in white matter, but not gray matter.
The investigators also examined fractional anisotropy, a measure of fiber density, axonal diameter, and myelination in white matter. In TBI subjects, there was more flortaucipir uptake in areas of decreased fractional anisotropy, including association, commissural, and projection tracts.
“Correlations were observed in the genu and body of the corpus callosum, as well as in several association tracts within the ipsilateral (right) hemisphere, including the cingulum bundle, inferior longitudinal fasciculus, uncinate fasciculus, and anterior thalamic radiation, but not in the contralateral hemisphere. Higher cortical flortaucipir [signal] was associated with reduced tissue density in remote white matter regions including the corpus callosum and right prefrontal white matter. The same analysis for gray matter density did not show an association.”
The increased tau signal in TBI subjects “is in keeping with a causative role for traumatic axonal injury in the pathophysiology of posttraumatic tau pathology,” the authors said. “Mechanical forces exerted at the time of head injury are thought to disrupt axonal organization, producing damage to microtubule structure and associated axonal tau. This damage may lead to hyperphosphorylation of tau, misfolding, and neurofibrillary tangle formation, which eventually causes neurodegeneration. Mechanical forces are maximal in points of geometric inflection such as the base of cortical sulci, where tau pathology is seen in chronic traumatic encephalopathy.”
These patterns suggest that tau imaging could provide valuable diagnostic information about the type of posttraumatic neurodegeneration, they said.
The work was supported by the Medical Research Council and UK Dementia Research Institute. None of the authors declared having any competing interests related to the current study. Some authors reported financial ties to pharmaceutical companies.
SOURCE: Gorgoraptis N et al. Sci Transl Med. 2019;11:eaaw1993. doi: 10.1126/scitranslmed.aaw1993.
FROM SCIENCE TRANSLATIONAL MEDICINE
Blood test may reveal brain injury
researchers reported Aug. 26 in BMJ Paediatrics Open.
“GFAP outperformed UCH-L1 in detecting concussion in both children and adults within 4 hours of injury,” reported lead author Linda Papa, MD, and collaborators. Dr. Papa is an emergency medicine doctor at Orlando Health. “UCH-L1 was expressed at much higher levels than GFAP in those with nonconcussive trauma, particularly in children. Elevations of these biomarkers in nonconcussive head trauma suggest possible subconcussive brain injury. GFAP could be potentially useful to detect concussion for up to a week post injury.”
In 2018 the Food and Drug Administration approved the use of these biomarkers to guide CT scan ordering in adults with mild to moderate traumatic brain injury, but investigators have not established their ability to detect concussion in children or adults. Clinicians lack an objective measure to diagnose concussion acutely.
To assess the ability of GFAP and UCH-L1 to detect concussion, Dr. Papa and colleagues conducted a prospective cohort study. The researchers enrolled trauma patients of all ages at three level I trauma centers in the United States. They included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and who presented within 4 hours of injury. Investigators screened for concussion symptoms, obtained biomarker data from 712 trauma patients, and conducted repeated blood sampling in adults.
They grouped patients by those with concussion (n = 371), those with head trauma without overt signs of concussion (n = 149), and those with peripheral trauma without head trauma or concussion (n = 192). The study included 175 children. Injury mechanisms included car crashes, falls, bicycle accidents, and sports injuries.
Patients with concussion had significantly higher GFAP concentrations, compared with patients with body trauma and patients with nonconcussive head trauma. UCH-L1 levels did not significantly differ between patients with concussion and head trauma controls, however.
“Based on these results, the potential utility of GFAP to distinguish concussion from body trauma controls over 7 days postinjury was fair to excellent,” with area under the receiver operating characteristics curves (AUCs) of 0.75-0.89, the researchers said. “UCH-L1’s ability was guarded and variable with AUCs from poor to good depending on timing of samples.” UCH-L1 demonstrated AUCs that ranged from 0.54 to 0.78; earlier samples performed better.
GFAP elevations in head trauma controls “may represent milder forms of concussion that do not elicit typical signs or symptoms associated with concussion,” the authors wrote. “These injuries may be irrelevant, or they may represent important trauma that is just below the level of clinical detection and referred to as subconcussive trauma. ... Biomarkers (such as GFAP and UCH-L1) could provide a more objective measure of injury and potentially identify those at risk for neurocognitive problems.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers, and coauthors receive contract research funding from Banyan Biomarkers.
SOURCE: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
researchers reported Aug. 26 in BMJ Paediatrics Open.
“GFAP outperformed UCH-L1 in detecting concussion in both children and adults within 4 hours of injury,” reported lead author Linda Papa, MD, and collaborators. Dr. Papa is an emergency medicine doctor at Orlando Health. “UCH-L1 was expressed at much higher levels than GFAP in those with nonconcussive trauma, particularly in children. Elevations of these biomarkers in nonconcussive head trauma suggest possible subconcussive brain injury. GFAP could be potentially useful to detect concussion for up to a week post injury.”
In 2018 the Food and Drug Administration approved the use of these biomarkers to guide CT scan ordering in adults with mild to moderate traumatic brain injury, but investigators have not established their ability to detect concussion in children or adults. Clinicians lack an objective measure to diagnose concussion acutely.
To assess the ability of GFAP and UCH-L1 to detect concussion, Dr. Papa and colleagues conducted a prospective cohort study. The researchers enrolled trauma patients of all ages at three level I trauma centers in the United States. They included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and who presented within 4 hours of injury. Investigators screened for concussion symptoms, obtained biomarker data from 712 trauma patients, and conducted repeated blood sampling in adults.
They grouped patients by those with concussion (n = 371), those with head trauma without overt signs of concussion (n = 149), and those with peripheral trauma without head trauma or concussion (n = 192). The study included 175 children. Injury mechanisms included car crashes, falls, bicycle accidents, and sports injuries.
Patients with concussion had significantly higher GFAP concentrations, compared with patients with body trauma and patients with nonconcussive head trauma. UCH-L1 levels did not significantly differ between patients with concussion and head trauma controls, however.
“Based on these results, the potential utility of GFAP to distinguish concussion from body trauma controls over 7 days postinjury was fair to excellent,” with area under the receiver operating characteristics curves (AUCs) of 0.75-0.89, the researchers said. “UCH-L1’s ability was guarded and variable with AUCs from poor to good depending on timing of samples.” UCH-L1 demonstrated AUCs that ranged from 0.54 to 0.78; earlier samples performed better.
GFAP elevations in head trauma controls “may represent milder forms of concussion that do not elicit typical signs or symptoms associated with concussion,” the authors wrote. “These injuries may be irrelevant, or they may represent important trauma that is just below the level of clinical detection and referred to as subconcussive trauma. ... Biomarkers (such as GFAP and UCH-L1) could provide a more objective measure of injury and potentially identify those at risk for neurocognitive problems.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers, and coauthors receive contract research funding from Banyan Biomarkers.
SOURCE: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
researchers reported Aug. 26 in BMJ Paediatrics Open.
“GFAP outperformed UCH-L1 in detecting concussion in both children and adults within 4 hours of injury,” reported lead author Linda Papa, MD, and collaborators. Dr. Papa is an emergency medicine doctor at Orlando Health. “UCH-L1 was expressed at much higher levels than GFAP in those with nonconcussive trauma, particularly in children. Elevations of these biomarkers in nonconcussive head trauma suggest possible subconcussive brain injury. GFAP could be potentially useful to detect concussion for up to a week post injury.”
In 2018 the Food and Drug Administration approved the use of these biomarkers to guide CT scan ordering in adults with mild to moderate traumatic brain injury, but investigators have not established their ability to detect concussion in children or adults. Clinicians lack an objective measure to diagnose concussion acutely.
To assess the ability of GFAP and UCH-L1 to detect concussion, Dr. Papa and colleagues conducted a prospective cohort study. The researchers enrolled trauma patients of all ages at three level I trauma centers in the United States. They included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and who presented within 4 hours of injury. Investigators screened for concussion symptoms, obtained biomarker data from 712 trauma patients, and conducted repeated blood sampling in adults.
They grouped patients by those with concussion (n = 371), those with head trauma without overt signs of concussion (n = 149), and those with peripheral trauma without head trauma or concussion (n = 192). The study included 175 children. Injury mechanisms included car crashes, falls, bicycle accidents, and sports injuries.
Patients with concussion had significantly higher GFAP concentrations, compared with patients with body trauma and patients with nonconcussive head trauma. UCH-L1 levels did not significantly differ between patients with concussion and head trauma controls, however.
“Based on these results, the potential utility of GFAP to distinguish concussion from body trauma controls over 7 days postinjury was fair to excellent,” with area under the receiver operating characteristics curves (AUCs) of 0.75-0.89, the researchers said. “UCH-L1’s ability was guarded and variable with AUCs from poor to good depending on timing of samples.” UCH-L1 demonstrated AUCs that ranged from 0.54 to 0.78; earlier samples performed better.
GFAP elevations in head trauma controls “may represent milder forms of concussion that do not elicit typical signs or symptoms associated with concussion,” the authors wrote. “These injuries may be irrelevant, or they may represent important trauma that is just below the level of clinical detection and referred to as subconcussive trauma. ... Biomarkers (such as GFAP and UCH-L1) could provide a more objective measure of injury and potentially identify those at risk for neurocognitive problems.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers, and coauthors receive contract research funding from Banyan Biomarkers.
SOURCE: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.
FROM BMJ PAEDIATRICS OPEN
Key clinical point: Levels of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) are lowest in patients with nonconcussive body trauma, higher in patients with nonconcussive head trauma, and highest in patients with concussion.
Major finding: GFAP was fair to excellent at distinguishing concussion from body trauma, with area under the receiver operating characteristics curves of 0.75-0.89.
Study details: A prospective cohort study of 712 trauma patients of all ages at three level I trauma centers in the United States. The study included patients with and without head trauma who had a Glasgow Coma Scale score of 15 and presented within 4 hours of injury.
Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Papa is an unpaid scientific consultant for Banyan Biomarkers, which developed kits to measure the biomarkers. Coauthors receive contract research funding from Banyan Biomarkers.
Source: Papa L et al. BMJ Paediatr Open. 2019 Aug 26. doi: 10.1136/bmjpo-2019-000473.