User login
Mild TBI May Increase Risk of Parkinson’s Disease Among Military Veterans
Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.
“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.
A Longitudinal Cohort Study
Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.
Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were age 18 or older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.
Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.
TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.
Prior TBI Was Associated With Minority Status
A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.
Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.
“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.
Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild
—Erica Tricarico
Suggested Reading
Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].
Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.
“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.
A Longitudinal Cohort Study
Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.
Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were age 18 or older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.
Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.
TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.
Prior TBI Was Associated With Minority Status
A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.
Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.
“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.
Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild
—Erica Tricarico
Suggested Reading
Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].
Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.
“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.
A Longitudinal Cohort Study
Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.
Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were age 18 or older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.
Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.
TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.
Prior TBI Was Associated With Minority Status
A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.
Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.
“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.
Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild
—Erica Tricarico
Suggested Reading
Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].
Michael Alosco, PhD
Vestibular/oculomotor component of concussion warrants more attention
NEW ORLEANS – Vestibular and oculomotor impairment is increasingly recognized as a common, underappreciated, and yet treatable aspect of sports concussions, Gary W. Dorshimer, MD, said at the annual meeting of the American College of Physicians.
A major advance in the diagnosis and treatment of this form of impairment has been achieved by researchers at the University of Pittsburgh Medical Center sports medicine concussion program.
“The Pitt group has come up with a nice exam to assess this part of the concussion injury, which doesn’t affect your memory, it doesn’t affect your cognition, it affects what I’ve found to be the thing that takes the longest to get better: the oculomotor/vestibular mechanism,” explained Dr. Dorshimer, chief of general internal medicine at Penn Medicine, Philadelphia, and team physician for the Philadelphia Flyers professional ice hockey team.
The exam, which the Pitt group has described in full detail (Am J Sports Med. 2014;42(10):2479-86), is known as the Vestibular/Ocular Motor Screening assessment, or VOMS. The tool has filled an unmet need in sports medicine, he said. It takes only a few minutes for a physician to perform. The rating scale assesses visual motion sensitivity, smooth eye pursuits, horizontal and vertical saccades, the vestibular ocular reflex, and convergence. Positive findings warrant specialized referral for targeted rehabilitation using visual-ocular and vestibular therapies.
The symptoms of sports concussion–related oculomotor/vestibular impairment may include nausea, vertigo, dizziness, blurred or double vision, difficulty tracking a moving target, and discomfort in busy environments. These symptoms often translate to difficulty reading and academic problems, which historically often were misinterpreted as cognitive impairments.
It’s estimated that oculomotor/vestibular impairment occurs in roughly 60% of sports concussions. These vestibular and/or vision symptoms are associated with protracted recovery. And preliminary evidence demonstrates that targeted physical therapies are effective in speeding recovery.
“It’s so important to be able to find this [impairment] because it’s something you can do something about. We find that when these things are off and people work on them, they get better. That’s why so many people in the field are now saying that if a patient works hard, does the rehabilitation, the majority of them are going to get better. And they won’t get better unless they press forward,” the internist said.
The VOMS screen is simple to perform. It entails tasks such as convergence testing, in which the physician moves a finger or pen steadily closer to the patient’s face; if the patient reports that the single object has turned into two at a distance of more than 6 cm, that’s a positive result indicative of convergence insufficiency.
In another task, the physician hold his two index fingers apart and has the patients move their eyes from finger to finger while holding their heads still.
“I’m not that interested in whether they’re catching the tips of fingers, I’m interested in if they can go fast, and can they go faster if I challenge them, or do they stop doing it? When people with ocular vestibular dysfunction start doing this task, they’re going to slow down. They can’t keep it up because it’s so unpleasant. It really bothers them a lot,” Dr. Dorshimer observed.
In his experience, another key element in a smooth and successful recovery from sports concussions, in addition to getting skilled help for vestibular/oculomotor impairment, if present, is to encourage a positive attitude.
“If you think you’re going to get CTE [chronic traumatic encephalopathy] when you get older because you got waffled a bit in sport, that’s just such a negative attitude. I mean, you can’t lie to them: We don’t know. But I take care of a ton of retired athletes who don’t have CTE. Maybe they’re going to have some tangles in their brains, but they don’t have it clinically. So you want them to keep a positive attitude,” he emphasized.
“CTE was around when your parents and grandparents were jocks. They went out on the playground and pummeled each other every day after school. There are probably all kinds of factors involved in CTE: the number of concussions, hereditary factors, alcohol, drugs. No one really knows yet,” he said.
Dr. Dorshimer reported having no financial conflicts regarding his presentation on the athlete as patient.
NEW ORLEANS – Vestibular and oculomotor impairment is increasingly recognized as a common, underappreciated, and yet treatable aspect of sports concussions, Gary W. Dorshimer, MD, said at the annual meeting of the American College of Physicians.
A major advance in the diagnosis and treatment of this form of impairment has been achieved by researchers at the University of Pittsburgh Medical Center sports medicine concussion program.
“The Pitt group has come up with a nice exam to assess this part of the concussion injury, which doesn’t affect your memory, it doesn’t affect your cognition, it affects what I’ve found to be the thing that takes the longest to get better: the oculomotor/vestibular mechanism,” explained Dr. Dorshimer, chief of general internal medicine at Penn Medicine, Philadelphia, and team physician for the Philadelphia Flyers professional ice hockey team.
The exam, which the Pitt group has described in full detail (Am J Sports Med. 2014;42(10):2479-86), is known as the Vestibular/Ocular Motor Screening assessment, or VOMS. The tool has filled an unmet need in sports medicine, he said. It takes only a few minutes for a physician to perform. The rating scale assesses visual motion sensitivity, smooth eye pursuits, horizontal and vertical saccades, the vestibular ocular reflex, and convergence. Positive findings warrant specialized referral for targeted rehabilitation using visual-ocular and vestibular therapies.
The symptoms of sports concussion–related oculomotor/vestibular impairment may include nausea, vertigo, dizziness, blurred or double vision, difficulty tracking a moving target, and discomfort in busy environments. These symptoms often translate to difficulty reading and academic problems, which historically often were misinterpreted as cognitive impairments.
It’s estimated that oculomotor/vestibular impairment occurs in roughly 60% of sports concussions. These vestibular and/or vision symptoms are associated with protracted recovery. And preliminary evidence demonstrates that targeted physical therapies are effective in speeding recovery.
“It’s so important to be able to find this [impairment] because it’s something you can do something about. We find that when these things are off and people work on them, they get better. That’s why so many people in the field are now saying that if a patient works hard, does the rehabilitation, the majority of them are going to get better. And they won’t get better unless they press forward,” the internist said.
The VOMS screen is simple to perform. It entails tasks such as convergence testing, in which the physician moves a finger or pen steadily closer to the patient’s face; if the patient reports that the single object has turned into two at a distance of more than 6 cm, that’s a positive result indicative of convergence insufficiency.
In another task, the physician hold his two index fingers apart and has the patients move their eyes from finger to finger while holding their heads still.
“I’m not that interested in whether they’re catching the tips of fingers, I’m interested in if they can go fast, and can they go faster if I challenge them, or do they stop doing it? When people with ocular vestibular dysfunction start doing this task, they’re going to slow down. They can’t keep it up because it’s so unpleasant. It really bothers them a lot,” Dr. Dorshimer observed.
In his experience, another key element in a smooth and successful recovery from sports concussions, in addition to getting skilled help for vestibular/oculomotor impairment, if present, is to encourage a positive attitude.
“If you think you’re going to get CTE [chronic traumatic encephalopathy] when you get older because you got waffled a bit in sport, that’s just such a negative attitude. I mean, you can’t lie to them: We don’t know. But I take care of a ton of retired athletes who don’t have CTE. Maybe they’re going to have some tangles in their brains, but they don’t have it clinically. So you want them to keep a positive attitude,” he emphasized.
“CTE was around when your parents and grandparents were jocks. They went out on the playground and pummeled each other every day after school. There are probably all kinds of factors involved in CTE: the number of concussions, hereditary factors, alcohol, drugs. No one really knows yet,” he said.
Dr. Dorshimer reported having no financial conflicts regarding his presentation on the athlete as patient.
NEW ORLEANS – Vestibular and oculomotor impairment is increasingly recognized as a common, underappreciated, and yet treatable aspect of sports concussions, Gary W. Dorshimer, MD, said at the annual meeting of the American College of Physicians.
A major advance in the diagnosis and treatment of this form of impairment has been achieved by researchers at the University of Pittsburgh Medical Center sports medicine concussion program.
“The Pitt group has come up with a nice exam to assess this part of the concussion injury, which doesn’t affect your memory, it doesn’t affect your cognition, it affects what I’ve found to be the thing that takes the longest to get better: the oculomotor/vestibular mechanism,” explained Dr. Dorshimer, chief of general internal medicine at Penn Medicine, Philadelphia, and team physician for the Philadelphia Flyers professional ice hockey team.
The exam, which the Pitt group has described in full detail (Am J Sports Med. 2014;42(10):2479-86), is known as the Vestibular/Ocular Motor Screening assessment, or VOMS. The tool has filled an unmet need in sports medicine, he said. It takes only a few minutes for a physician to perform. The rating scale assesses visual motion sensitivity, smooth eye pursuits, horizontal and vertical saccades, the vestibular ocular reflex, and convergence. Positive findings warrant specialized referral for targeted rehabilitation using visual-ocular and vestibular therapies.
The symptoms of sports concussion–related oculomotor/vestibular impairment may include nausea, vertigo, dizziness, blurred or double vision, difficulty tracking a moving target, and discomfort in busy environments. These symptoms often translate to difficulty reading and academic problems, which historically often were misinterpreted as cognitive impairments.
It’s estimated that oculomotor/vestibular impairment occurs in roughly 60% of sports concussions. These vestibular and/or vision symptoms are associated with protracted recovery. And preliminary evidence demonstrates that targeted physical therapies are effective in speeding recovery.
“It’s so important to be able to find this [impairment] because it’s something you can do something about. We find that when these things are off and people work on them, they get better. That’s why so many people in the field are now saying that if a patient works hard, does the rehabilitation, the majority of them are going to get better. And they won’t get better unless they press forward,” the internist said.
The VOMS screen is simple to perform. It entails tasks such as convergence testing, in which the physician moves a finger or pen steadily closer to the patient’s face; if the patient reports that the single object has turned into two at a distance of more than 6 cm, that’s a positive result indicative of convergence insufficiency.
In another task, the physician hold his two index fingers apart and has the patients move their eyes from finger to finger while holding their heads still.
“I’m not that interested in whether they’re catching the tips of fingers, I’m interested in if they can go fast, and can they go faster if I challenge them, or do they stop doing it? When people with ocular vestibular dysfunction start doing this task, they’re going to slow down. They can’t keep it up because it’s so unpleasant. It really bothers them a lot,” Dr. Dorshimer observed.
In his experience, another key element in a smooth and successful recovery from sports concussions, in addition to getting skilled help for vestibular/oculomotor impairment, if present, is to encourage a positive attitude.
“If you think you’re going to get CTE [chronic traumatic encephalopathy] when you get older because you got waffled a bit in sport, that’s just such a negative attitude. I mean, you can’t lie to them: We don’t know. But I take care of a ton of retired athletes who don’t have CTE. Maybe they’re going to have some tangles in their brains, but they don’t have it clinically. So you want them to keep a positive attitude,” he emphasized.
“CTE was around when your parents and grandparents were jocks. They went out on the playground and pummeled each other every day after school. There are probably all kinds of factors involved in CTE: the number of concussions, hereditary factors, alcohol, drugs. No one really knows yet,” he said.
Dr. Dorshimer reported having no financial conflicts regarding his presentation on the athlete as patient.
REPORTING FROM ACP INTERNAL MEDICINE
How Does TBI Differ Among Older Patients?
LOS ANGELES—Most older adults recover well from traumatic brain injury (TBI), according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Compared with younger patients, older adults endorse less independence after injury, but are less likely to report TBI-related neurobehavioral symptoms. A greater burden of preinjury disability among the elderly may explain these apparently conflicting results, according to the researchers.
Geriatric TBI is “a silent and growing epidemic,” said Raquel Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco. Older adults have the highest incidence of TBI-related emergency department visits, hospitalizations, and deaths, according to 2013 data from the CDC. Most research has indicated that this population has worse outcomes of TBI than younger populations do. Few studies, however, have examined age-related differences in neurobehavioral outcomes of TBI.
Injury Was More Severe Among Older Patients
To address this gap in the literature, Dr. Gardner and colleagues examined data from the TRACK-TBI pilot study. Eligible patients presented to participating trauma centers within 24 hours of sustaining a TBI that was severe enough to warrant head CT. The TRACK-TBI study excluded participants with a diagnosis of dementia or any pre-existing condition that would impair their ability to complete outcome assessments. Patients’ neurobehavioral outcomes were evaluated prospectively with measures such as the Glasgow Outcome Scale Extended (GOSE), Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF), Brief Symptom Inventory (BSI-18), Rivermead Post-Concussion Questionnaire (RPQ), Posttraumatic Stress Disorder Checklist-Civilian (PCL-C), and the Satisfaction With Life Scale (SWLS).
Dr. Gardner and colleagues categorized 586 patients as young (ie, younger than 40), middle-aged (ie, ages 40 to 59), or older (ie, age 60 or older). They compared baseline features and six-month neurobehavioral outcomes between the three groups using χ2, analysis of variance, and regression modeling.
Patients’ age ranged from 16 to 94. At baseline, the prevalence of female sex and white race increased with increasing age. Older adults were less likely to report a prior history of TBI than the other two age groups. TBI resulted from a fall for most older patients. At presentation, Glasgow Coma Scale scores did not differ significantly between the three patient groups, and older adults were less likely to report having experienced loss of consciousness or posttraumatic amnesia than the other groups.
Injury was more severe among older patients, however, as assessed by the Acute Injury Scale, the Injury Severity Scale, and CT pathology, compared with younger participants. Older patients also were more likely to be admitted to the intensive care unit.
Measures May Not Be Age-Appropriate
At six months, 415 of the participants completed the GOSE. The mortality rate was approximately 18% among older patients, compared with 7% among middle-aged patients and less than 1% among young patients. Among older patients who survived to six months, most achieved a good recovery, which was defined as a GOSE score of 7 to 8. After the researchers adjusted the data for baseline demographic differences, the rate of good recovery was not significantly different between the three age groups.
Older patients reported significantly less anxiety than other patients, as measured by the BSI-18. Older patients tended to report fewer symptoms overall on the BSI-18 and the RPQ, compared with the other groups. In addition, older patients reported fewer symptoms of PTSD and less dissatisfaction with life, compared with the other groups.
CHART-SF scores, however, were worse overall among older patients, said Dr. Gardner. Although they indicated better economic outcomes among older patients, compared with the other age groups, they also indicated less independence among older patients. Cognition and mobility in particular were worse among older patients than among the other groups.
Older patients were more likely to complete the GOSE than younger patients, but less likely to complete other assessments. The differences in response rates could create a misleadingly positive impression of six-month outcomes among older patients, said Dr. Gardner.
One interpretation of the results is that measures that are not age-appropriate are causing older patients to underreport TBI symptoms, she added. Survival bias also may partly explain the positive six-month outcomes. “We need studies that are truly representative of the entire geriatric TBI population and systematically measure, rather than exclude for, this huge heterogeneity in preinjury disability,” said Dr. Gardner. Investigators should take steps “to optimize enrollment, optimize retention, and optimize outcome completion in a frail and burdened population. We need to ultimately develop consensus NINDS geriatric TBI common data elements…. Only then can we unravel predictors of meaningful recovery in this vulnerable population, develop age-appropriate treatment guidelines, and improve outcomes.”
—Erik Greb
Suggested Reading
Yue JK, Winkler EA, Sharma S, et al. Temporal profile of care following mild traumatic brain injury: predictors of hospital admission, follow-up referral and six-month outcome. Brain Inj. 2017;31(13-14):1820-1829.
LOS ANGELES—Most older adults recover well from traumatic brain injury (TBI), according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Compared with younger patients, older adults endorse less independence after injury, but are less likely to report TBI-related neurobehavioral symptoms. A greater burden of preinjury disability among the elderly may explain these apparently conflicting results, according to the researchers.
Geriatric TBI is “a silent and growing epidemic,” said Raquel Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco. Older adults have the highest incidence of TBI-related emergency department visits, hospitalizations, and deaths, according to 2013 data from the CDC. Most research has indicated that this population has worse outcomes of TBI than younger populations do. Few studies, however, have examined age-related differences in neurobehavioral outcomes of TBI.
Injury Was More Severe Among Older Patients
To address this gap in the literature, Dr. Gardner and colleagues examined data from the TRACK-TBI pilot study. Eligible patients presented to participating trauma centers within 24 hours of sustaining a TBI that was severe enough to warrant head CT. The TRACK-TBI study excluded participants with a diagnosis of dementia or any pre-existing condition that would impair their ability to complete outcome assessments. Patients’ neurobehavioral outcomes were evaluated prospectively with measures such as the Glasgow Outcome Scale Extended (GOSE), Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF), Brief Symptom Inventory (BSI-18), Rivermead Post-Concussion Questionnaire (RPQ), Posttraumatic Stress Disorder Checklist-Civilian (PCL-C), and the Satisfaction With Life Scale (SWLS).
Dr. Gardner and colleagues categorized 586 patients as young (ie, younger than 40), middle-aged (ie, ages 40 to 59), or older (ie, age 60 or older). They compared baseline features and six-month neurobehavioral outcomes between the three groups using χ2, analysis of variance, and regression modeling.
Patients’ age ranged from 16 to 94. At baseline, the prevalence of female sex and white race increased with increasing age. Older adults were less likely to report a prior history of TBI than the other two age groups. TBI resulted from a fall for most older patients. At presentation, Glasgow Coma Scale scores did not differ significantly between the three patient groups, and older adults were less likely to report having experienced loss of consciousness or posttraumatic amnesia than the other groups.
Injury was more severe among older patients, however, as assessed by the Acute Injury Scale, the Injury Severity Scale, and CT pathology, compared with younger participants. Older patients also were more likely to be admitted to the intensive care unit.
Measures May Not Be Age-Appropriate
At six months, 415 of the participants completed the GOSE. The mortality rate was approximately 18% among older patients, compared with 7% among middle-aged patients and less than 1% among young patients. Among older patients who survived to six months, most achieved a good recovery, which was defined as a GOSE score of 7 to 8. After the researchers adjusted the data for baseline demographic differences, the rate of good recovery was not significantly different between the three age groups.
Older patients reported significantly less anxiety than other patients, as measured by the BSI-18. Older patients tended to report fewer symptoms overall on the BSI-18 and the RPQ, compared with the other groups. In addition, older patients reported fewer symptoms of PTSD and less dissatisfaction with life, compared with the other groups.
CHART-SF scores, however, were worse overall among older patients, said Dr. Gardner. Although they indicated better economic outcomes among older patients, compared with the other age groups, they also indicated less independence among older patients. Cognition and mobility in particular were worse among older patients than among the other groups.
Older patients were more likely to complete the GOSE than younger patients, but less likely to complete other assessments. The differences in response rates could create a misleadingly positive impression of six-month outcomes among older patients, said Dr. Gardner.
One interpretation of the results is that measures that are not age-appropriate are causing older patients to underreport TBI symptoms, she added. Survival bias also may partly explain the positive six-month outcomes. “We need studies that are truly representative of the entire geriatric TBI population and systematically measure, rather than exclude for, this huge heterogeneity in preinjury disability,” said Dr. Gardner. Investigators should take steps “to optimize enrollment, optimize retention, and optimize outcome completion in a frail and burdened population. We need to ultimately develop consensus NINDS geriatric TBI common data elements…. Only then can we unravel predictors of meaningful recovery in this vulnerable population, develop age-appropriate treatment guidelines, and improve outcomes.”
—Erik Greb
Suggested Reading
Yue JK, Winkler EA, Sharma S, et al. Temporal profile of care following mild traumatic brain injury: predictors of hospital admission, follow-up referral and six-month outcome. Brain Inj. 2017;31(13-14):1820-1829.
LOS ANGELES—Most older adults recover well from traumatic brain injury (TBI), according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Compared with younger patients, older adults endorse less independence after injury, but are less likely to report TBI-related neurobehavioral symptoms. A greater burden of preinjury disability among the elderly may explain these apparently conflicting results, according to the researchers.
Geriatric TBI is “a silent and growing epidemic,” said Raquel Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco. Older adults have the highest incidence of TBI-related emergency department visits, hospitalizations, and deaths, according to 2013 data from the CDC. Most research has indicated that this population has worse outcomes of TBI than younger populations do. Few studies, however, have examined age-related differences in neurobehavioral outcomes of TBI.
Injury Was More Severe Among Older Patients
To address this gap in the literature, Dr. Gardner and colleagues examined data from the TRACK-TBI pilot study. Eligible patients presented to participating trauma centers within 24 hours of sustaining a TBI that was severe enough to warrant head CT. The TRACK-TBI study excluded participants with a diagnosis of dementia or any pre-existing condition that would impair their ability to complete outcome assessments. Patients’ neurobehavioral outcomes were evaluated prospectively with measures such as the Glasgow Outcome Scale Extended (GOSE), Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF), Brief Symptom Inventory (BSI-18), Rivermead Post-Concussion Questionnaire (RPQ), Posttraumatic Stress Disorder Checklist-Civilian (PCL-C), and the Satisfaction With Life Scale (SWLS).
Dr. Gardner and colleagues categorized 586 patients as young (ie, younger than 40), middle-aged (ie, ages 40 to 59), or older (ie, age 60 or older). They compared baseline features and six-month neurobehavioral outcomes between the three groups using χ2, analysis of variance, and regression modeling.
Patients’ age ranged from 16 to 94. At baseline, the prevalence of female sex and white race increased with increasing age. Older adults were less likely to report a prior history of TBI than the other two age groups. TBI resulted from a fall for most older patients. At presentation, Glasgow Coma Scale scores did not differ significantly between the three patient groups, and older adults were less likely to report having experienced loss of consciousness or posttraumatic amnesia than the other groups.
Injury was more severe among older patients, however, as assessed by the Acute Injury Scale, the Injury Severity Scale, and CT pathology, compared with younger participants. Older patients also were more likely to be admitted to the intensive care unit.
Measures May Not Be Age-Appropriate
At six months, 415 of the participants completed the GOSE. The mortality rate was approximately 18% among older patients, compared with 7% among middle-aged patients and less than 1% among young patients. Among older patients who survived to six months, most achieved a good recovery, which was defined as a GOSE score of 7 to 8. After the researchers adjusted the data for baseline demographic differences, the rate of good recovery was not significantly different between the three age groups.
Older patients reported significantly less anxiety than other patients, as measured by the BSI-18. Older patients tended to report fewer symptoms overall on the BSI-18 and the RPQ, compared with the other groups. In addition, older patients reported fewer symptoms of PTSD and less dissatisfaction with life, compared with the other groups.
CHART-SF scores, however, were worse overall among older patients, said Dr. Gardner. Although they indicated better economic outcomes among older patients, compared with the other age groups, they also indicated less independence among older patients. Cognition and mobility in particular were worse among older patients than among the other groups.
Older patients were more likely to complete the GOSE than younger patients, but less likely to complete other assessments. The differences in response rates could create a misleadingly positive impression of six-month outcomes among older patients, said Dr. Gardner.
One interpretation of the results is that measures that are not age-appropriate are causing older patients to underreport TBI symptoms, she added. Survival bias also may partly explain the positive six-month outcomes. “We need studies that are truly representative of the entire geriatric TBI population and systematically measure, rather than exclude for, this huge heterogeneity in preinjury disability,” said Dr. Gardner. Investigators should take steps “to optimize enrollment, optimize retention, and optimize outcome completion in a frail and burdened population. We need to ultimately develop consensus NINDS geriatric TBI common data elements…. Only then can we unravel predictors of meaningful recovery in this vulnerable population, develop age-appropriate treatment guidelines, and improve outcomes.”
—Erik Greb
Suggested Reading
Yue JK, Winkler EA, Sharma S, et al. Temporal profile of care following mild traumatic brain injury: predictors of hospital admission, follow-up referral and six-month outcome. Brain Inj. 2017;31(13-14):1820-1829.
S100B biomarker could reduce CT scans in children with mTBI
according to Charlotte Oris, PharmD, of the University Hospital of Clermont-Ferrand, France, and her associates.
In a meta-analysis of eight prospective cohort studies including a total of 601 children published in Pediatrics, researchers looked at the association between S100B serum levels and CT findings in 373 patients. The median serum concentrations of S100B were 0.47 mcg/L for patients with intracerebral lesions and 0.21 mcg/L for those without lesions (P less than .001).
Additionally, researchers collected data from 358 individuals included in two studies for the origin of mTBI. The median concentrations of S100B were 0.39 mcg/L for road accidents, 0.29 mcg/L for domestic accidents, and 0.18 mcg/L for sport-related accidents. The difference was statistically significant between the road accidents group and the domestic accidents group (P less than .001) and the difference between the road accidents group and the sport-related accidents group (P less than .001). It is noted that S100B specificity could be higher after a sport-related trauma.
“S100B protein serum levels, in combination with the PECARN [Pediatric Emergency Care Applied Research Network] algorithm, could reduce the need for CT scans by one-third. In our additional analysis, based on 373 children, the importance of taking a blood sample 3 hours or less after trauma was underscored,” the researchers said.
“S100B represents a promising biomarker with 100% sensitivity. The limited specificity of S100B could be reevaluated for future research by using a combination of different brain biomarkers,” Dr. Oris and her colleagues concluded.
SOURCE: Oris C et al. Pediatrics. 2018. doi: 10.1542/peds.2018-0037.
according to Charlotte Oris, PharmD, of the University Hospital of Clermont-Ferrand, France, and her associates.
In a meta-analysis of eight prospective cohort studies including a total of 601 children published in Pediatrics, researchers looked at the association between S100B serum levels and CT findings in 373 patients. The median serum concentrations of S100B were 0.47 mcg/L for patients with intracerebral lesions and 0.21 mcg/L for those without lesions (P less than .001).
Additionally, researchers collected data from 358 individuals included in two studies for the origin of mTBI. The median concentrations of S100B were 0.39 mcg/L for road accidents, 0.29 mcg/L for domestic accidents, and 0.18 mcg/L for sport-related accidents. The difference was statistically significant between the road accidents group and the domestic accidents group (P less than .001) and the difference between the road accidents group and the sport-related accidents group (P less than .001). It is noted that S100B specificity could be higher after a sport-related trauma.
“S100B protein serum levels, in combination with the PECARN [Pediatric Emergency Care Applied Research Network] algorithm, could reduce the need for CT scans by one-third. In our additional analysis, based on 373 children, the importance of taking a blood sample 3 hours or less after trauma was underscored,” the researchers said.
“S100B represents a promising biomarker with 100% sensitivity. The limited specificity of S100B could be reevaluated for future research by using a combination of different brain biomarkers,” Dr. Oris and her colleagues concluded.
SOURCE: Oris C et al. Pediatrics. 2018. doi: 10.1542/peds.2018-0037.
according to Charlotte Oris, PharmD, of the University Hospital of Clermont-Ferrand, France, and her associates.
In a meta-analysis of eight prospective cohort studies including a total of 601 children published in Pediatrics, researchers looked at the association between S100B serum levels and CT findings in 373 patients. The median serum concentrations of S100B were 0.47 mcg/L for patients with intracerebral lesions and 0.21 mcg/L for those without lesions (P less than .001).
Additionally, researchers collected data from 358 individuals included in two studies for the origin of mTBI. The median concentrations of S100B were 0.39 mcg/L for road accidents, 0.29 mcg/L for domestic accidents, and 0.18 mcg/L for sport-related accidents. The difference was statistically significant between the road accidents group and the domestic accidents group (P less than .001) and the difference between the road accidents group and the sport-related accidents group (P less than .001). It is noted that S100B specificity could be higher after a sport-related trauma.
“S100B protein serum levels, in combination with the PECARN [Pediatric Emergency Care Applied Research Network] algorithm, could reduce the need for CT scans by one-third. In our additional analysis, based on 373 children, the importance of taking a blood sample 3 hours or less after trauma was underscored,” the researchers said.
“S100B represents a promising biomarker with 100% sensitivity. The limited specificity of S100B could be reevaluated for future research by using a combination of different brain biomarkers,” Dr. Oris and her colleagues concluded.
SOURCE: Oris C et al. Pediatrics. 2018. doi: 10.1542/peds.2018-0037.
Brain Stimulation May Enhance Memory
Electrical stimulation in the lateral temporal cortex enhances verbal memory performance, according to two studies in patients with epilepsy.
“While electrical stimulation of the brain is emerging as potential therapy for a wide range of neurologic and psychiatric diseases, little is known about its effect on memory,” said Gregory Worrell, MD, PhD, Professor of Neurology at the Mayo Clinic in Rochester, Minnesota, and an author of the studies. Electrical stimulation may have the potential to treat memory deficits and cognitive dysfunction in brain disorders such as traumatic brain injury and Alzheimer’s disease, the researchers said. 
The two studies were part of a multicenter project designed to assess the effects of electrical stimulation on memory-related brain function and were supported by the Defense Advanced Research Projects Agency’s Restoring Active Memory program.
Patients Were Tested During Seizure Monitoring
In the April issue of Brain, Michal T. Kucewicz, PhD, a researcher at the Mayo Clinic, and colleagues described a study of patients with epilepsy who were undergoing evaluation for resective surgery. As part of the evaluations, patients had intracranial subdural and depth electrode arrays implanted in cortical and subcortical brain regions.
After implantation, patients completed delayed free-recall memory tasks in which they learned lists of words for subsequent recall. Twelve words appeared one at a time on a laptop screen for 1.6 seconds each. Participants then solved a series of arithmetic problems. Afterward, participants had 30 seconds to verbally recall as many words as possible from the list in any order. Patients completed this procedure 25 times during each testing session. Twenty of the lists in each session were learned with stimulation (ie, with stimulation applied for two words and then turned off for two words throughout the list), and five lists were learned without stimulation. Participants completed at least two control sessions with no stimulation to reduce potential learning effects.
The investigators focused on 22 patients (nine males) who had electrodes implanted in four brain regions known to support declarative memory: the hippocampus (n = 6), the parahippocampal cortex (n = 7), the prefrontal cortex (n = 6), and the temporal cortex (n = 4). One subject received stimulation in two of the brain regions (ie, the temporal cortex and the parahippocampal cortex).
The number of sessions that patients completed was determined by the length of seizure monitoring (range, two days to 14 days) and patients’ willingness to participate in the study. The subjects were blinded to the stimulation site.
Within-Individual and Between-Group Effects
Stimulation in the lateral temporal cortex enhanced memory performance, whereas stimulation in other brain regions did not. “The positive effect of [lateral cortex] stimulation was reported in individual patients tested across multiple days of stimulation sessions, on the level of the group of patients stimulated in the temporal cortex, and between the four groups stimulated in different brain regions,” the researchers said.
Two of the four patients stimulated in the lateral temporal cortex had significantly improved recall with stimulation, and the other two patients showed a positive trend.
In the subject who received stimulation in two brain regions, stimulation in the dominant lateral temporal neocortex increased the number of remembered words above the normal range, whereas stimulation in the parahippocampal region did not.
Among the participants who received temporal cortex stimulation, memory performance within each session on the stimulated word lists was consistently higher than on the control lists without stimulation.
For the stimulated lists, memory enhancement was observed on the level of the entire list, with no difference in recall between stimulated and nonstimulated words. This finding suggests that the positive effect of stimulation lasted beyond the period of electrical current administration, the researchers said.
The study’s limitations include the small number of participants and their variable clinical characteristics (eg, epilepsy pathologies, medications, and baseline cognition). It is unclear whether electrical stimulation modulates memory processing, attention, perception, or other related processes, the researchers noted. It also is not known whether the positive effect generalizes to other verbal and nonverbal memory functions, or whether stimulation in the nondominant hemisphere would have a different effect.
The data “might provide a hint as to why some patients undergoing surgical removal of this region complain about verbal memory deficits,” Dr. Kucewicz and colleagues said.
“The next step for this project is to determine how to best apply electrical current in terms of the exact location within this area of the brain, timing, and parameters of stimulation,” said study author Brent Berry, MD, PhD, a Mayo Clinic researcher in the Department of Physiology and Biomedical Engineering.
A Closed-Loop Approach
In a study published February 6 in Nature Communications, Youssef Ezzyat, PhD, a senior data scientist at the University of Pennsylvania in Philadelphia, and colleagues found that a closed-loop stimulation system may identify periods of poor memory encoding and apply targeted stimulation to the lateral temporal cortex to compensate.
The investigators recruited 25 neurosurgical patients undergoing clinical monitoring for epilepsy to participate in sessions of a delayed free-recall memory task. Subjects completed at least three record-only sessions of free recall with which the researchers trained a system to use intracranial EEG activity during encoding to predict the likelihood of later word recall.
During subsequent sessions, if the system predicted that the probability of recall was less than 0.5, it triggered 500 ms of bipolar stimulation. The researchers found that lateral temporal cortex stimulation increased the relative probability of item recall by 15%.
“By developing patient-specific, personalized, machine-learning models, we could program our stimulator to deliver pulses only when memory was predicted to fail, giving this technology the best chance of restoring memory function,” said Michael Kahana, PhD, Professor of Psychology at the University of Pennsylvania and principal investigator of the Restoring Active Memory program. “This [approach] was important, because we knew from earlier work that stimulating the brain during periods of good function was likely to make memory worse.”
—Jake Remaly
Suggested Reading
Ezzyat Y, Wanda PA, Levy DF, et al. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018;9(1):365.
Hampson RE, Song D, Robinson BS, et al. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall. J Neural Eng. 2018;15(3):036014.
Inman CS, Manns JR, Bijanki KR, et al. Direct electrical stimulation of the amygdala enhances declarative memory in humans. Proc Natl Acad Sci U S A. 2018;115(1):98-103.
Kucewicz MT, Berry BM, Kremen V, et al. Electrical stimulation modulates high γ activity and human memory performance. eNeuro. 2018;5(1).
Kucewicz MT, Berry BM, Miller LR, et al. Evidence for verbal memory enhancement with electrical brain stimulation in the lateral temporal cortex. Brain. 2018;141(4):971-978.
Electrical stimulation in the lateral temporal cortex enhances verbal memory performance, according to two studies in patients with epilepsy.
“While electrical stimulation of the brain is emerging as potential therapy for a wide range of neurologic and psychiatric diseases, little is known about its effect on memory,” said Gregory Worrell, MD, PhD, Professor of Neurology at the Mayo Clinic in Rochester, Minnesota, and an author of the studies. Electrical stimulation may have the potential to treat memory deficits and cognitive dysfunction in brain disorders such as traumatic brain injury and Alzheimer’s disease, the researchers said.
The two studies were part of a multicenter project designed to assess the effects of electrical stimulation on memory-related brain function and were supported by the Defense Advanced Research Projects Agency’s Restoring Active Memory program.
Patients Were Tested During Seizure Monitoring
In the April issue of Brain, Michal T. Kucewicz, PhD, a researcher at the Mayo Clinic, and colleagues described a study of patients with epilepsy who were undergoing evaluation for resective surgery. As part of the evaluations, patients had intracranial subdural and depth electrode arrays implanted in cortical and subcortical brain regions.
After implantation, patients completed delayed free-recall memory tasks in which they learned lists of words for subsequent recall. Twelve words appeared one at a time on a laptop screen for 1.6 seconds each. Participants then solved a series of arithmetic problems. Afterward, participants had 30 seconds to verbally recall as many words as possible from the list in any order. Patients completed this procedure 25 times during each testing session. Twenty of the lists in each session were learned with stimulation (ie, with stimulation applied for two words and then turned off for two words throughout the list), and five lists were learned without stimulation. Participants completed at least two control sessions with no stimulation to reduce potential learning effects.
The investigators focused on 22 patients (nine males) who had electrodes implanted in four brain regions known to support declarative memory: the hippocampus (n = 6), the parahippocampal cortex (n = 7), the prefrontal cortex (n = 6), and the temporal cortex (n = 4). One subject received stimulation in two of the brain regions (ie, the temporal cortex and the parahippocampal cortex).
The number of sessions that patients completed was determined by the length of seizure monitoring (range, two days to 14 days) and patients’ willingness to participate in the study. The subjects were blinded to the stimulation site.
Within-Individual and Between-Group Effects
Stimulation in the lateral temporal cortex enhanced memory performance, whereas stimulation in other brain regions did not. “The positive effect of [lateral cortex] stimulation was reported in individual patients tested across multiple days of stimulation sessions, on the level of the group of patients stimulated in the temporal cortex, and between the four groups stimulated in different brain regions,” the researchers said.
Two of the four patients stimulated in the lateral temporal cortex had significantly improved recall with stimulation, and the other two patients showed a positive trend.
In the subject who received stimulation in two brain regions, stimulation in the dominant lateral temporal neocortex increased the number of remembered words above the normal range, whereas stimulation in the parahippocampal region did not.
Among the participants who received temporal cortex stimulation, memory performance within each session on the stimulated word lists was consistently higher than on the control lists without stimulation.
For the stimulated lists, memory enhancement was observed on the level of the entire list, with no difference in recall between stimulated and nonstimulated words. This finding suggests that the positive effect of stimulation lasted beyond the period of electrical current administration, the researchers said.
The study’s limitations include the small number of participants and their variable clinical characteristics (eg, epilepsy pathologies, medications, and baseline cognition). It is unclear whether electrical stimulation modulates memory processing, attention, perception, or other related processes, the researchers noted. It also is not known whether the positive effect generalizes to other verbal and nonverbal memory functions, or whether stimulation in the nondominant hemisphere would have a different effect.
The data “might provide a hint as to why some patients undergoing surgical removal of this region complain about verbal memory deficits,” Dr. Kucewicz and colleagues said.
“The next step for this project is to determine how to best apply electrical current in terms of the exact location within this area of the brain, timing, and parameters of stimulation,” said study author Brent Berry, MD, PhD, a Mayo Clinic researcher in the Department of Physiology and Biomedical Engineering.
A Closed-Loop Approach
In a study published February 6 in Nature Communications, Youssef Ezzyat, PhD, a senior data scientist at the University of Pennsylvania in Philadelphia, and colleagues found that a closed-loop stimulation system may identify periods of poor memory encoding and apply targeted stimulation to the lateral temporal cortex to compensate.
The investigators recruited 25 neurosurgical patients undergoing clinical monitoring for epilepsy to participate in sessions of a delayed free-recall memory task. Subjects completed at least three record-only sessions of free recall with which the researchers trained a system to use intracranial EEG activity during encoding to predict the likelihood of later word recall.
During subsequent sessions, if the system predicted that the probability of recall was less than 0.5, it triggered 500 ms of bipolar stimulation. The researchers found that lateral temporal cortex stimulation increased the relative probability of item recall by 15%.
“By developing patient-specific, personalized, machine-learning models, we could program our stimulator to deliver pulses only when memory was predicted to fail, giving this technology the best chance of restoring memory function,” said Michael Kahana, PhD, Professor of Psychology at the University of Pennsylvania and principal investigator of the Restoring Active Memory program. “This [approach] was important, because we knew from earlier work that stimulating the brain during periods of good function was likely to make memory worse.”
—Jake Remaly
Suggested Reading
Ezzyat Y, Wanda PA, Levy DF, et al. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018;9(1):365.
Hampson RE, Song D, Robinson BS, et al. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall. J Neural Eng. 2018;15(3):036014.
Inman CS, Manns JR, Bijanki KR, et al. Direct electrical stimulation of the amygdala enhances declarative memory in humans. Proc Natl Acad Sci U S A. 2018;115(1):98-103.
Kucewicz MT, Berry BM, Kremen V, et al. Electrical stimulation modulates high γ activity and human memory performance. eNeuro. 2018;5(1).
Kucewicz MT, Berry BM, Miller LR, et al. Evidence for verbal memory enhancement with electrical brain stimulation in the lateral temporal cortex. Brain. 2018;141(4):971-978.
Electrical stimulation in the lateral temporal cortex enhances verbal memory performance, according to two studies in patients with epilepsy.
“While electrical stimulation of the brain is emerging as potential therapy for a wide range of neurologic and psychiatric diseases, little is known about its effect on memory,” said Gregory Worrell, MD, PhD, Professor of Neurology at the Mayo Clinic in Rochester, Minnesota, and an author of the studies. Electrical stimulation may have the potential to treat memory deficits and cognitive dysfunction in brain disorders such as traumatic brain injury and Alzheimer’s disease, the researchers said.
The two studies were part of a multicenter project designed to assess the effects of electrical stimulation on memory-related brain function and were supported by the Defense Advanced Research Projects Agency’s Restoring Active Memory program.
Patients Were Tested During Seizure Monitoring
In the April issue of Brain, Michal T. Kucewicz, PhD, a researcher at the Mayo Clinic, and colleagues described a study of patients with epilepsy who were undergoing evaluation for resective surgery. As part of the evaluations, patients had intracranial subdural and depth electrode arrays implanted in cortical and subcortical brain regions.
After implantation, patients completed delayed free-recall memory tasks in which they learned lists of words for subsequent recall. Twelve words appeared one at a time on a laptop screen for 1.6 seconds each. Participants then solved a series of arithmetic problems. Afterward, participants had 30 seconds to verbally recall as many words as possible from the list in any order. Patients completed this procedure 25 times during each testing session. Twenty of the lists in each session were learned with stimulation (ie, with stimulation applied for two words and then turned off for two words throughout the list), and five lists were learned without stimulation. Participants completed at least two control sessions with no stimulation to reduce potential learning effects.
The investigators focused on 22 patients (nine males) who had electrodes implanted in four brain regions known to support declarative memory: the hippocampus (n = 6), the parahippocampal cortex (n = 7), the prefrontal cortex (n = 6), and the temporal cortex (n = 4). One subject received stimulation in two of the brain regions (ie, the temporal cortex and the parahippocampal cortex).
The number of sessions that patients completed was determined by the length of seizure monitoring (range, two days to 14 days) and patients’ willingness to participate in the study. The subjects were blinded to the stimulation site.
Within-Individual and Between-Group Effects
Stimulation in the lateral temporal cortex enhanced memory performance, whereas stimulation in other brain regions did not. “The positive effect of [lateral cortex] stimulation was reported in individual patients tested across multiple days of stimulation sessions, on the level of the group of patients stimulated in the temporal cortex, and between the four groups stimulated in different brain regions,” the researchers said.
Two of the four patients stimulated in the lateral temporal cortex had significantly improved recall with stimulation, and the other two patients showed a positive trend.
In the subject who received stimulation in two brain regions, stimulation in the dominant lateral temporal neocortex increased the number of remembered words above the normal range, whereas stimulation in the parahippocampal region did not.
Among the participants who received temporal cortex stimulation, memory performance within each session on the stimulated word lists was consistently higher than on the control lists without stimulation.
For the stimulated lists, memory enhancement was observed on the level of the entire list, with no difference in recall between stimulated and nonstimulated words. This finding suggests that the positive effect of stimulation lasted beyond the period of electrical current administration, the researchers said.
The study’s limitations include the small number of participants and their variable clinical characteristics (eg, epilepsy pathologies, medications, and baseline cognition). It is unclear whether electrical stimulation modulates memory processing, attention, perception, or other related processes, the researchers noted. It also is not known whether the positive effect generalizes to other verbal and nonverbal memory functions, or whether stimulation in the nondominant hemisphere would have a different effect.
The data “might provide a hint as to why some patients undergoing surgical removal of this region complain about verbal memory deficits,” Dr. Kucewicz and colleagues said.
“The next step for this project is to determine how to best apply electrical current in terms of the exact location within this area of the brain, timing, and parameters of stimulation,” said study author Brent Berry, MD, PhD, a Mayo Clinic researcher in the Department of Physiology and Biomedical Engineering.
A Closed-Loop Approach
In a study published February 6 in Nature Communications, Youssef Ezzyat, PhD, a senior data scientist at the University of Pennsylvania in Philadelphia, and colleagues found that a closed-loop stimulation system may identify periods of poor memory encoding and apply targeted stimulation to the lateral temporal cortex to compensate.
The investigators recruited 25 neurosurgical patients undergoing clinical monitoring for epilepsy to participate in sessions of a delayed free-recall memory task. Subjects completed at least three record-only sessions of free recall with which the researchers trained a system to use intracranial EEG activity during encoding to predict the likelihood of later word recall.
During subsequent sessions, if the system predicted that the probability of recall was less than 0.5, it triggered 500 ms of bipolar stimulation. The researchers found that lateral temporal cortex stimulation increased the relative probability of item recall by 15%.
“By developing patient-specific, personalized, machine-learning models, we could program our stimulator to deliver pulses only when memory was predicted to fail, giving this technology the best chance of restoring memory function,” said Michael Kahana, PhD, Professor of Psychology at the University of Pennsylvania and principal investigator of the Restoring Active Memory program. “This [approach] was important, because we knew from earlier work that stimulating the brain during periods of good function was likely to make memory worse.”
—Jake Remaly
Suggested Reading
Ezzyat Y, Wanda PA, Levy DF, et al. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018;9(1):365.
Hampson RE, Song D, Robinson BS, et al. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall. J Neural Eng. 2018;15(3):036014.
Inman CS, Manns JR, Bijanki KR, et al. Direct electrical stimulation of the amygdala enhances declarative memory in humans. Proc Natl Acad Sci U S A. 2018;115(1):98-103.
Kucewicz MT, Berry BM, Kremen V, et al. Electrical stimulation modulates high γ activity and human memory performance. eNeuro. 2018;5(1).
Kucewicz MT, Berry BM, Miller LR, et al. Evidence for verbal memory enhancement with electrical brain stimulation in the lateral temporal cortex. Brain. 2018;141(4):971-978.
Hyponatremia After Traumatic Brain Injury
Hyponatremia is a dangerous complication of major head trauma, and timely diagnosis and treatment can be fraught with “confounding factors” and complexity, say clinicians from the University of Newcastle and John Hunter Hospital in Australia. They reported a case of hyponatremia that required some clinical tightrope walking.
The patient, a 20-year-old university student, had fractured his skull in a skateboard fall while intoxicated. He was started on dexamethasone to reduce the risk of worsening cerebral edema. On day 3, he developed hypo-osmolar hyponatremia, which was worse on day 4, despite treatment, including IV fluid therapy, fluid restriction, and oral salt tablets. Although cognitively the patient was deteriorating, he seemed clinically euvolemic. However, the patient was in negative fluid balance, suggesting renal salt wasting (RSW). After a trial of isotonic normal saline, the patient’s serum sodium level fell further. The patient was then treated for suspected syndrome of inappropriate antidiuretic hormone (SIADH) with a hypertonic saline infusion. The rise in sodium was carefully controlled to avoid rapid overcorrection, which can lead to irreversible neurologic symptoms. Finally, the patient’s sodium level and neurologic status improved.
The clinicians say the case demonstrates the complexity of differentiating between the causes of hyponatremia after head injury. Volume status may be an indicator, they say, but current clinical and laboratory markers of volume status are often limited in accuracy. The hallmark of RSW is volume depletion, whereas diagnosis of SIADH depends on a coexisting euvolemic state (as with the patient).
As many as 10% of victims of traumatic brain injury develop hyponatremia, and it is associated with a worse prognosis, even in mild cases, the clinicians note. Making the right diagnosis is critical—the treatment chosen can easily compromise the outcome. Patients with neurosurgical conditions are often treated with considerable volumes of saline-containing fluid, with consequent dynamic changes in blood and extracellular volumes. Moreover, the patients have elevated levels of adrenergic hormones with their own confounding effects.
In the long term, the patient experienced significant neurologic sequelae, including prolonged posttraumatic amnesia. After extensive rehabilitation he was able to return to the university.
Hyponatremia is a dangerous complication of major head trauma, and timely diagnosis and treatment can be fraught with “confounding factors” and complexity, say clinicians from the University of Newcastle and John Hunter Hospital in Australia. They reported a case of hyponatremia that required some clinical tightrope walking.
The patient, a 20-year-old university student, had fractured his skull in a skateboard fall while intoxicated. He was started on dexamethasone to reduce the risk of worsening cerebral edema. On day 3, he developed hypo-osmolar hyponatremia, which was worse on day 4, despite treatment, including IV fluid therapy, fluid restriction, and oral salt tablets. Although cognitively the patient was deteriorating, he seemed clinically euvolemic. However, the patient was in negative fluid balance, suggesting renal salt wasting (RSW). After a trial of isotonic normal saline, the patient’s serum sodium level fell further. The patient was then treated for suspected syndrome of inappropriate antidiuretic hormone (SIADH) with a hypertonic saline infusion. The rise in sodium was carefully controlled to avoid rapid overcorrection, which can lead to irreversible neurologic symptoms. Finally, the patient’s sodium level and neurologic status improved.
The clinicians say the case demonstrates the complexity of differentiating between the causes of hyponatremia after head injury. Volume status may be an indicator, they say, but current clinical and laboratory markers of volume status are often limited in accuracy. The hallmark of RSW is volume depletion, whereas diagnosis of SIADH depends on a coexisting euvolemic state (as with the patient).
As many as 10% of victims of traumatic brain injury develop hyponatremia, and it is associated with a worse prognosis, even in mild cases, the clinicians note. Making the right diagnosis is critical—the treatment chosen can easily compromise the outcome. Patients with neurosurgical conditions are often treated with considerable volumes of saline-containing fluid, with consequent dynamic changes in blood and extracellular volumes. Moreover, the patients have elevated levels of adrenergic hormones with their own confounding effects.
In the long term, the patient experienced significant neurologic sequelae, including prolonged posttraumatic amnesia. After extensive rehabilitation he was able to return to the university.
Hyponatremia is a dangerous complication of major head trauma, and timely diagnosis and treatment can be fraught with “confounding factors” and complexity, say clinicians from the University of Newcastle and John Hunter Hospital in Australia. They reported a case of hyponatremia that required some clinical tightrope walking.
The patient, a 20-year-old university student, had fractured his skull in a skateboard fall while intoxicated. He was started on dexamethasone to reduce the risk of worsening cerebral edema. On day 3, he developed hypo-osmolar hyponatremia, which was worse on day 4, despite treatment, including IV fluid therapy, fluid restriction, and oral salt tablets. Although cognitively the patient was deteriorating, he seemed clinically euvolemic. However, the patient was in negative fluid balance, suggesting renal salt wasting (RSW). After a trial of isotonic normal saline, the patient’s serum sodium level fell further. The patient was then treated for suspected syndrome of inappropriate antidiuretic hormone (SIADH) with a hypertonic saline infusion. The rise in sodium was carefully controlled to avoid rapid overcorrection, which can lead to irreversible neurologic symptoms. Finally, the patient’s sodium level and neurologic status improved.
The clinicians say the case demonstrates the complexity of differentiating between the causes of hyponatremia after head injury. Volume status may be an indicator, they say, but current clinical and laboratory markers of volume status are often limited in accuracy. The hallmark of RSW is volume depletion, whereas diagnosis of SIADH depends on a coexisting euvolemic state (as with the patient).
As many as 10% of victims of traumatic brain injury develop hyponatremia, and it is associated with a worse prognosis, even in mild cases, the clinicians note. Making the right diagnosis is critical—the treatment chosen can easily compromise the outcome. Patients with neurosurgical conditions are often treated with considerable volumes of saline-containing fluid, with consequent dynamic changes in blood and extracellular volumes. Moreover, the patients have elevated levels of adrenergic hormones with their own confounding effects.
In the long term, the patient experienced significant neurologic sequelae, including prolonged posttraumatic amnesia. After extensive rehabilitation he was able to return to the university.
Filling a Gender Gap in Research
Women, the VA wants your brains. It sounds a little disconcerting at first, but the National Center for PTSD and the nonprofit PINK Concussions are encouraging women to donate their brains for research.
In the past, says Dr. Carolyn Clancy, executive in charge of Veterans Health Administration, “the focus on TBI and PTSD brain research has primarily been based on male brains, without any active recruitment for women.” There has been almost no postmortem brain tissue available for study of injury in women. The VA also notes a lack of research on chronic traumatic encephalopathy in women. Only 2 peer-reviewed journal articles, both published in the early 1990s, have focused on women.
Women who are interested can take the “PINK Brain Pledge,” a nonbinding promise to leave their brains to science. They do not have to have a history of TBI or PTSD; brains also are needed for controls.
Women, the VA wants your brains. It sounds a little disconcerting at first, but the National Center for PTSD and the nonprofit PINK Concussions are encouraging women to donate their brains for research.
In the past, says Dr. Carolyn Clancy, executive in charge of Veterans Health Administration, “the focus on TBI and PTSD brain research has primarily been based on male brains, without any active recruitment for women.” There has been almost no postmortem brain tissue available for study of injury in women. The VA also notes a lack of research on chronic traumatic encephalopathy in women. Only 2 peer-reviewed journal articles, both published in the early 1990s, have focused on women.
Women who are interested can take the “PINK Brain Pledge,” a nonbinding promise to leave their brains to science. They do not have to have a history of TBI or PTSD; brains also are needed for controls.
Women, the VA wants your brains. It sounds a little disconcerting at first, but the National Center for PTSD and the nonprofit PINK Concussions are encouraging women to donate their brains for research.
In the past, says Dr. Carolyn Clancy, executive in charge of Veterans Health Administration, “the focus on TBI and PTSD brain research has primarily been based on male brains, without any active recruitment for women.” There has been almost no postmortem brain tissue available for study of injury in women. The VA also notes a lack of research on chronic traumatic encephalopathy in women. Only 2 peer-reviewed journal articles, both published in the early 1990s, have focused on women.
Women who are interested can take the “PINK Brain Pledge,” a nonbinding promise to leave their brains to science. They do not have to have a history of TBI or PTSD; brains also are needed for controls.
Children, adolescents with TBI at risk of secondary ADHD
FROM JAMA PEDIATRICS
Children and adolescents with traumatic brain injury (TBI) might be at increased risk of developing attention-deficit/hyperactivity disorder (ADHD) years after the injury, a prospective cohort study published March 19 shows.
Severe TBI was associated with significantly increased risk of new onset ADHD versus controls in the study, which was based on parent-completed assessments done as late as 6.8 years after the initial injury, according to results presented in JAMA Pediatrics.
Although children with severe TBI were at highest risk, those with less severe TBI had about twice the risk of developing ADHD, compared with control subjects who had no brain injury, the study results suggest.
Taken together, the findings suggest a need for long-term monitoring for attention problems, wrote investigator Megan E. Narad, PhD, of Cincinnati Children’s Hospital Medical Center, and her co-authors.
“Physicians and other clinicians should continue to be vigilant in monitoring attention problems in patients with a history of brain injury, even if it has been a number of years since the injury, the injury was moderate in nature, or the patient experienced a predominantly positive recovery,” Dr. Narad and her colleagues wrote.
The results were based on long-term analysis of 187 children who were hospitalized for TBI or orthopedic injury between the ages of 3 and 7 years. That group included 81 children with TBI and 106 with orthopedic injury.
Parents completed assessments soon after the injury, then again at 6 months, 12 months, 18 months, 3.4 years, and 6.8 years afterward, according to the study.
Over the full follow-up period, 48 children (25.7%) met the investigators’ definition of “secondary ADHD,” or onset of ADHD symptoms after an injury. They found that compared with orthopedic injury, the severe TBI was associated with new ADHD (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26), the investigators reported.
In patients with mild or moderate TBI, associations with new onset ADHD did not meet the statistical significance threshol. However, compared with the orthopedic injury group, the risk for ADHD in TBI severity subgroups were up to 4 times higher.
This is not the first study showing an elevated risk of ADHD in TBI patients, but .
“Although most children with severe TBI who developed secondary ADHD did so within the first 18 months after injury, a portion of those with complicated mild and moderate TBI demonstrated new onset of secondary ADHD at the final two assessments, highlighting the importance of continued monitoring even years after TBI,” Dr. Narad and her colleagues wrote.
The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services.
Dr. Narad reported no relevant disclosures. Other study authors reported disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
SOURCE: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi: 10.1001/jamapediatrics.2017.5746.
FROM JAMA PEDIATRICS
Children and adolescents with traumatic brain injury (TBI) might be at increased risk of developing attention-deficit/hyperactivity disorder (ADHD) years after the injury, a prospective cohort study published March 19 shows.
Severe TBI was associated with significantly increased risk of new onset ADHD versus controls in the study, which was based on parent-completed assessments done as late as 6.8 years after the initial injury, according to results presented in JAMA Pediatrics.
Although children with severe TBI were at highest risk, those with less severe TBI had about twice the risk of developing ADHD, compared with control subjects who had no brain injury, the study results suggest.
Taken together, the findings suggest a need for long-term monitoring for attention problems, wrote investigator Megan E. Narad, PhD, of Cincinnati Children’s Hospital Medical Center, and her co-authors.
“Physicians and other clinicians should continue to be vigilant in monitoring attention problems in patients with a history of brain injury, even if it has been a number of years since the injury, the injury was moderate in nature, or the patient experienced a predominantly positive recovery,” Dr. Narad and her colleagues wrote.
The results were based on long-term analysis of 187 children who were hospitalized for TBI or orthopedic injury between the ages of 3 and 7 years. That group included 81 children with TBI and 106 with orthopedic injury.
Parents completed assessments soon after the injury, then again at 6 months, 12 months, 18 months, 3.4 years, and 6.8 years afterward, according to the study.
Over the full follow-up period, 48 children (25.7%) met the investigators’ definition of “secondary ADHD,” or onset of ADHD symptoms after an injury. They found that compared with orthopedic injury, the severe TBI was associated with new ADHD (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26), the investigators reported.
In patients with mild or moderate TBI, associations with new onset ADHD did not meet the statistical significance threshol. However, compared with the orthopedic injury group, the risk for ADHD in TBI severity subgroups were up to 4 times higher.
This is not the first study showing an elevated risk of ADHD in TBI patients, but .
“Although most children with severe TBI who developed secondary ADHD did so within the first 18 months after injury, a portion of those with complicated mild and moderate TBI demonstrated new onset of secondary ADHD at the final two assessments, highlighting the importance of continued monitoring even years after TBI,” Dr. Narad and her colleagues wrote.
The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services.
Dr. Narad reported no relevant disclosures. Other study authors reported disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
SOURCE: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi: 10.1001/jamapediatrics.2017.5746.
FROM JAMA PEDIATRICS
Children and adolescents with traumatic brain injury (TBI) might be at increased risk of developing attention-deficit/hyperactivity disorder (ADHD) years after the injury, a prospective cohort study published March 19 shows.
Severe TBI was associated with significantly increased risk of new onset ADHD versus controls in the study, which was based on parent-completed assessments done as late as 6.8 years after the initial injury, according to results presented in JAMA Pediatrics.
Although children with severe TBI were at highest risk, those with less severe TBI had about twice the risk of developing ADHD, compared with control subjects who had no brain injury, the study results suggest.
Taken together, the findings suggest a need for long-term monitoring for attention problems, wrote investigator Megan E. Narad, PhD, of Cincinnati Children’s Hospital Medical Center, and her co-authors.
“Physicians and other clinicians should continue to be vigilant in monitoring attention problems in patients with a history of brain injury, even if it has been a number of years since the injury, the injury was moderate in nature, or the patient experienced a predominantly positive recovery,” Dr. Narad and her colleagues wrote.
The results were based on long-term analysis of 187 children who were hospitalized for TBI or orthopedic injury between the ages of 3 and 7 years. That group included 81 children with TBI and 106 with orthopedic injury.
Parents completed assessments soon after the injury, then again at 6 months, 12 months, 18 months, 3.4 years, and 6.8 years afterward, according to the study.
Over the full follow-up period, 48 children (25.7%) met the investigators’ definition of “secondary ADHD,” or onset of ADHD symptoms after an injury. They found that compared with orthopedic injury, the severe TBI was associated with new ADHD (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26), the investigators reported.
In patients with mild or moderate TBI, associations with new onset ADHD did not meet the statistical significance threshol. However, compared with the orthopedic injury group, the risk for ADHD in TBI severity subgroups were up to 4 times higher.
This is not the first study showing an elevated risk of ADHD in TBI patients, but .
“Although most children with severe TBI who developed secondary ADHD did so within the first 18 months after injury, a portion of those with complicated mild and moderate TBI demonstrated new onset of secondary ADHD at the final two assessments, highlighting the importance of continued monitoring even years after TBI,” Dr. Narad and her colleagues wrote.
The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services.
Dr. Narad reported no relevant disclosures. Other study authors reported disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
SOURCE: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi: 10.1001/jamapediatrics.2017.5746.
Key clinical point: Children and adolescents with traumatic brain injury (TBI) should continue to be monitored for possible attention problems many years after the injury.
Major finding: In assessments taken up to 6.8 years after injury, severe TBI was associated with secondary ADHD, compared with a control group (hazard ratio, 3.62; 95% confidence interval, 1.59-8.26).
Study details: Analysis of a prospective concurrent cohort study including 187 children aged 3 to 7 years who were hospitalized for TBI or orthopedic injury.
Disclosures: The study was funded by several sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the state of Ohio’s Emergency Medical Services. The authors reported conflict of interest disclosures related to Akili Interactive Labs, Multi-Health Systems, Optimal Medicine, and IXICO.
Source: Narad ME et al. JAMA Pediatr. 2018 Mar 19. doi:10.1001/jamapediatrics.2017.5746.
Stroke Patients May Have a Wider Window of Treatment Opportunity
Thrombectomy is currently approved for use up to 6 hours after symptom onset; the researchers from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial discovered that even 16 hours after symptom onset, the procedure could improve outcomes compared with those of standard medical therapy.
Using automated software to analyze perfusion magnetic resonance imaging or computer tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.
In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy also was associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.
The DEFUSE 3 trial is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.
“These striking results will have an immediate impact and save people from lifelong disability or death,” said Walter Korshetz, MD, director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that 1 of 3 stroke patients with at-risk brain tissue improves, and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”
Thrombectomy is currently approved for use up to 6 hours after symptom onset; the researchers from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial discovered that even 16 hours after symptom onset, the procedure could improve outcomes compared with those of standard medical therapy.
Using automated software to analyze perfusion magnetic resonance imaging or computer tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.
In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy also was associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.
The DEFUSE 3 trial is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.
“These striking results will have an immediate impact and save people from lifelong disability or death,” said Walter Korshetz, MD, director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that 1 of 3 stroke patients with at-risk brain tissue improves, and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”
Thrombectomy is currently approved for use up to 6 hours after symptom onset; the researchers from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial discovered that even 16 hours after symptom onset, the procedure could improve outcomes compared with those of standard medical therapy.
Using automated software to analyze perfusion magnetic resonance imaging or computer tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.
In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy also was associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.
The DEFUSE 3 trial is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.
“These striking results will have an immediate impact and save people from lifelong disability or death,” said Walter Korshetz, MD, director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that 1 of 3 stroke patients with at-risk brain tissue improves, and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”