Traumatic Brain Injury

DTI Reveals Changes in Brain Connections in Early Alzheimer’s Disease
Changes in brain connections visible on MRI could represent an imaging biomarker of Alzheimer’s disease, according to a study presented at the meeting.

As many as five million Americans have Alzheimer’s disease, and this number is expected to increase to 14 million by 2050, according to the Centers for Disease Control and Prevention. Preventive treatments may be most effective before Alzheimer’s disease is diagnosed, such as when a person is experiencing mild cognitive impairment.

Previous efforts at early detection have focused on beta amyloid. For the current study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between various areas of the brain.

“The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said Jeffrey W. Prescott, MD, PhD, a radiology resident at Duke University Medical Center in Durham, North Carolina, and a coauthor of the study.

Dr. Prescott and colleagues analyzed data for 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative 2. The patients had undergone diffusion tensor imaging (DTI), which assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “Water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” said Dr. Prescott.

The researchers compared changes in the structural connectome with results from florbetapir PET imaging, a technique that measures the amount of beta amyloid plaque in the brain. The results showed a strong association between florbetapir uptake and decreases in the strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the Alzheimer’s brain—structural tissue changes and pathologic amyloid plaque deposition—and suggests a promising role for DTI as a possible diagnostic adjunct,” said Dr. Prescott.

Based on these findings, DTI may have a role in assessing brain damage in early Alzheimer’s disease and in monitoring the effect of new therapies.

“Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, Professor of Radiology at Duke University and senior author of the research. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain’s white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue studying this cohort of patients over time to gain a better understanding of how the disease evolves in individual patients. They also intend to incorporate functional imaging into their research to learn about how the relationship between function and structure changes with increasing amyloid burden.

Asymptomatic Atherosclerosis May Be Associated With Cognitive Impairment
A buildup of plaque in the body’s major arteries is associated with mild cognitive impairment, according to a study of approximately 2,000 adults conducted at the University of Texas (UT) Southwestern Medical Center.

“It is well established that plaque buildup in the arteries is a predictor of heart disease, but the relationship between atherosclerosis and brain health is less clear,” said Christopher D. Maroules, MD, a radiology resident at UT Southwestern Medical Center in Dallas. “Our findings suggest that atherosclerosis not only affects the heart, but also brain health.”

Researchers analyzed the test results of 1,903 participants (mean age, 44) in the Dallas Heart Study, a multiethnic population-based study of adults from Dallas County, Texas. The participants included men and women who had no symptoms of cardiovascular disease.

Study participants completed the Montreal Cognitive Assessment (MoCA), a 30-point standardized test for detecting mild cognitive impairment, and underwent MRI of the brain to measure white matter hyperintensity volume. Bright white spots known as high signal intensity areas on a brain MRI indicate abnormal changes within the white matter.

“Increased white matter hyperintensity volume is part of the normal aging process,” explained Dr. Maroules. “But excessive white matter hyperintensity volume is a marker for cognitive impairment.”

Study participants also underwent imaging exams to measure the buildup of plaque in the arteries in three distinct vascular areas of the body. They underwent MRI to measure wall thickness in the carotid arteries and in the abdominal aorta, and received CT to measure coronary artery calcium.

Using the results, researchers performed a statistical regression to understand the relationship between the incidence of atherosclerosis and mild cognitive impairment. After adjusting for traditional risk factors for atherosclerosis, including age, ethnicity, male sex, diabetes, hypertension, smoking, and BMI, the investigators found independent relationships between atherosclerosis in all three vascular areas of the body and cognitive health, as measured by MoCA scores, and white matter hyperintensity volume on MRI.

Individuals in the highest quartile of internal carotid wall thickness were 21% more likely to have cognitive impairment, as indicated by a low MoCA score. An increasing coronary artery calcium score was predictive of large white matter intensity volume on MRI.

“These results underscore the importance of identifying atherosclerosis in its early stages, not just to help preserve heart function, but also to preserve cognition and brain health,” said Dr. Maroules. The MRI and CT imaging techniques provide valuable prognostic information about an individual’s downstream health risks, he added.

“Plaque buildup in blood vessels throughout the body offers us a window into brain health. Imaging with CT and MRI has an important role in identifying patients who are at a higher risk for cognitive impairment.”

A Season of High School Football Without Concussion May Cause Brain Changes
Some high school football players exhibit measurable brain changes after a single season of play, even in the absence of concussion, according to a study presented at the meeting.

“This study adds to the growing body of evidence that a season of play in a contact sport can affect the brain in the absence of clinical findings,” said Christopher T. Whitlow, MD, PhD, MHA, Associate Professor of Radiology at Wake Forest School of Medicine and radiologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

In recent years, various reports have suggested the potential effects that participation in youth sports may have on the developing brain. Most of these studies have looked at brain changes as a result of concussion, however. Dr. Whitlow and colleagues set out to determine whether head impacts withstood in the course of a season of high school football produce white matter changes in the brain in the absence of clinically diagnosed concussion.

The researchers studied 24 high school football players between the ages of 16 and 18. For all games and practices, players were monitored with Head Impact Telemetry System (HITs) helmet-mounted accelerometers, which are used in youth and collegiate football to assess the frequency and severity of helmet impacts.

Risk-weighted cumulative exposure was computed from the HITs data and represented the risk of concussion over the course of the season. These data, along with the total number of impacts, were used to categorize the players as heavy hitters or light hitters. The researchers identified nine of the 24 participants as heavy hitters and 15 as light hitters. None of the players had concussion during the season.

All players underwent pre- and post-season evaluation with diffusion tensor imaging (DTI) of the brain. Diffusion tensor imaging measures fractional anisotropy, which indicates the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform, and fractional anisotropy is high. When water movement is more random, fractional anisotropy values decrease, thus suggesting microstructural abnormalities.

The results showed that both groups demonstrated global increases of fractional anisotropy over time, likely reflecting the effects of brain development. However, the heavy-hitter group showed statistically significant areas of decreased fractional anisotropy post-season in specific areas of the brain, including the splenium of the corpus callosum and deep white matter tracts.

“Our study found that players experiencing greater levels of head impacts have more fractional anisotropy loss, compared with players with lower impact exposure,” said Dr. Whitlow. “Similar brain MRI changes have been previously associated with mild traumatic brain injury. However, it is unclear whether or not these effects will be associated with any negative long-term consequences.” These findings are preliminary, and more study needs to be performed, concluded Dr. Whitlow.

Mild Coronary Artery Disease Increases Risk of Cardiovascular Events
Patients with diabetes and mild coronary artery disease have the same relative risk for a heart attack or other major adverse heart event as patients with diabetes and serious single-vessel obstructive disease, according to a long-term study.

Researchers at the University of British Columbia and St. Paul’s Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, which was developed to examine the prognostic value of cardiac computed tomography angiography (CCTA) for predicting adverse cardiac events related to coronary artery disease. The registry, which has CCTA data for 40,000 patients from 17 centers around the world, now has five-year follow-up data for 14,000 patients.

“The CONFIRM Registry is the largest long-term data set available and allowed us to evaluate the long-term prognostic value of CCTA in diabetic patients,” said Jonathan Leipsic, MD, vice chairman of the Department of Radiology at the University of British Columbia and study coauthor.

The researchers analyzed data for 1,823 patients with diabetes who underwent CCTA to detect and determine the extent of coronary artery disease. Men and women (median age, 61.7) in the study were categorized as having no coronary artery disease, mild disease (ie, coronary artery narrowed by less than 50%), or obstructive disease (ie, obstruction of more than 50% of the artery). Over a 5.2-year follow-up period, 246 deaths occurred, representing 13.5% of the total study group.

Major adverse cardiovascular event (MACE) data were available for 973 patients. During the follow-up period, 295 (30.3%) of the patients had a MACE, such as heart attack or a coronary revascularization.

The researchers found that both obstructive and mild, or nonobstructive, coronary artery disease, as determined by CCTA, were associated with patient deaths and MACE. Most importantly, the researchers found that the relative risk for death or MACE for a patient with mild coronary artery disease was comparable to that of patients with single vessel obstructive disease.

“Until now, two-year follow-up studies suggested that a diabetic patient with mild or nonobstructive coronary artery disease had a lower risk of major adverse cardiovascular events and death than patients with obstructive disease,” said Philipp Blanke, MD, a radiologist at the University of British Columbia and St. Paul’s Hospital and a coauthor of the study. “Our five-year follow-up data suggest that nonobstructive and obstructive coronary artery disease, as detected by cardiac CTA in diabetic patients, are both associated with higher rates of mortality.”

Researchers need a better understanding of the evolution of plaque in the arteries and of patient response to therapies, said Dr. Leipsic. “Cardiac CT angiography is helpful for identifying diabetic patients who are at higher risk for heart events and who may benefit from more aggressive therapy to help modify that risk,” he added.

Patients Prefer Direct Access to Imaging Records
Patients value direct, independent access to their medical exams, researchers reported.

Giampaolo Greco, PhD, MPH, Assistant Professor in the Department of Population Health Science and Policy at the Mount Sinai School of Medicine in New York City, and colleagues set out to evaluate patient and provider satisfaction with RSNA Image Share, an Internet-based interoperable image exchange system that gives patients ownership of their imaging exams and control over access to their imaging records. The network enables radiology sites to make results of imaging exams available for patients to incorporate in personal health record (PHR) accounts they can use to securely store, manage, and share their imaging records. Sites also can use the network to send patient imaging records to other participating sites to support better informed care.

For the study, patients undergoing radiologic exams at four academic centers were eligible to establish online PHR accounts using the RSNA Image Share network. Patients could then use their PHR accounts to maintain and share their images with selected providers, creating a detailed medical history accessible through any secure Internet connection.

Between July 2012 and August 2013, the study enrolled 2,562 patients, mean age 50.4, including a significant representation of older individuals. Older individuals have the highest healthcare utilization and often experience or perceive a significant barrier in using information technology.

The median number of exams uploaded per patient was six. Study participants were provided a brief survey to assess patient and physician experience with the exchange of images, and 502 patients completed and returned their surveys. Of these respondents, 448 patients identified the method used at the visit to share images: Internet, CDs, both Internet and CDs, or other, and 165 included a section completed by their physician.

Nearly all (96%) of the patients responded positively to having direct access to their medical images, and 78% viewed their images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users reported being able to access their images without difficulty, compared with CD users (88.3% vs 77.5%).

DTI Reveals Changes in Brain Connections in Early Alzheimer’s Disease
Changes in brain connections visible on MRI could represent an imaging biomarker of Alzheimer’s disease, according to a study presented at the meeting.

As many as five million Americans have Alzheimer’s disease, and this number is expected to increase to 14 million by 2050, according to the Centers for Disease Control and Prevention. Preventive treatments may be most effective before Alzheimer’s disease is diagnosed, such as when a person is experiencing mild cognitive impairment.

Previous efforts at early detection have focused on beta amyloid. For the current study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between various areas of the brain.

“The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said Jeffrey W. Prescott, MD, PhD, a radiology resident at Duke University Medical Center in Durham, North Carolina, and a coauthor of the study.

Dr. Prescott and colleagues analyzed data for 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative 2. The patients had undergone diffusion tensor imaging (DTI), which assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “Water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” said Dr. Prescott.

The researchers compared changes in the structural connectome with results from florbetapir PET imaging, a technique that measures the amount of beta amyloid plaque in the brain. The results showed a strong association between florbetapir uptake and decreases in the strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the Alzheimer’s brain—structural tissue changes and pathologic amyloid plaque deposition—and suggests a promising role for DTI as a possible diagnostic adjunct,” said Dr. Prescott.

Based on these findings, DTI may have a role in assessing brain damage in early Alzheimer’s disease and in monitoring the effect of new therapies.

“Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, Professor of Radiology at Duke University and senior author of the research. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain’s white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue studying this cohort of patients over time to gain a better understanding of how the disease evolves in individual patients. They also intend to incorporate functional imaging into their research to learn about how the relationship between function and structure changes with increasing amyloid burden.

Asymptomatic Atherosclerosis May Be Associated With Cognitive Impairment
A buildup of plaque in the body’s major arteries is associated with mild cognitive impairment, according to a study of approximately 2,000 adults conducted at the University of Texas (UT) Southwestern Medical Center.

“It is well established that plaque buildup in the arteries is a predictor of heart disease, but the relationship between atherosclerosis and brain health is less clear,” said Christopher D. Maroules, MD, a radiology resident at UT Southwestern Medical Center in Dallas. “Our findings suggest that atherosclerosis not only affects the heart, but also brain health.”

Researchers analyzed the test results of 1,903 participants (mean age, 44) in the Dallas Heart Study, a multiethnic population-based study of adults from Dallas County, Texas. The participants included men and women who had no symptoms of cardiovascular disease.

Study participants completed the Montreal Cognitive Assessment (MoCA), a 30-point standardized test for detecting mild cognitive impairment, and underwent MRI of the brain to measure white matter hyperintensity volume. Bright white spots known as high signal intensity areas on a brain MRI indicate abnormal changes within the white matter.

“Increased white matter hyperintensity volume is part of the normal aging process,” explained Dr. Maroules. “But excessive white matter hyperintensity volume is a marker for cognitive impairment.”

Study participants also underwent imaging exams to measure the buildup of plaque in the arteries in three distinct vascular areas of the body. They underwent MRI to measure wall thickness in the carotid arteries and in the abdominal aorta, and received CT to measure coronary artery calcium.

Using the results, researchers performed a statistical regression to understand the relationship between the incidence of atherosclerosis and mild cognitive impairment. After adjusting for traditional risk factors for atherosclerosis, including age, ethnicity, male sex, diabetes, hypertension, smoking, and BMI, the investigators found independent relationships between atherosclerosis in all three vascular areas of the body and cognitive health, as measured by MoCA scores, and white matter hyperintensity volume on MRI.

Individuals in the highest quartile of internal carotid wall thickness were 21% more likely to have cognitive impairment, as indicated by a low MoCA score. An increasing coronary artery calcium score was predictive of large white matter intensity volume on MRI.

“These results underscore the importance of identifying atherosclerosis in its early stages, not just to help preserve heart function, but also to preserve cognition and brain health,” said Dr. Maroules. The MRI and CT imaging techniques provide valuable prognostic information about an individual’s downstream health risks, he added.

“Plaque buildup in blood vessels throughout the body offers us a window into brain health. Imaging with CT and MRI has an important role in identifying patients who are at a higher risk for cognitive impairment.”

A Season of High School Football Without Concussion May Cause Brain Changes
Some high school football players exhibit measurable brain changes after a single season of play, even in the absence of concussion, according to a study presented at the meeting.

“This study adds to the growing body of evidence that a season of play in a contact sport can affect the brain in the absence of clinical findings,” said Christopher T. Whitlow, MD, PhD, MHA, Associate Professor of Radiology at Wake Forest School of Medicine and radiologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

In recent years, various reports have suggested the potential effects that participation in youth sports may have on the developing brain. Most of these studies have looked at brain changes as a result of concussion, however. Dr. Whitlow and colleagues set out to determine whether head impacts withstood in the course of a season of high school football produce white matter changes in the brain in the absence of clinically diagnosed concussion.

The researchers studied 24 high school football players between the ages of 16 and 18. For all games and practices, players were monitored with Head Impact Telemetry System (HITs) helmet-mounted accelerometers, which are used in youth and collegiate football to assess the frequency and severity of helmet impacts.

Risk-weighted cumulative exposure was computed from the HITs data and represented the risk of concussion over the course of the season. These data, along with the total number of impacts, were used to categorize the players as heavy hitters or light hitters. The researchers identified nine of the 24 participants as heavy hitters and 15 as light hitters. None of the players had concussion during the season.

All players underwent pre- and post-season evaluation with diffusion tensor imaging (DTI) of the brain. Diffusion tensor imaging measures fractional anisotropy, which indicates the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform, and fractional anisotropy is high. When water movement is more random, fractional anisotropy values decrease, thus suggesting microstructural abnormalities.

The results showed that both groups demonstrated global increases of fractional anisotropy over time, likely reflecting the effects of brain development. However, the heavy-hitter group showed statistically significant areas of decreased fractional anisotropy post-season in specific areas of the brain, including the splenium of the corpus callosum and deep white matter tracts.

“Our study found that players experiencing greater levels of head impacts have more fractional anisotropy loss, compared with players with lower impact exposure,” said Dr. Whitlow. “Similar brain MRI changes have been previously associated with mild traumatic brain injury. However, it is unclear whether or not these effects will be associated with any negative long-term consequences.” These findings are preliminary, and more study needs to be performed, concluded Dr. Whitlow.

Mild Coronary Artery Disease Increases Risk of Cardiovascular Events
Patients with diabetes and mild coronary artery disease have the same relative risk for a heart attack or other major adverse heart event as patients with diabetes and serious single-vessel obstructive disease, according to a long-term study.

Researchers at the University of British Columbia and St. Paul’s Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, which was developed to examine the prognostic value of cardiac computed tomography angiography (CCTA) for predicting adverse cardiac events related to coronary artery disease. The registry, which has CCTA data for 40,000 patients from 17 centers around the world, now has five-year follow-up data for 14,000 patients.

“The CONFIRM Registry is the largest long-term data set available and allowed us to evaluate the long-term prognostic value of CCTA in diabetic patients,” said Jonathan Leipsic, MD, vice chairman of the Department of Radiology at the University of British Columbia and study coauthor.

The researchers analyzed data for 1,823 patients with diabetes who underwent CCTA to detect and determine the extent of coronary artery disease. Men and women (median age, 61.7) in the study were categorized as having no coronary artery disease, mild disease (ie, coronary artery narrowed by less than 50%), or obstructive disease (ie, obstruction of more than 50% of the artery). Over a 5.2-year follow-up period, 246 deaths occurred, representing 13.5% of the total study group.

Major adverse cardiovascular event (MACE) data were available for 973 patients. During the follow-up period, 295 (30.3%) of the patients had a MACE, such as heart attack or a coronary revascularization.

The researchers found that both obstructive and mild, or nonobstructive, coronary artery disease, as determined by CCTA, were associated with patient deaths and MACE. Most importantly, the researchers found that the relative risk for death or MACE for a patient with mild coronary artery disease was comparable to that of patients with single vessel obstructive disease.

“Until now, two-year follow-up studies suggested that a diabetic patient with mild or nonobstructive coronary artery disease had a lower risk of major adverse cardiovascular events and death than patients with obstructive disease,” said Philipp Blanke, MD, a radiologist at the University of British Columbia and St. Paul’s Hospital and a coauthor of the study. “Our five-year follow-up data suggest that nonobstructive and obstructive coronary artery disease, as detected by cardiac CTA in diabetic patients, are both associated with higher rates of mortality.”

Researchers need a better understanding of the evolution of plaque in the arteries and of patient response to therapies, said Dr. Leipsic. “Cardiac CT angiography is helpful for identifying diabetic patients who are at higher risk for heart events and who may benefit from more aggressive therapy to help modify that risk,” he added.

Patients Prefer Direct Access to Imaging Records
Patients value direct, independent access to their medical exams, researchers reported.

Giampaolo Greco, PhD, MPH, Assistant Professor in the Department of Population Health Science and Policy at the Mount Sinai School of Medicine in New York City, and colleagues set out to evaluate patient and provider satisfaction with RSNA Image Share, an Internet-based interoperable image exchange system that gives patients ownership of their imaging exams and control over access to their imaging records. The network enables radiology sites to make results of imaging exams available for patients to incorporate in personal health record (PHR) accounts they can use to securely store, manage, and share their imaging records. Sites also can use the network to send patient imaging records to other participating sites to support better informed care.

For the study, patients undergoing radiologic exams at four academic centers were eligible to establish online PHR accounts using the RSNA Image Share network. Patients could then use their PHR accounts to maintain and share their images with selected providers, creating a detailed medical history accessible through any secure Internet connection.

Between July 2012 and August 2013, the study enrolled 2,562 patients, mean age 50.4, including a significant representation of older individuals. Older individuals have the highest healthcare utilization and often experience or perceive a significant barrier in using information technology.

The median number of exams uploaded per patient was six. Study participants were provided a brief survey to assess patient and physician experience with the exchange of images, and 502 patients completed and returned their surveys. Of these respondents, 448 patients identified the method used at the visit to share images: Internet, CDs, both Internet and CDs, or other, and 165 included a section completed by their physician.

Nearly all (96%) of the patients responded positively to having direct access to their medical images, and 78% viewed their images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users reported being able to access their images without difficulty, compared with CD users (88.3% vs 77.5%).

DTI Reveals Changes in Brain Connections in Early Alzheimer’s Disease
Changes in brain connections visible on MRI could represent an imaging biomarker of Alzheimer’s disease, according to a study presented at the meeting.

As many as five million Americans have Alzheimer’s disease, and this number is expected to increase to 14 million by 2050, according to the Centers for Disease Control and Prevention. Preventive treatments may be most effective before Alzheimer’s disease is diagnosed, such as when a person is experiencing mild cognitive impairment.

Previous efforts at early detection have focused on beta amyloid. For the current study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between various areas of the brain.

“The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said Jeffrey W. Prescott, MD, PhD, a radiology resident at Duke University Medical Center in Durham, North Carolina, and a coauthor of the study.

Dr. Prescott and colleagues analyzed data for 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative 2. The patients had undergone diffusion tensor imaging (DTI), which assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “Water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” said Dr. Prescott.

The researchers compared changes in the structural connectome with results from florbetapir PET imaging, a technique that measures the amount of beta amyloid plaque in the brain. The results showed a strong association between florbetapir uptake and decreases in the strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the Alzheimer’s brain—structural tissue changes and pathologic amyloid plaque deposition—and suggests a promising role for DTI as a possible diagnostic adjunct,” said Dr. Prescott.

Based on these findings, DTI may have a role in assessing brain damage in early Alzheimer’s disease and in monitoring the effect of new therapies.

“Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, Professor of Radiology at Duke University and senior author of the research. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain’s white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue studying this cohort of patients over time to gain a better understanding of how the disease evolves in individual patients. They also intend to incorporate functional imaging into their research to learn about how the relationship between function and structure changes with increasing amyloid burden.

Asymptomatic Atherosclerosis May Be Associated With Cognitive Impairment
A buildup of plaque in the body’s major arteries is associated with mild cognitive impairment, according to a study of approximately 2,000 adults conducted at the University of Texas (UT) Southwestern Medical Center.

“It is well established that plaque buildup in the arteries is a predictor of heart disease, but the relationship between atherosclerosis and brain health is less clear,” said Christopher D. Maroules, MD, a radiology resident at UT Southwestern Medical Center in Dallas. “Our findings suggest that atherosclerosis not only affects the heart, but also brain health.”

Researchers analyzed the test results of 1,903 participants (mean age, 44) in the Dallas Heart Study, a multiethnic population-based study of adults from Dallas County, Texas. The participants included men and women who had no symptoms of cardiovascular disease.

Study participants completed the Montreal Cognitive Assessment (MoCA), a 30-point standardized test for detecting mild cognitive impairment, and underwent MRI of the brain to measure white matter hyperintensity volume. Bright white spots known as high signal intensity areas on a brain MRI indicate abnormal changes within the white matter.

“Increased white matter hyperintensity volume is part of the normal aging process,” explained Dr. Maroules. “But excessive white matter hyperintensity volume is a marker for cognitive impairment.”

Study participants also underwent imaging exams to measure the buildup of plaque in the arteries in three distinct vascular areas of the body. They underwent MRI to measure wall thickness in the carotid arteries and in the abdominal aorta, and received CT to measure coronary artery calcium.

Using the results, researchers performed a statistical regression to understand the relationship between the incidence of atherosclerosis and mild cognitive impairment. After adjusting for traditional risk factors for atherosclerosis, including age, ethnicity, male sex, diabetes, hypertension, smoking, and BMI, the investigators found independent relationships between atherosclerosis in all three vascular areas of the body and cognitive health, as measured by MoCA scores, and white matter hyperintensity volume on MRI.

Individuals in the highest quartile of internal carotid wall thickness were 21% more likely to have cognitive impairment, as indicated by a low MoCA score. An increasing coronary artery calcium score was predictive of large white matter intensity volume on MRI.

“These results underscore the importance of identifying atherosclerosis in its early stages, not just to help preserve heart function, but also to preserve cognition and brain health,” said Dr. Maroules. The MRI and CT imaging techniques provide valuable prognostic information about an individual’s downstream health risks, he added.

“Plaque buildup in blood vessels throughout the body offers us a window into brain health. Imaging with CT and MRI has an important role in identifying patients who are at a higher risk for cognitive impairment.”

A Season of High School Football Without Concussion May Cause Brain Changes
Some high school football players exhibit measurable brain changes after a single season of play, even in the absence of concussion, according to a study presented at the meeting.

“This study adds to the growing body of evidence that a season of play in a contact sport can affect the brain in the absence of clinical findings,” said Christopher T. Whitlow, MD, PhD, MHA, Associate Professor of Radiology at Wake Forest School of Medicine and radiologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

In recent years, various reports have suggested the potential effects that participation in youth sports may have on the developing brain. Most of these studies have looked at brain changes as a result of concussion, however. Dr. Whitlow and colleagues set out to determine whether head impacts withstood in the course of a season of high school football produce white matter changes in the brain in the absence of clinically diagnosed concussion.

The researchers studied 24 high school football players between the ages of 16 and 18. For all games and practices, players were monitored with Head Impact Telemetry System (HITs) helmet-mounted accelerometers, which are used in youth and collegiate football to assess the frequency and severity of helmet impacts.

Risk-weighted cumulative exposure was computed from the HITs data and represented the risk of concussion over the course of the season. These data, along with the total number of impacts, were used to categorize the players as heavy hitters or light hitters. The researchers identified nine of the 24 participants as heavy hitters and 15 as light hitters. None of the players had concussion during the season.

All players underwent pre- and post-season evaluation with diffusion tensor imaging (DTI) of the brain. Diffusion tensor imaging measures fractional anisotropy, which indicates the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform, and fractional anisotropy is high. When water movement is more random, fractional anisotropy values decrease, thus suggesting microstructural abnormalities.

The results showed that both groups demonstrated global increases of fractional anisotropy over time, likely reflecting the effects of brain development. However, the heavy-hitter group showed statistically significant areas of decreased fractional anisotropy post-season in specific areas of the brain, including the splenium of the corpus callosum and deep white matter tracts.

“Our study found that players experiencing greater levels of head impacts have more fractional anisotropy loss, compared with players with lower impact exposure,” said Dr. Whitlow. “Similar brain MRI changes have been previously associated with mild traumatic brain injury. However, it is unclear whether or not these effects will be associated with any negative long-term consequences.” These findings are preliminary, and more study needs to be performed, concluded Dr. Whitlow.

Mild Coronary Artery Disease Increases Risk of Cardiovascular Events
Patients with diabetes and mild coronary artery disease have the same relative risk for a heart attack or other major adverse heart event as patients with diabetes and serious single-vessel obstructive disease, according to a long-term study.

Researchers at the University of British Columbia and St. Paul’s Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, which was developed to examine the prognostic value of cardiac computed tomography angiography (CCTA) for predicting adverse cardiac events related to coronary artery disease. The registry, which has CCTA data for 40,000 patients from 17 centers around the world, now has five-year follow-up data for 14,000 patients.

“The CONFIRM Registry is the largest long-term data set available and allowed us to evaluate the long-term prognostic value of CCTA in diabetic patients,” said Jonathan Leipsic, MD, vice chairman of the Department of Radiology at the University of British Columbia and study coauthor.

The researchers analyzed data for 1,823 patients with diabetes who underwent CCTA to detect and determine the extent of coronary artery disease. Men and women (median age, 61.7) in the study were categorized as having no coronary artery disease, mild disease (ie, coronary artery narrowed by less than 50%), or obstructive disease (ie, obstruction of more than 50% of the artery). Over a 5.2-year follow-up period, 246 deaths occurred, representing 13.5% of the total study group.

Major adverse cardiovascular event (MACE) data were available for 973 patients. During the follow-up period, 295 (30.3%) of the patients had a MACE, such as heart attack or a coronary revascularization.

The researchers found that both obstructive and mild, or nonobstructive, coronary artery disease, as determined by CCTA, were associated with patient deaths and MACE. Most importantly, the researchers found that the relative risk for death or MACE for a patient with mild coronary artery disease was comparable to that of patients with single vessel obstructive disease.

“Until now, two-year follow-up studies suggested that a diabetic patient with mild or nonobstructive coronary artery disease had a lower risk of major adverse cardiovascular events and death than patients with obstructive disease,” said Philipp Blanke, MD, a radiologist at the University of British Columbia and St. Paul’s Hospital and a coauthor of the study. “Our five-year follow-up data suggest that nonobstructive and obstructive coronary artery disease, as detected by cardiac CTA in diabetic patients, are both associated with higher rates of mortality.”

Researchers need a better understanding of the evolution of plaque in the arteries and of patient response to therapies, said Dr. Leipsic. “Cardiac CT angiography is helpful for identifying diabetic patients who are at higher risk for heart events and who may benefit from more aggressive therapy to help modify that risk,” he added.

Patients Prefer Direct Access to Imaging Records
Patients value direct, independent access to their medical exams, researchers reported.

Giampaolo Greco, PhD, MPH, Assistant Professor in the Department of Population Health Science and Policy at the Mount Sinai School of Medicine in New York City, and colleagues set out to evaluate patient and provider satisfaction with RSNA Image Share, an Internet-based interoperable image exchange system that gives patients ownership of their imaging exams and control over access to their imaging records. The network enables radiology sites to make results of imaging exams available for patients to incorporate in personal health record (PHR) accounts they can use to securely store, manage, and share their imaging records. Sites also can use the network to send patient imaging records to other participating sites to support better informed care.

For the study, patients undergoing radiologic exams at four academic centers were eligible to establish online PHR accounts using the RSNA Image Share network. Patients could then use their PHR accounts to maintain and share their images with selected providers, creating a detailed medical history accessible through any secure Internet connection.

Between July 2012 and August 2013, the study enrolled 2,562 patients, mean age 50.4, including a significant representation of older individuals. Older individuals have the highest healthcare utilization and often experience or perceive a significant barrier in using information technology.

The median number of exams uploaded per patient was six. Study participants were provided a brief survey to assess patient and physician experience with the exchange of images, and 502 patients completed and returned their surveys. Of these respondents, 448 patients identified the method used at the visit to share images: Internet, CDs, both Internet and CDs, or other, and 165 included a section completed by their physician.

Nearly all (96%) of the patients responded positively to having direct access to their medical images, and 78% viewed their images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users reported being able to access their images without difficulty, compared with CD users (88.3% vs 77.5%).

When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.

Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and increased the level of mature brain-derived neurotrophic factor.

“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”

Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.

Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.

These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.

When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.

Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and increased the level of mature brain-derived neurotrophic factor.

“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”

Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.

Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.

These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.

When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.

Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and increased the level of mature brain-derived neurotrophic factor.

“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”

Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.

Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.

These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.

Traumatic brain injury (TBI) appears to be associated with an increased risk of dementia in adults 55 and older, researchers reported online ahead of print October 27 in JAMA Neurology.

Controversy exists about whether there is a link between a single TBI and the risk of developing dementia. According to the CDC, Americans 55 and older account for more than 60% of all hospitalizations for TBI, with the highest rates of TBI-related emergency department visits, inpatient stays, and deaths happening among patients age 75 and older. Therefore, understanding the effects of a TBI and the development of dementia among middle-aged or older adults has important public health implications.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues examined the risk of dementia among adults age 55 and older with recent TBI, compared with adults with non-TBI body trauma (NTT), which was defined as fractures but not of the head or neck. The study included 164,661 patients identified in a statewide California administrative health database.

A total of 51,799 patients with trauma (31.5%) had TBI. Of those, 4,361 patients (8.4%) developed dementia, compared with 6,610 patients (5.9%) with NTT. The average time from trauma to dementia diagnosis was 3.2 years, and it was shorter in the TBI group, compared with the NTT group (3.1 vs 3.3 years). Moderate to severe TBI was associated with increased risk of dementia in persons age 55 or older, and mild TBI at age 65 or older increased the dementia risk.

“Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself,” the authors noted.

In a related editorial, Steven T. DeKosky, MD, Professor and Chair, Department of Neurology, University of Pittsburgh School of Medicine, stated that “Judicious use of data by skilled researchers who are familiar with the entire range of dementia research from pathobiology to health care needs will enable us to ask important questions, evolve new or more informed queries, and both lead and complement the translational questions that are before us. Dementia is both a global problem and a pathological conundrum; thus, the complementary use of big data and basic neuroscience analyses offers the most promise.”

Traumatic brain injury (TBI) appears to be associated with an increased risk of dementia in adults 55 and older, researchers reported online ahead of print October 27 in JAMA Neurology.

Controversy exists about whether there is a link between a single TBI and the risk of developing dementia. According to the CDC, Americans 55 and older account for more than 60% of all hospitalizations for TBI, with the highest rates of TBI-related emergency department visits, inpatient stays, and deaths happening among patients age 75 and older. Therefore, understanding the effects of a TBI and the development of dementia among middle-aged or older adults has important public health implications.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues examined the risk of dementia among adults age 55 and older with recent TBI, compared with adults with non-TBI body trauma (NTT), which was defined as fractures but not of the head or neck. The study included 164,661 patients identified in a statewide California administrative health database.

A total of 51,799 patients with trauma (31.5%) had TBI. Of those, 4,361 patients (8.4%) developed dementia, compared with 6,610 patients (5.9%) with NTT. The average time from trauma to dementia diagnosis was 3.2 years, and it was shorter in the TBI group, compared with the NTT group (3.1 vs 3.3 years). Moderate to severe TBI was associated with increased risk of dementia in persons age 55 or older, and mild TBI at age 65 or older increased the dementia risk.

“Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself,” the authors noted.

In a related editorial, Steven T. DeKosky, MD, Professor and Chair, Department of Neurology, University of Pittsburgh School of Medicine, stated that “Judicious use of data by skilled researchers who are familiar with the entire range of dementia research from pathobiology to health care needs will enable us to ask important questions, evolve new or more informed queries, and both lead and complement the translational questions that are before us. Dementia is both a global problem and a pathological conundrum; thus, the complementary use of big data and basic neuroscience analyses offers the most promise.”

Traumatic brain injury (TBI) appears to be associated with an increased risk of dementia in adults 55 and older, researchers reported online ahead of print October 27 in JAMA Neurology.

Controversy exists about whether there is a link between a single TBI and the risk of developing dementia. According to the CDC, Americans 55 and older account for more than 60% of all hospitalizations for TBI, with the highest rates of TBI-related emergency department visits, inpatient stays, and deaths happening among patients age 75 and older. Therefore, understanding the effects of a TBI and the development of dementia among middle-aged or older adults has important public health implications.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues examined the risk of dementia among adults age 55 and older with recent TBI, compared with adults with non-TBI body trauma (NTT), which was defined as fractures but not of the head or neck. The study included 164,661 patients identified in a statewide California administrative health database.

A total of 51,799 patients with trauma (31.5%) had TBI. Of those, 4,361 patients (8.4%) developed dementia, compared with 6,610 patients (5.9%) with NTT. The average time from trauma to dementia diagnosis was 3.2 years, and it was shorter in the TBI group, compared with the NTT group (3.1 vs 3.3 years). Moderate to severe TBI was associated with increased risk of dementia in persons age 55 or older, and mild TBI at age 65 or older increased the dementia risk.

“Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself,” the authors noted.

In a related editorial, Steven T. DeKosky, MD, Professor and Chair, Department of Neurology, University of Pittsburgh School of Medicine, stated that “Judicious use of data by skilled researchers who are familiar with the entire range of dementia research from pathobiology to health care needs will enable us to ask important questions, evolve new or more informed queries, and both lead and complement the translational questions that are before us. Dementia is both a global problem and a pathological conundrum; thus, the complementary use of big data and basic neuroscience analyses offers the most promise.”

SAN DIEGO—With all the media attention drawn to the effects of sports-related concussion in recent years, a significant portion of schools in the United States have adopted return-to-play guidelines, but only a minority have return-to-learn protocols in place, according to a physician speaking at the 2014 Annual Meeting of the American Academy of Pediatrics.

Literature on the topic is scarce, but one survey of school nurses in Illinois found that 57% of schools in that state had return-to-play protocols, while 30% had protocols in place for returning to the classroom, said Kelsey Logan, MD, Director of the Division of Sports Medicine at Cincinnati Children’s Hospital Medical Center. A survey of youth in Nebraska who had sustained concussions in sports found that a minority (42%) of their teachers provided extra assistance in the classroom following their injury.

Cognitive Activity Can Prolong Recovery
Limiting cognitive activities “is a big part of their stress in getting over their injury,” said Dr. Logan. “I talk to the families about decreasing their child’s emotional stress, and academics are largely a cause of this. They’re stressed from day one about the work they’re missing.… If we address those [concerns] up front, they tend to be a little less stressed.”

Increasing cognitive activity soon after a concussive injury “worsens symptoms and prolongs recovery,” noted Dr. Logan. “That often takes several conversations with patients and parents before they understand that concept. Many times parents want you to micromanage their kid’s day—tell them exactly what they can and can’t do. That’s not really our role. I cannot predict whether 15 versus 20 minutes of looking on a computer is going to make their symptoms worse. Understanding concepts is important. When you start to experience a big gap in energy and your symptoms get worse, you need to back off. Our goal is to determine the appropriate balance of cognitive activity and cognitive rest.”

Creating a Return-to-Learn Plan
Developing a return-to-learning plan following a concussion starts with an assessment of the patient’s symptoms, which vary from individual to individual. “You can’t predict exactly what a person’s going to go through,” said Dr. Logan, one of the authors of a guideline on return to learning that was published in Pediatrics in 2013. “It’s important to consider physical, cognitive, emotional, and sleep symptoms.... Some patients will have many emotional symptoms after a concussion; others won’t. This is why it’s so important for primary care pediatricians to be treating concussions because they know their patients.”

Dr. Logan recommends that patients and their families use checklists to document symptoms, track their severity and progression, and target symptoms to address with school personnel. The ideal role of family members and friends is to enforce rest and reduce stimulation, while the role of the medical team is to evaluate symptoms, prescribe physical and cognitive rest, and get input from family members and school personnel on the patient’s progress. The chief goal is to help the patient get the most out of the school day without worsening symptoms. This process starts with limitations on school time.

“For an athlete who has a constant headache, I would recommend that she stay out of school until she feels a little bit better,” said Dr. Logan. “There’s not a specific symptom score that she needs to meet to go back to school. It’s when the family and the patient feel that she can go to school and concentrate. You don’t want to throw that athlete back into a full school day right away. You want to start with a few hours of school, maybe a half-day, depending on symptoms.”

The Importance of Rest Breaks
Acutely concussed athletes can only concentrate for 30- to 45-minute blocks of time, added Dr. Logan, so “I like to prescribe rest breaks. I try to get them to recognize that if they go to a hard class like calculus and have to work hard for 45 minutes or so, they’re probably going to be fried for the next period, so there needs to be something a little less onerous like study hall, or lunch, where they can rest. They need to use common sense during the day.”

During office visits, Dr. Logan reviews the school day schedule with patients, “and we try to target different areas where they can feel comfortable to rest. I’m asking their opinion on where the best spots in their day are to get some rest. Because if I just say, ‘you’re going to do this, this, and this, what’s their likelihood of following through with those instructions? It’s really low.”

Reducing the Burden of Schoolwork
Dr. Logan recommends limiting computer time, reading, math, and note-taking during recovery, because each task tends to cause symptoms to worsen. “Having either the teacher’s notes supplied to them or having another student take notes for them may allow them to tolerate more class time than they would if they were trying to take notes,” said Dr. Logan. “Listen to lectures only.” At home, students should perform only activities that don’t exacerbate symptoms. This means limiting instant messaging, texting, watching TV, and playing video games.

A subset of concussed patients are overstimulated by light and sound, “so it’s important to ask about that and make adjustments in the school day,” said Dr. Logan. “This [approach] would involve reducing sound and light when you can and wearing sunglasses and earplugs.”

Dr. Logan recommends delaying tests that may fall in the time line of recovery, such as midterms, finals, or college-readiness tests such as the SAT. “A brain-injured person is not going to do well on any of these tests,” she said. “In notes to school personnel, write ‘no testing for now,’ or ‘postpone testing.’ ”

—Doug Brunk

SAN DIEGO—With all the media attention drawn to the effects of sports-related concussion in recent years, a significant portion of schools in the United States have adopted return-to-play guidelines, but only a minority have return-to-learn protocols in place, according to a physician speaking at the 2014 Annual Meeting of the American Academy of Pediatrics.

Literature on the topic is scarce, but one survey of school nurses in Illinois found that 57% of schools in that state had return-to-play protocols, while 30% had protocols in place for returning to the classroom, said Kelsey Logan, MD, Director of the Division of Sports Medicine at Cincinnati Children’s Hospital Medical Center. A survey of youth in Nebraska who had sustained concussions in sports found that a minority (42%) of their teachers provided extra assistance in the classroom following their injury.

Cognitive Activity Can Prolong Recovery
Limiting cognitive activities “is a big part of their stress in getting over their injury,” said Dr. Logan. “I talk to the families about decreasing their child’s emotional stress, and academics are largely a cause of this. They’re stressed from day one about the work they’re missing.… If we address those [concerns] up front, they tend to be a little less stressed.”

Increasing cognitive activity soon after a concussive injury “worsens symptoms and prolongs recovery,” noted Dr. Logan. “That often takes several conversations with patients and parents before they understand that concept. Many times parents want you to micromanage their kid’s day—tell them exactly what they can and can’t do. That’s not really our role. I cannot predict whether 15 versus 20 minutes of looking on a computer is going to make their symptoms worse. Understanding concepts is important. When you start to experience a big gap in energy and your symptoms get worse, you need to back off. Our goal is to determine the appropriate balance of cognitive activity and cognitive rest.”

Creating a Return-to-Learn Plan
Developing a return-to-learning plan following a concussion starts with an assessment of the patient’s symptoms, which vary from individual to individual. “You can’t predict exactly what a person’s going to go through,” said Dr. Logan, one of the authors of a guideline on return to learning that was published in Pediatrics in 2013. “It’s important to consider physical, cognitive, emotional, and sleep symptoms.... Some patients will have many emotional symptoms after a concussion; others won’t. This is why it’s so important for primary care pediatricians to be treating concussions because they know their patients.”

Dr. Logan recommends that patients and their families use checklists to document symptoms, track their severity and progression, and target symptoms to address with school personnel. The ideal role of family members and friends is to enforce rest and reduce stimulation, while the role of the medical team is to evaluate symptoms, prescribe physical and cognitive rest, and get input from family members and school personnel on the patient’s progress. The chief goal is to help the patient get the most out of the school day without worsening symptoms. This process starts with limitations on school time.

“For an athlete who has a constant headache, I would recommend that she stay out of school until she feels a little bit better,” said Dr. Logan. “There’s not a specific symptom score that she needs to meet to go back to school. It’s when the family and the patient feel that she can go to school and concentrate. You don’t want to throw that athlete back into a full school day right away. You want to start with a few hours of school, maybe a half-day, depending on symptoms.”

The Importance of Rest Breaks
Acutely concussed athletes can only concentrate for 30- to 45-minute blocks of time, added Dr. Logan, so “I like to prescribe rest breaks. I try to get them to recognize that if they go to a hard class like calculus and have to work hard for 45 minutes or so, they’re probably going to be fried for the next period, so there needs to be something a little less onerous like study hall, or lunch, where they can rest. They need to use common sense during the day.”

During office visits, Dr. Logan reviews the school day schedule with patients, “and we try to target different areas where they can feel comfortable to rest. I’m asking their opinion on where the best spots in their day are to get some rest. Because if I just say, ‘you’re going to do this, this, and this, what’s their likelihood of following through with those instructions? It’s really low.”

Reducing the Burden of Schoolwork
Dr. Logan recommends limiting computer time, reading, math, and note-taking during recovery, because each task tends to cause symptoms to worsen. “Having either the teacher’s notes supplied to them or having another student take notes for them may allow them to tolerate more class time than they would if they were trying to take notes,” said Dr. Logan. “Listen to lectures only.” At home, students should perform only activities that don’t exacerbate symptoms. This means limiting instant messaging, texting, watching TV, and playing video games.

A subset of concussed patients are overstimulated by light and sound, “so it’s important to ask about that and make adjustments in the school day,” said Dr. Logan. “This [approach] would involve reducing sound and light when you can and wearing sunglasses and earplugs.”

Dr. Logan recommends delaying tests that may fall in the time line of recovery, such as midterms, finals, or college-readiness tests such as the SAT. “A brain-injured person is not going to do well on any of these tests,” she said. “In notes to school personnel, write ‘no testing for now,’ or ‘postpone testing.’ ”

—Doug Brunk

SAN DIEGO—With all the media attention drawn to the effects of sports-related concussion in recent years, a significant portion of schools in the United States have adopted return-to-play guidelines, but only a minority have return-to-learn protocols in place, according to a physician speaking at the 2014 Annual Meeting of the American Academy of Pediatrics.

Literature on the topic is scarce, but one survey of school nurses in Illinois found that 57% of schools in that state had return-to-play protocols, while 30% had protocols in place for returning to the classroom, said Kelsey Logan, MD, Director of the Division of Sports Medicine at Cincinnati Children’s Hospital Medical Center. A survey of youth in Nebraska who had sustained concussions in sports found that a minority (42%) of their teachers provided extra assistance in the classroom following their injury.

Cognitive Activity Can Prolong Recovery
Limiting cognitive activities “is a big part of their stress in getting over their injury,” said Dr. Logan. “I talk to the families about decreasing their child’s emotional stress, and academics are largely a cause of this. They’re stressed from day one about the work they’re missing.… If we address those [concerns] up front, they tend to be a little less stressed.”

Increasing cognitive activity soon after a concussive injury “worsens symptoms and prolongs recovery,” noted Dr. Logan. “That often takes several conversations with patients and parents before they understand that concept. Many times parents want you to micromanage their kid’s day—tell them exactly what they can and can’t do. That’s not really our role. I cannot predict whether 15 versus 20 minutes of looking on a computer is going to make their symptoms worse. Understanding concepts is important. When you start to experience a big gap in energy and your symptoms get worse, you need to back off. Our goal is to determine the appropriate balance of cognitive activity and cognitive rest.”

Creating a Return-to-Learn Plan
Developing a return-to-learning plan following a concussion starts with an assessment of the patient’s symptoms, which vary from individual to individual. “You can’t predict exactly what a person’s going to go through,” said Dr. Logan, one of the authors of a guideline on return to learning that was published in Pediatrics in 2013. “It’s important to consider physical, cognitive, emotional, and sleep symptoms.... Some patients will have many emotional symptoms after a concussion; others won’t. This is why it’s so important for primary care pediatricians to be treating concussions because they know their patients.”

Dr. Logan recommends that patients and their families use checklists to document symptoms, track their severity and progression, and target symptoms to address with school personnel. The ideal role of family members and friends is to enforce rest and reduce stimulation, while the role of the medical team is to evaluate symptoms, prescribe physical and cognitive rest, and get input from family members and school personnel on the patient’s progress. The chief goal is to help the patient get the most out of the school day without worsening symptoms. This process starts with limitations on school time.

“For an athlete who has a constant headache, I would recommend that she stay out of school until she feels a little bit better,” said Dr. Logan. “There’s not a specific symptom score that she needs to meet to go back to school. It’s when the family and the patient feel that she can go to school and concentrate. You don’t want to throw that athlete back into a full school day right away. You want to start with a few hours of school, maybe a half-day, depending on symptoms.”

The Importance of Rest Breaks
Acutely concussed athletes can only concentrate for 30- to 45-minute blocks of time, added Dr. Logan, so “I like to prescribe rest breaks. I try to get them to recognize that if they go to a hard class like calculus and have to work hard for 45 minutes or so, they’re probably going to be fried for the next period, so there needs to be something a little less onerous like study hall, or lunch, where they can rest. They need to use common sense during the day.”

During office visits, Dr. Logan reviews the school day schedule with patients, “and we try to target different areas where they can feel comfortable to rest. I’m asking their opinion on where the best spots in their day are to get some rest. Because if I just say, ‘you’re going to do this, this, and this, what’s their likelihood of following through with those instructions? It’s really low.”

Reducing the Burden of Schoolwork
Dr. Logan recommends limiting computer time, reading, math, and note-taking during recovery, because each task tends to cause symptoms to worsen. “Having either the teacher’s notes supplied to them or having another student take notes for them may allow them to tolerate more class time than they would if they were trying to take notes,” said Dr. Logan. “Listen to lectures only.” At home, students should perform only activities that don’t exacerbate symptoms. This means limiting instant messaging, texting, watching TV, and playing video games.

A subset of concussed patients are overstimulated by light and sound, “so it’s important to ask about that and make adjustments in the school day,” said Dr. Logan. “This [approach] would involve reducing sound and light when you can and wearing sunglasses and earplugs.”

Dr. Logan recommends delaying tests that may fall in the time line of recovery, such as midterms, finals, or college-readiness tests such as the SAT. “A brain-injured person is not going to do well on any of these tests,” she said. “In notes to school personnel, write ‘no testing for now,’ or ‘postpone testing.’ ”

—Doug Brunk

PHILADELPHIA—Head trauma among ice hockey players may produce abnormalities in brain function, as assessed by neuropsychologic testing, diffusion tensor imaging, quantitative EEG, and postmortem studies, according to research reported at the 66th Annual Meeting of the American Academy of Neurology (AAN).

“The relationship between these measures in the short term and midterm and postmortem findings of chronic traumatic encephalopathy (CTE) is still unclear,” stated Ozan Toy, a medical student at the Commonwealth Medical College in Scranton, Pennsylvania, and colleagues.

Head Impact Injuries in Hockey
The researchers conducted a literature review regarding the effect of concussions in male ice hockey players. In addition, a Google search was performed to obtain information regarding professional hockey players who have been diagnosed with CTE.

In one of the studies reviewed, Gaetz and colleagues reported that electrophysiologic evidence from a cohort of junior hockey players showed that multiple concussions can lead to long-term neurologic symptoms, including headache, decreased memory, and decreased thinking speed, which correlate with electrophysiologic deficits related to attention, working memory, and mental processing. The study authors concluded that multiple concussions in hockey players can lead to neurologic deficits that can linger for at least six months postconcussion.

In 2012, Koerte et al found that diffusion tensor imaging revealed changes in white matter diffusivity in 17 male ice hockey players (ages 20 to 26) throughout the course of one season. Also in 2012, Bazarian and colleagues found that two high school ice hockey players who had multiple subconcussive head blows had significant changes in a percentage of their white matter that was more than three times higher than in controls.

Furthermore, in 2013 McKee and colleagues found that in eight subjects who were examined postmortem for CTE and who had a history of playing amateur and professional ice hockey, five had a presence of CTE on examination. Of the five players who underwent neuropathologic analysis, four showed signs of CTE. Three of the former National Hockey League players had stage II CTE, and one had stage III CTE and Lewy body disease; one of the four was nonsymptomatic at the time of death.

CNS Injuries in Ice Hockey
In a related study presented at the AAN Meeting, Mr. Toy and colleagues found that concussion (0.2 to 6.6 per 1,000 player hours) and spinal cord injury (five per 1,000 player hours) were the most common CNS injuries among ice hockey players.

Other reported injuries were second impact syndrome, subarachnoid hemorrhage, subdural hematoma, epidural hematoma, spinal cord concussion, and vertebral hemorrhage.

“Although numerous measures have been taken to decrease the incidence of CNS injuries in ice hockey, it has been difficult to measure the impact of those changes,” stated Mr. Toy. “Nonetheless, knowledge of the potential for CNS injuries and the mechanisms of those injuries helps inform the athletes and trainers to make more informed decisions regarding play.”

—Colby Stong

PHILADELPHIA—Head trauma among ice hockey players may produce abnormalities in brain function, as assessed by neuropsychologic testing, diffusion tensor imaging, quantitative EEG, and postmortem studies, according to research reported at the 66th Annual Meeting of the American Academy of Neurology (AAN).

“The relationship between these measures in the short term and midterm and postmortem findings of chronic traumatic encephalopathy (CTE) is still unclear,” stated Ozan Toy, a medical student at the Commonwealth Medical College in Scranton, Pennsylvania, and colleagues.

Head Impact Injuries in Hockey
The researchers conducted a literature review regarding the effect of concussions in male ice hockey players. In addition, a Google search was performed to obtain information regarding professional hockey players who have been diagnosed with CTE.

In one of the studies reviewed, Gaetz and colleagues reported that electrophysiologic evidence from a cohort of junior hockey players showed that multiple concussions can lead to long-term neurologic symptoms, including headache, decreased memory, and decreased thinking speed, which correlate with electrophysiologic deficits related to attention, working memory, and mental processing. The study authors concluded that multiple concussions in hockey players can lead to neurologic deficits that can linger for at least six months postconcussion.

In 2012, Koerte et al found that diffusion tensor imaging revealed changes in white matter diffusivity in 17 male ice hockey players (ages 20 to 26) throughout the course of one season. Also in 2012, Bazarian and colleagues found that two high school ice hockey players who had multiple subconcussive head blows had significant changes in a percentage of their white matter that was more than three times higher than in controls.

Furthermore, in 2013 McKee and colleagues found that in eight subjects who were examined postmortem for CTE and who had a history of playing amateur and professional ice hockey, five had a presence of CTE on examination. Of the five players who underwent neuropathologic analysis, four showed signs of CTE. Three of the former National Hockey League players had stage II CTE, and one had stage III CTE and Lewy body disease; one of the four was nonsymptomatic at the time of death.

CNS Injuries in Ice Hockey
In a related study presented at the AAN Meeting, Mr. Toy and colleagues found that concussion (0.2 to 6.6 per 1,000 player hours) and spinal cord injury (five per 1,000 player hours) were the most common CNS injuries among ice hockey players.

Other reported injuries were second impact syndrome, subarachnoid hemorrhage, subdural hematoma, epidural hematoma, spinal cord concussion, and vertebral hemorrhage.

“Although numerous measures have been taken to decrease the incidence of CNS injuries in ice hockey, it has been difficult to measure the impact of those changes,” stated Mr. Toy. “Nonetheless, knowledge of the potential for CNS injuries and the mechanisms of those injuries helps inform the athletes and trainers to make more informed decisions regarding play.”

—Colby Stong

PHILADELPHIA—Head trauma among ice hockey players may produce abnormalities in brain function, as assessed by neuropsychologic testing, diffusion tensor imaging, quantitative EEG, and postmortem studies, according to research reported at the 66th Annual Meeting of the American Academy of Neurology (AAN).

“The relationship between these measures in the short term and midterm and postmortem findings of chronic traumatic encephalopathy (CTE) is still unclear,” stated Ozan Toy, a medical student at the Commonwealth Medical College in Scranton, Pennsylvania, and colleagues.

Head Impact Injuries in Hockey
The researchers conducted a literature review regarding the effect of concussions in male ice hockey players. In addition, a Google search was performed to obtain information regarding professional hockey players who have been diagnosed with CTE.

In one of the studies reviewed, Gaetz and colleagues reported that electrophysiologic evidence from a cohort of junior hockey players showed that multiple concussions can lead to long-term neurologic symptoms, including headache, decreased memory, and decreased thinking speed, which correlate with electrophysiologic deficits related to attention, working memory, and mental processing. The study authors concluded that multiple concussions in hockey players can lead to neurologic deficits that can linger for at least six months postconcussion.

In 2012, Koerte et al found that diffusion tensor imaging revealed changes in white matter diffusivity in 17 male ice hockey players (ages 20 to 26) throughout the course of one season. Also in 2012, Bazarian and colleagues found that two high school ice hockey players who had multiple subconcussive head blows had significant changes in a percentage of their white matter that was more than three times higher than in controls.

Furthermore, in 2013 McKee and colleagues found that in eight subjects who were examined postmortem for CTE and who had a history of playing amateur and professional ice hockey, five had a presence of CTE on examination. Of the five players who underwent neuropathologic analysis, four showed signs of CTE. Three of the former National Hockey League players had stage II CTE, and one had stage III CTE and Lewy body disease; one of the four was nonsymptomatic at the time of death.

CNS Injuries in Ice Hockey
In a related study presented at the AAN Meeting, Mr. Toy and colleagues found that concussion (0.2 to 6.6 per 1,000 player hours) and spinal cord injury (five per 1,000 player hours) were the most common CNS injuries among ice hockey players.

Other reported injuries were second impact syndrome, subarachnoid hemorrhage, subdural hematoma, epidural hematoma, spinal cord concussion, and vertebral hemorrhage.

“Although numerous measures have been taken to decrease the incidence of CNS injuries in ice hockey, it has been difficult to measure the impact of those changes,” stated Mr. Toy. “Nonetheless, knowledge of the potential for CNS injuries and the mechanisms of those injuries helps inform the athletes and trainers to make more informed decisions regarding play.”

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

Bioengineers at Tufts University in Boston, Massachusetts have created 3-dimensional (3D), functional brainlike tissue that can be kept alive in a laboratory for more than 2 months. It is a major research achievement that promises to advance research into brain injury and disease.

The tissue was developed at the Tufts Tissue Engineering Resource Center, which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The researchers generated the brainlike tissue by creating a novel composite structure of 2 biomaterials: a spongy scaffold of silk protein that neurons can attach to and a softer, collagen-based gel to encourage axon growth.

The 3D aspect of the new tissue represents a step beyond the current research situation, in which scientists grow neurons in petri dishes. Neurons grown that way can’t duplicate the compartmentalization of gray and white matter in the brain, which is critical to research into brain injuries and diseases that affect those areas differently. Moreover, attempts to grow neurons in 3D gel environments have produced tissue models that don’t allow for tissue-level function, according to a NIBIB release. By contrast, neurons in the 3D tissue act more like those seen in a rat brain, with similar electrical activity and responsiveness to stimuli such as neurotoxins. The gel-based neurons begin to deteriorate within 24 hours.

The longevity and functionality of the new tissue allow researchers to track tissue response and repair in real time, over longer periods. David Kaplan, PhD, director of the Tufts Tissue Engineering Resource Center and lead investigator, said, “The fact that we can maintain this tissue for months in the lab means we can start to look at neurological diseases in ways that you can’t otherwise because you need long timeframes to study some of the key brain diseases.”

The discovery could bring new treatments for veterans with brain injuries. In early experiments, the researchers studied chemical and electrical changes that immediately follow traumatic brain injury and changes in the brain as it responds to a drug. Calling the work “an exceptional feat,” Rosemarie Hunziker, PhD, program director of Tissue Engineering at NIBIB, said, “The hope is that use of this model could lead to an acceleration of therapies for brain dysfunction.”

Bioengineers at Tufts University in Boston, Massachusetts have created 3-dimensional (3D), functional brainlike tissue that can be kept alive in a laboratory for more than 2 months. It is a major research achievement that promises to advance research into brain injury and disease.

The tissue was developed at the Tufts Tissue Engineering Resource Center, which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The researchers generated the brainlike tissue by creating a novel composite structure of 2 biomaterials: a spongy scaffold of silk protein that neurons can attach to and a softer, collagen-based gel to encourage axon growth.

The 3D aspect of the new tissue represents a step beyond the current research situation, in which scientists grow neurons in petri dishes. Neurons grown that way can’t duplicate the compartmentalization of gray and white matter in the brain, which is critical to research into brain injuries and diseases that affect those areas differently. Moreover, attempts to grow neurons in 3D gel environments have produced tissue models that don’t allow for tissue-level function, according to a NIBIB release. By contrast, neurons in the 3D tissue act more like those seen in a rat brain, with similar electrical activity and responsiveness to stimuli such as neurotoxins. The gel-based neurons begin to deteriorate within 24 hours.

The longevity and functionality of the new tissue allow researchers to track tissue response and repair in real time, over longer periods. David Kaplan, PhD, director of the Tufts Tissue Engineering Resource Center and lead investigator, said, “The fact that we can maintain this tissue for months in the lab means we can start to look at neurological diseases in ways that you can’t otherwise because you need long timeframes to study some of the key brain diseases.”

The discovery could bring new treatments for veterans with brain injuries. In early experiments, the researchers studied chemical and electrical changes that immediately follow traumatic brain injury and changes in the brain as it responds to a drug. Calling the work “an exceptional feat,” Rosemarie Hunziker, PhD, program director of Tissue Engineering at NIBIB, said, “The hope is that use of this model could lead to an acceleration of therapies for brain dysfunction.”

Bioengineers at Tufts University in Boston, Massachusetts have created 3-dimensional (3D), functional brainlike tissue that can be kept alive in a laboratory for more than 2 months. It is a major research achievement that promises to advance research into brain injury and disease.

The tissue was developed at the Tufts Tissue Engineering Resource Center, which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The researchers generated the brainlike tissue by creating a novel composite structure of 2 biomaterials: a spongy scaffold of silk protein that neurons can attach to and a softer, collagen-based gel to encourage axon growth.

The 3D aspect of the new tissue represents a step beyond the current research situation, in which scientists grow neurons in petri dishes. Neurons grown that way can’t duplicate the compartmentalization of gray and white matter in the brain, which is critical to research into brain injuries and diseases that affect those areas differently. Moreover, attempts to grow neurons in 3D gel environments have produced tissue models that don’t allow for tissue-level function, according to a NIBIB release. By contrast, neurons in the 3D tissue act more like those seen in a rat brain, with similar electrical activity and responsiveness to stimuli such as neurotoxins. The gel-based neurons begin to deteriorate within 24 hours.

The longevity and functionality of the new tissue allow researchers to track tissue response and repair in real time, over longer periods. David Kaplan, PhD, director of the Tufts Tissue Engineering Resource Center and lead investigator, said, “The fact that we can maintain this tissue for months in the lab means we can start to look at neurological diseases in ways that you can’t otherwise because you need long timeframes to study some of the key brain diseases.”

The discovery could bring new treatments for veterans with brain injuries. In early experiments, the researchers studied chemical and electrical changes that immediately follow traumatic brain injury and changes in the brain as it responds to a drug. Calling the work “an exceptional feat,” Rosemarie Hunziker, PhD, program director of Tissue Engineering at NIBIB, said, “The hope is that use of this model could lead to an acceleration of therapies for brain dysfunction.”

According to the DoD, 300,707 U.S. service members were diagnosed with a traumatic brain injury (TBI) between 2000 and the first quarter of 2014. Of those, 82% had mild TBI (mTBI), also known as a concussion. Usually, a patient recovers from concussion relatively quickly—in days to weeks. But some patients, especially those with preexisting and concomitant conditions, have persistent symptoms that interfere with daily life. The most common of these symptoms are sleep disturbances, usually insomnia, which is a critical issue, given that sleep is so important to the brain’s—and the rest of the body’s—ability to heal. Poor sleep also exacerbates other symptoms, such as pain and irritability, has a negative impact on cognition, and may partially mediate the development of posttraumatic stress disorder or depression.

The Defense and Veterans Brain Injury Center (DVBIC) has released a new clinical recommendation and support tools to help clinicians identify and treat post-TBI sleep disturbances. The suite includes Management of Sleep Disturbances Following Concussion/Mild Traumatic Brain Injury: Guidance for Primary Care Management in Deployed and Non-Deployed Settings, a companion clinical support tool, and a fact sheet for patients. The clinical recommendation (CR) and companion tool are based on a review of current literature and expert contributions from the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, in collaboration with clinical subject matter experts.

The CR strongly advises that all patients with concussion be screened for a sleep disorder. The key question to ask during the patient interview is “Are you experiencing frequent difficulty in falling or staying asleep, excessive daytime sleepiness, or unusual events during sleep?”

The DVBIC Clinical Affairs Officer PHS Capt. Cynthia Spells says “the initial step in the diagnosis of a sleep disorder includes a focused sleep assessment.” The clinical interview should include the “3 Ps”: predisposing, precipitating, and perpetuating factors. Predisposing factors include excessive weight, older age, and medications. Precipitating factors include concussion, deployment, and acute stress. Perpetuating factors include excessive use of caffeine or other stimulants, time zone changes, and familial stress. Noting that comorbid conditions are common with sleep disorders, the CR notes an anxiety disorder postinjury is a more significant predictor of sleep disruption than is pain, other comorbid conditions, or the adverse effects of medication.

A guide for primary care providers (PCPs) in addition to giving an overview of the suite and how to use the components provides insight into the research and science behind managing TBI-related sleep disturbances. The clinical support tool is an algorithm for PCPs to use in assessing sleep disturbances, a step-by-step process to determine the level of care required. The tool is offered as a pocket-sized reference card and can be downloaded. (Health care providers can also take a self-guided course in identifying and treating mTBI at http://www.brainlinemilitary.org.)

According to the CR, nonpharmacologic measures are the first-line treatment for post-TBI sleep problems. These include teaching patients good sleep hygiene and stimulus control; that is, doing as much as possible to physically and environmentally promote sleep. (See App Corner) The patient fact sheet gives tips on getting a healthy night’ s sleep, such as avoiding naps, avoiding alcohol close to bedtime, and getting exposure to natural light as much as possible.

The CR and other components are available at https://dvbic.dcoe.mil/resources/management-sleep-disturbances.

According to the DoD, 300,707 U.S. service members were diagnosed with a traumatic brain injury (TBI) between 2000 and the first quarter of 2014. Of those, 82% had mild TBI (mTBI), also known as a concussion. Usually, a patient recovers from concussion relatively quickly—in days to weeks. But some patients, especially those with preexisting and concomitant conditions, have persistent symptoms that interfere with daily life. The most common of these symptoms are sleep disturbances, usually insomnia, which is a critical issue, given that sleep is so important to the brain’s—and the rest of the body’s—ability to heal. Poor sleep also exacerbates other symptoms, such as pain and irritability, has a negative impact on cognition, and may partially mediate the development of posttraumatic stress disorder or depression.

The Defense and Veterans Brain Injury Center (DVBIC) has released a new clinical recommendation and support tools to help clinicians identify and treat post-TBI sleep disturbances. The suite includes Management of Sleep Disturbances Following Concussion/Mild Traumatic Brain Injury: Guidance for Primary Care Management in Deployed and Non-Deployed Settings, a companion clinical support tool, and a fact sheet for patients. The clinical recommendation (CR) and companion tool are based on a review of current literature and expert contributions from the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, in collaboration with clinical subject matter experts.

The CR strongly advises that all patients with concussion be screened for a sleep disorder. The key question to ask during the patient interview is “Are you experiencing frequent difficulty in falling or staying asleep, excessive daytime sleepiness, or unusual events during sleep?”

The DVBIC Clinical Affairs Officer PHS Capt. Cynthia Spells says “the initial step in the diagnosis of a sleep disorder includes a focused sleep assessment.” The clinical interview should include the “3 Ps”: predisposing, precipitating, and perpetuating factors. Predisposing factors include excessive weight, older age, and medications. Precipitating factors include concussion, deployment, and acute stress. Perpetuating factors include excessive use of caffeine or other stimulants, time zone changes, and familial stress. Noting that comorbid conditions are common with sleep disorders, the CR notes an anxiety disorder postinjury is a more significant predictor of sleep disruption than is pain, other comorbid conditions, or the adverse effects of medication.

A guide for primary care providers (PCPs) in addition to giving an overview of the suite and how to use the components provides insight into the research and science behind managing TBI-related sleep disturbances. The clinical support tool is an algorithm for PCPs to use in assessing sleep disturbances, a step-by-step process to determine the level of care required. The tool is offered as a pocket-sized reference card and can be downloaded. (Health care providers can also take a self-guided course in identifying and treating mTBI at http://www.brainlinemilitary.org.)

According to the CR, nonpharmacologic measures are the first-line treatment for post-TBI sleep problems. These include teaching patients good sleep hygiene and stimulus control; that is, doing as much as possible to physically and environmentally promote sleep. (See App Corner) The patient fact sheet gives tips on getting a healthy night’ s sleep, such as avoiding naps, avoiding alcohol close to bedtime, and getting exposure to natural light as much as possible.

The CR and other components are available at https://dvbic.dcoe.mil/resources/management-sleep-disturbances.

According to the DoD, 300,707 U.S. service members were diagnosed with a traumatic brain injury (TBI) between 2000 and the first quarter of 2014. Of those, 82% had mild TBI (mTBI), also known as a concussion. Usually, a patient recovers from concussion relatively quickly—in days to weeks. But some patients, especially those with preexisting and concomitant conditions, have persistent symptoms that interfere with daily life. The most common of these symptoms are sleep disturbances, usually insomnia, which is a critical issue, given that sleep is so important to the brain’s—and the rest of the body’s—ability to heal. Poor sleep also exacerbates other symptoms, such as pain and irritability, has a negative impact on cognition, and may partially mediate the development of posttraumatic stress disorder or depression.

The Defense and Veterans Brain Injury Center (DVBIC) has released a new clinical recommendation and support tools to help clinicians identify and treat post-TBI sleep disturbances. The suite includes Management of Sleep Disturbances Following Concussion/Mild Traumatic Brain Injury: Guidance for Primary Care Management in Deployed and Non-Deployed Settings, a companion clinical support tool, and a fact sheet for patients. The clinical recommendation (CR) and companion tool are based on a review of current literature and expert contributions from the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, in collaboration with clinical subject matter experts.

The CR strongly advises that all patients with concussion be screened for a sleep disorder. The key question to ask during the patient interview is “Are you experiencing frequent difficulty in falling or staying asleep, excessive daytime sleepiness, or unusual events during sleep?”

The DVBIC Clinical Affairs Officer PHS Capt. Cynthia Spells says “the initial step in the diagnosis of a sleep disorder includes a focused sleep assessment.” The clinical interview should include the “3 Ps”: predisposing, precipitating, and perpetuating factors. Predisposing factors include excessive weight, older age, and medications. Precipitating factors include concussion, deployment, and acute stress. Perpetuating factors include excessive use of caffeine or other stimulants, time zone changes, and familial stress. Noting that comorbid conditions are common with sleep disorders, the CR notes an anxiety disorder postinjury is a more significant predictor of sleep disruption than is pain, other comorbid conditions, or the adverse effects of medication.

A guide for primary care providers (PCPs) in addition to giving an overview of the suite and how to use the components provides insight into the research and science behind managing TBI-related sleep disturbances. The clinical support tool is an algorithm for PCPs to use in assessing sleep disturbances, a step-by-step process to determine the level of care required. The tool is offered as a pocket-sized reference card and can be downloaded. (Health care providers can also take a self-guided course in identifying and treating mTBI at http://www.brainlinemilitary.org.)

According to the CR, nonpharmacologic measures are the first-line treatment for post-TBI sleep problems. These include teaching patients good sleep hygiene and stimulus control; that is, doing as much as possible to physically and environmentally promote sleep. (See App Corner) The patient fact sheet gives tips on getting a healthy night’ s sleep, such as avoiding naps, avoiding alcohol close to bedtime, and getting exposure to natural light as much as possible.

The CR and other components are available at https://dvbic.dcoe.mil/resources/management-sleep-disturbances.