A test used to detect Zika virus is producing a larger-than-expected number of false-positive results, according to a safety alert issued by the Food and Drug Administration.

The ZIKV Detect IgM Capture ELISA test is the first commercially available Zika serological IgM test – it was approved by the FDA in August 2016 and is used by several commercial laboratories. The test reports only presumptive positive results and a sample has to be sent to the Centers for Disease Control and Prevention for confirmation. Final results can take up to a month to be delivered. In most instances, the preliminary test results have matched the confirmed sample results.

[email protected]

A test used to detect Zika virus is producing a larger-than-expected number of false-positive results, according to a safety alert issued by the Food and Drug Administration.

The ZIKV Detect IgM Capture ELISA test is the first commercially available Zika serological IgM test – it was approved by the FDA in August 2016 and is used by several commercial laboratories. The test reports only presumptive positive results and a sample has to be sent to the Centers for Disease Control and Prevention for confirmation. Final results can take up to a month to be delivered. In most instances, the preliminary test results have matched the confirmed sample results.

[email protected]

A test used to detect Zika virus is producing a larger-than-expected number of false-positive results, according to a safety alert issued by the Food and Drug Administration.

The ZIKV Detect IgM Capture ELISA test is the first commercially available Zika serological IgM test – it was approved by the FDA in August 2016 and is used by several commercial laboratories. The test reports only presumptive positive results and a sample has to be sent to the Centers for Disease Control and Prevention for confirmation. Final results can take up to a month to be delivered. In most instances, the preliminary test results have matched the confirmed sample results.

[email protected]

Studies Provide More Insight Into Zika Effects

Three studies reported on the effects of the Zika virus outbreak in Brazil. The first study examined CT findings of the CNS in 16 newborn babies with congenital Zika virus infection confirmed by tests in CSF. The researchers identified a pattern of CT brain findings in the babies, including decreased brain volume, simplified gyral pattern, calcifications, ventricular dilatation, and prominent occipital bone.

"We live in Pernambuco, a state in northeastern Brazil, which had the highest number of patients with microcephaly during the Zika outbreak in our country," said Natacha Calheiros de Lima Petribu, MD, of the Department of Radiology at Barão de Lucena Hospital. "Our study proves that Zika virus infection can cause congenital brain damage in babies with and without microcephaly."  

Another study analyzed the imaging results of three target groups affected by Zika: adults who developed acute neurologic syndrome, newborns with vertical infection with neurologic disorders, and pregnant women with rash outbreaks suggestive of Zika. Many of the adults had symptoms of Guillain-Barré syndrome. A few showed inflammation of the brain and spinal cord (ie, Bickerstaff's encephalitis) or brainstem and spinal cord lesions. Common MRI findings included enhancement of certain spinal and facial nerves. In the newborns, MRI showed orbital injuries and anatomical changes in brain tissue.  

"It was alarming to find so many cases of neurologic syndromes in adults, some very serious, related to Zika virus infection," said study author Emerson de Melo Casagrande, MD, of the Department of Radiology at Antonio Pedro University Hospital--Federal Fluminense University. "We have also noticed a difference between these syndromes, even though the trigger was the same."

In a third study, ultrasound and fetal MRI were performed on pregnant patients with Zika virus infection at different gestational ages. Once the babies were born, they underwent ultrasound, CT, and MRI. The researchers then created 3-D virtual and physical models of the skulls. More than half of the babies had microcephaly, brain calcifications, and loss of brain tissue volume, along with other structural changes.

"The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly," said study author Heron Werner Jr, MD, PhD, of the Department of Radiology at Clínica de Diagnóstico por Imagem. "An early diagnosis may help in treating these babies after birth. Moreover, the knowledge of abnormalities present in the CNS may give hints about the pathophysiology of the disease."

Head Impacts Lead to Brain Changes in High School Football Players

Brain imaging exams performed on high school football players after a single season reveal changes in the gray and white matter that correlated with exposure to head impacts, according to researchers.

"It is important to understand the potential changes occurring in the brain related to youth contact sports," said Elizabeth Moody Davenport, PhD, a postdoctoral researcher at UT Southwestern Medical Center in Dallas. "We know that some professional football players suffer from a serious condition called chronic traumatic encephalopathy or CTE. We are attempting to find out when and how that process starts, so that we can keep sports a healthy activity for millions of children and adolescents."

The study included 24 players from a high school football team in North Carolina, each of whom wore a helmet outfitted with the Head Impact Telemetry System (HITS) during all practices and games. The helmets are lined with six accelerometers that measure the magnitude, location, and direction of a hit. Data from the helmets can be uploaded to a computer for analysis.  

"We saw changes in these young players' brains on both structural and functional imaging after a single season of football," said Dr. Davenport.  

In the study, each player underwent pre- and post-season imaging, including a specialized MRI scan, from which diffusion tensor imaging and diffusion kurtosis imaging data were extracted to measure the brain's white matter integrity, and a magnetoencephalography (MEG) scan, which records and analyzes the magnetic fields produced by brain waves. Diffusion imaging can measure the structural white matter changes in the brain, and MEG assesses changes in function.

"MEG can be used to measure delta waves in the brain, which are a type of distress signal," said Dr. Davenport. "Delta waves represent slow wave activity that increases after brain injuries. The delta waves we saw came from the surface of the brain, while diffusion imaging is a measure of the white matter deeper in the brain."  

The research team calculated the change in imaging metrics between the pre- and post-season imaging exams. They measured abnormalities observed on diffusion imaging and abnormally increased delta-wave activity on MEG. The imaging results were then combined with player-specific impact data from the HITS. None of the 24 players were diagnosed with a concussion during the study.

Players with greater head impact exposure had the greatest change in diffusion imaging and MEG metrics. "Change in diffusion imaging metrics correlated most to linear acceleration, similar to the impact of a car crash," said Dr. Davenport. "MEG changes correlated most to rotational impact, similar to a boxer's punch. These results demonstrate that you need both imaging metrics to assess impact exposure, because they correlate with different biomechanical processes."

Similar studies are being conducted this fall, and a consortium has been formed to continue the brain imaging research in youth contact sports across the country, said Dr. Davenport. "Without a larger population that is closely followed in a longitudinal study, it is difficult to know the long-term effects of these changes," she said. "We do not know if the brain's developmental trajectory is altered, or if the off-season time allows for the brain to return to normal."

Depression in Soldiers Linked to Brain Disruption From Injury

Using multiple brain imaging techniques, researchers have found that a disruption of the circuitry in the brain's cognitive-emotional pathways may provide a physical foundation for depression symptoms in some service members who have had mild traumatic brain injury (mTBI) in combat. "We can link these connectivity changes in the brain to poor top-down emotional processing and greater maladaptive rumination, or worrying, in symptomatic depressed soldiers after mTBI," said Ping-Hong Yeh, PhD, scientist and physicist at the National Intrepid Center of Excellence, Walter Reed National Military Medical Center in Bethesda, Maryland.

According to the Defense and Veterans Brain Injury Center, 352,619 service members worldwide have been diagnosed with TBI since 2000, the majority of these cases being mTBI. In addition, psychiatric disorders, such as anxiety and major depressive disorders, are becoming common in military personnel with brain injuries.

"With the increased survival of soldiers due to improvements in body armor and advanced medical care, there has been an increase in the number of soldiers surviving major trauma. Consequently, a large number of soldiers are returning from war with mTBI," said Dr. Yeh. "Mood disorders are common in military-related mTBI patients. This is an ongoing problem facing a large number of warriors in current areas of conflict, and it is likely to be a persistent problem for the foreseeable future."

For the study, researchers used diffusion-weighted imaging (DWI) and resting-state functional MRI (fMRI) to examine 130 active male service members diagnosed with mTBI and a control group of 52 men without mTBI. Depression symptoms were rated based on the Beck Depression Inventory (BDI), a 21-item, self-reporting assessment that measures characteristic attitudes and symptoms of depression. Patients with a BDI score greater than 20 are considered to have moderate to severe depression symptoms.

BDI scores showed that 75 of the patients with mTBI had moderate to severe depression symptoms. Imaging results showed that white matter tracts—the circuits that connect brain regions critical for cognitive and emotional control—were disrupted in the patients with moderate to severe depression symptoms. Researchers also saw changes in the gray matter cognitive-emotional networks in these patients.

"We found consistencies in the locations of disrupted neurocircuitry, as revealed by DWI and resting-state fMRI, that are unique to the clinical symptoms of mTBI patients," said Dr. Yeh. "We have related the brain structural and functional changes in cognitive-emotional networks to depressive symptoms in mTBI patients."  

This research can possibly lead to treatment strategies in the future, he added. "Though the results of this study were not applied directly to patient care, the neuroimaging changes we found might be incorporated into treatment plans for personalized medicine in the future."  

Short-Term Sleep Deprivation Affects Heart Function

Getting too little sleep takes a toll on your heart, researchers reported. People who work in fire and emergency medical services, medical residencies, and other high-stress jobs are often called upon to work 24-hour shifts with little opportunity for sleep. While it is known that extreme fatigue can affect many physical, cognitive, and emotional processes, this is the first study to examine how working a 24-hour shift specifically affects cardiac function.

"For the first time, we have shown that short-term sleep deprivation in the context of 24-hour shifts can lead to a significant increase in cardiac contractility, blood pressure, and heart rate," said study author Daniel Kuetting, MD, of the Department of Diagnostic and Interventional Radiology at the University of Bonn in Germany.  

For the study, Dr. Kuetting and colleagues recruited 20 healthy radiologists (19 men) with a mean age of 31.6. Each of the study participants underwent cardiovascular magnetic resonance (CMR) imaging with strain analysis before and after a 24-hour shift with an average of three hours of sleep.

"Cardiac function in the context of sleep deprivation has not previously been investigated with CMR strain analysis, the most sensitive parameter of cardiac contractility," said Dr. Kuetting. The researchers also collected blood and urine samples from the participants and measured blood pressure and heart rate.  

Following short-term sleep deprivation, the participants showed significant increases in mean peak systolic strain (-23.4 vs -21.9), systolic (118.5 mmHg vs 112.8 mmHg) and diastolic (69.2 mmHg vs 62.9 mmHg) blood pressure and heart rate (68.9 bpm vs 63.0 bpm). In addition, the participants had significant increases in levels of thyroid stimulating hormone (TSH), thyroid hormones FT3 and FT4, and cortisol.  

Although the researchers were able to perform follow-up examinations of half of the participants after regular sleep, further study in a larger cohort is needed to determine possible long-term effects of sleep loss, said Dr. Kuetting.

"The study was designed to investigate real-life work-related sleep deprivation," said Dr. Kuetting. "While the participants were not permitted to consume caffeine or food and beverages containing theobromine, such as chocolate, nuts, or tea, we did not take into account factors like individual stress level or environmental stimuli."

As people continue to work longer hours or work at more than one job to make ends meet, it is critical to investigate the detrimental effects of too much work and not enough sleep. The results of this pilot study are transferable to other professions in which long periods of uninterrupted labor are common, said Dr. Kuetting. "These findings may help us better understand how workload and shift duration affect public health."  

Aerobic Exercise Preserves Brain Volume and Improves Cognitive Function

Using a new MRI technique, researchers have found that adults with mild cognitive impairment (MCI) who exercised four times per week during a six-month period experienced an increase in brain volume in specific areas of the brain, but adults who participated in aerobic exercise experienced greater gains than those who just stretched.  

"Even over a short period of time, we saw aerobic exercise lead to a remarkable change in the brain," said Laura D. Baker, PhD, Associate Professor of Gerontology and Geriatric Medicine at Wake Forest School of Medicine (WFSM) in Winston-Salem, North Carolina.

The study included 35 adults with MCI participating in a randomized, controlled trial of exercise intervention. The participants were separated into two groups. Sixteen adults (average age, 63) engaged in aerobic activity, including treadmill, stationary bike, or elliptical training, four times per week for six months. A control group of 19 adults (average age, 67) participated in stretching exercises with the same frequency. High-resolution brain MR images were acquired from all participants before and after the six-month activity period. The MRI results were compared using conventional and biomechanical metrics to measure the change in brain volume and shape.  

"We used high-resolution MR images to measure anatomical changes within areas of the brain to obtain volumetric data and directional information," said Jeongchul Kim, PhD, a coinvestigator at WFSM.  

The analysis revealed that for both the aerobic and stretching groups, brain volume increased in most gray matter regions, including the temporal lobe, which supports short-term memory.  

"Compared to the stretching group, the aerobic activity group had greater preservation of total brain volume, increased local gray matter volume, and increased directional stretch of brain tissue," said Dr. Kim.  

Among participants of the stretching group, the analysis revealed a local contraction, or atrophy, within the white matter connecting fibers. Such directional deformation, or shape change, is partially related to volume loss, but not always, according to Dr. Kim.

"Directional changes in the brain without local volume changes could be a novel biomarker for neurologic disease," he said. "It may be a more sensitive marker for the tiny changes that occur in a specific brain region before volumetric changes are detectable on MRI."  

Both MRI measures are important to the treatment of MCI and Alzheimer's disease, which require the careful tracking of changes in the brain while patients engage in interventions, including diet and exercise, to slow the progression of the disease.  

Study participants were tested to determine the effect of exercise intervention on cognitive performance. Participants in the aerobic exercise group showed statistically significant improvement in executive function after six months, whereas the stretching group did not improve.  

"Any type of exercise can be beneficial," said Dr. Kim. "If possible, aerobic activity may create potential benefits for higher cognitive functioning."    

Studies Provide More Insight Into Zika Effects

Three studies reported on the effects of the Zika virus outbreak in Brazil. The first study examined CT findings of the CNS in 16 newborn babies with congenital Zika virus infection confirmed by tests in CSF. The researchers identified a pattern of CT brain findings in the babies, including decreased brain volume, simplified gyral pattern, calcifications, ventricular dilatation, and prominent occipital bone.

"We live in Pernambuco, a state in northeastern Brazil, which had the highest number of patients with microcephaly during the Zika outbreak in our country," said Natacha Calheiros de Lima Petribu, MD, of the Department of Radiology at Barão de Lucena Hospital. "Our study proves that Zika virus infection can cause congenital brain damage in babies with and without microcephaly."  

Another study analyzed the imaging results of three target groups affected by Zika: adults who developed acute neurologic syndrome, newborns with vertical infection with neurologic disorders, and pregnant women with rash outbreaks suggestive of Zika. Many of the adults had symptoms of Guillain-Barré syndrome. A few showed inflammation of the brain and spinal cord (ie, Bickerstaff's encephalitis) or brainstem and spinal cord lesions. Common MRI findings included enhancement of certain spinal and facial nerves. In the newborns, MRI showed orbital injuries and anatomical changes in brain tissue.  

"It was alarming to find so many cases of neurologic syndromes in adults, some very serious, related to Zika virus infection," said study author Emerson de Melo Casagrande, MD, of the Department of Radiology at Antonio Pedro University Hospital--Federal Fluminense University. "We have also noticed a difference between these syndromes, even though the trigger was the same."

In a third study, ultrasound and fetal MRI were performed on pregnant patients with Zika virus infection at different gestational ages. Once the babies were born, they underwent ultrasound, CT, and MRI. The researchers then created 3-D virtual and physical models of the skulls. More than half of the babies had microcephaly, brain calcifications, and loss of brain tissue volume, along with other structural changes.

"The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly," said study author Heron Werner Jr, MD, PhD, of the Department of Radiology at Clínica de Diagnóstico por Imagem. "An early diagnosis may help in treating these babies after birth. Moreover, the knowledge of abnormalities present in the CNS may give hints about the pathophysiology of the disease."

Head Impacts Lead to Brain Changes in High School Football Players

Brain imaging exams performed on high school football players after a single season reveal changes in the gray and white matter that correlated with exposure to head impacts, according to researchers.

"It is important to understand the potential changes occurring in the brain related to youth contact sports," said Elizabeth Moody Davenport, PhD, a postdoctoral researcher at UT Southwestern Medical Center in Dallas. "We know that some professional football players suffer from a serious condition called chronic traumatic encephalopathy or CTE. We are attempting to find out when and how that process starts, so that we can keep sports a healthy activity for millions of children and adolescents."

The study included 24 players from a high school football team in North Carolina, each of whom wore a helmet outfitted with the Head Impact Telemetry System (HITS) during all practices and games. The helmets are lined with six accelerometers that measure the magnitude, location, and direction of a hit. Data from the helmets can be uploaded to a computer for analysis.  

"We saw changes in these young players' brains on both structural and functional imaging after a single season of football," said Dr. Davenport.  

In the study, each player underwent pre- and post-season imaging, including a specialized MRI scan, from which diffusion tensor imaging and diffusion kurtosis imaging data were extracted to measure the brain's white matter integrity, and a magnetoencephalography (MEG) scan, which records and analyzes the magnetic fields produced by brain waves. Diffusion imaging can measure the structural white matter changes in the brain, and MEG assesses changes in function.

"MEG can be used to measure delta waves in the brain, which are a type of distress signal," said Dr. Davenport. "Delta waves represent slow wave activity that increases after brain injuries. The delta waves we saw came from the surface of the brain, while diffusion imaging is a measure of the white matter deeper in the brain."  

The research team calculated the change in imaging metrics between the pre- and post-season imaging exams. They measured abnormalities observed on diffusion imaging and abnormally increased delta-wave activity on MEG. The imaging results were then combined with player-specific impact data from the HITS. None of the 24 players were diagnosed with a concussion during the study.

Players with greater head impact exposure had the greatest change in diffusion imaging and MEG metrics. "Change in diffusion imaging metrics correlated most to linear acceleration, similar to the impact of a car crash," said Dr. Davenport. "MEG changes correlated most to rotational impact, similar to a boxer's punch. These results demonstrate that you need both imaging metrics to assess impact exposure, because they correlate with different biomechanical processes."

Similar studies are being conducted this fall, and a consortium has been formed to continue the brain imaging research in youth contact sports across the country, said Dr. Davenport. "Without a larger population that is closely followed in a longitudinal study, it is difficult to know the long-term effects of these changes," she said. "We do not know if the brain's developmental trajectory is altered, or if the off-season time allows for the brain to return to normal."

Depression in Soldiers Linked to Brain Disruption From Injury

Using multiple brain imaging techniques, researchers have found that a disruption of the circuitry in the brain's cognitive-emotional pathways may provide a physical foundation for depression symptoms in some service members who have had mild traumatic brain injury (mTBI) in combat. "We can link these connectivity changes in the brain to poor top-down emotional processing and greater maladaptive rumination, or worrying, in symptomatic depressed soldiers after mTBI," said Ping-Hong Yeh, PhD, scientist and physicist at the National Intrepid Center of Excellence, Walter Reed National Military Medical Center in Bethesda, Maryland.

According to the Defense and Veterans Brain Injury Center, 352,619 service members worldwide have been diagnosed with TBI since 2000, the majority of these cases being mTBI. In addition, psychiatric disorders, such as anxiety and major depressive disorders, are becoming common in military personnel with brain injuries.

"With the increased survival of soldiers due to improvements in body armor and advanced medical care, there has been an increase in the number of soldiers surviving major trauma. Consequently, a large number of soldiers are returning from war with mTBI," said Dr. Yeh. "Mood disorders are common in military-related mTBI patients. This is an ongoing problem facing a large number of warriors in current areas of conflict, and it is likely to be a persistent problem for the foreseeable future."

For the study, researchers used diffusion-weighted imaging (DWI) and resting-state functional MRI (fMRI) to examine 130 active male service members diagnosed with mTBI and a control group of 52 men without mTBI. Depression symptoms were rated based on the Beck Depression Inventory (BDI), a 21-item, self-reporting assessment that measures characteristic attitudes and symptoms of depression. Patients with a BDI score greater than 20 are considered to have moderate to severe depression symptoms.

BDI scores showed that 75 of the patients with mTBI had moderate to severe depression symptoms. Imaging results showed that white matter tracts—the circuits that connect brain regions critical for cognitive and emotional control—were disrupted in the patients with moderate to severe depression symptoms. Researchers also saw changes in the gray matter cognitive-emotional networks in these patients.

"We found consistencies in the locations of disrupted neurocircuitry, as revealed by DWI and resting-state fMRI, that are unique to the clinical symptoms of mTBI patients," said Dr. Yeh. "We have related the brain structural and functional changes in cognitive-emotional networks to depressive symptoms in mTBI patients."  

This research can possibly lead to treatment strategies in the future, he added. "Though the results of this study were not applied directly to patient care, the neuroimaging changes we found might be incorporated into treatment plans for personalized medicine in the future."  

Short-Term Sleep Deprivation Affects Heart Function

Getting too little sleep takes a toll on your heart, researchers reported. People who work in fire and emergency medical services, medical residencies, and other high-stress jobs are often called upon to work 24-hour shifts with little opportunity for sleep. While it is known that extreme fatigue can affect many physical, cognitive, and emotional processes, this is the first study to examine how working a 24-hour shift specifically affects cardiac function.

"For the first time, we have shown that short-term sleep deprivation in the context of 24-hour shifts can lead to a significant increase in cardiac contractility, blood pressure, and heart rate," said study author Daniel Kuetting, MD, of the Department of Diagnostic and Interventional Radiology at the University of Bonn in Germany.  

For the study, Dr. Kuetting and colleagues recruited 20 healthy radiologists (19 men) with a mean age of 31.6. Each of the study participants underwent cardiovascular magnetic resonance (CMR) imaging with strain analysis before and after a 24-hour shift with an average of three hours of sleep.

"Cardiac function in the context of sleep deprivation has not previously been investigated with CMR strain analysis, the most sensitive parameter of cardiac contractility," said Dr. Kuetting. The researchers also collected blood and urine samples from the participants and measured blood pressure and heart rate.  

Following short-term sleep deprivation, the participants showed significant increases in mean peak systolic strain (-23.4 vs -21.9), systolic (118.5 mmHg vs 112.8 mmHg) and diastolic (69.2 mmHg vs 62.9 mmHg) blood pressure and heart rate (68.9 bpm vs 63.0 bpm). In addition, the participants had significant increases in levels of thyroid stimulating hormone (TSH), thyroid hormones FT3 and FT4, and cortisol.  

Although the researchers were able to perform follow-up examinations of half of the participants after regular sleep, further study in a larger cohort is needed to determine possible long-term effects of sleep loss, said Dr. Kuetting.

"The study was designed to investigate real-life work-related sleep deprivation," said Dr. Kuetting. "While the participants were not permitted to consume caffeine or food and beverages containing theobromine, such as chocolate, nuts, or tea, we did not take into account factors like individual stress level or environmental stimuli."

As people continue to work longer hours or work at more than one job to make ends meet, it is critical to investigate the detrimental effects of too much work and not enough sleep. The results of this pilot study are transferable to other professions in which long periods of uninterrupted labor are common, said Dr. Kuetting. "These findings may help us better understand how workload and shift duration affect public health."  

Aerobic Exercise Preserves Brain Volume and Improves Cognitive Function

Using a new MRI technique, researchers have found that adults with mild cognitive impairment (MCI) who exercised four times per week during a six-month period experienced an increase in brain volume in specific areas of the brain, but adults who participated in aerobic exercise experienced greater gains than those who just stretched.  

"Even over a short period of time, we saw aerobic exercise lead to a remarkable change in the brain," said Laura D. Baker, PhD, Associate Professor of Gerontology and Geriatric Medicine at Wake Forest School of Medicine (WFSM) in Winston-Salem, North Carolina.

The study included 35 adults with MCI participating in a randomized, controlled trial of exercise intervention. The participants were separated into two groups. Sixteen adults (average age, 63) engaged in aerobic activity, including treadmill, stationary bike, or elliptical training, four times per week for six months. A control group of 19 adults (average age, 67) participated in stretching exercises with the same frequency. High-resolution brain MR images were acquired from all participants before and after the six-month activity period. The MRI results were compared using conventional and biomechanical metrics to measure the change in brain volume and shape.  

"We used high-resolution MR images to measure anatomical changes within areas of the brain to obtain volumetric data and directional information," said Jeongchul Kim, PhD, a coinvestigator at WFSM.  

The analysis revealed that for both the aerobic and stretching groups, brain volume increased in most gray matter regions, including the temporal lobe, which supports short-term memory.  

"Compared to the stretching group, the aerobic activity group had greater preservation of total brain volume, increased local gray matter volume, and increased directional stretch of brain tissue," said Dr. Kim.  

Among participants of the stretching group, the analysis revealed a local contraction, or atrophy, within the white matter connecting fibers. Such directional deformation, or shape change, is partially related to volume loss, but not always, according to Dr. Kim.

"Directional changes in the brain without local volume changes could be a novel biomarker for neurologic disease," he said. "It may be a more sensitive marker for the tiny changes that occur in a specific brain region before volumetric changes are detectable on MRI."  

Both MRI measures are important to the treatment of MCI and Alzheimer's disease, which require the careful tracking of changes in the brain while patients engage in interventions, including diet and exercise, to slow the progression of the disease.  

Study participants were tested to determine the effect of exercise intervention on cognitive performance. Participants in the aerobic exercise group showed statistically significant improvement in executive function after six months, whereas the stretching group did not improve.  

"Any type of exercise can be beneficial," said Dr. Kim. "If possible, aerobic activity may create potential benefits for higher cognitive functioning."    

Studies Provide More Insight Into Zika Effects

Three studies reported on the effects of the Zika virus outbreak in Brazil. The first study examined CT findings of the CNS in 16 newborn babies with congenital Zika virus infection confirmed by tests in CSF. The researchers identified a pattern of CT brain findings in the babies, including decreased brain volume, simplified gyral pattern, calcifications, ventricular dilatation, and prominent occipital bone.

"We live in Pernambuco, a state in northeastern Brazil, which had the highest number of patients with microcephaly during the Zika outbreak in our country," said Natacha Calheiros de Lima Petribu, MD, of the Department of Radiology at Barão de Lucena Hospital. "Our study proves that Zika virus infection can cause congenital brain damage in babies with and without microcephaly."  

Another study analyzed the imaging results of three target groups affected by Zika: adults who developed acute neurologic syndrome, newborns with vertical infection with neurologic disorders, and pregnant women with rash outbreaks suggestive of Zika. Many of the adults had symptoms of Guillain-Barré syndrome. A few showed inflammation of the brain and spinal cord (ie, Bickerstaff's encephalitis) or brainstem and spinal cord lesions. Common MRI findings included enhancement of certain spinal and facial nerves. In the newborns, MRI showed orbital injuries and anatomical changes in brain tissue.  

"It was alarming to find so many cases of neurologic syndromes in adults, some very serious, related to Zika virus infection," said study author Emerson de Melo Casagrande, MD, of the Department of Radiology at Antonio Pedro University Hospital--Federal Fluminense University. "We have also noticed a difference between these syndromes, even though the trigger was the same."

In a third study, ultrasound and fetal MRI were performed on pregnant patients with Zika virus infection at different gestational ages. Once the babies were born, they underwent ultrasound, CT, and MRI. The researchers then created 3-D virtual and physical models of the skulls. More than half of the babies had microcephaly, brain calcifications, and loss of brain tissue volume, along with other structural changes.

"The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly," said study author Heron Werner Jr, MD, PhD, of the Department of Radiology at Clínica de Diagnóstico por Imagem. "An early diagnosis may help in treating these babies after birth. Moreover, the knowledge of abnormalities present in the CNS may give hints about the pathophysiology of the disease."

Head Impacts Lead to Brain Changes in High School Football Players

Brain imaging exams performed on high school football players after a single season reveal changes in the gray and white matter that correlated with exposure to head impacts, according to researchers.

"It is important to understand the potential changes occurring in the brain related to youth contact sports," said Elizabeth Moody Davenport, PhD, a postdoctoral researcher at UT Southwestern Medical Center in Dallas. "We know that some professional football players suffer from a serious condition called chronic traumatic encephalopathy or CTE. We are attempting to find out when and how that process starts, so that we can keep sports a healthy activity for millions of children and adolescents."

The study included 24 players from a high school football team in North Carolina, each of whom wore a helmet outfitted with the Head Impact Telemetry System (HITS) during all practices and games. The helmets are lined with six accelerometers that measure the magnitude, location, and direction of a hit. Data from the helmets can be uploaded to a computer for analysis.  

"We saw changes in these young players' brains on both structural and functional imaging after a single season of football," said Dr. Davenport.  

In the study, each player underwent pre- and post-season imaging, including a specialized MRI scan, from which diffusion tensor imaging and diffusion kurtosis imaging data were extracted to measure the brain's white matter integrity, and a magnetoencephalography (MEG) scan, which records and analyzes the magnetic fields produced by brain waves. Diffusion imaging can measure the structural white matter changes in the brain, and MEG assesses changes in function.

"MEG can be used to measure delta waves in the brain, which are a type of distress signal," said Dr. Davenport. "Delta waves represent slow wave activity that increases after brain injuries. The delta waves we saw came from the surface of the brain, while diffusion imaging is a measure of the white matter deeper in the brain."  

The research team calculated the change in imaging metrics between the pre- and post-season imaging exams. They measured abnormalities observed on diffusion imaging and abnormally increased delta-wave activity on MEG. The imaging results were then combined with player-specific impact data from the HITS. None of the 24 players were diagnosed with a concussion during the study.

Players with greater head impact exposure had the greatest change in diffusion imaging and MEG metrics. "Change in diffusion imaging metrics correlated most to linear acceleration, similar to the impact of a car crash," said Dr. Davenport. "MEG changes correlated most to rotational impact, similar to a boxer's punch. These results demonstrate that you need both imaging metrics to assess impact exposure, because they correlate with different biomechanical processes."

Similar studies are being conducted this fall, and a consortium has been formed to continue the brain imaging research in youth contact sports across the country, said Dr. Davenport. "Without a larger population that is closely followed in a longitudinal study, it is difficult to know the long-term effects of these changes," she said. "We do not know if the brain's developmental trajectory is altered, or if the off-season time allows for the brain to return to normal."

Depression in Soldiers Linked to Brain Disruption From Injury

Using multiple brain imaging techniques, researchers have found that a disruption of the circuitry in the brain's cognitive-emotional pathways may provide a physical foundation for depression symptoms in some service members who have had mild traumatic brain injury (mTBI) in combat. "We can link these connectivity changes in the brain to poor top-down emotional processing and greater maladaptive rumination, or worrying, in symptomatic depressed soldiers after mTBI," said Ping-Hong Yeh, PhD, scientist and physicist at the National Intrepid Center of Excellence, Walter Reed National Military Medical Center in Bethesda, Maryland.

According to the Defense and Veterans Brain Injury Center, 352,619 service members worldwide have been diagnosed with TBI since 2000, the majority of these cases being mTBI. In addition, psychiatric disorders, such as anxiety and major depressive disorders, are becoming common in military personnel with brain injuries.

"With the increased survival of soldiers due to improvements in body armor and advanced medical care, there has been an increase in the number of soldiers surviving major trauma. Consequently, a large number of soldiers are returning from war with mTBI," said Dr. Yeh. "Mood disorders are common in military-related mTBI patients. This is an ongoing problem facing a large number of warriors in current areas of conflict, and it is likely to be a persistent problem for the foreseeable future."

For the study, researchers used diffusion-weighted imaging (DWI) and resting-state functional MRI (fMRI) to examine 130 active male service members diagnosed with mTBI and a control group of 52 men without mTBI. Depression symptoms were rated based on the Beck Depression Inventory (BDI), a 21-item, self-reporting assessment that measures characteristic attitudes and symptoms of depression. Patients with a BDI score greater than 20 are considered to have moderate to severe depression symptoms.

BDI scores showed that 75 of the patients with mTBI had moderate to severe depression symptoms. Imaging results showed that white matter tracts—the circuits that connect brain regions critical for cognitive and emotional control—were disrupted in the patients with moderate to severe depression symptoms. Researchers also saw changes in the gray matter cognitive-emotional networks in these patients.

"We found consistencies in the locations of disrupted neurocircuitry, as revealed by DWI and resting-state fMRI, that are unique to the clinical symptoms of mTBI patients," said Dr. Yeh. "We have related the brain structural and functional changes in cognitive-emotional networks to depressive symptoms in mTBI patients."  

This research can possibly lead to treatment strategies in the future, he added. "Though the results of this study were not applied directly to patient care, the neuroimaging changes we found might be incorporated into treatment plans for personalized medicine in the future."  

Short-Term Sleep Deprivation Affects Heart Function

Getting too little sleep takes a toll on your heart, researchers reported. People who work in fire and emergency medical services, medical residencies, and other high-stress jobs are often called upon to work 24-hour shifts with little opportunity for sleep. While it is known that extreme fatigue can affect many physical, cognitive, and emotional processes, this is the first study to examine how working a 24-hour shift specifically affects cardiac function.

"For the first time, we have shown that short-term sleep deprivation in the context of 24-hour shifts can lead to a significant increase in cardiac contractility, blood pressure, and heart rate," said study author Daniel Kuetting, MD, of the Department of Diagnostic and Interventional Radiology at the University of Bonn in Germany.  

For the study, Dr. Kuetting and colleagues recruited 20 healthy radiologists (19 men) with a mean age of 31.6. Each of the study participants underwent cardiovascular magnetic resonance (CMR) imaging with strain analysis before and after a 24-hour shift with an average of three hours of sleep.

"Cardiac function in the context of sleep deprivation has not previously been investigated with CMR strain analysis, the most sensitive parameter of cardiac contractility," said Dr. Kuetting. The researchers also collected blood and urine samples from the participants and measured blood pressure and heart rate.  

Following short-term sleep deprivation, the participants showed significant increases in mean peak systolic strain (-23.4 vs -21.9), systolic (118.5 mmHg vs 112.8 mmHg) and diastolic (69.2 mmHg vs 62.9 mmHg) blood pressure and heart rate (68.9 bpm vs 63.0 bpm). In addition, the participants had significant increases in levels of thyroid stimulating hormone (TSH), thyroid hormones FT3 and FT4, and cortisol.  

Although the researchers were able to perform follow-up examinations of half of the participants after regular sleep, further study in a larger cohort is needed to determine possible long-term effects of sleep loss, said Dr. Kuetting.

"The study was designed to investigate real-life work-related sleep deprivation," said Dr. Kuetting. "While the participants were not permitted to consume caffeine or food and beverages containing theobromine, such as chocolate, nuts, or tea, we did not take into account factors like individual stress level or environmental stimuli."

As people continue to work longer hours or work at more than one job to make ends meet, it is critical to investigate the detrimental effects of too much work and not enough sleep. The results of this pilot study are transferable to other professions in which long periods of uninterrupted labor are common, said Dr. Kuetting. "These findings may help us better understand how workload and shift duration affect public health."  

Aerobic Exercise Preserves Brain Volume and Improves Cognitive Function

Using a new MRI technique, researchers have found that adults with mild cognitive impairment (MCI) who exercised four times per week during a six-month period experienced an increase in brain volume in specific areas of the brain, but adults who participated in aerobic exercise experienced greater gains than those who just stretched.  

"Even over a short period of time, we saw aerobic exercise lead to a remarkable change in the brain," said Laura D. Baker, PhD, Associate Professor of Gerontology and Geriatric Medicine at Wake Forest School of Medicine (WFSM) in Winston-Salem, North Carolina.

The study included 35 adults with MCI participating in a randomized, controlled trial of exercise intervention. The participants were separated into two groups. Sixteen adults (average age, 63) engaged in aerobic activity, including treadmill, stationary bike, or elliptical training, four times per week for six months. A control group of 19 adults (average age, 67) participated in stretching exercises with the same frequency. High-resolution brain MR images were acquired from all participants before and after the six-month activity period. The MRI results were compared using conventional and biomechanical metrics to measure the change in brain volume and shape.  

"We used high-resolution MR images to measure anatomical changes within areas of the brain to obtain volumetric data and directional information," said Jeongchul Kim, PhD, a coinvestigator at WFSM.  

The analysis revealed that for both the aerobic and stretching groups, brain volume increased in most gray matter regions, including the temporal lobe, which supports short-term memory.  

"Compared to the stretching group, the aerobic activity group had greater preservation of total brain volume, increased local gray matter volume, and increased directional stretch of brain tissue," said Dr. Kim.  

Among participants of the stretching group, the analysis revealed a local contraction, or atrophy, within the white matter connecting fibers. Such directional deformation, or shape change, is partially related to volume loss, but not always, according to Dr. Kim.

"Directional changes in the brain without local volume changes could be a novel biomarker for neurologic disease," he said. "It may be a more sensitive marker for the tiny changes that occur in a specific brain region before volumetric changes are detectable on MRI."  

Both MRI measures are important to the treatment of MCI and Alzheimer's disease, which require the careful tracking of changes in the brain while patients engage in interventions, including diet and exercise, to slow the progression of the disease.  

Study participants were tested to determine the effect of exercise intervention on cognitive performance. Participants in the aerobic exercise group showed statistically significant improvement in executive function after six months, whereas the stretching group did not improve.  

"Any type of exercise can be beneficial," said Dr. Kim. "If possible, aerobic activity may create potential benefits for higher cognitive functioning."    

Patients with epilepsy who also have periventricular nodular heterotopia (PVNH) are difficult to manage surgically because the relative influence of the nodular tissue and the overlying cortex on the generation of seizures is variable. A review of the relevant medical literature suggests that inter-ictal spiking from nodules often occurs in patients with PVNH, but it is rare for patients to experience seizures arising from the nodular tissue alone. It is more likely to find that the onset of seizures occurs simultaneously with overlying neocortex or mesial temporal structures.    

Thompson SA, Kalamangalam GP, Tandon N. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia. Seizure. 2016;41:211-216.

Patients with epilepsy who also have periventricular nodular heterotopia (PVNH) are difficult to manage surgically because the relative influence of the nodular tissue and the overlying cortex on the generation of seizures is variable. A review of the relevant medical literature suggests that inter-ictal spiking from nodules often occurs in patients with PVNH, but it is rare for patients to experience seizures arising from the nodular tissue alone. It is more likely to find that the onset of seizures occurs simultaneously with overlying neocortex or mesial temporal structures.    

Thompson SA, Kalamangalam GP, Tandon N. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia. Seizure. 2016;41:211-216.

Patients with epilepsy who also have periventricular nodular heterotopia (PVNH) are difficult to manage surgically because the relative influence of the nodular tissue and the overlying cortex on the generation of seizures is variable. A review of the relevant medical literature suggests that inter-ictal spiking from nodules often occurs in patients with PVNH, but it is rare for patients to experience seizures arising from the nodular tissue alone. It is more likely to find that the onset of seizures occurs simultaneously with overlying neocortex or mesial temporal structures.    

Thompson SA, Kalamangalam GP, Tandon N. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia. Seizure. 2016;41:211-216.

Despite the fact that hormonal contraceptives interact with certain antiepileptic drugs, a recent study has shown that only 35% of 397 female patients with epilepsy were given any clinician counseling about contraceptive choices during their first clinic visit. And these patients were unlikely to receive contraceptive counseling during subsequent visits. The implications of these findings are troubling:  Many antiepileptic agents decrease the efficacy of hormonal contraceptives by inducing hepatic enzymes, and estrogen-containing contraceptives are known to accelerate the metabolism of lamotrigine, an antiepileptic drug commonly prescribed in women of child-bearing age. Espinera et al also found that when women with epilepsy are given advice about the advantages of IUDs, they are far more likely to switch to IUDs, which are highly effective without AED drug interactions.

Espinera AR, Gavvala J, Bellinski I, et al. Counseling by epileptologists affects contraceptive choices of women with epilepsy. Epilepsy Behav. 2016;65:1-6.

Despite the fact that hormonal contraceptives interact with certain antiepileptic drugs, a recent study has shown that only 35% of 397 female patients with epilepsy were given any clinician counseling about contraceptive choices during their first clinic visit. And these patients were unlikely to receive contraceptive counseling during subsequent visits. The implications of these findings are troubling:  Many antiepileptic agents decrease the efficacy of hormonal contraceptives by inducing hepatic enzymes, and estrogen-containing contraceptives are known to accelerate the metabolism of lamotrigine, an antiepileptic drug commonly prescribed in women of child-bearing age. Espinera et al also found that when women with epilepsy are given advice about the advantages of IUDs, they are far more likely to switch to IUDs, which are highly effective without AED drug interactions.

Espinera AR, Gavvala J, Bellinski I, et al. Counseling by epileptologists affects contraceptive choices of women with epilepsy. Epilepsy Behav. 2016;65:1-6.

Despite the fact that hormonal contraceptives interact with certain antiepileptic drugs, a recent study has shown that only 35% of 397 female patients with epilepsy were given any clinician counseling about contraceptive choices during their first clinic visit. And these patients were unlikely to receive contraceptive counseling during subsequent visits. The implications of these findings are troubling:  Many antiepileptic agents decrease the efficacy of hormonal contraceptives by inducing hepatic enzymes, and estrogen-containing contraceptives are known to accelerate the metabolism of lamotrigine, an antiepileptic drug commonly prescribed in women of child-bearing age. Espinera et al also found that when women with epilepsy are given advice about the advantages of IUDs, they are far more likely to switch to IUDs, which are highly effective without AED drug interactions.

Espinera AR, Gavvala J, Bellinski I, et al. Counseling by epileptologists affects contraceptive choices of women with epilepsy. Epilepsy Behav. 2016;65:1-6.

Young adults with epilepsy are at greater risk for neurodevelopmental and behavioral disorders than some other patient populations, according to a recent case-control study that looked at hospital admissions, outpatients, and ED visits for adults with epilepsy, migraine, or leg fracture. The study cohort consisted of 5666 adult epilepsy patients  between 19 and 25 years of age who were seen in hospitals and EDs, 17,507 patients with migraine, and 5966 patients with leg fractures. The researchers found that 51.8% of patients with epilepsy had behavioral health issues versus 37.6% of those with migraine and 21.6% of patients with fractures. Similarly, patients with epilepsy were 297% more likely to have a neurodevelopmental disorder compared with those with migraine.

Wagner JL, Wilson DA, Kellermann T, el al. Behavioral health in young adults with epilepsy: Implications for transition of care. Epilepsy Behav. 2016;65:7-12.

Young adults with epilepsy are at greater risk for neurodevelopmental and behavioral disorders than some other patient populations, according to a recent case-control study that looked at hospital admissions, outpatients, and ED visits for adults with epilepsy, migraine, or leg fracture. The study cohort consisted of 5666 adult epilepsy patients  between 19 and 25 years of age who were seen in hospitals and EDs, 17,507 patients with migraine, and 5966 patients with leg fractures. The researchers found that 51.8% of patients with epilepsy had behavioral health issues versus 37.6% of those with migraine and 21.6% of patients with fractures. Similarly, patients with epilepsy were 297% more likely to have a neurodevelopmental disorder compared with those with migraine.

Wagner JL, Wilson DA, Kellermann T, el al. Behavioral health in young adults with epilepsy: Implications for transition of care. Epilepsy Behav. 2016;65:7-12.

Young adults with epilepsy are at greater risk for neurodevelopmental and behavioral disorders than some other patient populations, according to a recent case-control study that looked at hospital admissions, outpatients, and ED visits for adults with epilepsy, migraine, or leg fracture. The study cohort consisted of 5666 adult epilepsy patients  between 19 and 25 years of age who were seen in hospitals and EDs, 17,507 patients with migraine, and 5966 patients with leg fractures. The researchers found that 51.8% of patients with epilepsy had behavioral health issues versus 37.6% of those with migraine and 21.6% of patients with fractures. Similarly, patients with epilepsy were 297% more likely to have a neurodevelopmental disorder compared with those with migraine.

Wagner JL, Wilson DA, Kellermann T, el al. Behavioral health in young adults with epilepsy: Implications for transition of care. Epilepsy Behav. 2016;65:7-12.

To determine how well pregnant women with epilepsy adhere to their medication regimen, Ernst et al studied their intake of antiepileptic medication by providing them with an iPod Touch loaded with a mobile app specifically designed to track such data. Eighty-six women with epilepsy monitored their seizures and medication use. The study found that 75% of the women had tracked their medication usage for more than 80% of the days they were enrolled in the experiment. Among this subgroup, adherence to the anti-epilepsy drug regimen was 97.7%; 44% said they had missed taking their medication for at least one day. The investigators speculate that the high adherence rate may have been the result of using the mobile app itself.

Ernst L. Harden CL, Pennell PB, et al.  Medication adherence in women with epilepsy who are planning pregnancy. Epilepsia. 2016; 57(12):2039-2044.

To determine how well pregnant women with epilepsy adhere to their medication regimen, Ernst et al studied their intake of antiepileptic medication by providing them with an iPod Touch loaded with a mobile app specifically designed to track such data. Eighty-six women with epilepsy monitored their seizures and medication use. The study found that 75% of the women had tracked their medication usage for more than 80% of the days they were enrolled in the experiment. Among this subgroup, adherence to the anti-epilepsy drug regimen was 97.7%; 44% said they had missed taking their medication for at least one day. The investigators speculate that the high adherence rate may have been the result of using the mobile app itself.

Ernst L. Harden CL, Pennell PB, et al.  Medication adherence in women with epilepsy who are planning pregnancy. Epilepsia. 2016; 57(12):2039-2044.

To determine how well pregnant women with epilepsy adhere to their medication regimen, Ernst et al studied their intake of antiepileptic medication by providing them with an iPod Touch loaded with a mobile app specifically designed to track such data. Eighty-six women with epilepsy monitored their seizures and medication use. The study found that 75% of the women had tracked their medication usage for more than 80% of the days they were enrolled in the experiment. Among this subgroup, adherence to the anti-epilepsy drug regimen was 97.7%; 44% said they had missed taking their medication for at least one day. The investigators speculate that the high adherence rate may have been the result of using the mobile app itself.

Ernst L. Harden CL, Pennell PB, et al.  Medication adherence in women with epilepsy who are planning pregnancy. Epilepsia. 2016; 57(12):2039-2044.

Among patients who have experienced traumatic brain injury, those who have had immediate or late seizures during an acute hospital stay are at increased of developing later posttraumatic seizures. Researchers found that new onset posttraumatic seizures were mostly likely to occur between the time patients were discharged from inpatient rehabilitation and 1 year (9.2%). By year 5, the cumulative incidence of such seizures was 20.5%. A patient’s race, intracranial pathology, and neurosurgical procedures also factored into their relative risk of posttraumatic seizures.

Ritter AC, Wagner AK, Fabio A, et al.  Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A Traumatic Brain Injury Model Systems Study. Epilepsia. 2016;57(12):1968-1977.

Among patients who have experienced traumatic brain injury, those who have had immediate or late seizures during an acute hospital stay are at increased of developing later posttraumatic seizures. Researchers found that new onset posttraumatic seizures were mostly likely to occur between the time patients were discharged from inpatient rehabilitation and 1 year (9.2%). By year 5, the cumulative incidence of such seizures was 20.5%. A patient’s race, intracranial pathology, and neurosurgical procedures also factored into their relative risk of posttraumatic seizures.

Ritter AC, Wagner AK, Fabio A, et al.  Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A Traumatic Brain Injury Model Systems Study. Epilepsia. 2016;57(12):1968-1977.

Among patients who have experienced traumatic brain injury, those who have had immediate or late seizures during an acute hospital stay are at increased of developing later posttraumatic seizures. Researchers found that new onset posttraumatic seizures were mostly likely to occur between the time patients were discharged from inpatient rehabilitation and 1 year (9.2%). By year 5, the cumulative incidence of such seizures was 20.5%. A patient’s race, intracranial pathology, and neurosurgical procedures also factored into their relative risk of posttraumatic seizures.

Ritter AC, Wagner AK, Fabio A, et al.  Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A Traumatic Brain Injury Model Systems Study. Epilepsia. 2016;57(12):1968-1977.

Induced hypothermia does not improve clinical outcomes among patients with convulsive status epilepticus (CSE), according to a new multicenter study published in the New England Journal of Medicine. To reach that conclusion, investigators assigned 270 critically ill patients with CSE on mechanical ventilation to either standard care or standard care plus hypothermia, which lowered their body temperature to 32 to 34⁰C for 24 hours. To measure the impact of hypothermia, researchers used the Glasgow Outcome Scale (GOS) score and defined success as a GOS score of 5, which represents no or minimal neurologic deficit, at 90 days. Forty-nine percent of patients on hypothermia achieved a score of 5, compared to 43% of those on standard care, which was statistically insignificant (P=.43).

Legriel S, Lemiale V, Schenck, M, et al.  Hypothermia for Neuroprotection in Convulsive Status Epilepticus.  N Engl J Med. 2016;375(25):2457-2467.

Induced hypothermia does not improve clinical outcomes among patients with convulsive status epilepticus (CSE), according to a new multicenter study published in the New England Journal of Medicine. To reach that conclusion, investigators assigned 270 critically ill patients with CSE on mechanical ventilation to either standard care or standard care plus hypothermia, which lowered their body temperature to 32 to 34⁰C for 24 hours. To measure the impact of hypothermia, researchers used the Glasgow Outcome Scale (GOS) score and defined success as a GOS score of 5, which represents no or minimal neurologic deficit, at 90 days. Forty-nine percent of patients on hypothermia achieved a score of 5, compared to 43% of those on standard care, which was statistically insignificant (P=.43).

Legriel S, Lemiale V, Schenck, M, et al.  Hypothermia for Neuroprotection in Convulsive Status Epilepticus.  N Engl J Med. 2016;375(25):2457-2467.

Induced hypothermia does not improve clinical outcomes among patients with convulsive status epilepticus (CSE), according to a new multicenter study published in the New England Journal of Medicine. To reach that conclusion, investigators assigned 270 critically ill patients with CSE on mechanical ventilation to either standard care or standard care plus hypothermia, which lowered their body temperature to 32 to 34⁰C for 24 hours. To measure the impact of hypothermia, researchers used the Glasgow Outcome Scale (GOS) score and defined success as a GOS score of 5, which represents no or minimal neurologic deficit, at 90 days. Forty-nine percent of patients on hypothermia achieved a score of 5, compared to 43% of those on standard care, which was statistically insignificant (P=.43).

Legriel S, Lemiale V, Schenck, M, et al.  Hypothermia for Neuroprotection in Convulsive Status Epilepticus.  N Engl J Med. 2016;375(25):2457-2467.

This new phase III trial of solanezumab reveals that the drug is not effective for patients with mild Alzheimer’s disease, despite the hint that it was possibly effective based on post hoc analyses of earlier studies with this drug.

The findings expose the hazards of such post hoc analyses, typically done when the desired results are not observed, in the hope of squeezing lemonade from lemons. Although the subanalysis of patients with mild Alzheimer’s disease in the earlier studies suggested a 34% slowing of cognitive decline, as assessed by ADAS-Cog, an incremental slowing of 11% was seen in the new study that was not even statistically significant. While some secondary end points reached statistical significance, the slowing was so modest as to make no practical difference clinically.

I cannot emphasize enough that such equivocal results as seen in EXPEDITION3 do absolutely nothing to either confirm or deny the amyloid hypothesis. By now, there have been so many of these studies with antiamyloid agents, with little or no hint of efficacy, that we have long passed the definition of insanity: doing the same thing over and over in the hope of getting a different result.

The combination of all these clinical trial failures with the result of imaging studies that have shown amyloid deposition some 20 years before the expected onset of symptoms clearly tells us that antiamyloid agents should only be considered as potential prophylactics. By the time symptoms appear, disease progression is largely independent of amyloid and may be primarily tau-driven, spreading from neuron to neuron even when amyloid is effectively targeted by therapeutics. Even the A4 and DIAN studies are likely initiating treatment too late to make anything more than a modest effect with little practical value clinically. I am not suggesting that we drop amyloid as a target, only that we stop making these incremental changes in clinical trial design in the hope of getting a different result.

—Michael S. Wolfe, PhD
Mathias P. Mertes Professor of Medicinal Chemistry
University of Kansas, Lawrence

This new phase III trial of solanezumab reveals that the drug is not effective for patients with mild Alzheimer’s disease, despite the hint that it was possibly effective based on post hoc analyses of earlier studies with this drug.

The findings expose the hazards of such post hoc analyses, typically done when the desired results are not observed, in the hope of squeezing lemonade from lemons. Although the subanalysis of patients with mild Alzheimer’s disease in the earlier studies suggested a 34% slowing of cognitive decline, as assessed by ADAS-Cog, an incremental slowing of 11% was seen in the new study that was not even statistically significant. While some secondary end points reached statistical significance, the slowing was so modest as to make no practical difference clinically.

I cannot emphasize enough that such equivocal results as seen in EXPEDITION3 do absolutely nothing to either confirm or deny the amyloid hypothesis. By now, there have been so many of these studies with antiamyloid agents, with little or no hint of efficacy, that we have long passed the definition of insanity: doing the same thing over and over in the hope of getting a different result.

The combination of all these clinical trial failures with the result of imaging studies that have shown amyloid deposition some 20 years before the expected onset of symptoms clearly tells us that antiamyloid agents should only be considered as potential prophylactics. By the time symptoms appear, disease progression is largely independent of amyloid and may be primarily tau-driven, spreading from neuron to neuron even when amyloid is effectively targeted by therapeutics. Even the A4 and DIAN studies are likely initiating treatment too late to make anything more than a modest effect with little practical value clinically. I am not suggesting that we drop amyloid as a target, only that we stop making these incremental changes in clinical trial design in the hope of getting a different result.

—Michael S. Wolfe, PhD
Mathias P. Mertes Professor of Medicinal Chemistry
University of Kansas, Lawrence

This new phase III trial of solanezumab reveals that the drug is not effective for patients with mild Alzheimer’s disease, despite the hint that it was possibly effective based on post hoc analyses of earlier studies with this drug.

The findings expose the hazards of such post hoc analyses, typically done when the desired results are not observed, in the hope of squeezing lemonade from lemons. Although the subanalysis of patients with mild Alzheimer’s disease in the earlier studies suggested a 34% slowing of cognitive decline, as assessed by ADAS-Cog, an incremental slowing of 11% was seen in the new study that was not even statistically significant. While some secondary end points reached statistical significance, the slowing was so modest as to make no practical difference clinically.

I cannot emphasize enough that such equivocal results as seen in EXPEDITION3 do absolutely nothing to either confirm or deny the amyloid hypothesis. By now, there have been so many of these studies with antiamyloid agents, with little or no hint of efficacy, that we have long passed the definition of insanity: doing the same thing over and over in the hope of getting a different result.

The combination of all these clinical trial failures with the result of imaging studies that have shown amyloid deposition some 20 years before the expected onset of symptoms clearly tells us that antiamyloid agents should only be considered as potential prophylactics. By the time symptoms appear, disease progression is largely independent of amyloid and may be primarily tau-driven, spreading from neuron to neuron even when amyloid is effectively targeted by therapeutics. Even the A4 and DIAN studies are likely initiating treatment too late to make anything more than a modest effect with little practical value clinically. I am not suggesting that we drop amyloid as a target, only that we stop making these incremental changes in clinical trial design in the hope of getting a different result.

—Michael S. Wolfe, PhD
Mathias P. Mertes Professor of Medicinal Chemistry
University of Kansas, Lawrence

BOSTON – Lysosomal acid lipase deficiency (LAL-D), a rare genetic cause of marked dyslipidemia that causes early multisystem organ damage, was effectively treated by a human recombinant enzyme to replace deficient lysosomal acid lipase, and the replacement enzyme was well tolerated over a 76-week trial.

LAL-D, when it begins in infancy, is usually fatal within the first year.
 

When LAL-D occurs later in life, it’s believed to be an “underappreciated cause of fibrosis, cirrhosis, severe dyslipidemia, and early-onset atherosclerosis,” according to Katryn Furuya, MD, and the coauthors of a poster presentation given at the annual meeting of the American Association for the Study of Liver Diseases.

Supplying the human recombinant lysosomal acid lipase, termed sebelipase alfa (SA), to children and adults with LAL-D over a 76-week period resulted in a reduction in alanine aminotransferase (ALT) for 98% of participants, normalization of ALT for 51% of participants, and normalization of aspartate aminotransferase (AST) levels for 65% of patients. Patients on SA also experienced reductions in serum triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and liver fat and total liver volume. “We’re basically replacing what they’re missing,” senior author Barbara Burton, MD, said in an interview.

[email protected]

On Twitter @karioakes

BOSTON – Lysosomal acid lipase deficiency (LAL-D), a rare genetic cause of marked dyslipidemia that causes early multisystem organ damage, was effectively treated by a human recombinant enzyme to replace deficient lysosomal acid lipase, and the replacement enzyme was well tolerated over a 76-week trial.

LAL-D, when it begins in infancy, is usually fatal within the first year.
 

When LAL-D occurs later in life, it’s believed to be an “underappreciated cause of fibrosis, cirrhosis, severe dyslipidemia, and early-onset atherosclerosis,” according to Katryn Furuya, MD, and the coauthors of a poster presentation given at the annual meeting of the American Association for the Study of Liver Diseases.

Supplying the human recombinant lysosomal acid lipase, termed sebelipase alfa (SA), to children and adults with LAL-D over a 76-week period resulted in a reduction in alanine aminotransferase (ALT) for 98% of participants, normalization of ALT for 51% of participants, and normalization of aspartate aminotransferase (AST) levels for 65% of patients. Patients on SA also experienced reductions in serum triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and liver fat and total liver volume. “We’re basically replacing what they’re missing,” senior author Barbara Burton, MD, said in an interview.

[email protected]

On Twitter @karioakes

BOSTON – Lysosomal acid lipase deficiency (LAL-D), a rare genetic cause of marked dyslipidemia that causes early multisystem organ damage, was effectively treated by a human recombinant enzyme to replace deficient lysosomal acid lipase, and the replacement enzyme was well tolerated over a 76-week trial.

LAL-D, when it begins in infancy, is usually fatal within the first year.
 

When LAL-D occurs later in life, it’s believed to be an “underappreciated cause of fibrosis, cirrhosis, severe dyslipidemia, and early-onset atherosclerosis,” according to Katryn Furuya, MD, and the coauthors of a poster presentation given at the annual meeting of the American Association for the Study of Liver Diseases.

Supplying the human recombinant lysosomal acid lipase, termed sebelipase alfa (SA), to children and adults with LAL-D over a 76-week period resulted in a reduction in alanine aminotransferase (ALT) for 98% of participants, normalization of ALT for 51% of participants, and normalization of aspartate aminotransferase (AST) levels for 65% of patients. Patients on SA also experienced reductions in serum triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and liver fat and total liver volume. “We’re basically replacing what they’re missing,” senior author Barbara Burton, MD, said in an interview.

[email protected]

On Twitter @karioakes