User login
Breathe2Relax
The Breathe2Relax app is centered around the basic concept that breathing into the belly—diaphragmatic breathing—provides deeper relaxation than does breathing into the chest. Designed for use by individuals with PTSD and TBI, the app helps with mood stabilization, anger control, and anxiety management. It is a portable stress management tool with breathing exercises documented to decrease the body’s “fight-or-flight” stress response.
Setup
Although you can jump right into the guided breathing exercises, you may find a richer experience by exploring the setup menu of the app before beginning. (TIP: Skip the Personalize button and go straight to Setup.) Setting up the app to your personal preferences will reduce the chances of growing agitated when you begin the breathing exercises.
Almost every element you encounter while using the app can be modified: scenery (eg, mountain meadows or the cosmos), background music (mostly instrumental and earth sounds, plus a choice for no music at all), inhale and exhale lengths set to tenths of a second, whether a breathing metronome and visual prompts will display during the exercise, and whether a voice will prompt breathing instructions. Additional modifications include how many cycles of inhalations/exhalations will be provided, whether you want to track your stress levels (these can be graphed later and tracked over time), and, importantly, whether you want this data to be saved and transmitted to T2 for survey data (there is a choice to remain anonymous) or to disenroll from the study and delete all stored information.
Breathe
Once all of your preferences are set, they will remain saved in the app until you change them. If you already know how to breathe diaphragmatically, click “Breathe” to begin a breathing session. If you are uncertain or need a refresher, click “Show Me How” to watch a 2-minute instructional video. As noted during this instruction, “Be patient. Although breathing sounds like it should be easy to do, diaphragmatic breathing takes practice.” It is recommended that this practice be done every day for maximum benefit, and it is okay to practice when you’re already feeling relaxed.
When you are ready to work through the breathing session, begin by rating your stress level. If you want to skip this step, go ahead and hit “Skip.” If you never want to enter this information when you enter the breathing session portion of the app, click the box that reads “Do Not Show Again” or return to the Setup menu and select “OFF” under Stress Tracking Information. However, by taking just a moment to note stress levels before (and after), you will see over time how you are performing and whether or not this is a beneficial exercise for you. Oftentimes, we don’t accurately perceive our own emotions and reactions, so graphing this output can help limit personal bias.
If you are following the breathing metronome, you will see it rise and fall with each breath until the session is complete. You will then be prompted to record your ending stress level and can click “Finish” to return to the home screen.
Results
The benefit of tracking stress levels during breathing sessions is revealed in a simple line graph. A thin line is produced using starting stress levels and a thick line is produced using ending stress levels. Sometimes the breathing session will result in a dramatic shift in stress level reduction, sometimes an insignificant reduction, and sometimes it may seemingly increase stress levels. If the latter happens, it is possible you were unable to focus on the exercise enough to properly engage in diaphragmatic breathing, or maybe one of the app settings has agitated you and it’s time to update your settings in the Setup menu.
Learning
Read about or watch information on stress by selecting 1 of 3 topics. “Biology of Stress” covers what happens in the body during stress, the consequences of stress on the body, how breathing can help control the stress response, and the resilience of the mind and body after handling a stressful episode. “Diaphragmatic Breathing” explains what the diaphragm is, the difference in oxygen levels supplied to the body during chest breathing and diaphragmatic breathing, and how to determine what kind of a breather you are. Access the Body Scanner under “Effects of Stress on the Body” to learn about the effects of stress on 10 different areas of the body.
Wellness Tips
On the home screen is a button called “Tip.” Tucked away in this little, unsuspecting corner of the app are wellness tips, such as “If you’re feeling guilty about something, remember that self-forgiveness means recognizing mistakes and accepting shortcomings” and “Don’t believe everything you think: Challenge your negative thoughts. Is there evidence to support the way you perceive the situation?” These tips don’t rotate frequently, but it’s a nice surprise when a new one displays.
Final Thoughts
This app can be used in several different ways, serving as a stand-alone stress management tool or in tandem with clinical care directed by a health care provider. As is noted by T2, “Due to its portability, this guided exercise is easily accessible when it is needed most.” And although the app was designed for individuals with PTSD and TBI, anybody who wants to feel more relaxed can access this free tool and reap the many benefits provided through diaphragmatic breathing.
The Breathe2Relax app is centered around the basic concept that breathing into the belly—diaphragmatic breathing—provides deeper relaxation than does breathing into the chest. Designed for use by individuals with PTSD and TBI, the app helps with mood stabilization, anger control, and anxiety management. It is a portable stress management tool with breathing exercises documented to decrease the body’s “fight-or-flight” stress response.
Setup
Although you can jump right into the guided breathing exercises, you may find a richer experience by exploring the setup menu of the app before beginning. (TIP: Skip the Personalize button and go straight to Setup.) Setting up the app to your personal preferences will reduce the chances of growing agitated when you begin the breathing exercises.
Almost every element you encounter while using the app can be modified: scenery (eg, mountain meadows or the cosmos), background music (mostly instrumental and earth sounds, plus a choice for no music at all), inhale and exhale lengths set to tenths of a second, whether a breathing metronome and visual prompts will display during the exercise, and whether a voice will prompt breathing instructions. Additional modifications include how many cycles of inhalations/exhalations will be provided, whether you want to track your stress levels (these can be graphed later and tracked over time), and, importantly, whether you want this data to be saved and transmitted to T2 for survey data (there is a choice to remain anonymous) or to disenroll from the study and delete all stored information.
Breathe
Once all of your preferences are set, they will remain saved in the app until you change them. If you already know how to breathe diaphragmatically, click “Breathe” to begin a breathing session. If you are uncertain or need a refresher, click “Show Me How” to watch a 2-minute instructional video. As noted during this instruction, “Be patient. Although breathing sounds like it should be easy to do, diaphragmatic breathing takes practice.” It is recommended that this practice be done every day for maximum benefit, and it is okay to practice when you’re already feeling relaxed.
When you are ready to work through the breathing session, begin by rating your stress level. If you want to skip this step, go ahead and hit “Skip.” If you never want to enter this information when you enter the breathing session portion of the app, click the box that reads “Do Not Show Again” or return to the Setup menu and select “OFF” under Stress Tracking Information. However, by taking just a moment to note stress levels before (and after), you will see over time how you are performing and whether or not this is a beneficial exercise for you. Oftentimes, we don’t accurately perceive our own emotions and reactions, so graphing this output can help limit personal bias.
If you are following the breathing metronome, you will see it rise and fall with each breath until the session is complete. You will then be prompted to record your ending stress level and can click “Finish” to return to the home screen.
Results
The benefit of tracking stress levels during breathing sessions is revealed in a simple line graph. A thin line is produced using starting stress levels and a thick line is produced using ending stress levels. Sometimes the breathing session will result in a dramatic shift in stress level reduction, sometimes an insignificant reduction, and sometimes it may seemingly increase stress levels. If the latter happens, it is possible you were unable to focus on the exercise enough to properly engage in diaphragmatic breathing, or maybe one of the app settings has agitated you and it’s time to update your settings in the Setup menu.
Learning
Read about or watch information on stress by selecting 1 of 3 topics. “Biology of Stress” covers what happens in the body during stress, the consequences of stress on the body, how breathing can help control the stress response, and the resilience of the mind and body after handling a stressful episode. “Diaphragmatic Breathing” explains what the diaphragm is, the difference in oxygen levels supplied to the body during chest breathing and diaphragmatic breathing, and how to determine what kind of a breather you are. Access the Body Scanner under “Effects of Stress on the Body” to learn about the effects of stress on 10 different areas of the body.
Wellness Tips
On the home screen is a button called “Tip.” Tucked away in this little, unsuspecting corner of the app are wellness tips, such as “If you’re feeling guilty about something, remember that self-forgiveness means recognizing mistakes and accepting shortcomings” and “Don’t believe everything you think: Challenge your negative thoughts. Is there evidence to support the way you perceive the situation?” These tips don’t rotate frequently, but it’s a nice surprise when a new one displays.
Final Thoughts
This app can be used in several different ways, serving as a stand-alone stress management tool or in tandem with clinical care directed by a health care provider. As is noted by T2, “Due to its portability, this guided exercise is easily accessible when it is needed most.” And although the app was designed for individuals with PTSD and TBI, anybody who wants to feel more relaxed can access this free tool and reap the many benefits provided through diaphragmatic breathing.
The Breathe2Relax app is centered around the basic concept that breathing into the belly—diaphragmatic breathing—provides deeper relaxation than does breathing into the chest. Designed for use by individuals with PTSD and TBI, the app helps with mood stabilization, anger control, and anxiety management. It is a portable stress management tool with breathing exercises documented to decrease the body’s “fight-or-flight” stress response.
Setup
Although you can jump right into the guided breathing exercises, you may find a richer experience by exploring the setup menu of the app before beginning. (TIP: Skip the Personalize button and go straight to Setup.) Setting up the app to your personal preferences will reduce the chances of growing agitated when you begin the breathing exercises.
Almost every element you encounter while using the app can be modified: scenery (eg, mountain meadows or the cosmos), background music (mostly instrumental and earth sounds, plus a choice for no music at all), inhale and exhale lengths set to tenths of a second, whether a breathing metronome and visual prompts will display during the exercise, and whether a voice will prompt breathing instructions. Additional modifications include how many cycles of inhalations/exhalations will be provided, whether you want to track your stress levels (these can be graphed later and tracked over time), and, importantly, whether you want this data to be saved and transmitted to T2 for survey data (there is a choice to remain anonymous) or to disenroll from the study and delete all stored information.
Breathe
Once all of your preferences are set, they will remain saved in the app until you change them. If you already know how to breathe diaphragmatically, click “Breathe” to begin a breathing session. If you are uncertain or need a refresher, click “Show Me How” to watch a 2-minute instructional video. As noted during this instruction, “Be patient. Although breathing sounds like it should be easy to do, diaphragmatic breathing takes practice.” It is recommended that this practice be done every day for maximum benefit, and it is okay to practice when you’re already feeling relaxed.
When you are ready to work through the breathing session, begin by rating your stress level. If you want to skip this step, go ahead and hit “Skip.” If you never want to enter this information when you enter the breathing session portion of the app, click the box that reads “Do Not Show Again” or return to the Setup menu and select “OFF” under Stress Tracking Information. However, by taking just a moment to note stress levels before (and after), you will see over time how you are performing and whether or not this is a beneficial exercise for you. Oftentimes, we don’t accurately perceive our own emotions and reactions, so graphing this output can help limit personal bias.
If you are following the breathing metronome, you will see it rise and fall with each breath until the session is complete. You will then be prompted to record your ending stress level and can click “Finish” to return to the home screen.
Results
The benefit of tracking stress levels during breathing sessions is revealed in a simple line graph. A thin line is produced using starting stress levels and a thick line is produced using ending stress levels. Sometimes the breathing session will result in a dramatic shift in stress level reduction, sometimes an insignificant reduction, and sometimes it may seemingly increase stress levels. If the latter happens, it is possible you were unable to focus on the exercise enough to properly engage in diaphragmatic breathing, or maybe one of the app settings has agitated you and it’s time to update your settings in the Setup menu.
Learning
Read about or watch information on stress by selecting 1 of 3 topics. “Biology of Stress” covers what happens in the body during stress, the consequences of stress on the body, how breathing can help control the stress response, and the resilience of the mind and body after handling a stressful episode. “Diaphragmatic Breathing” explains what the diaphragm is, the difference in oxygen levels supplied to the body during chest breathing and diaphragmatic breathing, and how to determine what kind of a breather you are. Access the Body Scanner under “Effects of Stress on the Body” to learn about the effects of stress on 10 different areas of the body.
Wellness Tips
On the home screen is a button called “Tip.” Tucked away in this little, unsuspecting corner of the app are wellness tips, such as “If you’re feeling guilty about something, remember that self-forgiveness means recognizing mistakes and accepting shortcomings” and “Don’t believe everything you think: Challenge your negative thoughts. Is there evidence to support the way you perceive the situation?” These tips don’t rotate frequently, but it’s a nice surprise when a new one displays.
Final Thoughts
This app can be used in several different ways, serving as a stand-alone stress management tool or in tandem with clinical care directed by a health care provider. As is noted by T2, “Due to its portability, this guided exercise is easily accessible when it is needed most.” And although the app was designed for individuals with PTSD and TBI, anybody who wants to feel more relaxed can access this free tool and reap the many benefits provided through diaphragmatic breathing.
Deployment-Related Brain Injury Is Strongly Associated With Migraine in Iraq and Afghanistan Veterans
Veterans who were deployed to combat zones in the Iraq and Afghanistan wars and experienced traumatic brain injury (TBI) have a strong and highly significant increase in the frequency and intensity of headaches, the majority of which are migraines, according to researchers.
The incidence of chronic daily headache (ie, 15 or more headache days per month) was three times greater, compared with controls, and the incidence of frequent headache (ie, 10 to 14 headache days per month) was 4.5 times greater in these soldiers than in control groups, reported lead author James R. Couch, MD, of the University of Oklahoma School of Medicine in Oklahoma City, and colleagues. “Combat zone deployment by itself is stressful. Since TBI is the signature injury of these wars and occurs in 15% to 20% of deployed soldiers, and both TBI and stress are known to be associated with headache, we sought to evaluate the differences in headache occurrence and severity between those who were deployed and those who were deployed and also experienced a TBI,” Dr. Couch said.
Dr. Couch and his team evaluated 53 pairs of deployed veterans with TBI and a matched group of veterans who were deployed but did not sustain a TBI (controls). All subjects with deployment-related TBI had headache, while 11 (23.9%) controls had no headache. In addition, 89% of headaches in the deployed veterans with TBI were migraine, compared with 40% in the control group. All subjects with deployment-related TBI reported significantly greater frequency and intensity of headache than the control group did.
Veterans who were deployed to combat zones in the Iraq and Afghanistan wars and experienced traumatic brain injury (TBI) have a strong and highly significant increase in the frequency and intensity of headaches, the majority of which are migraines, according to researchers.
The incidence of chronic daily headache (ie, 15 or more headache days per month) was three times greater, compared with controls, and the incidence of frequent headache (ie, 10 to 14 headache days per month) was 4.5 times greater in these soldiers than in control groups, reported lead author James R. Couch, MD, of the University of Oklahoma School of Medicine in Oklahoma City, and colleagues. “Combat zone deployment by itself is stressful. Since TBI is the signature injury of these wars and occurs in 15% to 20% of deployed soldiers, and both TBI and stress are known to be associated with headache, we sought to evaluate the differences in headache occurrence and severity between those who were deployed and those who were deployed and also experienced a TBI,” Dr. Couch said.
Dr. Couch and his team evaluated 53 pairs of deployed veterans with TBI and a matched group of veterans who were deployed but did not sustain a TBI (controls). All subjects with deployment-related TBI had headache, while 11 (23.9%) controls had no headache. In addition, 89% of headaches in the deployed veterans with TBI were migraine, compared with 40% in the control group. All subjects with deployment-related TBI reported significantly greater frequency and intensity of headache than the control group did.
Veterans who were deployed to combat zones in the Iraq and Afghanistan wars and experienced traumatic brain injury (TBI) have a strong and highly significant increase in the frequency and intensity of headaches, the majority of which are migraines, according to researchers.
The incidence of chronic daily headache (ie, 15 or more headache days per month) was three times greater, compared with controls, and the incidence of frequent headache (ie, 10 to 14 headache days per month) was 4.5 times greater in these soldiers than in control groups, reported lead author James R. Couch, MD, of the University of Oklahoma School of Medicine in Oklahoma City, and colleagues. “Combat zone deployment by itself is stressful. Since TBI is the signature injury of these wars and occurs in 15% to 20% of deployed soldiers, and both TBI and stress are known to be associated with headache, we sought to evaluate the differences in headache occurrence and severity between those who were deployed and those who were deployed and also experienced a TBI,” Dr. Couch said.
Dr. Couch and his team evaluated 53 pairs of deployed veterans with TBI and a matched group of veterans who were deployed but did not sustain a TBI (controls). All subjects with deployment-related TBI had headache, while 11 (23.9%) controls had no headache. In addition, 89% of headaches in the deployed veterans with TBI were migraine, compared with 40% in the control group. All subjects with deployment-related TBI reported significantly greater frequency and intensity of headache than the control group did.
New and Noteworthy Information—June 2014
Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.
People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.
Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.
The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.
The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.
The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.
Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.
The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]
Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.
A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.
Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.
Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.
Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.
—Erik Greb
Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.
People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.
Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.
The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.
The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.
The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.
Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.
The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]
Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.
A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.
Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.
Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.
Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.
—Erik Greb
Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.
People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.
Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.
The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.
The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.
The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.
Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.
The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]
Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.
A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.
Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.
Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.
Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.
—Erik Greb
Concussion—A Public Health Crisis
SAN FRANCISCO—Concussion is a public health crisis, given the huge population at risk and the limitations of current diagnostic and treatment methods, according to an overview on imaging concussion presented at the Seventh Annual Winter Conference of the Headache Cooperative of the Pacific.
Although many experts consider concussion to be a functional disturbance rather than a structural injury, it is associated with structural abnormalities. Similarly, although guidelines state that evidence of concussion is rarely found on conventional neuroimaging, some neurologists question this assertion.
“Concussion is a structural injury, and in most cases it is not normal on standard imaging modalities,” said David W. Dodick, MD, Professor of Neurology at the Mayo Clinic in Phoenix. But many concussions are silent, and most go unreported, often because an athlete wants to continue to play in a game. In addition, neurologists have no biomarker for concussion and no definitive treatment.
Players Endure Multiple Hits
Although a single concussion can have long-term sequelae, repeated hits to the head are of particular concern. A recent study found that varsity football and hockey players sustain an average of 1,000 hits each season at a mean acceleration of 20 G—a force comparable to that of a car driving at 35 mph and hitting a brick wall, said Dr. Dodick.
In another recent study, researchers used functional MRI to test cognition in football players ages 15 to 19 before and after the playing season. Although none of the athletes tested had had a symptomatic concussion, their ability to complete the assigned task and their overall cognitive function were markedly lower postseason. The extent of impairment correlated with the number of hits to the head that they had sustained.
The near death of a high school football player from second impact syndrome led to laws limiting postconcussion return to play in all 50 states. Although children may be sidelined for 30 days, however, cognitive symptoms can take six weeks or more to resolve—and 44% to 50% of athletes have three or more symptoms at one year.
Researchers Find Evidence of Degenerative Disease
After repeated head injuries, athletes are at high risk for chronic traumatic encephalopathy (CTE), the progressive neurodegenerative disease that helped raise public awareness of the danger associated with sports-related trauma. Researchers at Boston University have examined the brains of more than 100 deceased athletes and found evidence of tauopathy in 70 of them, reported Dr. Dodick. Unlike the neurofibrillary tangles found in Alzheimer’s disease, those characteristic of CTE cluster in the subcortical regions of the brain.
Researchers at the University of California, Los Angeles, successfully used PET scans with tau ligand to detect in vivo evidence of CTE. They scanned the brains of five retired football players and found tau deposits associated with trauma in each.
“Metabolic brain imaging with tau ligand is perhaps one of the greatest advances in the field,” said Dr. Dodick. Although CTE usually develops within five to 10 years of an athlete’s retirement, early indicators of the disease were found in the brain of a 17-year-old football player who committed suicide.
When Is Postconcussion Imaging Indicated?
The Institute of Medicine’s sports-related concussion guideline states that traditional CT and MRI are of little diagnostic value. The American Academy of Neurology calls for CT only when a more serious traumatic brain injury (TBI) is suspected. The Zurich consensus statement concludes that CT and MRI contribute little to the evaluation of concussion.
“If I stopped here, you would go back and say, ‘There is no need to image the brain in routine concussion,’” Dr. Dodick said. He went on to review both traditional and newer imaging modalities and the Mayo Clinic’s unvalidated concussion protocol, which recommends imaging for every patient.
CT Is Overused, but MRI Can Be Revealing
CT is the mainstay of imaging TBI in an emergency setting, but it has little value in the evaluation of concussion in outpatient settings, said Dr. Dodick. Even in emergency departments, overuse is increasingly common and costly and unnecessarily exposes patients to high doses of radiation.
Although the role of MRI in concussion is controversial, “we image everybody who comes to us for concussion evaluation,” said Dr. Dodick. MRI can detect contusions, edema, traumatic axonal injury (TAI), and subacute or remote hemorrhages that CT often misses. In a study of 135 patients with mild TBI, 27% of those with normal CT scans had abnormal MRIs.
Susceptibility-Weighted Imaging
The Mayo Clinic’s protocol includes susceptibility weighted imaging (SWI), with brain imaging sequences including sagittal T1 and axial 3D T1, axial T2, 3D fluid attenuated inversion recovery, single voxel magnetic resonance spectroscopy (MRS), and axial diffusion tensor imaging (DTI). SWI “is probably the most important thing we do,” said Dr. Dodick.
He recalled the case of a 19-year-old hockey player whom he was asked to clear for return to play. Gradient echo imaging was normal, as were the athlete’s neurologic exam and impact test, but SWI revealed multiple areas of TAI.
Magnetic Resonance Spectroscopy
Sometimes referred to as a virtual biopsy, MRS detects changes in metabolites in the brain. Most notably, the technique identifies changes in N-acetylaspartate (NAA), a marker of neuronal and axonal health that declines in TBI.
In a study of professional soccer players with a baseline NAA:creatine ratio greater than 2, participants’ postconcussion ratio was less than 2. Although the athletes reported complete symptom resolution on day 3, brain imaging did not return to normal for one month or longer. Because of the lag time between symptom resolution and metabolic recovery, Dr. Dodick said, “I’m cautious, with children and youth in particular, about sending them back to play.”
Diffusion Tensor Imaging
DTI, another element of the Mayo Clinic’s concussion protocol, is based on the diffusivity of water, which is variably restricted in different tissues. In CSF, for example, diffusion of water is isotropic. In white matter, diffusion is highly anisotropic, and a reduction of fractional anisotropy (FA) correlates with the loss or destruction of white matter.
Multiple DTI studies have been conducted in the past 30 years. Despite various limitations, the findings provide striking evidence of small and subtle brain abnormalities in most athletes, said Dr. Dodick. A study comparing patients with mild TBI vs patients with moderate-to-severe TBI, for example, found a graded alteration in white matter integrity. Patients with mild TBI also had abnormalities.
Notably, evidence of abnormalities has been found even in the absence of symptomatic concussion. “You can alter brain structure and function without clinical symptomatology,” said Dr. Dodick.
Patients may ask whether these brain changes are reversible. Dr. Dodick described a patient who underwent DTI immediately after concussion and again 16 months later. At the time of the second imaging, the abnormal reduction of FA showed a loss of integrity. “That [injury] probably does not repair itself,” he said. At least in some cases, the changes can be persistent.
Current Imaging Can Guide Clinical Practice
“There is great potential for advanced brain imaging of concussion,” said Dr. Dodick, “but you can detect and characterize brain abnormalities that will guide your clinical decision making” here and now. Even if testing is limited to SWI, he added, it will identify many abnormalities that otherwise would be missed.
If in vivo testing for CTE is proven to be effective, “we’ll be able to premortem early detect those at risk for neurodegenerative disease,” said Dr. Dodick. “The holy grail, of course, is that this would be used in future research to evaluate interventions and new treatments.”
—Helen Lippman
Suggested Reading
Hart J Jr, Kraut MA, Womack KB, et al. Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurol. 2013;70(3):326-335.
Tavender EJ, Bosch M, Green S, et al. Quality and consistency of guidelines for the management of mild traumatic brain injury in the emergency department. Acad Emerg Med. 2011;18(8):880-889.
Yuh EL, Mukherjee P, Lingsma HF, et al. Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol. 2013;73(2):224-235.
SAN FRANCISCO—Concussion is a public health crisis, given the huge population at risk and the limitations of current diagnostic and treatment methods, according to an overview on imaging concussion presented at the Seventh Annual Winter Conference of the Headache Cooperative of the Pacific.
Although many experts consider concussion to be a functional disturbance rather than a structural injury, it is associated with structural abnormalities. Similarly, although guidelines state that evidence of concussion is rarely found on conventional neuroimaging, some neurologists question this assertion.
“Concussion is a structural injury, and in most cases it is not normal on standard imaging modalities,” said David W. Dodick, MD, Professor of Neurology at the Mayo Clinic in Phoenix. But many concussions are silent, and most go unreported, often because an athlete wants to continue to play in a game. In addition, neurologists have no biomarker for concussion and no definitive treatment.
Players Endure Multiple Hits
Although a single concussion can have long-term sequelae, repeated hits to the head are of particular concern. A recent study found that varsity football and hockey players sustain an average of 1,000 hits each season at a mean acceleration of 20 G—a force comparable to that of a car driving at 35 mph and hitting a brick wall, said Dr. Dodick.
In another recent study, researchers used functional MRI to test cognition in football players ages 15 to 19 before and after the playing season. Although none of the athletes tested had had a symptomatic concussion, their ability to complete the assigned task and their overall cognitive function were markedly lower postseason. The extent of impairment correlated with the number of hits to the head that they had sustained.
The near death of a high school football player from second impact syndrome led to laws limiting postconcussion return to play in all 50 states. Although children may be sidelined for 30 days, however, cognitive symptoms can take six weeks or more to resolve—and 44% to 50% of athletes have three or more symptoms at one year.
Researchers Find Evidence of Degenerative Disease
After repeated head injuries, athletes are at high risk for chronic traumatic encephalopathy (CTE), the progressive neurodegenerative disease that helped raise public awareness of the danger associated with sports-related trauma. Researchers at Boston University have examined the brains of more than 100 deceased athletes and found evidence of tauopathy in 70 of them, reported Dr. Dodick. Unlike the neurofibrillary tangles found in Alzheimer’s disease, those characteristic of CTE cluster in the subcortical regions of the brain.
Researchers at the University of California, Los Angeles, successfully used PET scans with tau ligand to detect in vivo evidence of CTE. They scanned the brains of five retired football players and found tau deposits associated with trauma in each.
“Metabolic brain imaging with tau ligand is perhaps one of the greatest advances in the field,” said Dr. Dodick. Although CTE usually develops within five to 10 years of an athlete’s retirement, early indicators of the disease were found in the brain of a 17-year-old football player who committed suicide.
When Is Postconcussion Imaging Indicated?
The Institute of Medicine’s sports-related concussion guideline states that traditional CT and MRI are of little diagnostic value. The American Academy of Neurology calls for CT only when a more serious traumatic brain injury (TBI) is suspected. The Zurich consensus statement concludes that CT and MRI contribute little to the evaluation of concussion.
“If I stopped here, you would go back and say, ‘There is no need to image the brain in routine concussion,’” Dr. Dodick said. He went on to review both traditional and newer imaging modalities and the Mayo Clinic’s unvalidated concussion protocol, which recommends imaging for every patient.
CT Is Overused, but MRI Can Be Revealing
CT is the mainstay of imaging TBI in an emergency setting, but it has little value in the evaluation of concussion in outpatient settings, said Dr. Dodick. Even in emergency departments, overuse is increasingly common and costly and unnecessarily exposes patients to high doses of radiation.
Although the role of MRI in concussion is controversial, “we image everybody who comes to us for concussion evaluation,” said Dr. Dodick. MRI can detect contusions, edema, traumatic axonal injury (TAI), and subacute or remote hemorrhages that CT often misses. In a study of 135 patients with mild TBI, 27% of those with normal CT scans had abnormal MRIs.
Susceptibility-Weighted Imaging
The Mayo Clinic’s protocol includes susceptibility weighted imaging (SWI), with brain imaging sequences including sagittal T1 and axial 3D T1, axial T2, 3D fluid attenuated inversion recovery, single voxel magnetic resonance spectroscopy (MRS), and axial diffusion tensor imaging (DTI). SWI “is probably the most important thing we do,” said Dr. Dodick.
He recalled the case of a 19-year-old hockey player whom he was asked to clear for return to play. Gradient echo imaging was normal, as were the athlete’s neurologic exam and impact test, but SWI revealed multiple areas of TAI.
Magnetic Resonance Spectroscopy
Sometimes referred to as a virtual biopsy, MRS detects changes in metabolites in the brain. Most notably, the technique identifies changes in N-acetylaspartate (NAA), a marker of neuronal and axonal health that declines in TBI.
In a study of professional soccer players with a baseline NAA:creatine ratio greater than 2, participants’ postconcussion ratio was less than 2. Although the athletes reported complete symptom resolution on day 3, brain imaging did not return to normal for one month or longer. Because of the lag time between symptom resolution and metabolic recovery, Dr. Dodick said, “I’m cautious, with children and youth in particular, about sending them back to play.”
Diffusion Tensor Imaging
DTI, another element of the Mayo Clinic’s concussion protocol, is based on the diffusivity of water, which is variably restricted in different tissues. In CSF, for example, diffusion of water is isotropic. In white matter, diffusion is highly anisotropic, and a reduction of fractional anisotropy (FA) correlates with the loss or destruction of white matter.
Multiple DTI studies have been conducted in the past 30 years. Despite various limitations, the findings provide striking evidence of small and subtle brain abnormalities in most athletes, said Dr. Dodick. A study comparing patients with mild TBI vs patients with moderate-to-severe TBI, for example, found a graded alteration in white matter integrity. Patients with mild TBI also had abnormalities.
Notably, evidence of abnormalities has been found even in the absence of symptomatic concussion. “You can alter brain structure and function without clinical symptomatology,” said Dr. Dodick.
Patients may ask whether these brain changes are reversible. Dr. Dodick described a patient who underwent DTI immediately after concussion and again 16 months later. At the time of the second imaging, the abnormal reduction of FA showed a loss of integrity. “That [injury] probably does not repair itself,” he said. At least in some cases, the changes can be persistent.
Current Imaging Can Guide Clinical Practice
“There is great potential for advanced brain imaging of concussion,” said Dr. Dodick, “but you can detect and characterize brain abnormalities that will guide your clinical decision making” here and now. Even if testing is limited to SWI, he added, it will identify many abnormalities that otherwise would be missed.
If in vivo testing for CTE is proven to be effective, “we’ll be able to premortem early detect those at risk for neurodegenerative disease,” said Dr. Dodick. “The holy grail, of course, is that this would be used in future research to evaluate interventions and new treatments.”
—Helen Lippman
SAN FRANCISCO—Concussion is a public health crisis, given the huge population at risk and the limitations of current diagnostic and treatment methods, according to an overview on imaging concussion presented at the Seventh Annual Winter Conference of the Headache Cooperative of the Pacific.
Although many experts consider concussion to be a functional disturbance rather than a structural injury, it is associated with structural abnormalities. Similarly, although guidelines state that evidence of concussion is rarely found on conventional neuroimaging, some neurologists question this assertion.
“Concussion is a structural injury, and in most cases it is not normal on standard imaging modalities,” said David W. Dodick, MD, Professor of Neurology at the Mayo Clinic in Phoenix. But many concussions are silent, and most go unreported, often because an athlete wants to continue to play in a game. In addition, neurologists have no biomarker for concussion and no definitive treatment.
Players Endure Multiple Hits
Although a single concussion can have long-term sequelae, repeated hits to the head are of particular concern. A recent study found that varsity football and hockey players sustain an average of 1,000 hits each season at a mean acceleration of 20 G—a force comparable to that of a car driving at 35 mph and hitting a brick wall, said Dr. Dodick.
In another recent study, researchers used functional MRI to test cognition in football players ages 15 to 19 before and after the playing season. Although none of the athletes tested had had a symptomatic concussion, their ability to complete the assigned task and their overall cognitive function were markedly lower postseason. The extent of impairment correlated with the number of hits to the head that they had sustained.
The near death of a high school football player from second impact syndrome led to laws limiting postconcussion return to play in all 50 states. Although children may be sidelined for 30 days, however, cognitive symptoms can take six weeks or more to resolve—and 44% to 50% of athletes have three or more symptoms at one year.
Researchers Find Evidence of Degenerative Disease
After repeated head injuries, athletes are at high risk for chronic traumatic encephalopathy (CTE), the progressive neurodegenerative disease that helped raise public awareness of the danger associated with sports-related trauma. Researchers at Boston University have examined the brains of more than 100 deceased athletes and found evidence of tauopathy in 70 of them, reported Dr. Dodick. Unlike the neurofibrillary tangles found in Alzheimer’s disease, those characteristic of CTE cluster in the subcortical regions of the brain.
Researchers at the University of California, Los Angeles, successfully used PET scans with tau ligand to detect in vivo evidence of CTE. They scanned the brains of five retired football players and found tau deposits associated with trauma in each.
“Metabolic brain imaging with tau ligand is perhaps one of the greatest advances in the field,” said Dr. Dodick. Although CTE usually develops within five to 10 years of an athlete’s retirement, early indicators of the disease were found in the brain of a 17-year-old football player who committed suicide.
When Is Postconcussion Imaging Indicated?
The Institute of Medicine’s sports-related concussion guideline states that traditional CT and MRI are of little diagnostic value. The American Academy of Neurology calls for CT only when a more serious traumatic brain injury (TBI) is suspected. The Zurich consensus statement concludes that CT and MRI contribute little to the evaluation of concussion.
“If I stopped here, you would go back and say, ‘There is no need to image the brain in routine concussion,’” Dr. Dodick said. He went on to review both traditional and newer imaging modalities and the Mayo Clinic’s unvalidated concussion protocol, which recommends imaging for every patient.
CT Is Overused, but MRI Can Be Revealing
CT is the mainstay of imaging TBI in an emergency setting, but it has little value in the evaluation of concussion in outpatient settings, said Dr. Dodick. Even in emergency departments, overuse is increasingly common and costly and unnecessarily exposes patients to high doses of radiation.
Although the role of MRI in concussion is controversial, “we image everybody who comes to us for concussion evaluation,” said Dr. Dodick. MRI can detect contusions, edema, traumatic axonal injury (TAI), and subacute or remote hemorrhages that CT often misses. In a study of 135 patients with mild TBI, 27% of those with normal CT scans had abnormal MRIs.
Susceptibility-Weighted Imaging
The Mayo Clinic’s protocol includes susceptibility weighted imaging (SWI), with brain imaging sequences including sagittal T1 and axial 3D T1, axial T2, 3D fluid attenuated inversion recovery, single voxel magnetic resonance spectroscopy (MRS), and axial diffusion tensor imaging (DTI). SWI “is probably the most important thing we do,” said Dr. Dodick.
He recalled the case of a 19-year-old hockey player whom he was asked to clear for return to play. Gradient echo imaging was normal, as were the athlete’s neurologic exam and impact test, but SWI revealed multiple areas of TAI.
Magnetic Resonance Spectroscopy
Sometimes referred to as a virtual biopsy, MRS detects changes in metabolites in the brain. Most notably, the technique identifies changes in N-acetylaspartate (NAA), a marker of neuronal and axonal health that declines in TBI.
In a study of professional soccer players with a baseline NAA:creatine ratio greater than 2, participants’ postconcussion ratio was less than 2. Although the athletes reported complete symptom resolution on day 3, brain imaging did not return to normal for one month or longer. Because of the lag time between symptom resolution and metabolic recovery, Dr. Dodick said, “I’m cautious, with children and youth in particular, about sending them back to play.”
Diffusion Tensor Imaging
DTI, another element of the Mayo Clinic’s concussion protocol, is based on the diffusivity of water, which is variably restricted in different tissues. In CSF, for example, diffusion of water is isotropic. In white matter, diffusion is highly anisotropic, and a reduction of fractional anisotropy (FA) correlates with the loss or destruction of white matter.
Multiple DTI studies have been conducted in the past 30 years. Despite various limitations, the findings provide striking evidence of small and subtle brain abnormalities in most athletes, said Dr. Dodick. A study comparing patients with mild TBI vs patients with moderate-to-severe TBI, for example, found a graded alteration in white matter integrity. Patients with mild TBI also had abnormalities.
Notably, evidence of abnormalities has been found even in the absence of symptomatic concussion. “You can alter brain structure and function without clinical symptomatology,” said Dr. Dodick.
Patients may ask whether these brain changes are reversible. Dr. Dodick described a patient who underwent DTI immediately after concussion and again 16 months later. At the time of the second imaging, the abnormal reduction of FA showed a loss of integrity. “That [injury] probably does not repair itself,” he said. At least in some cases, the changes can be persistent.
Current Imaging Can Guide Clinical Practice
“There is great potential for advanced brain imaging of concussion,” said Dr. Dodick, “but you can detect and characterize brain abnormalities that will guide your clinical decision making” here and now. Even if testing is limited to SWI, he added, it will identify many abnormalities that otherwise would be missed.
If in vivo testing for CTE is proven to be effective, “we’ll be able to premortem early detect those at risk for neurodegenerative disease,” said Dr. Dodick. “The holy grail, of course, is that this would be used in future research to evaluate interventions and new treatments.”
—Helen Lippman
Suggested Reading
Hart J Jr, Kraut MA, Womack KB, et al. Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurol. 2013;70(3):326-335.
Tavender EJ, Bosch M, Green S, et al. Quality and consistency of guidelines for the management of mild traumatic brain injury in the emergency department. Acad Emerg Med. 2011;18(8):880-889.
Yuh EL, Mukherjee P, Lingsma HF, et al. Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol. 2013;73(2):224-235.
Suggested Reading
Hart J Jr, Kraut MA, Womack KB, et al. Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurol. 2013;70(3):326-335.
Tavender EJ, Bosch M, Green S, et al. Quality and consistency of guidelines for the management of mild traumatic brain injury in the emergency department. Acad Emerg Med. 2011;18(8):880-889.
Yuh EL, Mukherjee P, Lingsma HF, et al. Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol. 2013;73(2):224-235.
Link Between PTSD and TBI Is Only the Beginning for MRS Study
April 25, 2014
A fundamental challenge for any study examining the impact of military service on the health of military personnel is establishing a baseline. Whether heart disease or posttraumatic stress disorder (PTSD), the symptoms often appear after (sometimes long after) the service has ended. The longitudinal Marine Resiliency Study (MRS I) and its successor MRS II are seeking to resolve that issue in a novel approach that brings together the Department of Veterans Affairs, U.S. Marine Corps, and Navy Medicine.
In the MRS study, a cohort of about 2,600 Marines (MRS-I) in 4 battalions and about 1,300 Marines (MRS-II) in 2 battalions deployed to Iraq or Afghanistan underwent a scientifically rigorous examination a month prior to deployment. This baseline was established using self-reported questionnaires, clinical interviews, and laboratory examinations. Follow-up examinations were repeated at 3 months (MRS-I and MRS-II) and again at 6 months post-deployment (MRS-I).
The program is ambitious, Dr. Dewleen Baker of the VA San Diego Health Care System told Federal Practitioner. “MRS was designed to provide broad-based (psychosocial, psychophysiological, and biological) prospective, longitudinal data, with a goal toward ultimate integrated analyses of variables, to determine risk and resilience for post-deployment mental health outcomes, i.e,. PTSD and co-occurring disorders,” she explained. “Analyses have just begun, and we are working our way through aspects of the data toward more integrated approaches.”
In one of the first of many reports to come out of MRS, the researchers found that the probability of developing PTSD was highest for participants with severe pre-deployment symptoms, high combat intensity, and deployment-related traumatic brain injury (TBI). Most significant, the researchers found that TBI doubled or nearly doubled the PTSD rates for participants with less severe pre-deployment PTSD symptoms. According to Baker:
By contrast, deployment-related mild TBI increases post-deployment symptom scores by 23%, and moderate-to-severe injuries increase scores by 71%. Our findings suggest that TBI may be a very important risk factor of PTSD, even when accounting for preexisting symptoms and combat intensity.
Our study focused on the impact of pre-deployment symptoms, combat intensity and TBI; however, it is important to consider other factors of psychological risk and resilience. Genes, coping style, and social support are just a few of the many other factors that may influence an individual’s response to stress.
Creating a rigorous cross-agency research study required tact, diligence, and patience from the MRS team. “Each agency has their own unique culture and institutional rules, regulations, and bureaucracy, so ideas, programs, etc, must be vetted across all agencies and reconciled—the various cultures/agencies to be reconciled include DoD, VA and academia.” Baker explained. “In addition in regards to initiation of studies for MRS II, for the past couple years, we also interface with NIMH as well as Headquarters Marine Corps; NIMH has the role of scientific review of MRS-II studies carried out under Headquarters Marine Corps/BUMED funding.”
The MRS-I and II studies may very well provide a template for future studies. The MRS team included a military liaison to work with the active duty Marines and attached Sailors, gather data, schedule meetings, and to report findings. “This study has a lot of experience working within and across these agencies,” Baker noted, “It’s an excellent model for future VA/DOD joint projects.”
April 25, 2014
A fundamental challenge for any study examining the impact of military service on the health of military personnel is establishing a baseline. Whether heart disease or posttraumatic stress disorder (PTSD), the symptoms often appear after (sometimes long after) the service has ended. The longitudinal Marine Resiliency Study (MRS I) and its successor MRS II are seeking to resolve that issue in a novel approach that brings together the Department of Veterans Affairs, U.S. Marine Corps, and Navy Medicine.
In the MRS study, a cohort of about 2,600 Marines (MRS-I) in 4 battalions and about 1,300 Marines (MRS-II) in 2 battalions deployed to Iraq or Afghanistan underwent a scientifically rigorous examination a month prior to deployment. This baseline was established using self-reported questionnaires, clinical interviews, and laboratory examinations. Follow-up examinations were repeated at 3 months (MRS-I and MRS-II) and again at 6 months post-deployment (MRS-I).
The program is ambitious, Dr. Dewleen Baker of the VA San Diego Health Care System told Federal Practitioner. “MRS was designed to provide broad-based (psychosocial, psychophysiological, and biological) prospective, longitudinal data, with a goal toward ultimate integrated analyses of variables, to determine risk and resilience for post-deployment mental health outcomes, i.e,. PTSD and co-occurring disorders,” she explained. “Analyses have just begun, and we are working our way through aspects of the data toward more integrated approaches.”
In one of the first of many reports to come out of MRS, the researchers found that the probability of developing PTSD was highest for participants with severe pre-deployment symptoms, high combat intensity, and deployment-related traumatic brain injury (TBI). Most significant, the researchers found that TBI doubled or nearly doubled the PTSD rates for participants with less severe pre-deployment PTSD symptoms. According to Baker:
By contrast, deployment-related mild TBI increases post-deployment symptom scores by 23%, and moderate-to-severe injuries increase scores by 71%. Our findings suggest that TBI may be a very important risk factor of PTSD, even when accounting for preexisting symptoms and combat intensity.
Our study focused on the impact of pre-deployment symptoms, combat intensity and TBI; however, it is important to consider other factors of psychological risk and resilience. Genes, coping style, and social support are just a few of the many other factors that may influence an individual’s response to stress.
Creating a rigorous cross-agency research study required tact, diligence, and patience from the MRS team. “Each agency has their own unique culture and institutional rules, regulations, and bureaucracy, so ideas, programs, etc, must be vetted across all agencies and reconciled—the various cultures/agencies to be reconciled include DoD, VA and academia.” Baker explained. “In addition in regards to initiation of studies for MRS II, for the past couple years, we also interface with NIMH as well as Headquarters Marine Corps; NIMH has the role of scientific review of MRS-II studies carried out under Headquarters Marine Corps/BUMED funding.”
The MRS-I and II studies may very well provide a template for future studies. The MRS team included a military liaison to work with the active duty Marines and attached Sailors, gather data, schedule meetings, and to report findings. “This study has a lot of experience working within and across these agencies,” Baker noted, “It’s an excellent model for future VA/DOD joint projects.”
April 25, 2014
A fundamental challenge for any study examining the impact of military service on the health of military personnel is establishing a baseline. Whether heart disease or posttraumatic stress disorder (PTSD), the symptoms often appear after (sometimes long after) the service has ended. The longitudinal Marine Resiliency Study (MRS I) and its successor MRS II are seeking to resolve that issue in a novel approach that brings together the Department of Veterans Affairs, U.S. Marine Corps, and Navy Medicine.
In the MRS study, a cohort of about 2,600 Marines (MRS-I) in 4 battalions and about 1,300 Marines (MRS-II) in 2 battalions deployed to Iraq or Afghanistan underwent a scientifically rigorous examination a month prior to deployment. This baseline was established using self-reported questionnaires, clinical interviews, and laboratory examinations. Follow-up examinations were repeated at 3 months (MRS-I and MRS-II) and again at 6 months post-deployment (MRS-I).
The program is ambitious, Dr. Dewleen Baker of the VA San Diego Health Care System told Federal Practitioner. “MRS was designed to provide broad-based (psychosocial, psychophysiological, and biological) prospective, longitudinal data, with a goal toward ultimate integrated analyses of variables, to determine risk and resilience for post-deployment mental health outcomes, i.e,. PTSD and co-occurring disorders,” she explained. “Analyses have just begun, and we are working our way through aspects of the data toward more integrated approaches.”
In one of the first of many reports to come out of MRS, the researchers found that the probability of developing PTSD was highest for participants with severe pre-deployment symptoms, high combat intensity, and deployment-related traumatic brain injury (TBI). Most significant, the researchers found that TBI doubled or nearly doubled the PTSD rates for participants with less severe pre-deployment PTSD symptoms. According to Baker:
By contrast, deployment-related mild TBI increases post-deployment symptom scores by 23%, and moderate-to-severe injuries increase scores by 71%. Our findings suggest that TBI may be a very important risk factor of PTSD, even when accounting for preexisting symptoms and combat intensity.
Our study focused on the impact of pre-deployment symptoms, combat intensity and TBI; however, it is important to consider other factors of psychological risk and resilience. Genes, coping style, and social support are just a few of the many other factors that may influence an individual’s response to stress.
Creating a rigorous cross-agency research study required tact, diligence, and patience from the MRS team. “Each agency has their own unique culture and institutional rules, regulations, and bureaucracy, so ideas, programs, etc, must be vetted across all agencies and reconciled—the various cultures/agencies to be reconciled include DoD, VA and academia.” Baker explained. “In addition in regards to initiation of studies for MRS II, for the past couple years, we also interface with NIMH as well as Headquarters Marine Corps; NIMH has the role of scientific review of MRS-II studies carried out under Headquarters Marine Corps/BUMED funding.”
The MRS-I and II studies may very well provide a template for future studies. The MRS team included a military liaison to work with the active duty Marines and attached Sailors, gather data, schedule meetings, and to report findings. “This study has a lot of experience working within and across these agencies,” Baker noted, “It’s an excellent model for future VA/DOD joint projects.”
Back to School With TBI
To show that veterans with traumatic brain injury (TBI) can successfully return to school, the Defense and Veterans Brain Injury Center (DVBIC) created Back to School: Guide to Academic Success After Traumatic Brain Injury, available at http://www.dvbic.org/material/back-school-guide. The guide offers information on a variety of pertinent subjects from symptom management to choosing a school and adjusting to civilian campus culture.
The detailed Frequently Asked Questions section offers tips on topics such as how to talk about TBI with professors, where to get help on campus, as well as financial aid and tuition assistance.
Sections of the guide address ways the service member-student can work through deficits; for example, learning new ways of doing things, such as using assistive technology or participating in online classes, which could be beneficial for someone who needs multiple breaks. Students with TBI may be able to arrange to get extra time to finish assignments, take tests in different formats, or use tape recorders instead of taking notes by hand.
In the Maximize Your Learning section, students can tailor individual solutions to learning problems, such as attention issues and thought processing. For the student who has trouble remembering recent conversations, directions, and due dates, “Tips for Success” include having a large calendar in view, recording and playing back lectures, and recapping conversations.
The Make the Transition section reminds the service member of strengths gained in the military that can translate to the school environment: leadership, discipline, teamwork, communication, determination, punctuality. These skills may help the student identify goals quickly, work well on team projects, and meet deadlines.
The guide offers students examples of cognitive technology they can take advantage of, such as a screen reader, which identifies and interprets written material on a computer screen and reads the material out loud.
According to the DVBIC, health care providers can also use the guide as a teaching tool to help patients.
To show that veterans with traumatic brain injury (TBI) can successfully return to school, the Defense and Veterans Brain Injury Center (DVBIC) created Back to School: Guide to Academic Success After Traumatic Brain Injury, available at http://www.dvbic.org/material/back-school-guide. The guide offers information on a variety of pertinent subjects from symptom management to choosing a school and adjusting to civilian campus culture.
The detailed Frequently Asked Questions section offers tips on topics such as how to talk about TBI with professors, where to get help on campus, as well as financial aid and tuition assistance.
Sections of the guide address ways the service member-student can work through deficits; for example, learning new ways of doing things, such as using assistive technology or participating in online classes, which could be beneficial for someone who needs multiple breaks. Students with TBI may be able to arrange to get extra time to finish assignments, take tests in different formats, or use tape recorders instead of taking notes by hand.
In the Maximize Your Learning section, students can tailor individual solutions to learning problems, such as attention issues and thought processing. For the student who has trouble remembering recent conversations, directions, and due dates, “Tips for Success” include having a large calendar in view, recording and playing back lectures, and recapping conversations.
The Make the Transition section reminds the service member of strengths gained in the military that can translate to the school environment: leadership, discipline, teamwork, communication, determination, punctuality. These skills may help the student identify goals quickly, work well on team projects, and meet deadlines.
The guide offers students examples of cognitive technology they can take advantage of, such as a screen reader, which identifies and interprets written material on a computer screen and reads the material out loud.
According to the DVBIC, health care providers can also use the guide as a teaching tool to help patients.
To show that veterans with traumatic brain injury (TBI) can successfully return to school, the Defense and Veterans Brain Injury Center (DVBIC) created Back to School: Guide to Academic Success After Traumatic Brain Injury, available at http://www.dvbic.org/material/back-school-guide. The guide offers information on a variety of pertinent subjects from symptom management to choosing a school and adjusting to civilian campus culture.
The detailed Frequently Asked Questions section offers tips on topics such as how to talk about TBI with professors, where to get help on campus, as well as financial aid and tuition assistance.
Sections of the guide address ways the service member-student can work through deficits; for example, learning new ways of doing things, such as using assistive technology or participating in online classes, which could be beneficial for someone who needs multiple breaks. Students with TBI may be able to arrange to get extra time to finish assignments, take tests in different formats, or use tape recorders instead of taking notes by hand.
In the Maximize Your Learning section, students can tailor individual solutions to learning problems, such as attention issues and thought processing. For the student who has trouble remembering recent conversations, directions, and due dates, “Tips for Success” include having a large calendar in view, recording and playing back lectures, and recapping conversations.
The Make the Transition section reminds the service member of strengths gained in the military that can translate to the school environment: leadership, discipline, teamwork, communication, determination, punctuality. These skills may help the student identify goals quickly, work well on team projects, and meet deadlines.
The guide offers students examples of cognitive technology they can take advantage of, such as a screen reader, which identifies and interprets written material on a computer screen and reads the material out loud.
According to the DVBIC, health care providers can also use the guide as a teaching tool to help patients.
Traumatic Brain Injury
Expanded Disability Pay for Patients With TBI
The VA has developed new regulations that could make getting additional disability pay easier now for some veterans who have traumatic brain injury (TBI) in addition to Parkinson disease, certain types of dementia, depression, unprovoked seizures, or certain diseases of the hypothalamus and pituitary glands.
The new regulations, which took effect in January, were born of a 2008 Institute of Medicine report, Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury. That report was based on a consensus by a National Academy of Sciences committee of experts, which found “sufficient evidence” to link moderate or severe levels of TBI with the other illnesses. The committee noted that even mild TBI is associated with adverse consequences, including memory loss, Alzheimer-like dementia, and seizures.
According to the new regulations if veterans with service-connected TBI also have 1 of the 5 associated illnesses, the second illness will be considered service-connected in the calculations of disability compensation. Eligibility for expanded benefits will depend on the severity of the TBI and the time between the injury causing the TBI and the onset of the second illness. However, veterans can still file a claim to establish direct service connection for those conditions even if they don’t meet the time and severity standards in the new regulation.
Service members who are within 180 days of discharge can file a predischarge claim for TBI online at http://www.eBenefits.va.gov. Veterans who have questions or want to file new disability claims can also use the eBenefits website. The published final rule is available at http://www.regulations.gov.
The VA has developed new regulations that could make getting additional disability pay easier now for some veterans who have traumatic brain injury (TBI) in addition to Parkinson disease, certain types of dementia, depression, unprovoked seizures, or certain diseases of the hypothalamus and pituitary glands.
The new regulations, which took effect in January, were born of a 2008 Institute of Medicine report, Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury. That report was based on a consensus by a National Academy of Sciences committee of experts, which found “sufficient evidence” to link moderate or severe levels of TBI with the other illnesses. The committee noted that even mild TBI is associated with adverse consequences, including memory loss, Alzheimer-like dementia, and seizures.
According to the new regulations if veterans with service-connected TBI also have 1 of the 5 associated illnesses, the second illness will be considered service-connected in the calculations of disability compensation. Eligibility for expanded benefits will depend on the severity of the TBI and the time between the injury causing the TBI and the onset of the second illness. However, veterans can still file a claim to establish direct service connection for those conditions even if they don’t meet the time and severity standards in the new regulation.
Service members who are within 180 days of discharge can file a predischarge claim for TBI online at http://www.eBenefits.va.gov. Veterans who have questions or want to file new disability claims can also use the eBenefits website. The published final rule is available at http://www.regulations.gov.
The VA has developed new regulations that could make getting additional disability pay easier now for some veterans who have traumatic brain injury (TBI) in addition to Parkinson disease, certain types of dementia, depression, unprovoked seizures, or certain diseases of the hypothalamus and pituitary glands.
The new regulations, which took effect in January, were born of a 2008 Institute of Medicine report, Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury. That report was based on a consensus by a National Academy of Sciences committee of experts, which found “sufficient evidence” to link moderate or severe levels of TBI with the other illnesses. The committee noted that even mild TBI is associated with adverse consequences, including memory loss, Alzheimer-like dementia, and seizures.
According to the new regulations if veterans with service-connected TBI also have 1 of the 5 associated illnesses, the second illness will be considered service-connected in the calculations of disability compensation. Eligibility for expanded benefits will depend on the severity of the TBI and the time between the injury causing the TBI and the onset of the second illness. However, veterans can still file a claim to establish direct service connection for those conditions even if they don’t meet the time and severity standards in the new regulation.
Service members who are within 180 days of discharge can file a predischarge claim for TBI online at http://www.eBenefits.va.gov. Veterans who have questions or want to file new disability claims can also use the eBenefits website. The published final rule is available at http://www.regulations.gov.
New and Noteworthy Information—January 2014
The Bacille Calmette-Guérin (BCG) vaccine may benefit patients with clinically isolated syndrome (CIS), according to research published online ahead of print December 4, 2013, in Neurology. A total of 82 participants with CIS were randomized to BCG or placebo and monitored monthly with brain MRI for six months. All patients subsequently received IM interferon β-1a for 12 months. In an open-label extension phase, patients received disease-modifying therapies (DMTs) recommended by their neurologists. During the initial six months, the number of cumulative lesions was significantly lower among vaccinated subjects. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18. After 60 months, the probability of clinically definite multiple sclerosis was lower in the BCG plus DMT arm, and more vaccinated people remained DMT-free.
Exercise programs may significantly improve the ability of people with dementia to perform activities of daily living, according to a study published online ahead of print December 4, 2013, in the Cochrane Library. Exercise also may improve cognition in these patients, but may not affect depression. Investigators reviewed randomized controlled trials in which older people diagnosed with dementia were allocated to exercise programs or to control groups, which received standard care or social contact. Sixteen trials with 937 participants met the inclusion criteria. The trials were highly heterogeneous in terms of subtype and severity of participants’ dementia, and type, duration, and frequency of exercise. The researchers found that informal caregivers’ burden may be reduced when the family member with dementia participates in an exercise program.
Thrombin activity may enable neurologists to detect multiple sclerosis (MS) before clinical signs of the disease are present, according to research published online ahead of print November 29, 2013, in Annals of Neurology. Using a novel molecular probe, investigators characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded the onset of neurologic signs; increased at disease peak; and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Scientists may be able to use thrombin activity to develop sensitive probes for the preclinical detection and monitoring of neuroinflammation and MS progression, according to the investigators.
An athlete with concussion symptoms should not be allowed to return to play on the same day, according to the latest consensus statement on sports-related concussion, which was summarized in the December 2013 issue of Neurosurgery. The Concussion in Sport Group (CISG 4) based its recommendations on the advice of an expert panel that was sponsored by five international sports governing bodies. Between 80% and 90% of concussions resolve within seven to 10 days, but recovery may take longer in children and adolescents, according to the consensus statement. The updated statement emphasizes the distinction between concussion and mild traumatic brain injury. The CISG 4 suggests that patients with concussion have normal findings on brain neuroimaging studies (eg, CT scan), but those with traumatic brain injury have abnormal imaging findings.
Vitamin D may prevent multiple sclerosis (MS) by blocking T helper (TH) cells from migrating into the CNS, according to research published online ahead of print December 9, 2013, in Proceedings of the National Academy of Sciences. Investigators administered 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D, to animals with experimental autoimmune encephalomyelitis, a mouse model of MS. Myelin-reactive TH cells were generated in the presence of 1,25(OH)2D3, secreted proinflammatory cytokines, and did not preferentially differentiate into suppressor T cells. The cells left the lymph node, entered the peripheral circulation, and migrated to the immunization sites. TH cells from 1,25(OH)2D3-treated mice were unable to enter the CNS parenchyma, however. Instead, the cells were maintained in the periphery. The mice developed experimental autoimmune encephalomyelitis when treatment ceased.
Among people with type 2 diabetes, dementia incidence may be highest among Native Americans and African Americans and lowest among Asians, according to a study published online ahead of print November 22, 2013, in Diabetes Care. Scientists identified 22,171 patients age 60 or older with diabetes and without preexisting dementia in the Kaiser Permanente Northern California Diabetes Registry. The investigators abstracted prevalent medical history and dementia incidence from medical records and calculated age-adjusted incidence densities. Dementia was diagnosed in 17.1% of patients. Age-adjusted dementia incidence densities were 34/1,000 person-years among Native Americans, 27/1,000 person-years among African Americans, and 19/1,000 person-years among Asians. Hazard ratios (relative to Asians) were 1.64 for Native Americans, 1.44 for African Americans, 1.30 for non-Hispanic whites, and 1.19 for Latinos.
Veterans with blast injuries have changes in brain tissue that may be apparent on imaging years later, according to data presented at the 99th Annual Meeting of the Radiological Society of North America. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with mild traumatic brain injury with those of 10 healthy controls. The average time elapsed between the blast-induced injury and DTI scan among the patients was 51.3 months. FA values were significantly different between the two groups, and the researchers found significant correlations between FA values and attention, delayed memory, and psychomotor test scores. The results suggest that blast injury may have a long-term impact on the brain.
Among college athletes, head impact exposure may be related to white matter diffusion measures and cognition during the course of one playing season, even in the absence of diagnosed concussion, according to data published online ahead of print December 11, 2013, in Neurology. Researchers prospectively studied 79 noncontact sport athletes and 80 nonconcussed varsity football and ice hockey players who wore helmets that recorded the acceleration-time history of the head following impact. Mean diffusivity (MD) in the corpus callosum was significantly different between groups. Measures of head impact exposure correlated with white matter diffusivity measures in the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.
Among veterans, traumatic brain injury (TBI) during the most recent deployment is the strongest predictor of postdeployment symptoms of post-traumatic stress disorder (PTSD), even when accounting for predeployment symptoms, prior TBI, and combat intensity, according to research published online ahead of print December 11, 2013, in JAMA Psychiatry. A total of 1,648 active-duty Marine and Navy servicemen underwent clinical interviews and completed self-assessments approximately one month before a seven-month deployment and three to six months after deployment. At the predeployment assessment, 56.8% of participants reported prior TBI. At postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments. Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. TBI doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.
Fidgetin inhibition could promote tissue regeneration and repair the broken cell connections that occur in spinal cord injury and other conditions, according to research presented at the 2013 Annual Meeting of the American Society for Cell Biology. Fidgetin prunes unstable microtubule scaffolding in cells, as well as unneeded connections in the neuronal network as the latter grows. Researchers used a novel nanoparticle technology to block fidgetin in the injured nerves of adult rats. The nanoparticles were infused with small interfering RNA that bound the messenger RNA (mRNA) transcribed from the fidgetin gene. The mRNA for fidgetin was not translated, and the cell did not produce fidgetin. Blocking fidgetin restarted tissue growth in the animals. The technique could benefit patients with myocardial infarction or chronic cutaneous wounds.
Deep brain stimulation may improve driving ability for people with Parkinson’s disease, according to a study published online ahead of print December 18, 2013, in Neurology. Investigators studied 23 people who had deep brain stimulators, 21 people with Parkinson’s disease without stimulators, and 21 healthy individuals. Participants were tested with a driving simulator. Individuals with stimulators completed the test once with the stimulator on, once with it off, and once with the stimulator off after receiving levodopa. People with Parkinson’s disease without stimulators performed worse than controls in almost every category. People with stimulators did not perform significantly worse than the controls. Participants with stimulators had an average of 3.8 slight driving errors on the test, compared with 7.5 for the controls and 11.4 for people with Parkinson’s disease without stimulators.
Gadolinium-based contrast medium (Gd-CM) may be associated with abnormalities on brain MRI, according to research published online ahead of print December 17, 2013, in Radiology. Researchers compared unenhanced T1-weighted MR images of 19 patients who had undergone six or more contrast-enhanced brain scans with images of 16 people who had received six or fewer unenhanced scans. The hyperintensity of the dentate nucleus and globus pallidus correlated with the number of Gd-CM administrations. Hyperintensity in the dentate nucleus and globus pallidus on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations, according to the researchers. Because gadolinium has a high signal intensity in the body, the data suggest that the toxic gadolinium component remains in the body in patients with normal renal function.
—Erik Greb
The Bacille Calmette-Guérin (BCG) vaccine may benefit patients with clinically isolated syndrome (CIS), according to research published online ahead of print December 4, 2013, in Neurology. A total of 82 participants with CIS were randomized to BCG or placebo and monitored monthly with brain MRI for six months. All patients subsequently received IM interferon β-1a for 12 months. In an open-label extension phase, patients received disease-modifying therapies (DMTs) recommended by their neurologists. During the initial six months, the number of cumulative lesions was significantly lower among vaccinated subjects. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18. After 60 months, the probability of clinically definite multiple sclerosis was lower in the BCG plus DMT arm, and more vaccinated people remained DMT-free.
Exercise programs may significantly improve the ability of people with dementia to perform activities of daily living, according to a study published online ahead of print December 4, 2013, in the Cochrane Library. Exercise also may improve cognition in these patients, but may not affect depression. Investigators reviewed randomized controlled trials in which older people diagnosed with dementia were allocated to exercise programs or to control groups, which received standard care or social contact. Sixteen trials with 937 participants met the inclusion criteria. The trials were highly heterogeneous in terms of subtype and severity of participants’ dementia, and type, duration, and frequency of exercise. The researchers found that informal caregivers’ burden may be reduced when the family member with dementia participates in an exercise program.
Thrombin activity may enable neurologists to detect multiple sclerosis (MS) before clinical signs of the disease are present, according to research published online ahead of print November 29, 2013, in Annals of Neurology. Using a novel molecular probe, investigators characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded the onset of neurologic signs; increased at disease peak; and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Scientists may be able to use thrombin activity to develop sensitive probes for the preclinical detection and monitoring of neuroinflammation and MS progression, according to the investigators.
An athlete with concussion symptoms should not be allowed to return to play on the same day, according to the latest consensus statement on sports-related concussion, which was summarized in the December 2013 issue of Neurosurgery. The Concussion in Sport Group (CISG 4) based its recommendations on the advice of an expert panel that was sponsored by five international sports governing bodies. Between 80% and 90% of concussions resolve within seven to 10 days, but recovery may take longer in children and adolescents, according to the consensus statement. The updated statement emphasizes the distinction between concussion and mild traumatic brain injury. The CISG 4 suggests that patients with concussion have normal findings on brain neuroimaging studies (eg, CT scan), but those with traumatic brain injury have abnormal imaging findings.
Vitamin D may prevent multiple sclerosis (MS) by blocking T helper (TH) cells from migrating into the CNS, according to research published online ahead of print December 9, 2013, in Proceedings of the National Academy of Sciences. Investigators administered 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D, to animals with experimental autoimmune encephalomyelitis, a mouse model of MS. Myelin-reactive TH cells were generated in the presence of 1,25(OH)2D3, secreted proinflammatory cytokines, and did not preferentially differentiate into suppressor T cells. The cells left the lymph node, entered the peripheral circulation, and migrated to the immunization sites. TH cells from 1,25(OH)2D3-treated mice were unable to enter the CNS parenchyma, however. Instead, the cells were maintained in the periphery. The mice developed experimental autoimmune encephalomyelitis when treatment ceased.
Among people with type 2 diabetes, dementia incidence may be highest among Native Americans and African Americans and lowest among Asians, according to a study published online ahead of print November 22, 2013, in Diabetes Care. Scientists identified 22,171 patients age 60 or older with diabetes and without preexisting dementia in the Kaiser Permanente Northern California Diabetes Registry. The investigators abstracted prevalent medical history and dementia incidence from medical records and calculated age-adjusted incidence densities. Dementia was diagnosed in 17.1% of patients. Age-adjusted dementia incidence densities were 34/1,000 person-years among Native Americans, 27/1,000 person-years among African Americans, and 19/1,000 person-years among Asians. Hazard ratios (relative to Asians) were 1.64 for Native Americans, 1.44 for African Americans, 1.30 for non-Hispanic whites, and 1.19 for Latinos.
Veterans with blast injuries have changes in brain tissue that may be apparent on imaging years later, according to data presented at the 99th Annual Meeting of the Radiological Society of North America. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with mild traumatic brain injury with those of 10 healthy controls. The average time elapsed between the blast-induced injury and DTI scan among the patients was 51.3 months. FA values were significantly different between the two groups, and the researchers found significant correlations between FA values and attention, delayed memory, and psychomotor test scores. The results suggest that blast injury may have a long-term impact on the brain.
Among college athletes, head impact exposure may be related to white matter diffusion measures and cognition during the course of one playing season, even in the absence of diagnosed concussion, according to data published online ahead of print December 11, 2013, in Neurology. Researchers prospectively studied 79 noncontact sport athletes and 80 nonconcussed varsity football and ice hockey players who wore helmets that recorded the acceleration-time history of the head following impact. Mean diffusivity (MD) in the corpus callosum was significantly different between groups. Measures of head impact exposure correlated with white matter diffusivity measures in the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.
Among veterans, traumatic brain injury (TBI) during the most recent deployment is the strongest predictor of postdeployment symptoms of post-traumatic stress disorder (PTSD), even when accounting for predeployment symptoms, prior TBI, and combat intensity, according to research published online ahead of print December 11, 2013, in JAMA Psychiatry. A total of 1,648 active-duty Marine and Navy servicemen underwent clinical interviews and completed self-assessments approximately one month before a seven-month deployment and three to six months after deployment. At the predeployment assessment, 56.8% of participants reported prior TBI. At postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments. Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. TBI doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.
Fidgetin inhibition could promote tissue regeneration and repair the broken cell connections that occur in spinal cord injury and other conditions, according to research presented at the 2013 Annual Meeting of the American Society for Cell Biology. Fidgetin prunes unstable microtubule scaffolding in cells, as well as unneeded connections in the neuronal network as the latter grows. Researchers used a novel nanoparticle technology to block fidgetin in the injured nerves of adult rats. The nanoparticles were infused with small interfering RNA that bound the messenger RNA (mRNA) transcribed from the fidgetin gene. The mRNA for fidgetin was not translated, and the cell did not produce fidgetin. Blocking fidgetin restarted tissue growth in the animals. The technique could benefit patients with myocardial infarction or chronic cutaneous wounds.
Deep brain stimulation may improve driving ability for people with Parkinson’s disease, according to a study published online ahead of print December 18, 2013, in Neurology. Investigators studied 23 people who had deep brain stimulators, 21 people with Parkinson’s disease without stimulators, and 21 healthy individuals. Participants were tested with a driving simulator. Individuals with stimulators completed the test once with the stimulator on, once with it off, and once with the stimulator off after receiving levodopa. People with Parkinson’s disease without stimulators performed worse than controls in almost every category. People with stimulators did not perform significantly worse than the controls. Participants with stimulators had an average of 3.8 slight driving errors on the test, compared with 7.5 for the controls and 11.4 for people with Parkinson’s disease without stimulators.
Gadolinium-based contrast medium (Gd-CM) may be associated with abnormalities on brain MRI, according to research published online ahead of print December 17, 2013, in Radiology. Researchers compared unenhanced T1-weighted MR images of 19 patients who had undergone six or more contrast-enhanced brain scans with images of 16 people who had received six or fewer unenhanced scans. The hyperintensity of the dentate nucleus and globus pallidus correlated with the number of Gd-CM administrations. Hyperintensity in the dentate nucleus and globus pallidus on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations, according to the researchers. Because gadolinium has a high signal intensity in the body, the data suggest that the toxic gadolinium component remains in the body in patients with normal renal function.
—Erik Greb
The Bacille Calmette-Guérin (BCG) vaccine may benefit patients with clinically isolated syndrome (CIS), according to research published online ahead of print December 4, 2013, in Neurology. A total of 82 participants with CIS were randomized to BCG or placebo and monitored monthly with brain MRI for six months. All patients subsequently received IM interferon β-1a for 12 months. In an open-label extension phase, patients received disease-modifying therapies (DMTs) recommended by their neurologists. During the initial six months, the number of cumulative lesions was significantly lower among vaccinated subjects. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18. After 60 months, the probability of clinically definite multiple sclerosis was lower in the BCG plus DMT arm, and more vaccinated people remained DMT-free.
Exercise programs may significantly improve the ability of people with dementia to perform activities of daily living, according to a study published online ahead of print December 4, 2013, in the Cochrane Library. Exercise also may improve cognition in these patients, but may not affect depression. Investigators reviewed randomized controlled trials in which older people diagnosed with dementia were allocated to exercise programs or to control groups, which received standard care or social contact. Sixteen trials with 937 participants met the inclusion criteria. The trials were highly heterogeneous in terms of subtype and severity of participants’ dementia, and type, duration, and frequency of exercise. The researchers found that informal caregivers’ burden may be reduced when the family member with dementia participates in an exercise program.
Thrombin activity may enable neurologists to detect multiple sclerosis (MS) before clinical signs of the disease are present, according to research published online ahead of print November 29, 2013, in Annals of Neurology. Using a novel molecular probe, investigators characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded the onset of neurologic signs; increased at disease peak; and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Scientists may be able to use thrombin activity to develop sensitive probes for the preclinical detection and monitoring of neuroinflammation and MS progression, according to the investigators.
An athlete with concussion symptoms should not be allowed to return to play on the same day, according to the latest consensus statement on sports-related concussion, which was summarized in the December 2013 issue of Neurosurgery. The Concussion in Sport Group (CISG 4) based its recommendations on the advice of an expert panel that was sponsored by five international sports governing bodies. Between 80% and 90% of concussions resolve within seven to 10 days, but recovery may take longer in children and adolescents, according to the consensus statement. The updated statement emphasizes the distinction between concussion and mild traumatic brain injury. The CISG 4 suggests that patients with concussion have normal findings on brain neuroimaging studies (eg, CT scan), but those with traumatic brain injury have abnormal imaging findings.
Vitamin D may prevent multiple sclerosis (MS) by blocking T helper (TH) cells from migrating into the CNS, according to research published online ahead of print December 9, 2013, in Proceedings of the National Academy of Sciences. Investigators administered 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D, to animals with experimental autoimmune encephalomyelitis, a mouse model of MS. Myelin-reactive TH cells were generated in the presence of 1,25(OH)2D3, secreted proinflammatory cytokines, and did not preferentially differentiate into suppressor T cells. The cells left the lymph node, entered the peripheral circulation, and migrated to the immunization sites. TH cells from 1,25(OH)2D3-treated mice were unable to enter the CNS parenchyma, however. Instead, the cells were maintained in the periphery. The mice developed experimental autoimmune encephalomyelitis when treatment ceased.
Among people with type 2 diabetes, dementia incidence may be highest among Native Americans and African Americans and lowest among Asians, according to a study published online ahead of print November 22, 2013, in Diabetes Care. Scientists identified 22,171 patients age 60 or older with diabetes and without preexisting dementia in the Kaiser Permanente Northern California Diabetes Registry. The investigators abstracted prevalent medical history and dementia incidence from medical records and calculated age-adjusted incidence densities. Dementia was diagnosed in 17.1% of patients. Age-adjusted dementia incidence densities were 34/1,000 person-years among Native Americans, 27/1,000 person-years among African Americans, and 19/1,000 person-years among Asians. Hazard ratios (relative to Asians) were 1.64 for Native Americans, 1.44 for African Americans, 1.30 for non-Hispanic whites, and 1.19 for Latinos.
Veterans with blast injuries have changes in brain tissue that may be apparent on imaging years later, according to data presented at the 99th Annual Meeting of the Radiological Society of North America. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with mild traumatic brain injury with those of 10 healthy controls. The average time elapsed between the blast-induced injury and DTI scan among the patients was 51.3 months. FA values were significantly different between the two groups, and the researchers found significant correlations between FA values and attention, delayed memory, and psychomotor test scores. The results suggest that blast injury may have a long-term impact on the brain.
Among college athletes, head impact exposure may be related to white matter diffusion measures and cognition during the course of one playing season, even in the absence of diagnosed concussion, according to data published online ahead of print December 11, 2013, in Neurology. Researchers prospectively studied 79 noncontact sport athletes and 80 nonconcussed varsity football and ice hockey players who wore helmets that recorded the acceleration-time history of the head following impact. Mean diffusivity (MD) in the corpus callosum was significantly different between groups. Measures of head impact exposure correlated with white matter diffusivity measures in the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.
Among veterans, traumatic brain injury (TBI) during the most recent deployment is the strongest predictor of postdeployment symptoms of post-traumatic stress disorder (PTSD), even when accounting for predeployment symptoms, prior TBI, and combat intensity, according to research published online ahead of print December 11, 2013, in JAMA Psychiatry. A total of 1,648 active-duty Marine and Navy servicemen underwent clinical interviews and completed self-assessments approximately one month before a seven-month deployment and three to six months after deployment. At the predeployment assessment, 56.8% of participants reported prior TBI. At postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments. Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. TBI doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.
Fidgetin inhibition could promote tissue regeneration and repair the broken cell connections that occur in spinal cord injury and other conditions, according to research presented at the 2013 Annual Meeting of the American Society for Cell Biology. Fidgetin prunes unstable microtubule scaffolding in cells, as well as unneeded connections in the neuronal network as the latter grows. Researchers used a novel nanoparticle technology to block fidgetin in the injured nerves of adult rats. The nanoparticles were infused with small interfering RNA that bound the messenger RNA (mRNA) transcribed from the fidgetin gene. The mRNA for fidgetin was not translated, and the cell did not produce fidgetin. Blocking fidgetin restarted tissue growth in the animals. The technique could benefit patients with myocardial infarction or chronic cutaneous wounds.
Deep brain stimulation may improve driving ability for people with Parkinson’s disease, according to a study published online ahead of print December 18, 2013, in Neurology. Investigators studied 23 people who had deep brain stimulators, 21 people with Parkinson’s disease without stimulators, and 21 healthy individuals. Participants were tested with a driving simulator. Individuals with stimulators completed the test once with the stimulator on, once with it off, and once with the stimulator off after receiving levodopa. People with Parkinson’s disease without stimulators performed worse than controls in almost every category. People with stimulators did not perform significantly worse than the controls. Participants with stimulators had an average of 3.8 slight driving errors on the test, compared with 7.5 for the controls and 11.4 for people with Parkinson’s disease without stimulators.
Gadolinium-based contrast medium (Gd-CM) may be associated with abnormalities on brain MRI, according to research published online ahead of print December 17, 2013, in Radiology. Researchers compared unenhanced T1-weighted MR images of 19 patients who had undergone six or more contrast-enhanced brain scans with images of 16 people who had received six or fewer unenhanced scans. The hyperintensity of the dentate nucleus and globus pallidus correlated with the number of Gd-CM administrations. Hyperintensity in the dentate nucleus and globus pallidus on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations, according to the researchers. Because gadolinium has a high signal intensity in the body, the data suggest that the toxic gadolinium component remains in the body in patients with normal renal function.
—Erik Greb
New and Noteworthy Information—December 2013
Mild traumatic brain injury (TBI) may be associated with increased cortical fractional anisotropy, but not with cortical or subcortical atrophy, according to research published online ahead of print November 20 in Neurology. Investigators evaluated 50 patients and 50 sex-, age-, and education-matched controls with a clinical and neuroimaging battery approximately 14 days after TBI. A total of 26 patients returned for follow-up four months after injury. Patients had increased fractional anisotropy in the bilateral superior frontal cortex during the semiacute phase of injury. Fractional anisotropy in the left superior frontal cortex remained elevated at four months after injury. The researchers found no significant differences between patients and matched controls on neuropsychologic testing or measures of gray matter atrophy or mean diffusivity at either time point.
Researchers detailed the early clinical course, morbidity, and mortality of the 2012 outbreak of fungal infections associated with methylprednisolone injections in two articles published October 24, 2013, in the New England Journal of Medicine. As of July 1, 2013, a total of 749 cases of infection had been reported in 20 states, including 61 deaths. Of 728 patients for whom data were available, 31% had meningitis and no other documented infection. Of 328 patients without peripheral joint infection who were included in one investigation, 81% had CNS infection, and 19% had non-CNS infections only. The investigators found evidence of Exserohilum rostratum in 36% of patients for whom samples were available. Patients’ median age was 64, and the median incubation period was 47 days. Forty patients had a stroke.
An algorithm may accurately predict time to death, institutionalization, and need for full-time care in patients with Alzheimer’s disease, according to an article published online ahead of print September 24 in the Journal of Alzheimer’s Disease. Investigators followed two study cohorts with mild Alzheimer’s disease for 10 years. The first cohort included 252 patients, and the second included 254 patients. Participants underwent semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. For each of the three outcome measures, the predicted survival curves were well within the 95% confidence intervals of the observed survival curves. The actual and predicted survival curves were statistically equivalent. The algorithm can be adapted to predict other important disease end points, according to the researchers.
High pulse pressure may be associated with increased CSF phosphorylated tau and decreased β-amyloid 1–42 (Aβ1–42) in cognitively normal older adults, according to research published online ahead of print November 13 in Neurology. A total of 177 cognitively normal, stroke-free older adults underwent blood pressure assessment for determination of pulse pressure, as well as lumbar puncture for measurement of CSF Aβ1–42 and phosphorylated tau. High pulse pressure was associated with increased phosphorylated tau, reduced Aβ1–42, and increased phosphorylated tau to Aβ1–42 ratio. After controlling for covariates, the investigators found that pulse pressure remained associated with phosphorylated tau and phosphorylated tau to Aβ1–42 ratio, but was no longer associated with Aβ1–42. The relationship between pulse pressure and CSF biomarkers is age-dependent, said the researchers.
Acute stroke care in hospitals with neurology residency programs may be associated with an increased use of thrombolytics, investigators reported online ahead of print November 1 in Neurology. The disparities between the thrombolysis rates in hospitals with neurology residency programs and those in other teaching hospitals and nonteaching hospitals may be greater among elderly patients. Researchers retrospectively studied a nationally representative sample of patients with ischemic stroke. A total of 712,433 individuals from 6,839 hospital samples were included. Of these patients, 10.1%, 29.1%, and 60.8% were treated in hospitals with neurology residency programs, other teaching hospitals, and nonteaching hospitals, respectively. Patients in hospitals with neurology residency programs received thrombolysis more frequently (3.74%) than those in other teaching hospitals (2.28%) and those in nonteaching hospitals (1.44%).
The FDA has approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat partial-onset seizures associated with epilepsy. In three large, phase III safety and efficacy trials that included more than 1,400 patients with inadequately controlled partial-onset seizures, eslicarbazepine acetate was associated with statistically significant reductions in standardized seizure frequency, compared with placebo. Significantly more patients who received eslicarbazepine acetate had a reduction in seizure frequency of 50% or more, compared with controls. The most common side effects include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, and blurred vision. Eslicarbazepine acetate will not be classified as a controlled substance. Sunovion (Marlborough, Massachusetts) markets the drug and expects it to be available in the US during the second quarter of 2014.
The FDA has approved the NeuroPace RNS System, a device intended to reduce the frequency of seizures in patients with epilepsy who have not responded well to medications. The device consists of a small neurostimulator implanted within the skull. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. When it detects abnormal electrical activity, the neurostimulator delivers electrical stimulation to normalize brain activity and prevent seizures. In a randomized study of 191 patients, the average number of seizures per month was reduced by approximately 38% at three months in patients in whom the device was turned on. The RNS System is manufactured by NeuroPace (Mountainview, California).
Reducing blood pressure with antihypertensive medications may not decrease the likelihood of death and major disability among patients with acute ischemic stroke, according to a study published online ahead of print November 17 in JAMA. Researchers studied 4,071 patients with nonthrombolyzed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were randomized to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. The researchers found no difference in the rates of death and major disability between the treatment groups.
Persons with high urinary concentrations of tungsten may have an increased risk of stroke, according to a study published November 11 in PLOS One. Investigators analyzed associations between tungsten, commonly used in mobile phones and computers, and cardiovascular disease or stroke using crude and adjusted logistic regression models in a cohort of 8,614 adults (ages 18 to 74) with 193 reported stroke diagnoses and 428 reported diagnoses of cardiovascular disease. The researchers also stratified the data to characterize associations in a subset of individuals between ages 18 and 50. Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (odds ratio: 1.66). The association between tungsten and stroke in the young age category was still evident (odds ratio: 2.17).
Traumatic brain injury (TBI) may be associated with increased amyloid deposition, according to research published online ahead of print November 11 in JAMA Neurology. Investigators used carbon 11-labeled Pittsburgh Compound B ([11C]PiB) PET to image amyloid deposition in 11 controls and 15 patients between one and 361 days after TBI. Compared with the controls, the patients with TBI had significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum, but not in the thalamus or white matter. The investigators observed increases in [11C]PiB distribution volume ratios in patients with TBI across most cortical subregions. The increases were replicated using comparisons of standardized uptake value ratios and could not be accounted for by methodologic confounders.
Compared with persons who speak only one language, bilingual individuals may have a delayed onset of dementia, according to a study published online ahead of print November 6 in Neurology. Investigators reviewed case records of 648 patients with dementia (391 bilinguals) diagnosed in a specialist clinic. They compared age at onset of first symptoms between monolingual and bilingual groups and examined the influence of the number of languages spoken, education, occupation, and other potentially interacting variables. Bilingual patients developed dementia 4.5 years later than the monolingual patients. The researchers found a significant difference in age at onset of Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. The age difference was also observed in illiterate patients. The investigators found no additional benefit to speaking more than two languages.
Temporal lobe epilepsy (TLE) may entail altered structural connectivity in the brain, according to a study published online ahead of print November 8 in Radiology. Investigators analyzed 60-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MRI volumes for 24 patients with left TLE and 24 healthy control subjects. MP-RAGE volumes were segmented into 1,015 regions of interest that spanned the entire brain. Patients with TLE had 22% to 45% reduced distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with healthy subjects. Local connectivity, as measured by means of network efficiency, was increased by 85% to 270% in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE, compared with healthy subjects.
Gray matter damage may be a key factor associated with long-term accumulation of disability and cognitive impairment in multiple sclerosis (MS), according to research published November 12 in Neurology. Investigators obtained conventional and magnetization transfer (MT) MRI brain scans at baseline and at 12 months for 73 patients with MS, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score and the MS severity score for a median of 13.3 years. At 13-year follow-up, 66% of patients had significant worsening of disability, and 37% had worse cognition. The multivariable model identified baseline gray matter fraction as the only predictor of disability worsening. Baseline disease duration and average gray matter lesion MT ratio were independent variables associated with cognitive deterioration.
—Erik Greb
Senior Associate Editor
Mild traumatic brain injury (TBI) may be associated with increased cortical fractional anisotropy, but not with cortical or subcortical atrophy, according to research published online ahead of print November 20 in Neurology. Investigators evaluated 50 patients and 50 sex-, age-, and education-matched controls with a clinical and neuroimaging battery approximately 14 days after TBI. A total of 26 patients returned for follow-up four months after injury. Patients had increased fractional anisotropy in the bilateral superior frontal cortex during the semiacute phase of injury. Fractional anisotropy in the left superior frontal cortex remained elevated at four months after injury. The researchers found no significant differences between patients and matched controls on neuropsychologic testing or measures of gray matter atrophy or mean diffusivity at either time point.
Researchers detailed the early clinical course, morbidity, and mortality of the 2012 outbreak of fungal infections associated with methylprednisolone injections in two articles published October 24, 2013, in the New England Journal of Medicine. As of July 1, 2013, a total of 749 cases of infection had been reported in 20 states, including 61 deaths. Of 728 patients for whom data were available, 31% had meningitis and no other documented infection. Of 328 patients without peripheral joint infection who were included in one investigation, 81% had CNS infection, and 19% had non-CNS infections only. The investigators found evidence of Exserohilum rostratum in 36% of patients for whom samples were available. Patients’ median age was 64, and the median incubation period was 47 days. Forty patients had a stroke.
An algorithm may accurately predict time to death, institutionalization, and need for full-time care in patients with Alzheimer’s disease, according to an article published online ahead of print September 24 in the Journal of Alzheimer’s Disease. Investigators followed two study cohorts with mild Alzheimer’s disease for 10 years. The first cohort included 252 patients, and the second included 254 patients. Participants underwent semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. For each of the three outcome measures, the predicted survival curves were well within the 95% confidence intervals of the observed survival curves. The actual and predicted survival curves were statistically equivalent. The algorithm can be adapted to predict other important disease end points, according to the researchers.
High pulse pressure may be associated with increased CSF phosphorylated tau and decreased β-amyloid 1–42 (Aβ1–42) in cognitively normal older adults, according to research published online ahead of print November 13 in Neurology. A total of 177 cognitively normal, stroke-free older adults underwent blood pressure assessment for determination of pulse pressure, as well as lumbar puncture for measurement of CSF Aβ1–42 and phosphorylated tau. High pulse pressure was associated with increased phosphorylated tau, reduced Aβ1–42, and increased phosphorylated tau to Aβ1–42 ratio. After controlling for covariates, the investigators found that pulse pressure remained associated with phosphorylated tau and phosphorylated tau to Aβ1–42 ratio, but was no longer associated with Aβ1–42. The relationship between pulse pressure and CSF biomarkers is age-dependent, said the researchers.
Acute stroke care in hospitals with neurology residency programs may be associated with an increased use of thrombolytics, investigators reported online ahead of print November 1 in Neurology. The disparities between the thrombolysis rates in hospitals with neurology residency programs and those in other teaching hospitals and nonteaching hospitals may be greater among elderly patients. Researchers retrospectively studied a nationally representative sample of patients with ischemic stroke. A total of 712,433 individuals from 6,839 hospital samples were included. Of these patients, 10.1%, 29.1%, and 60.8% were treated in hospitals with neurology residency programs, other teaching hospitals, and nonteaching hospitals, respectively. Patients in hospitals with neurology residency programs received thrombolysis more frequently (3.74%) than those in other teaching hospitals (2.28%) and those in nonteaching hospitals (1.44%).
The FDA has approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat partial-onset seizures associated with epilepsy. In three large, phase III safety and efficacy trials that included more than 1,400 patients with inadequately controlled partial-onset seizures, eslicarbazepine acetate was associated with statistically significant reductions in standardized seizure frequency, compared with placebo. Significantly more patients who received eslicarbazepine acetate had a reduction in seizure frequency of 50% or more, compared with controls. The most common side effects include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, and blurred vision. Eslicarbazepine acetate will not be classified as a controlled substance. Sunovion (Marlborough, Massachusetts) markets the drug and expects it to be available in the US during the second quarter of 2014.
The FDA has approved the NeuroPace RNS System, a device intended to reduce the frequency of seizures in patients with epilepsy who have not responded well to medications. The device consists of a small neurostimulator implanted within the skull. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. When it detects abnormal electrical activity, the neurostimulator delivers electrical stimulation to normalize brain activity and prevent seizures. In a randomized study of 191 patients, the average number of seizures per month was reduced by approximately 38% at three months in patients in whom the device was turned on. The RNS System is manufactured by NeuroPace (Mountainview, California).
Reducing blood pressure with antihypertensive medications may not decrease the likelihood of death and major disability among patients with acute ischemic stroke, according to a study published online ahead of print November 17 in JAMA. Researchers studied 4,071 patients with nonthrombolyzed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were randomized to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. The researchers found no difference in the rates of death and major disability between the treatment groups.
Persons with high urinary concentrations of tungsten may have an increased risk of stroke, according to a study published November 11 in PLOS One. Investigators analyzed associations between tungsten, commonly used in mobile phones and computers, and cardiovascular disease or stroke using crude and adjusted logistic regression models in a cohort of 8,614 adults (ages 18 to 74) with 193 reported stroke diagnoses and 428 reported diagnoses of cardiovascular disease. The researchers also stratified the data to characterize associations in a subset of individuals between ages 18 and 50. Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (odds ratio: 1.66). The association between tungsten and stroke in the young age category was still evident (odds ratio: 2.17).
Traumatic brain injury (TBI) may be associated with increased amyloid deposition, according to research published online ahead of print November 11 in JAMA Neurology. Investigators used carbon 11-labeled Pittsburgh Compound B ([11C]PiB) PET to image amyloid deposition in 11 controls and 15 patients between one and 361 days after TBI. Compared with the controls, the patients with TBI had significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum, but not in the thalamus or white matter. The investigators observed increases in [11C]PiB distribution volume ratios in patients with TBI across most cortical subregions. The increases were replicated using comparisons of standardized uptake value ratios and could not be accounted for by methodologic confounders.
Compared with persons who speak only one language, bilingual individuals may have a delayed onset of dementia, according to a study published online ahead of print November 6 in Neurology. Investigators reviewed case records of 648 patients with dementia (391 bilinguals) diagnosed in a specialist clinic. They compared age at onset of first symptoms between monolingual and bilingual groups and examined the influence of the number of languages spoken, education, occupation, and other potentially interacting variables. Bilingual patients developed dementia 4.5 years later than the monolingual patients. The researchers found a significant difference in age at onset of Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. The age difference was also observed in illiterate patients. The investigators found no additional benefit to speaking more than two languages.
Temporal lobe epilepsy (TLE) may entail altered structural connectivity in the brain, according to a study published online ahead of print November 8 in Radiology. Investigators analyzed 60-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MRI volumes for 24 patients with left TLE and 24 healthy control subjects. MP-RAGE volumes were segmented into 1,015 regions of interest that spanned the entire brain. Patients with TLE had 22% to 45% reduced distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with healthy subjects. Local connectivity, as measured by means of network efficiency, was increased by 85% to 270% in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE, compared with healthy subjects.
Gray matter damage may be a key factor associated with long-term accumulation of disability and cognitive impairment in multiple sclerosis (MS), according to research published November 12 in Neurology. Investigators obtained conventional and magnetization transfer (MT) MRI brain scans at baseline and at 12 months for 73 patients with MS, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score and the MS severity score for a median of 13.3 years. At 13-year follow-up, 66% of patients had significant worsening of disability, and 37% had worse cognition. The multivariable model identified baseline gray matter fraction as the only predictor of disability worsening. Baseline disease duration and average gray matter lesion MT ratio were independent variables associated with cognitive deterioration.
—Erik Greb
Senior Associate Editor
Mild traumatic brain injury (TBI) may be associated with increased cortical fractional anisotropy, but not with cortical or subcortical atrophy, according to research published online ahead of print November 20 in Neurology. Investigators evaluated 50 patients and 50 sex-, age-, and education-matched controls with a clinical and neuroimaging battery approximately 14 days after TBI. A total of 26 patients returned for follow-up four months after injury. Patients had increased fractional anisotropy in the bilateral superior frontal cortex during the semiacute phase of injury. Fractional anisotropy in the left superior frontal cortex remained elevated at four months after injury. The researchers found no significant differences between patients and matched controls on neuropsychologic testing or measures of gray matter atrophy or mean diffusivity at either time point.
Researchers detailed the early clinical course, morbidity, and mortality of the 2012 outbreak of fungal infections associated with methylprednisolone injections in two articles published October 24, 2013, in the New England Journal of Medicine. As of July 1, 2013, a total of 749 cases of infection had been reported in 20 states, including 61 deaths. Of 728 patients for whom data were available, 31% had meningitis and no other documented infection. Of 328 patients without peripheral joint infection who were included in one investigation, 81% had CNS infection, and 19% had non-CNS infections only. The investigators found evidence of Exserohilum rostratum in 36% of patients for whom samples were available. Patients’ median age was 64, and the median incubation period was 47 days. Forty patients had a stroke.
An algorithm may accurately predict time to death, institutionalization, and need for full-time care in patients with Alzheimer’s disease, according to an article published online ahead of print September 24 in the Journal of Alzheimer’s Disease. Investigators followed two study cohorts with mild Alzheimer’s disease for 10 years. The first cohort included 252 patients, and the second included 254 patients. Participants underwent semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. For each of the three outcome measures, the predicted survival curves were well within the 95% confidence intervals of the observed survival curves. The actual and predicted survival curves were statistically equivalent. The algorithm can be adapted to predict other important disease end points, according to the researchers.
High pulse pressure may be associated with increased CSF phosphorylated tau and decreased β-amyloid 1–42 (Aβ1–42) in cognitively normal older adults, according to research published online ahead of print November 13 in Neurology. A total of 177 cognitively normal, stroke-free older adults underwent blood pressure assessment for determination of pulse pressure, as well as lumbar puncture for measurement of CSF Aβ1–42 and phosphorylated tau. High pulse pressure was associated with increased phosphorylated tau, reduced Aβ1–42, and increased phosphorylated tau to Aβ1–42 ratio. After controlling for covariates, the investigators found that pulse pressure remained associated with phosphorylated tau and phosphorylated tau to Aβ1–42 ratio, but was no longer associated with Aβ1–42. The relationship between pulse pressure and CSF biomarkers is age-dependent, said the researchers.
Acute stroke care in hospitals with neurology residency programs may be associated with an increased use of thrombolytics, investigators reported online ahead of print November 1 in Neurology. The disparities between the thrombolysis rates in hospitals with neurology residency programs and those in other teaching hospitals and nonteaching hospitals may be greater among elderly patients. Researchers retrospectively studied a nationally representative sample of patients with ischemic stroke. A total of 712,433 individuals from 6,839 hospital samples were included. Of these patients, 10.1%, 29.1%, and 60.8% were treated in hospitals with neurology residency programs, other teaching hospitals, and nonteaching hospitals, respectively. Patients in hospitals with neurology residency programs received thrombolysis more frequently (3.74%) than those in other teaching hospitals (2.28%) and those in nonteaching hospitals (1.44%).
The FDA has approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat partial-onset seizures associated with epilepsy. In three large, phase III safety and efficacy trials that included more than 1,400 patients with inadequately controlled partial-onset seizures, eslicarbazepine acetate was associated with statistically significant reductions in standardized seizure frequency, compared with placebo. Significantly more patients who received eslicarbazepine acetate had a reduction in seizure frequency of 50% or more, compared with controls. The most common side effects include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, and blurred vision. Eslicarbazepine acetate will not be classified as a controlled substance. Sunovion (Marlborough, Massachusetts) markets the drug and expects it to be available in the US during the second quarter of 2014.
The FDA has approved the NeuroPace RNS System, a device intended to reduce the frequency of seizures in patients with epilepsy who have not responded well to medications. The device consists of a small neurostimulator implanted within the skull. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. When it detects abnormal electrical activity, the neurostimulator delivers electrical stimulation to normalize brain activity and prevent seizures. In a randomized study of 191 patients, the average number of seizures per month was reduced by approximately 38% at three months in patients in whom the device was turned on. The RNS System is manufactured by NeuroPace (Mountainview, California).
Reducing blood pressure with antihypertensive medications may not decrease the likelihood of death and major disability among patients with acute ischemic stroke, according to a study published online ahead of print November 17 in JAMA. Researchers studied 4,071 patients with nonthrombolyzed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were randomized to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. The researchers found no difference in the rates of death and major disability between the treatment groups.
Persons with high urinary concentrations of tungsten may have an increased risk of stroke, according to a study published November 11 in PLOS One. Investigators analyzed associations between tungsten, commonly used in mobile phones and computers, and cardiovascular disease or stroke using crude and adjusted logistic regression models in a cohort of 8,614 adults (ages 18 to 74) with 193 reported stroke diagnoses and 428 reported diagnoses of cardiovascular disease. The researchers also stratified the data to characterize associations in a subset of individuals between ages 18 and 50. Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (odds ratio: 1.66). The association between tungsten and stroke in the young age category was still evident (odds ratio: 2.17).
Traumatic brain injury (TBI) may be associated with increased amyloid deposition, according to research published online ahead of print November 11 in JAMA Neurology. Investigators used carbon 11-labeled Pittsburgh Compound B ([11C]PiB) PET to image amyloid deposition in 11 controls and 15 patients between one and 361 days after TBI. Compared with the controls, the patients with TBI had significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum, but not in the thalamus or white matter. The investigators observed increases in [11C]PiB distribution volume ratios in patients with TBI across most cortical subregions. The increases were replicated using comparisons of standardized uptake value ratios and could not be accounted for by methodologic confounders.
Compared with persons who speak only one language, bilingual individuals may have a delayed onset of dementia, according to a study published online ahead of print November 6 in Neurology. Investigators reviewed case records of 648 patients with dementia (391 bilinguals) diagnosed in a specialist clinic. They compared age at onset of first symptoms between monolingual and bilingual groups and examined the influence of the number of languages spoken, education, occupation, and other potentially interacting variables. Bilingual patients developed dementia 4.5 years later than the monolingual patients. The researchers found a significant difference in age at onset of Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. The age difference was also observed in illiterate patients. The investigators found no additional benefit to speaking more than two languages.
Temporal lobe epilepsy (TLE) may entail altered structural connectivity in the brain, according to a study published online ahead of print November 8 in Radiology. Investigators analyzed 60-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MRI volumes for 24 patients with left TLE and 24 healthy control subjects. MP-RAGE volumes were segmented into 1,015 regions of interest that spanned the entire brain. Patients with TLE had 22% to 45% reduced distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with healthy subjects. Local connectivity, as measured by means of network efficiency, was increased by 85% to 270% in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE, compared with healthy subjects.
Gray matter damage may be a key factor associated with long-term accumulation of disability and cognitive impairment in multiple sclerosis (MS), according to research published November 12 in Neurology. Investigators obtained conventional and magnetization transfer (MT) MRI brain scans at baseline and at 12 months for 73 patients with MS, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score and the MS severity score for a median of 13.3 years. At 13-year follow-up, 66% of patients had significant worsening of disability, and 37% had worse cognition. The multivariable model identified baseline gray matter fraction as the only predictor of disability worsening. Baseline disease duration and average gray matter lesion MT ratio were independent variables associated with cognitive deterioration.
—Erik Greb
Senior Associate Editor