Traumatic Brain Injury

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.

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

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:

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:

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:

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.”