Traumatic Brain Injury

Patients with traumatic brain injury (TBI) who were treated with citicoline failed to show improvements in functional and cognitive status, according to results of a multicenter phase III trial reported in the November 21, 2012, issue of JAMA. Citicoline proved to be no better than placebo at improving function or cognition after TBI in the first large randomized clinical trial to test it in this patient population.

Citicoline, an endogenous compound that is an intermediate in the biosynthesis of phosphatidylcholine from choline, is thought to have a range of neuroprotective properties and has been approved as a treatment for TBI in 59 countries other than the United States. But it is widely available in the US as a nutraceutical used for various neurologic disorders, said lead author Ross D. Zafonte, DO, of the Department of Physical Medicine and Rehabilitation at Harvard Medical School in Boston, and his associates.

Given these new findings, “the worldwide use of citicoline for TBI should now be questioned,” the investigators wrote.

It’s likely that no single therapeutic agent will ever be sufficient to improve functional outcomes in TBI, because so many pathologic mechanisms are at work, including hematoma, edema, infarction, contusions, and inflammation, Robert L. Ruff, MD, PhD, and Ronald G. Riechers II, MD, of the Neurology and Polytrauma Services and the Department of Neurology at the Cleveland (Ohio) Veterans Affairs Medical Center said in an accompanying editorial. “The diverse and complex nature of the pathologic mechanisms activated by TBI suggests that multimodal treatment interventions may be needed to improve recovery.”

Dr. Zafonte and his colleagues conducted the Citicoline Brain Injury Treatment Trial (COBRIT), the first large, phase III, double-blind study to compare citicoline with placebo in the acute and postacute phases after TBI. They enrolled patients with a broad range of severity of injury who had presented to eight level I trauma centers across the country.

The 1,213 study subjects ranged in age from 18 to 70, and the study population was ethnically and demographically diverse. As is typical for TBI patients, three-quarters of the study subjects were male, and more than half were younger than 45.

These patients were randomly assigned to receive 90 days of either citicoline (607 patients) or identical-looking placebo (606) through an enteral route; those who could not swallow the regular oral tablets received the compound as crushed tablets mixed with water or saline and administered through a nasogastric or percutaneous endoscopic gastrostomy tube. The dosage was 2,000 mg per day. Treatment commenced within 24 hours of sustaining the injury.

The primary outcome of the study was functional status and cognitive performance at 90 days, as measured by all nine components of the TBI Clinical Trials Network Core Battery. These components included the Glasgow Outcome Scale-Extended (GOS-E) instrument.

COBRIT was halted early when an interim analysis indicated that further accrual would not change the main outcome: Patients given citicoline did not differ from those given placebo when tested using the combined battery (odds ratio, 0.98) or when tested on any of the individual elements of the battery.

In particular, rates of improvement on the GOS-E were almost exactly the same: 35.4% among subjects given citicoline and 35.6% among those given placebo, the researchers reported. These findings did not change when the data were adjusted to account for patients’ results on the Abbreviated Injury Score at baseline or when the subjects were categorized by the severity of their TBI. The results also did not change when the analysis was restricted to only subjects who took at least 75% of their assigned study medication. There also were no significant differences between the groups in any measure at 180 days postinjury.

A total of 73 subjects died during the study, with no significant difference in survival between the groups.

Similarly, there were no differences between the groups in the overall rates of adverse events or in the rates of serious adverse events.

Patients with traumatic brain injury (TBI) who were treated with citicoline failed to show improvements in functional and cognitive status, according to results of a multicenter phase III trial reported in the November 21, 2012, issue of JAMA. Citicoline proved to be no better than placebo at improving function or cognition after TBI in the first large randomized clinical trial to test it in this patient population.

Citicoline, an endogenous compound that is an intermediate in the biosynthesis of phosphatidylcholine from choline, is thought to have a range of neuroprotective properties and has been approved as a treatment for TBI in 59 countries other than the United States. But it is widely available in the US as a nutraceutical used for various neurologic disorders, said lead author Ross D. Zafonte, DO, of the Department of Physical Medicine and Rehabilitation at Harvard Medical School in Boston, and his associates.

Given these new findings, “the worldwide use of citicoline for TBI should now be questioned,” the investigators wrote.

It’s likely that no single therapeutic agent will ever be sufficient to improve functional outcomes in TBI, because so many pathologic mechanisms are at work, including hematoma, edema, infarction, contusions, and inflammation, Robert L. Ruff, MD, PhD, and Ronald G. Riechers II, MD, of the Neurology and Polytrauma Services and the Department of Neurology at the Cleveland (Ohio) Veterans Affairs Medical Center said in an accompanying editorial. “The diverse and complex nature of the pathologic mechanisms activated by TBI suggests that multimodal treatment interventions may be needed to improve recovery.”

Dr. Zafonte and his colleagues conducted the Citicoline Brain Injury Treatment Trial (COBRIT), the first large, phase III, double-blind study to compare citicoline with placebo in the acute and postacute phases after TBI. They enrolled patients with a broad range of severity of injury who had presented to eight level I trauma centers across the country.

The 1,213 study subjects ranged in age from 18 to 70, and the study population was ethnically and demographically diverse. As is typical for TBI patients, three-quarters of the study subjects were male, and more than half were younger than 45.

These patients were randomly assigned to receive 90 days of either citicoline (607 patients) or identical-looking placebo (606) through an enteral route; those who could not swallow the regular oral tablets received the compound as crushed tablets mixed with water or saline and administered through a nasogastric or percutaneous endoscopic gastrostomy tube. The dosage was 2,000 mg per day. Treatment commenced within 24 hours of sustaining the injury.

The primary outcome of the study was functional status and cognitive performance at 90 days, as measured by all nine components of the TBI Clinical Trials Network Core Battery. These components included the Glasgow Outcome Scale-Extended (GOS-E) instrument.

COBRIT was halted early when an interim analysis indicated that further accrual would not change the main outcome: Patients given citicoline did not differ from those given placebo when tested using the combined battery (odds ratio, 0.98) or when tested on any of the individual elements of the battery.

In particular, rates of improvement on the GOS-E were almost exactly the same: 35.4% among subjects given citicoline and 35.6% among those given placebo, the researchers reported. These findings did not change when the data were adjusted to account for patients’ results on the Abbreviated Injury Score at baseline or when the subjects were categorized by the severity of their TBI. The results also did not change when the analysis was restricted to only subjects who took at least 75% of their assigned study medication. There also were no significant differences between the groups in any measure at 180 days postinjury.

A total of 73 subjects died during the study, with no significant difference in survival between the groups.

Similarly, there were no differences between the groups in the overall rates of adverse events or in the rates of serious adverse events.

Patients with traumatic brain injury (TBI) who were treated with citicoline failed to show improvements in functional and cognitive status, according to results of a multicenter phase III trial reported in the November 21, 2012, issue of JAMA. Citicoline proved to be no better than placebo at improving function or cognition after TBI in the first large randomized clinical trial to test it in this patient population.

Citicoline, an endogenous compound that is an intermediate in the biosynthesis of phosphatidylcholine from choline, is thought to have a range of neuroprotective properties and has been approved as a treatment for TBI in 59 countries other than the United States. But it is widely available in the US as a nutraceutical used for various neurologic disorders, said lead author Ross D. Zafonte, DO, of the Department of Physical Medicine and Rehabilitation at Harvard Medical School in Boston, and his associates.

Given these new findings, “the worldwide use of citicoline for TBI should now be questioned,” the investigators wrote.

It’s likely that no single therapeutic agent will ever be sufficient to improve functional outcomes in TBI, because so many pathologic mechanisms are at work, including hematoma, edema, infarction, contusions, and inflammation, Robert L. Ruff, MD, PhD, and Ronald G. Riechers II, MD, of the Neurology and Polytrauma Services and the Department of Neurology at the Cleveland (Ohio) Veterans Affairs Medical Center said in an accompanying editorial. “The diverse and complex nature of the pathologic mechanisms activated by TBI suggests that multimodal treatment interventions may be needed to improve recovery.”

Dr. Zafonte and his colleagues conducted the Citicoline Brain Injury Treatment Trial (COBRIT), the first large, phase III, double-blind study to compare citicoline with placebo in the acute and postacute phases after TBI. They enrolled patients with a broad range of severity of injury who had presented to eight level I trauma centers across the country.

The 1,213 study subjects ranged in age from 18 to 70, and the study population was ethnically and demographically diverse. As is typical for TBI patients, three-quarters of the study subjects were male, and more than half were younger than 45.

These patients were randomly assigned to receive 90 days of either citicoline (607 patients) or identical-looking placebo (606) through an enteral route; those who could not swallow the regular oral tablets received the compound as crushed tablets mixed with water or saline and administered through a nasogastric or percutaneous endoscopic gastrostomy tube. The dosage was 2,000 mg per day. Treatment commenced within 24 hours of sustaining the injury.

The primary outcome of the study was functional status and cognitive performance at 90 days, as measured by all nine components of the TBI Clinical Trials Network Core Battery. These components included the Glasgow Outcome Scale-Extended (GOS-E) instrument.

COBRIT was halted early when an interim analysis indicated that further accrual would not change the main outcome: Patients given citicoline did not differ from those given placebo when tested using the combined battery (odds ratio, 0.98) or when tested on any of the individual elements of the battery.

In particular, rates of improvement on the GOS-E were almost exactly the same: 35.4% among subjects given citicoline and 35.6% among those given placebo, the researchers reported. These findings did not change when the data were adjusted to account for patients’ results on the Abbreviated Injury Score at baseline or when the subjects were categorized by the severity of their TBI. The results also did not change when the analysis was restricted to only subjects who took at least 75% of their assigned study medication. There also were no significant differences between the groups in any measure at 180 days postinjury.

A total of 73 subjects died during the study, with no significant difference in survival between the groups.

Similarly, there were no differences between the groups in the overall rates of adverse events or in the rates of serious adverse events.

MRI may be better than CT scans at predicting whether patients with mild traumatic brain injuries (mTBI) are likely to have persistent neurologic problems, according to the results of a clinical trial published in the December 2012 Annals of Neurology.

Approximately 15% of patients with mTBI have measurable neurologic deficits at one year after injury, but clinicians have no definitive method of predicting patient outcomes.

To address this clinical need, Esther Yuh, MD, PhD, Assistant Professor in Residence at the University of California, San Francisco, School of Medicine, and her colleagues examined the potential of MRI to predict patient outcome three months after mTBI. The researchers prospectively followed 135 patients who were evaluated for acute head injury in the emergency departments of three level I trauma centers—San Francisco General Hospital and Trauma Center, the University of Pittsburgh Medical Center, and the University Medical Center Brackenridge in Austin, Texas. These centers were part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study (TRACK-TBI).

Patient Characteristics
Patients came from highly diverse socioeconomic backgrounds, had few exclusion factors, and ranged from age 15 to 86, with a mean age of 40. All patients underwent CT scans when they were admitted, and early brain MRI was performed approximately a week later.

The investigators used univariate and multivariate logistic regression to determine demographic, clinical, socioeconomic, CT, and MRI features that predicted outcomes at three months following the brain injury. Outcomes were assessed with the eight-point Extended Glasgow Outcome scale, a well-validated summary assessment suitable for clinical trials.

Multivariate models of the three-month outcome scale were analyzed based on three sets of predictive variables. The first set examined only clinical, demographic, and socioeconomic variables, the second set incorporated head CT features, and the third set used all the preceding variables, as well as brain MRI features.

Evidence of subarachnoid hemorrhage on CT was associated with a multivariate odds ratio of 3.5 for poorer three-month outcome, after accounting for demographic, clinical, and socioeconomic factors, said the researchers.

Normal CT Is Not Enough
However, 27% of patients who were admitted with normal head CT had an abnormal early brain MRI. After adjusting for head CT findings and demographic, clinical, and socioeconomic factors, the investigators found that one or more brain contusions and four or more foci of hemorrhagic axonal injury on MRI were each independently associated with poorer three-month outcome. Multivariate odds ratios were 4.5 and 3.2, respectively.

This work raises questions of how we’re currently managing patients via CT scan,” said senior author Geoff Manley, MD, PhD, Chief of Neurosurgery at San Francisco General Hospital. “Having a normal CT scan doesn’t, in fact, say you’re normal,” he added.

A Step Forward
Each year, at least 1.7 million Americans seek medical attention for acute head injuries, and 75% of those injuries are mTBIs, most with mild symptoms such as temporary loss of consciousness, vomiting, or amnesia.

The majority of patients with mTBI recover fully, but approximately one in six eventually develop persistent and sometimes permanent disability from the injury. In the past, some socioeconomic factors have helped to predict disability, but Dr. Yuh’s study shows that an imaging feature can help to predict the rate or extent of a patient’s recovery.

According to Dr. Manley, this study represents an important step toward developing a more quantitative, precise method of evaluating, monitoring, and treating patients with mTBI. At present, performing routine brain MRI on mTBI patients may not be cost-effective, but smaller and less-costly MRI scanners that examine only the patient’s head are in development. Furthermore, continuing advances in the MRI field may eventually reduce expenses to a manageable level.

The study’s strengths are its greater specification of types of lesions that may predict outcome, control for other predictors, multicenter patient sample, and use of TBI Common Data Elements to categorize the imaging results, the investigators said.

They believe the findings will benefit clinicians and researchers conducting clinical trials. “Progress beyond mere definition of mTBI toward evidence-based diagnosis is essential for clinical trials that evaluate treatments and, ultimately, more effective triage to follow-up care,” stated the authors.

MRI may be better than CT scans at predicting whether patients with mild traumatic brain injuries (mTBI) are likely to have persistent neurologic problems, according to the results of a clinical trial published in the December 2012 Annals of Neurology.

Approximately 15% of patients with mTBI have measurable neurologic deficits at one year after injury, but clinicians have no definitive method of predicting patient outcomes.

To address this clinical need, Esther Yuh, MD, PhD, Assistant Professor in Residence at the University of California, San Francisco, School of Medicine, and her colleagues examined the potential of MRI to predict patient outcome three months after mTBI. The researchers prospectively followed 135 patients who were evaluated for acute head injury in the emergency departments of three level I trauma centers—San Francisco General Hospital and Trauma Center, the University of Pittsburgh Medical Center, and the University Medical Center Brackenridge in Austin, Texas. These centers were part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study (TRACK-TBI).

Patient Characteristics
Patients came from highly diverse socioeconomic backgrounds, had few exclusion factors, and ranged from age 15 to 86, with a mean age of 40. All patients underwent CT scans when they were admitted, and early brain MRI was performed approximately a week later.

The investigators used univariate and multivariate logistic regression to determine demographic, clinical, socioeconomic, CT, and MRI features that predicted outcomes at three months following the brain injury. Outcomes were assessed with the eight-point Extended Glasgow Outcome scale, a well-validated summary assessment suitable for clinical trials.

Multivariate models of the three-month outcome scale were analyzed based on three sets of predictive variables. The first set examined only clinical, demographic, and socioeconomic variables, the second set incorporated head CT features, and the third set used all the preceding variables, as well as brain MRI features.

Evidence of subarachnoid hemorrhage on CT was associated with a multivariate odds ratio of 3.5 for poorer three-month outcome, after accounting for demographic, clinical, and socioeconomic factors, said the researchers.

Normal CT Is Not Enough
However, 27% of patients who were admitted with normal head CT had an abnormal early brain MRI. After adjusting for head CT findings and demographic, clinical, and socioeconomic factors, the investigators found that one or more brain contusions and four or more foci of hemorrhagic axonal injury on MRI were each independently associated with poorer three-month outcome. Multivariate odds ratios were 4.5 and 3.2, respectively.

This work raises questions of how we’re currently managing patients via CT scan,” said senior author Geoff Manley, MD, PhD, Chief of Neurosurgery at San Francisco General Hospital. “Having a normal CT scan doesn’t, in fact, say you’re normal,” he added.

A Step Forward
Each year, at least 1.7 million Americans seek medical attention for acute head injuries, and 75% of those injuries are mTBIs, most with mild symptoms such as temporary loss of consciousness, vomiting, or amnesia.

The majority of patients with mTBI recover fully, but approximately one in six eventually develop persistent and sometimes permanent disability from the injury. In the past, some socioeconomic factors have helped to predict disability, but Dr. Yuh’s study shows that an imaging feature can help to predict the rate or extent of a patient’s recovery.

According to Dr. Manley, this study represents an important step toward developing a more quantitative, precise method of evaluating, monitoring, and treating patients with mTBI. At present, performing routine brain MRI on mTBI patients may not be cost-effective, but smaller and less-costly MRI scanners that examine only the patient’s head are in development. Furthermore, continuing advances in the MRI field may eventually reduce expenses to a manageable level.

The study’s strengths are its greater specification of types of lesions that may predict outcome, control for other predictors, multicenter patient sample, and use of TBI Common Data Elements to categorize the imaging results, the investigators said.

They believe the findings will benefit clinicians and researchers conducting clinical trials. “Progress beyond mere definition of mTBI toward evidence-based diagnosis is essential for clinical trials that evaluate treatments and, ultimately, more effective triage to follow-up care,” stated the authors.

MRI may be better than CT scans at predicting whether patients with mild traumatic brain injuries (mTBI) are likely to have persistent neurologic problems, according to the results of a clinical trial published in the December 2012 Annals of Neurology.

Approximately 15% of patients with mTBI have measurable neurologic deficits at one year after injury, but clinicians have no definitive method of predicting patient outcomes.

To address this clinical need, Esther Yuh, MD, PhD, Assistant Professor in Residence at the University of California, San Francisco, School of Medicine, and her colleagues examined the potential of MRI to predict patient outcome three months after mTBI. The researchers prospectively followed 135 patients who were evaluated for acute head injury in the emergency departments of three level I trauma centers—San Francisco General Hospital and Trauma Center, the University of Pittsburgh Medical Center, and the University Medical Center Brackenridge in Austin, Texas. These centers were part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study (TRACK-TBI).

Patient Characteristics
Patients came from highly diverse socioeconomic backgrounds, had few exclusion factors, and ranged from age 15 to 86, with a mean age of 40. All patients underwent CT scans when they were admitted, and early brain MRI was performed approximately a week later.

The investigators used univariate and multivariate logistic regression to determine demographic, clinical, socioeconomic, CT, and MRI features that predicted outcomes at three months following the brain injury. Outcomes were assessed with the eight-point Extended Glasgow Outcome scale, a well-validated summary assessment suitable for clinical trials.

Multivariate models of the three-month outcome scale were analyzed based on three sets of predictive variables. The first set examined only clinical, demographic, and socioeconomic variables, the second set incorporated head CT features, and the third set used all the preceding variables, as well as brain MRI features.

Evidence of subarachnoid hemorrhage on CT was associated with a multivariate odds ratio of 3.5 for poorer three-month outcome, after accounting for demographic, clinical, and socioeconomic factors, said the researchers.

Normal CT Is Not Enough
However, 27% of patients who were admitted with normal head CT had an abnormal early brain MRI. After adjusting for head CT findings and demographic, clinical, and socioeconomic factors, the investigators found that one or more brain contusions and four or more foci of hemorrhagic axonal injury on MRI were each independently associated with poorer three-month outcome. Multivariate odds ratios were 4.5 and 3.2, respectively.

This work raises questions of how we’re currently managing patients via CT scan,” said senior author Geoff Manley, MD, PhD, Chief of Neurosurgery at San Francisco General Hospital. “Having a normal CT scan doesn’t, in fact, say you’re normal,” he added.

A Step Forward
Each year, at least 1.7 million Americans seek medical attention for acute head injuries, and 75% of those injuries are mTBIs, most with mild symptoms such as temporary loss of consciousness, vomiting, or amnesia.

The majority of patients with mTBI recover fully, but approximately one in six eventually develop persistent and sometimes permanent disability from the injury. In the past, some socioeconomic factors have helped to predict disability, but Dr. Yuh’s study shows that an imaging feature can help to predict the rate or extent of a patient’s recovery.

According to Dr. Manley, this study represents an important step toward developing a more quantitative, precise method of evaluating, monitoring, and treating patients with mTBI. At present, performing routine brain MRI on mTBI patients may not be cost-effective, but smaller and less-costly MRI scanners that examine only the patient’s head are in development. Furthermore, continuing advances in the MRI field may eventually reduce expenses to a manageable level.

The study’s strengths are its greater specification of types of lesions that may predict outcome, control for other predictors, multicenter patient sample, and use of TBI Common Data Elements to categorize the imaging results, the investigators said.

They believe the findings will benefit clinicians and researchers conducting clinical trials. “Progress beyond mere definition of mTBI toward evidence-based diagnosis is essential for clinical trials that evaluate treatments and, ultimately, more effective triage to follow-up care,” stated the authors.

Diffusion Tensor Imaging Suggests Brain Compensation After Traumatic Injury
A special MRI technique may be able to predict which patients who have experienced concussions will improve, according to researchers. The results suggest that in some patients, the brain may change to compensate for the damage caused by the injury.

“This finding could lead to strategies for preventing and repairing the damage that accompanies traumatic brain injury [TBI],” said Michael Lipton, MD, PhD, Associate Director of the Gruss Magnetic Resonance Research Center at Albert Einstein College of Medicine of Yeshiva University and Medical Director of MRI Services at Montefiore Medical Center, both in Bronx, New York.

Each year, 1.7 million people in the United States sustain a TBI, according to the CDC. Concussions and other mild TBIs (or mTBIs) account for at least 75% of these injuries. Following a concussion, some patients experience a brief loss of consciousness. Other symptoms include headache, dizziness, memory loss, attention deficit, depression, and anxiety. Some of these conditions may persist for months or years in as many as 30% of patients.

The study involved 17 patients who were admitted to the emergency department at Montefiore and Jacobi Medical Centers and diagnosed with mTBI. Within two weeks of their injuries, the patients underwent diffusion tensor imaging (DTI), which reveals the movement of water molecules within and along axons. DTI allows researchers to measure the uniformity of water movement (fractional anisotropy) throughout the brain. Areas of low fractional anisotropy indicate axonal injury, and areas of abnormally high fractional anisotropy indicate changes in the brain.

“In a TBI, it’s not one specific area that is affected, but multiple areas of the brain that are interconnected by axons,” said Dr. Lipton. “Abnormally low fractional anisotropy within white matter has been correlated with cognitive impairment in concussion patients. We believe that high fractional anisotropy is evidence not of axonal injury, but of brain changes that are occurring in response to the trauma.”

One year after their brain injury, the patients completed two standard questionnaires to assess their postconcussion symptoms and evaluate their health status and quality of life. “Most TBI studies assess cognitive function, but it is not at all clear if and how well such measures assess real-life functioning,” said Dr. Lipton. “Our questionnaires asked about postconcussion symptoms and how those symptoms affected patients’ health and quality of life.”

After comparing the DTI data to the patient questionnaires, the researchers found that abnormally high fractional anisotropy predicted fewer postconcussion symptoms and better functioning. The results suggest that the brain may be actively compensating for its injuries in patients who exhibit areas of high fractional anisotropy on DTI.

“These results could lead to better treatment for concussion if we can find ways to enhance the brain’s compensatory mechanisms,” Dr. Lipton said.

Exercise Rate Related to Improvements in Parkinson’s Disease
People with Parkinson’s disease may benefit from exercise programs on stationary bicycles, and patients who pedal fastest may obtain the greatest benefit. Functional connectivity MRI (fcMRI) data showed that faster pedaling led to greater connectivity in brain areas associated with motor ability.

After Jay L. Alberts, PhD, a neuroscientist at the Cleveland Clinic Lerner Research Institute, rode a tandem bicycle across Iowa with a patient with Parkinson’s disease, the patient experienced improvements in her symptoms.

“The finding was serendipitous,” said Dr. Alberts. “I was pedaling faster than she was, which forced her to pedal faster. She had improvements in her upper extremity function, so we started to look at the possible mechanism behind this improved function.”

As part of this inquiry, Dr. Alberts, researcher Chintan Shah, BS, and their Cleveland Clinic colleagues used fcMRI to study the effect of exercise on 26 patients with Parkinson’s disease.

“By measuring changes in blood oxygenation levels in the brain, fcMRI allows us to look at the functional connectivity between different brain regions,” said Mr. Shah.

The patients underwent bicycle exercise sessions three times per week for eight weeks. Some patients exercised at a voluntary level, and others underwent forced-rate exercise, pedaling at a speed above their voluntary rate. The researchers induced forced-rate activity with a modified exercise bike.

“We developed an algorithm to control a motor on the bike and used a controller to sense the patient’s rate of exertion and adjust the motor based on his or her input,” said Dr. Alberts.

The researchers conducted fcMRI before and after the eight weeks of exercise therapy and again as follow-up four weeks later. The team calculated brain activation and connectivity levels from the fcMRI results and correlated the data with average pedaling rate. Results showed increases in task-related connectivity between the primary motor cortex and the posterior region of the thalamus. Faster pedaling rate was the key factor related to these improvements, which were still evident at follow-up.

“The results show that forced-rate bicycle exercise is an effective, low-cost therapy for Parkinson’s disease,” Mr. Shah said.

Dr. Alberts noted that that while faster pedaling led to more significant results, not all patients with Parkinson’s disease need to do forced-rate exercise to see improvement. “We’re now looking at this phenomenon in patients with exercise bikes in their home, and other exercises like swimming and rowing on tandem machines may provide similar benefits,” he said.

Gender-Based Differences Observed in Alzheimer’s Disease
All patients with Alzheimer’s disease lose brain cells, which leads to atrophy of the brain. However, the pattern of gray matter loss is significantly different between men and women, according to investigators.

“We found that the extent and distribution of regional gray matter volume loss in the brain was strongly influenced by gender,” said lead researcher Maria Vittoria Spampinato, MD, Associate Professor of Radiology at the Medical University of South Carolina in Charleston.

“There is a strong interest in using MRI to assess brain atrophy with the purpose of monitoring dementia progression noninvasively and to aid in understanding which factors can influence brain atrophy progression and distribution in the Alzheimer’s brain,” said Dr. Spampinato.

Dr. Spampinato and colleagues analyzed data on 109 patients, including 60 men and 49 women (mean age, 77), who participated in the Alzheimer’s Disease Neuroimaging Initiative, a major study that followed hundreds of cognitively healthy individuals and patients with mild cognitive impairment (MCI) and Alzheimer’s disease for five years.

During the five-year period, each of the 109 patients progressed from amnestic MCI to Alzheimer’s disease. Using MRI scans of the patients’ brains taken when they were diagnosed with Alzheimer’s disease and 12 months before and after the diagnosis, the researchers created brain maps that illustrated gray matter changes.

The brain maps revealed that, compared with male patients, women had greater atrophy in gray matter 12 months before their Alzheimer’s disease diagnosis and at the time of their diagnosis. The brain maps also showed that men and women in the study lost gray matter volume in different areas of the brain as their disease progressed from MCI to Alzheimer’s disease.

“The female patients in our study initially had more gray matter atrophy than the male patients, but over time, the men caught up,” said Dr. Spampinato. “In the men, the disease developed more aggressively in a shorter period of time.”

The gender differences in atrophy patterns may have important implications for the development of therapies for MCI and Alzheimer’s disease. “These differences should be taken into consideration when testing new drugs in clinical trials,” said Dr. Spampinato. “Knowing the difference between the male and female patterns of atrophy will help researchers better decipher a patient’s response to drug therapy.”

Active Lifestyle May Boost Brain Structure and Slow Alzheimer’s Disease
An active lifestyle may help preserve gray matter in the brains of older adults and could reduce the burden of dementia and Alzheimer’s disease.

To study how an active lifestyle can influence brain structure, Cyrus Raji, MD, PhD, radiology resident at the University of California in Los Angeles, and colleagues examined 876 adults (average age, 78), drawn from the multisite Cardiovascular Health Study. The patients’ condition ranged from normal cognition to Alzheimer’s dementia.

“We had 20 years of clinical data on this group, including BMI and lifestyle habits,” said Dr. Raji. “We drew our patients from four sites across the country, and we were able to assess energy output in the form of kilocalories per week.” The lifestyle factors examined included recreational sports, gardening and yard work, bicycling, dancing, and riding an exercise bicycle.

The researchers used MRI and voxel-based morphometry to model the relationships between energy output and gray matter volume. “Voxel-based morphometry is an advanced method that allows a computer to analyze an MR image and build a mathematical model that helps us to understand the relationship between active lifestyle and gray matter volume,” said Dr. Raji. “Gray matter volume is a key marker of brain health. Larger gray matter volume means a healthier brain. Shrinking volume is seen in Alzheimer’s disease.”

After controlling for age, head size, cognitive impairment, gender, BMI, education, study site location, and white matter disease, the researchers found a strong association between energy output and gray matter volumes in areas of the brain crucial for cognitive function. Greater caloric expenditure was related to larger gray matter volumes in the frontal, temporal, and parietal lobes, including the hippocampus, posterior cingulate, and basal ganglia. There was a strong association between high-energy output and greater gray matter volume in patients with mild cognitive impairment and Alzheimer’s disease.

“Gray matter includes neurons that function in cognition and higher-order cognitive processes,” said Dr. Raji. “The areas of the brain that benefited from an active lifestyle are the ones that consume the most energy and are very sensitive to damage.”

A key aspect of the study was its focus on having variety in lifestyle choices, Dr. Raji noted. “What struck me most about the study results is that it is not one, but a combination of lifestyle choices and activities that benefit the brain,” he said.

The positive influence of an active lifestyle on the brain likely resulted from improved vascular health. “Virtually all of the physical activities examined in this study are some variation of aerobic physical activity, which we know from other work can improve cerebral blood flow and strengthen neuronal connections,” he said. “Additional work needs to be done. However, our initial results show that brain aging can be alleviated through an active lifestyle.”

Researchers Find Physiologic Evidence of Chemo Brain
Chemotherapy may induce changes in the brain that may affect concentration and memory. Using PET and CT, researchers detected physiologic evidence of chemo brain, a common side effect in patients undergoing chemotherapy for cancer treatment.

“The chemo brain phenomenon is described as ‘mental fog’ and ‘loss of coping skills’ by patients who receive chemotherapy,” said Rachel A. Lagos, DO, diagnostic radiology resident at the West Virginia University School of Medicine and West Virginia University Hospitals in Morgantown. “Because this is such a common patient complaint, health care providers have generically referred to its occurrence as ‘chemo brain’ for more than two decades.”

Although the complaint may be common, the cause of chemo brain has been difficult to pinpoint. Previous MRI studies have found small changes in brain volume after chemotherapy, but no definitive link has been found.

Instead of studying chemotherapy’s effect on the brain’s appearance, Dr. Lagos and colleagues set out to identify its effect on brain function. By using PET and CT, they were able to assess changes to the brain’s metabolism after chemotherapy.

“When we looked at the results, we were surprised at how obvious the changes were,” Dr. Lagos said. “Chemo brain phenomenon is more than a feeling. It is not depression. It is a change in brain function observable on PET and CT brain imaging.”

Dr. Lagos and colleagues analyzed PET and CT brain imaging results from 128 patients who had undergone chemotherapy for breast cancer. They used special software to help discern differences in brain metabolism before and after chemotherapy. Results were correlated with patient history, neurologic examinations, and chemotherapy regimens.

PET and CT results demonstrated statistically significant decreases in regional brain metabolism that were closely associated with symptoms of chemo brain phenomenon. “The study shows that there are specific areas of the brain that use less energy following chemotherapy,” said Dr. Lagos. “These brain areas are the ones known to be responsible for planning and prioritizing.” PET and CT could possibly be used to facilitate clinical diagnosis and allow for earlier intervention.

Research has already shown that patients with chemo brain can benefit from the assistance of nutritionists, exercise therapists, massage therapists, and counselors. In one study, cancer patients receiving chemotherapy complained of losing their ability to prepare family meals. “When the researchers provided these patients with written and planned menus for each meal, the women were able to buy the groceries, prepare the meals, and enjoy them with their families,” said Dr. Lagos.

Future studies could lead the way to better treatment for patients experiencing this condition. “The next step is to establish a prospective study that begins assessing new patients at the time of cancer diagnosis,” said Dr. Lagos. “The prospective study has the potential to establish an understanding of the change in brain neurotransmitters during chemotherapy, which may lead to improved treatment or prevention.”

Diffusion Tensor Imaging Suggests Brain Compensation After Traumatic Injury
A special MRI technique may be able to predict which patients who have experienced concussions will improve, according to researchers. The results suggest that in some patients, the brain may change to compensate for the damage caused by the injury.

“This finding could lead to strategies for preventing and repairing the damage that accompanies traumatic brain injury [TBI],” said Michael Lipton, MD, PhD, Associate Director of the Gruss Magnetic Resonance Research Center at Albert Einstein College of Medicine of Yeshiva University and Medical Director of MRI Services at Montefiore Medical Center, both in Bronx, New York.

Each year, 1.7 million people in the United States sustain a TBI, according to the CDC. Concussions and other mild TBIs (or mTBIs) account for at least 75% of these injuries. Following a concussion, some patients experience a brief loss of consciousness. Other symptoms include headache, dizziness, memory loss, attention deficit, depression, and anxiety. Some of these conditions may persist for months or years in as many as 30% of patients.

The study involved 17 patients who were admitted to the emergency department at Montefiore and Jacobi Medical Centers and diagnosed with mTBI. Within two weeks of their injuries, the patients underwent diffusion tensor imaging (DTI), which reveals the movement of water molecules within and along axons. DTI allows researchers to measure the uniformity of water movement (fractional anisotropy) throughout the brain. Areas of low fractional anisotropy indicate axonal injury, and areas of abnormally high fractional anisotropy indicate changes in the brain.

“In a TBI, it’s not one specific area that is affected, but multiple areas of the brain that are interconnected by axons,” said Dr. Lipton. “Abnormally low fractional anisotropy within white matter has been correlated with cognitive impairment in concussion patients. We believe that high fractional anisotropy is evidence not of axonal injury, but of brain changes that are occurring in response to the trauma.”

One year after their brain injury, the patients completed two standard questionnaires to assess their postconcussion symptoms and evaluate their health status and quality of life. “Most TBI studies assess cognitive function, but it is not at all clear if and how well such measures assess real-life functioning,” said Dr. Lipton. “Our questionnaires asked about postconcussion symptoms and how those symptoms affected patients’ health and quality of life.”

After comparing the DTI data to the patient questionnaires, the researchers found that abnormally high fractional anisotropy predicted fewer postconcussion symptoms and better functioning. The results suggest that the brain may be actively compensating for its injuries in patients who exhibit areas of high fractional anisotropy on DTI.

“These results could lead to better treatment for concussion if we can find ways to enhance the brain’s compensatory mechanisms,” Dr. Lipton said.

Exercise Rate Related to Improvements in Parkinson’s Disease
People with Parkinson’s disease may benefit from exercise programs on stationary bicycles, and patients who pedal fastest may obtain the greatest benefit. Functional connectivity MRI (fcMRI) data showed that faster pedaling led to greater connectivity in brain areas associated with motor ability.

After Jay L. Alberts, PhD, a neuroscientist at the Cleveland Clinic Lerner Research Institute, rode a tandem bicycle across Iowa with a patient with Parkinson’s disease, the patient experienced improvements in her symptoms.

“The finding was serendipitous,” said Dr. Alberts. “I was pedaling faster than she was, which forced her to pedal faster. She had improvements in her upper extremity function, so we started to look at the possible mechanism behind this improved function.”

As part of this inquiry, Dr. Alberts, researcher Chintan Shah, BS, and their Cleveland Clinic colleagues used fcMRI to study the effect of exercise on 26 patients with Parkinson’s disease.

“By measuring changes in blood oxygenation levels in the brain, fcMRI allows us to look at the functional connectivity between different brain regions,” said Mr. Shah.

The patients underwent bicycle exercise sessions three times per week for eight weeks. Some patients exercised at a voluntary level, and others underwent forced-rate exercise, pedaling at a speed above their voluntary rate. The researchers induced forced-rate activity with a modified exercise bike.

“We developed an algorithm to control a motor on the bike and used a controller to sense the patient’s rate of exertion and adjust the motor based on his or her input,” said Dr. Alberts.

The researchers conducted fcMRI before and after the eight weeks of exercise therapy and again as follow-up four weeks later. The team calculated brain activation and connectivity levels from the fcMRI results and correlated the data with average pedaling rate. Results showed increases in task-related connectivity between the primary motor cortex and the posterior region of the thalamus. Faster pedaling rate was the key factor related to these improvements, which were still evident at follow-up.

“The results show that forced-rate bicycle exercise is an effective, low-cost therapy for Parkinson’s disease,” Mr. Shah said.

Dr. Alberts noted that that while faster pedaling led to more significant results, not all patients with Parkinson’s disease need to do forced-rate exercise to see improvement. “We’re now looking at this phenomenon in patients with exercise bikes in their home, and other exercises like swimming and rowing on tandem machines may provide similar benefits,” he said.

Gender-Based Differences Observed in Alzheimer’s Disease
All patients with Alzheimer’s disease lose brain cells, which leads to atrophy of the brain. However, the pattern of gray matter loss is significantly different between men and women, according to investigators.

“We found that the extent and distribution of regional gray matter volume loss in the brain was strongly influenced by gender,” said lead researcher Maria Vittoria Spampinato, MD, Associate Professor of Radiology at the Medical University of South Carolina in Charleston.

“There is a strong interest in using MRI to assess brain atrophy with the purpose of monitoring dementia progression noninvasively and to aid in understanding which factors can influence brain atrophy progression and distribution in the Alzheimer’s brain,” said Dr. Spampinato.

Dr. Spampinato and colleagues analyzed data on 109 patients, including 60 men and 49 women (mean age, 77), who participated in the Alzheimer’s Disease Neuroimaging Initiative, a major study that followed hundreds of cognitively healthy individuals and patients with mild cognitive impairment (MCI) and Alzheimer’s disease for five years.

During the five-year period, each of the 109 patients progressed from amnestic MCI to Alzheimer’s disease. Using MRI scans of the patients’ brains taken when they were diagnosed with Alzheimer’s disease and 12 months before and after the diagnosis, the researchers created brain maps that illustrated gray matter changes.

The brain maps revealed that, compared with male patients, women had greater atrophy in gray matter 12 months before their Alzheimer’s disease diagnosis and at the time of their diagnosis. The brain maps also showed that men and women in the study lost gray matter volume in different areas of the brain as their disease progressed from MCI to Alzheimer’s disease.

“The female patients in our study initially had more gray matter atrophy than the male patients, but over time, the men caught up,” said Dr. Spampinato. “In the men, the disease developed more aggressively in a shorter period of time.”

The gender differences in atrophy patterns may have important implications for the development of therapies for MCI and Alzheimer’s disease. “These differences should be taken into consideration when testing new drugs in clinical trials,” said Dr. Spampinato. “Knowing the difference between the male and female patterns of atrophy will help researchers better decipher a patient’s response to drug therapy.”

Active Lifestyle May Boost Brain Structure and Slow Alzheimer’s Disease
An active lifestyle may help preserve gray matter in the brains of older adults and could reduce the burden of dementia and Alzheimer’s disease.

To study how an active lifestyle can influence brain structure, Cyrus Raji, MD, PhD, radiology resident at the University of California in Los Angeles, and colleagues examined 876 adults (average age, 78), drawn from the multisite Cardiovascular Health Study. The patients’ condition ranged from normal cognition to Alzheimer’s dementia.

“We had 20 years of clinical data on this group, including BMI and lifestyle habits,” said Dr. Raji. “We drew our patients from four sites across the country, and we were able to assess energy output in the form of kilocalories per week.” The lifestyle factors examined included recreational sports, gardening and yard work, bicycling, dancing, and riding an exercise bicycle.

The researchers used MRI and voxel-based morphometry to model the relationships between energy output and gray matter volume. “Voxel-based morphometry is an advanced method that allows a computer to analyze an MR image and build a mathematical model that helps us to understand the relationship between active lifestyle and gray matter volume,” said Dr. Raji. “Gray matter volume is a key marker of brain health. Larger gray matter volume means a healthier brain. Shrinking volume is seen in Alzheimer’s disease.”

After controlling for age, head size, cognitive impairment, gender, BMI, education, study site location, and white matter disease, the researchers found a strong association between energy output and gray matter volumes in areas of the brain crucial for cognitive function. Greater caloric expenditure was related to larger gray matter volumes in the frontal, temporal, and parietal lobes, including the hippocampus, posterior cingulate, and basal ganglia. There was a strong association between high-energy output and greater gray matter volume in patients with mild cognitive impairment and Alzheimer’s disease.

“Gray matter includes neurons that function in cognition and higher-order cognitive processes,” said Dr. Raji. “The areas of the brain that benefited from an active lifestyle are the ones that consume the most energy and are very sensitive to damage.”

A key aspect of the study was its focus on having variety in lifestyle choices, Dr. Raji noted. “What struck me most about the study results is that it is not one, but a combination of lifestyle choices and activities that benefit the brain,” he said.

The positive influence of an active lifestyle on the brain likely resulted from improved vascular health. “Virtually all of the physical activities examined in this study are some variation of aerobic physical activity, which we know from other work can improve cerebral blood flow and strengthen neuronal connections,” he said. “Additional work needs to be done. However, our initial results show that brain aging can be alleviated through an active lifestyle.”

Researchers Find Physiologic Evidence of Chemo Brain
Chemotherapy may induce changes in the brain that may affect concentration and memory. Using PET and CT, researchers detected physiologic evidence of chemo brain, a common side effect in patients undergoing chemotherapy for cancer treatment.

“The chemo brain phenomenon is described as ‘mental fog’ and ‘loss of coping skills’ by patients who receive chemotherapy,” said Rachel A. Lagos, DO, diagnostic radiology resident at the West Virginia University School of Medicine and West Virginia University Hospitals in Morgantown. “Because this is such a common patient complaint, health care providers have generically referred to its occurrence as ‘chemo brain’ for more than two decades.”

Although the complaint may be common, the cause of chemo brain has been difficult to pinpoint. Previous MRI studies have found small changes in brain volume after chemotherapy, but no definitive link has been found.

Instead of studying chemotherapy’s effect on the brain’s appearance, Dr. Lagos and colleagues set out to identify its effect on brain function. By using PET and CT, they were able to assess changes to the brain’s metabolism after chemotherapy.

“When we looked at the results, we were surprised at how obvious the changes were,” Dr. Lagos said. “Chemo brain phenomenon is more than a feeling. It is not depression. It is a change in brain function observable on PET and CT brain imaging.”

Dr. Lagos and colleagues analyzed PET and CT brain imaging results from 128 patients who had undergone chemotherapy for breast cancer. They used special software to help discern differences in brain metabolism before and after chemotherapy. Results were correlated with patient history, neurologic examinations, and chemotherapy regimens.

PET and CT results demonstrated statistically significant decreases in regional brain metabolism that were closely associated with symptoms of chemo brain phenomenon. “The study shows that there are specific areas of the brain that use less energy following chemotherapy,” said Dr. Lagos. “These brain areas are the ones known to be responsible for planning and prioritizing.” PET and CT could possibly be used to facilitate clinical diagnosis and allow for earlier intervention.

Research has already shown that patients with chemo brain can benefit from the assistance of nutritionists, exercise therapists, massage therapists, and counselors. In one study, cancer patients receiving chemotherapy complained of losing their ability to prepare family meals. “When the researchers provided these patients with written and planned menus for each meal, the women were able to buy the groceries, prepare the meals, and enjoy them with their families,” said Dr. Lagos.

Future studies could lead the way to better treatment for patients experiencing this condition. “The next step is to establish a prospective study that begins assessing new patients at the time of cancer diagnosis,” said Dr. Lagos. “The prospective study has the potential to establish an understanding of the change in brain neurotransmitters during chemotherapy, which may lead to improved treatment or prevention.”

Diffusion Tensor Imaging Suggests Brain Compensation After Traumatic Injury
A special MRI technique may be able to predict which patients who have experienced concussions will improve, according to researchers. The results suggest that in some patients, the brain may change to compensate for the damage caused by the injury.

“This finding could lead to strategies for preventing and repairing the damage that accompanies traumatic brain injury [TBI],” said Michael Lipton, MD, PhD, Associate Director of the Gruss Magnetic Resonance Research Center at Albert Einstein College of Medicine of Yeshiva University and Medical Director of MRI Services at Montefiore Medical Center, both in Bronx, New York.

Each year, 1.7 million people in the United States sustain a TBI, according to the CDC. Concussions and other mild TBIs (or mTBIs) account for at least 75% of these injuries. Following a concussion, some patients experience a brief loss of consciousness. Other symptoms include headache, dizziness, memory loss, attention deficit, depression, and anxiety. Some of these conditions may persist for months or years in as many as 30% of patients.

The study involved 17 patients who were admitted to the emergency department at Montefiore and Jacobi Medical Centers and diagnosed with mTBI. Within two weeks of their injuries, the patients underwent diffusion tensor imaging (DTI), which reveals the movement of water molecules within and along axons. DTI allows researchers to measure the uniformity of water movement (fractional anisotropy) throughout the brain. Areas of low fractional anisotropy indicate axonal injury, and areas of abnormally high fractional anisotropy indicate changes in the brain.

“In a TBI, it’s not one specific area that is affected, but multiple areas of the brain that are interconnected by axons,” said Dr. Lipton. “Abnormally low fractional anisotropy within white matter has been correlated with cognitive impairment in concussion patients. We believe that high fractional anisotropy is evidence not of axonal injury, but of brain changes that are occurring in response to the trauma.”

One year after their brain injury, the patients completed two standard questionnaires to assess their postconcussion symptoms and evaluate their health status and quality of life. “Most TBI studies assess cognitive function, but it is not at all clear if and how well such measures assess real-life functioning,” said Dr. Lipton. “Our questionnaires asked about postconcussion symptoms and how those symptoms affected patients’ health and quality of life.”

After comparing the DTI data to the patient questionnaires, the researchers found that abnormally high fractional anisotropy predicted fewer postconcussion symptoms and better functioning. The results suggest that the brain may be actively compensating for its injuries in patients who exhibit areas of high fractional anisotropy on DTI.

“These results could lead to better treatment for concussion if we can find ways to enhance the brain’s compensatory mechanisms,” Dr. Lipton said.

Exercise Rate Related to Improvements in Parkinson’s Disease
People with Parkinson’s disease may benefit from exercise programs on stationary bicycles, and patients who pedal fastest may obtain the greatest benefit. Functional connectivity MRI (fcMRI) data showed that faster pedaling led to greater connectivity in brain areas associated with motor ability.

After Jay L. Alberts, PhD, a neuroscientist at the Cleveland Clinic Lerner Research Institute, rode a tandem bicycle across Iowa with a patient with Parkinson’s disease, the patient experienced improvements in her symptoms.

“The finding was serendipitous,” said Dr. Alberts. “I was pedaling faster than she was, which forced her to pedal faster. She had improvements in her upper extremity function, so we started to look at the possible mechanism behind this improved function.”

As part of this inquiry, Dr. Alberts, researcher Chintan Shah, BS, and their Cleveland Clinic colleagues used fcMRI to study the effect of exercise on 26 patients with Parkinson’s disease.

“By measuring changes in blood oxygenation levels in the brain, fcMRI allows us to look at the functional connectivity between different brain regions,” said Mr. Shah.

The patients underwent bicycle exercise sessions three times per week for eight weeks. Some patients exercised at a voluntary level, and others underwent forced-rate exercise, pedaling at a speed above their voluntary rate. The researchers induced forced-rate activity with a modified exercise bike.

“We developed an algorithm to control a motor on the bike and used a controller to sense the patient’s rate of exertion and adjust the motor based on his or her input,” said Dr. Alberts.

The researchers conducted fcMRI before and after the eight weeks of exercise therapy and again as follow-up four weeks later. The team calculated brain activation and connectivity levels from the fcMRI results and correlated the data with average pedaling rate. Results showed increases in task-related connectivity between the primary motor cortex and the posterior region of the thalamus. Faster pedaling rate was the key factor related to these improvements, which were still evident at follow-up.

“The results show that forced-rate bicycle exercise is an effective, low-cost therapy for Parkinson’s disease,” Mr. Shah said.

Dr. Alberts noted that that while faster pedaling led to more significant results, not all patients with Parkinson’s disease need to do forced-rate exercise to see improvement. “We’re now looking at this phenomenon in patients with exercise bikes in their home, and other exercises like swimming and rowing on tandem machines may provide similar benefits,” he said.

Gender-Based Differences Observed in Alzheimer’s Disease
All patients with Alzheimer’s disease lose brain cells, which leads to atrophy of the brain. However, the pattern of gray matter loss is significantly different between men and women, according to investigators.

“We found that the extent and distribution of regional gray matter volume loss in the brain was strongly influenced by gender,” said lead researcher Maria Vittoria Spampinato, MD, Associate Professor of Radiology at the Medical University of South Carolina in Charleston.

“There is a strong interest in using MRI to assess brain atrophy with the purpose of monitoring dementia progression noninvasively and to aid in understanding which factors can influence brain atrophy progression and distribution in the Alzheimer’s brain,” said Dr. Spampinato.

Dr. Spampinato and colleagues analyzed data on 109 patients, including 60 men and 49 women (mean age, 77), who participated in the Alzheimer’s Disease Neuroimaging Initiative, a major study that followed hundreds of cognitively healthy individuals and patients with mild cognitive impairment (MCI) and Alzheimer’s disease for five years.

During the five-year period, each of the 109 patients progressed from amnestic MCI to Alzheimer’s disease. Using MRI scans of the patients’ brains taken when they were diagnosed with Alzheimer’s disease and 12 months before and after the diagnosis, the researchers created brain maps that illustrated gray matter changes.

The brain maps revealed that, compared with male patients, women had greater atrophy in gray matter 12 months before their Alzheimer’s disease diagnosis and at the time of their diagnosis. The brain maps also showed that men and women in the study lost gray matter volume in different areas of the brain as their disease progressed from MCI to Alzheimer’s disease.

“The female patients in our study initially had more gray matter atrophy than the male patients, but over time, the men caught up,” said Dr. Spampinato. “In the men, the disease developed more aggressively in a shorter period of time.”

The gender differences in atrophy patterns may have important implications for the development of therapies for MCI and Alzheimer’s disease. “These differences should be taken into consideration when testing new drugs in clinical trials,” said Dr. Spampinato. “Knowing the difference between the male and female patterns of atrophy will help researchers better decipher a patient’s response to drug therapy.”

Active Lifestyle May Boost Brain Structure and Slow Alzheimer’s Disease
An active lifestyle may help preserve gray matter in the brains of older adults and could reduce the burden of dementia and Alzheimer’s disease.

To study how an active lifestyle can influence brain structure, Cyrus Raji, MD, PhD, radiology resident at the University of California in Los Angeles, and colleagues examined 876 adults (average age, 78), drawn from the multisite Cardiovascular Health Study. The patients’ condition ranged from normal cognition to Alzheimer’s dementia.

“We had 20 years of clinical data on this group, including BMI and lifestyle habits,” said Dr. Raji. “We drew our patients from four sites across the country, and we were able to assess energy output in the form of kilocalories per week.” The lifestyle factors examined included recreational sports, gardening and yard work, bicycling, dancing, and riding an exercise bicycle.

The researchers used MRI and voxel-based morphometry to model the relationships between energy output and gray matter volume. “Voxel-based morphometry is an advanced method that allows a computer to analyze an MR image and build a mathematical model that helps us to understand the relationship between active lifestyle and gray matter volume,” said Dr. Raji. “Gray matter volume is a key marker of brain health. Larger gray matter volume means a healthier brain. Shrinking volume is seen in Alzheimer’s disease.”

After controlling for age, head size, cognitive impairment, gender, BMI, education, study site location, and white matter disease, the researchers found a strong association between energy output and gray matter volumes in areas of the brain crucial for cognitive function. Greater caloric expenditure was related to larger gray matter volumes in the frontal, temporal, and parietal lobes, including the hippocampus, posterior cingulate, and basal ganglia. There was a strong association between high-energy output and greater gray matter volume in patients with mild cognitive impairment and Alzheimer’s disease.

“Gray matter includes neurons that function in cognition and higher-order cognitive processes,” said Dr. Raji. “The areas of the brain that benefited from an active lifestyle are the ones that consume the most energy and are very sensitive to damage.”

A key aspect of the study was its focus on having variety in lifestyle choices, Dr. Raji noted. “What struck me most about the study results is that it is not one, but a combination of lifestyle choices and activities that benefit the brain,” he said.

The positive influence of an active lifestyle on the brain likely resulted from improved vascular health. “Virtually all of the physical activities examined in this study are some variation of aerobic physical activity, which we know from other work can improve cerebral blood flow and strengthen neuronal connections,” he said. “Additional work needs to be done. However, our initial results show that brain aging can be alleviated through an active lifestyle.”

Researchers Find Physiologic Evidence of Chemo Brain
Chemotherapy may induce changes in the brain that may affect concentration and memory. Using PET and CT, researchers detected physiologic evidence of chemo brain, a common side effect in patients undergoing chemotherapy for cancer treatment.

“The chemo brain phenomenon is described as ‘mental fog’ and ‘loss of coping skills’ by patients who receive chemotherapy,” said Rachel A. Lagos, DO, diagnostic radiology resident at the West Virginia University School of Medicine and West Virginia University Hospitals in Morgantown. “Because this is such a common patient complaint, health care providers have generically referred to its occurrence as ‘chemo brain’ for more than two decades.”

Although the complaint may be common, the cause of chemo brain has been difficult to pinpoint. Previous MRI studies have found small changes in brain volume after chemotherapy, but no definitive link has been found.

Instead of studying chemotherapy’s effect on the brain’s appearance, Dr. Lagos and colleagues set out to identify its effect on brain function. By using PET and CT, they were able to assess changes to the brain’s metabolism after chemotherapy.

“When we looked at the results, we were surprised at how obvious the changes were,” Dr. Lagos said. “Chemo brain phenomenon is more than a feeling. It is not depression. It is a change in brain function observable on PET and CT brain imaging.”

Dr. Lagos and colleagues analyzed PET and CT brain imaging results from 128 patients who had undergone chemotherapy for breast cancer. They used special software to help discern differences in brain metabolism before and after chemotherapy. Results were correlated with patient history, neurologic examinations, and chemotherapy regimens.

PET and CT results demonstrated statistically significant decreases in regional brain metabolism that were closely associated with symptoms of chemo brain phenomenon. “The study shows that there are specific areas of the brain that use less energy following chemotherapy,” said Dr. Lagos. “These brain areas are the ones known to be responsible for planning and prioritizing.” PET and CT could possibly be used to facilitate clinical diagnosis and allow for earlier intervention.

Research has already shown that patients with chemo brain can benefit from the assistance of nutritionists, exercise therapists, massage therapists, and counselors. In one study, cancer patients receiving chemotherapy complained of losing their ability to prepare family meals. “When the researchers provided these patients with written and planned menus for each meal, the women were able to buy the groceries, prepare the meals, and enjoy them with their families,” said Dr. Lagos.

Future studies could lead the way to better treatment for patients experiencing this condition. “The next step is to establish a prospective study that begins assessing new patients at the time of cancer diagnosis,” said Dr. Lagos. “The prospective study has the potential to establish an understanding of the change in brain neurotransmitters during chemotherapy, which may lead to improved treatment or prevention.”

LOS ANGELES—Among US soldiers returning from deployment, 29% of those with mild traumatic brain injury (TBI) had migraine, and 12% of those without TBI had migraine, according to data presented at the 54th Annual Scientific Meeting of the American Headache Society. “This rate is considerably higher than you would generally find in a young male population,” said Ann I. Scher, PhD, Associate Professor of Epidemiology at Uniformed Services University in Bethesda, Maryland.

Among returning soldiers with migraine, 36% of those with TBI reported visual auralike symptoms, compared with 20% of those without TBI. Dr. Scher and her colleagues considered many of the auras typical, because they had a gradual onset and lasted for the appropriate amount of time (ie, 5 to 60 minutes). Most soldiers’ auras were atypical, however, either because they did not meet these criteria or soldiers were not certain whether they did.

An Ongoing Study of Soldiers With and Without TBI
These epidemiologic data are preliminary results from an ongoing study that Dr. Scher and her colleagues are conducting. The researchers plan to recruit 1,500 soldiers returning from deployment, including 750 who screen positive for mild TBI and 750 who screen negative. To screen positive for TBI, a soldier must report a relevant injury that resulted in an alteration of consciousness, such as momentary confusion. Soldiers will be enrolled at Fort Bragg and Fort Carson.

Dr. Scher presented data for 174 soldiers with mild TBI and 202 controls, all enrolled at Fort Carson. “None of these soldiers was medically evacuated, so these are all mild injuries,” she said. Headaches were assessed with a self-administered questionnaire adapted from one developed by Richard Lipton, MD, Professor of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and Walter F. Stewart, PhD, Associate Professor of Epidemiology at Johns Hopkins University in Baltimore. Participants also completed the Chronic Pain Grade questionnaire developed by Michael von Korff, ScD, Senior Investigator at Group Health Research Institute in Seattle. The investigators are conducting three-month, six-month, and one-year follow-ups.

TBI Is Linked to Probable Migraine and Chronic Daily Headache
To date, 94% of participants with TBI were men. Men accounted for 98% of soldiers who screened negative for TBI. Approximately 69% of soldiers with TBI were Caucasian, compared with 62% of soldiers without TBI. About 8% of soldiers with TBI were African American, compared with 13% of soldiers without TBI. Slightly more soldiers reporting TBI were in combat-related occupational categories (57%), compared with soldiers without TBI (50%). Head injuries among soldiers in both combat and combat support roles sometimes were due to motor vehicle accidents and falls, said Dr. Scher.

In addition to soldiers meeting all criteria for migraine, 24% of soldiers with TBI had probable migraine, compared with 20% of returning soldiers without TBI. About 9% of returning soldiers with TBI had not had a headache in the previous year, compared with 21% of returning soldiers without TBI.

Approximately 22% of soldiers with TBI had chronic daily headache, including 9% with a continuous chronic daily headache. About 7% of returning soldiers without TBI had chronic daily headache. One of these soldiers had a continuous headache, and the rest had episodic very frequent headache or headache-free periods. Chronic daily headache was “considerably more common” than might be expected, said Dr. Scher. “Based on civilian populations, it should have been prevalent in 1 to 2% of men.”

Assessing Chronic Pain in Soldiers
In the chronic pain assessment, which used slightly different questions, headache and migraine, the most common symptoms, were reported by 71% of soldiers with TBI and 51% of soldiers without TBI. Back pain, however, was considered the most bothersome symptom by 34% of all soldiers, regardless of TBI history. Nearly 25% of all soldiers reported joint pain, and 6% reported neck pain. The heavy equipment that soldiers carry could explain these symptoms, according to Dr. Scher. The pain “is presumably transient, and we’ll have follow-up interviews, but for now, we can see at baseline that there’s really a lot of pain in general in this cohort,” she added.     

                                   
Implications for the Treatment of Post-Traumatic Headache
The diagnostic criteria for post-traumatic headache, which are being revised, should perhaps be modified to reflect these and other data, said Dr. Scher. According to the criteria, post-traumatic headache has “no typical characteristics,” but the data suggest that post-traumatic headache often takes the form of migraine or chronic daily headache.

The criteria also require headache to occur within seven days of injury or of regaining consciousness after injury. “The seven-day rule is not optimal,” Dr. Scher told Neurology Reviews. “I don’t think we know what the number should be. Hopefully, in the future we’ll have a more empirical case definition—one that we can justify with data.

“When we finish our study and some of the other ongoing studies, we’ll have a much better idea of what the post-traumatic headache phenotype is,” added Dr. Scher. “Once we have a better feeling for what the phenotype is, we can start talking about focused clinical trials in this population.”
In addition to her ongoing study, Dr. Scher plans to examine whether continuous headache and auralike symptoms could be useful diagnostic markers for combat-related post-traumatic headaches.                                      

LOS ANGELES—Among US soldiers returning from deployment, 29% of those with mild traumatic brain injury (TBI) had migraine, and 12% of those without TBI had migraine, according to data presented at the 54th Annual Scientific Meeting of the American Headache Society. “This rate is considerably higher than you would generally find in a young male population,” said Ann I. Scher, PhD, Associate Professor of Epidemiology at Uniformed Services University in Bethesda, Maryland.

Among returning soldiers with migraine, 36% of those with TBI reported visual auralike symptoms, compared with 20% of those without TBI. Dr. Scher and her colleagues considered many of the auras typical, because they had a gradual onset and lasted for the appropriate amount of time (ie, 5 to 60 minutes). Most soldiers’ auras were atypical, however, either because they did not meet these criteria or soldiers were not certain whether they did.

An Ongoing Study of Soldiers With and Without TBI
These epidemiologic data are preliminary results from an ongoing study that Dr. Scher and her colleagues are conducting. The researchers plan to recruit 1,500 soldiers returning from deployment, including 750 who screen positive for mild TBI and 750 who screen negative. To screen positive for TBI, a soldier must report a relevant injury that resulted in an alteration of consciousness, such as momentary confusion. Soldiers will be enrolled at Fort Bragg and Fort Carson.

Dr. Scher presented data for 174 soldiers with mild TBI and 202 controls, all enrolled at Fort Carson. “None of these soldiers was medically evacuated, so these are all mild injuries,” she said. Headaches were assessed with a self-administered questionnaire adapted from one developed by Richard Lipton, MD, Professor of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and Walter F. Stewart, PhD, Associate Professor of Epidemiology at Johns Hopkins University in Baltimore. Participants also completed the Chronic Pain Grade questionnaire developed by Michael von Korff, ScD, Senior Investigator at Group Health Research Institute in Seattle. The investigators are conducting three-month, six-month, and one-year follow-ups.

TBI Is Linked to Probable Migraine and Chronic Daily Headache
To date, 94% of participants with TBI were men. Men accounted for 98% of soldiers who screened negative for TBI. Approximately 69% of soldiers with TBI were Caucasian, compared with 62% of soldiers without TBI. About 8% of soldiers with TBI were African American, compared with 13% of soldiers without TBI. Slightly more soldiers reporting TBI were in combat-related occupational categories (57%), compared with soldiers without TBI (50%). Head injuries among soldiers in both combat and combat support roles sometimes were due to motor vehicle accidents and falls, said Dr. Scher.

In addition to soldiers meeting all criteria for migraine, 24% of soldiers with TBI had probable migraine, compared with 20% of returning soldiers without TBI. About 9% of returning soldiers with TBI had not had a headache in the previous year, compared with 21% of returning soldiers without TBI.

Approximately 22% of soldiers with TBI had chronic daily headache, including 9% with a continuous chronic daily headache. About 7% of returning soldiers without TBI had chronic daily headache. One of these soldiers had a continuous headache, and the rest had episodic very frequent headache or headache-free periods. Chronic daily headache was “considerably more common” than might be expected, said Dr. Scher. “Based on civilian populations, it should have been prevalent in 1 to 2% of men.”

Assessing Chronic Pain in Soldiers
In the chronic pain assessment, which used slightly different questions, headache and migraine, the most common symptoms, were reported by 71% of soldiers with TBI and 51% of soldiers without TBI. Back pain, however, was considered the most bothersome symptom by 34% of all soldiers, regardless of TBI history. Nearly 25% of all soldiers reported joint pain, and 6% reported neck pain. The heavy equipment that soldiers carry could explain these symptoms, according to Dr. Scher. The pain “is presumably transient, and we’ll have follow-up interviews, but for now, we can see at baseline that there’s really a lot of pain in general in this cohort,” she added.     

                                   
Implications for the Treatment of Post-Traumatic Headache
The diagnostic criteria for post-traumatic headache, which are being revised, should perhaps be modified to reflect these and other data, said Dr. Scher. According to the criteria, post-traumatic headache has “no typical characteristics,” but the data suggest that post-traumatic headache often takes the form of migraine or chronic daily headache.

The criteria also require headache to occur within seven days of injury or of regaining consciousness after injury. “The seven-day rule is not optimal,” Dr. Scher told Neurology Reviews. “I don’t think we know what the number should be. Hopefully, in the future we’ll have a more empirical case definition—one that we can justify with data.

“When we finish our study and some of the other ongoing studies, we’ll have a much better idea of what the post-traumatic headache phenotype is,” added Dr. Scher. “Once we have a better feeling for what the phenotype is, we can start talking about focused clinical trials in this population.”
In addition to her ongoing study, Dr. Scher plans to examine whether continuous headache and auralike symptoms could be useful diagnostic markers for combat-related post-traumatic headaches.                                      

LOS ANGELES—Among US soldiers returning from deployment, 29% of those with mild traumatic brain injury (TBI) had migraine, and 12% of those without TBI had migraine, according to data presented at the 54th Annual Scientific Meeting of the American Headache Society. “This rate is considerably higher than you would generally find in a young male population,” said Ann I. Scher, PhD, Associate Professor of Epidemiology at Uniformed Services University in Bethesda, Maryland.

Among returning soldiers with migraine, 36% of those with TBI reported visual auralike symptoms, compared with 20% of those without TBI. Dr. Scher and her colleagues considered many of the auras typical, because they had a gradual onset and lasted for the appropriate amount of time (ie, 5 to 60 minutes). Most soldiers’ auras were atypical, however, either because they did not meet these criteria or soldiers were not certain whether they did.

An Ongoing Study of Soldiers With and Without TBI
These epidemiologic data are preliminary results from an ongoing study that Dr. Scher and her colleagues are conducting. The researchers plan to recruit 1,500 soldiers returning from deployment, including 750 who screen positive for mild TBI and 750 who screen negative. To screen positive for TBI, a soldier must report a relevant injury that resulted in an alteration of consciousness, such as momentary confusion. Soldiers will be enrolled at Fort Bragg and Fort Carson.

Dr. Scher presented data for 174 soldiers with mild TBI and 202 controls, all enrolled at Fort Carson. “None of these soldiers was medically evacuated, so these are all mild injuries,” she said. Headaches were assessed with a self-administered questionnaire adapted from one developed by Richard Lipton, MD, Professor of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and Walter F. Stewart, PhD, Associate Professor of Epidemiology at Johns Hopkins University in Baltimore. Participants also completed the Chronic Pain Grade questionnaire developed by Michael von Korff, ScD, Senior Investigator at Group Health Research Institute in Seattle. The investigators are conducting three-month, six-month, and one-year follow-ups.

TBI Is Linked to Probable Migraine and Chronic Daily Headache
To date, 94% of participants with TBI were men. Men accounted for 98% of soldiers who screened negative for TBI. Approximately 69% of soldiers with TBI were Caucasian, compared with 62% of soldiers without TBI. About 8% of soldiers with TBI were African American, compared with 13% of soldiers without TBI. Slightly more soldiers reporting TBI were in combat-related occupational categories (57%), compared with soldiers without TBI (50%). Head injuries among soldiers in both combat and combat support roles sometimes were due to motor vehicle accidents and falls, said Dr. Scher.

In addition to soldiers meeting all criteria for migraine, 24% of soldiers with TBI had probable migraine, compared with 20% of returning soldiers without TBI. About 9% of returning soldiers with TBI had not had a headache in the previous year, compared with 21% of returning soldiers without TBI.

Approximately 22% of soldiers with TBI had chronic daily headache, including 9% with a continuous chronic daily headache. About 7% of returning soldiers without TBI had chronic daily headache. One of these soldiers had a continuous headache, and the rest had episodic very frequent headache or headache-free periods. Chronic daily headache was “considerably more common” than might be expected, said Dr. Scher. “Based on civilian populations, it should have been prevalent in 1 to 2% of men.”

Assessing Chronic Pain in Soldiers
In the chronic pain assessment, which used slightly different questions, headache and migraine, the most common symptoms, were reported by 71% of soldiers with TBI and 51% of soldiers without TBI. Back pain, however, was considered the most bothersome symptom by 34% of all soldiers, regardless of TBI history. Nearly 25% of all soldiers reported joint pain, and 6% reported neck pain. The heavy equipment that soldiers carry could explain these symptoms, according to Dr. Scher. The pain “is presumably transient, and we’ll have follow-up interviews, but for now, we can see at baseline that there’s really a lot of pain in general in this cohort,” she added.     

                                   
Implications for the Treatment of Post-Traumatic Headache
The diagnostic criteria for post-traumatic headache, which are being revised, should perhaps be modified to reflect these and other data, said Dr. Scher. According to the criteria, post-traumatic headache has “no typical characteristics,” but the data suggest that post-traumatic headache often takes the form of migraine or chronic daily headache.

The criteria also require headache to occur within seven days of injury or of regaining consciousness after injury. “The seven-day rule is not optimal,” Dr. Scher told Neurology Reviews. “I don’t think we know what the number should be. Hopefully, in the future we’ll have a more empirical case definition—one that we can justify with data.

“When we finish our study and some of the other ongoing studies, we’ll have a much better idea of what the post-traumatic headache phenotype is,” added Dr. Scher. “Once we have a better feeling for what the phenotype is, we can start talking about focused clinical trials in this population.”
In addition to her ongoing study, Dr. Scher plans to examine whether continuous headache and auralike symptoms could be useful diagnostic markers for combat-related post-traumatic headaches.                                      

LOS ANGELES—Veterans with traumatic brain injury (TBI) do not show improvement in symptoms of postconcussion syndrome after eight years of follow-up, researchers reported at the 54th Annual Scientific Meeting of the American Headache Society.

“More attention must be focused on recognition and treatment of this syndrome in this group of individuals who are in the prime years of their lives,” said James R. Couch, MD, PhD, Professor of Neurology at the University of Oklahoma Medical Center and Veterans Affairs Medical Center in Oklahoma City, and his colleagues.

Evaluating Veterans With TBI
In this retrospective study, the investigators evaluated data from veterans who served between 2002 and 2010 and were seen at the Oklahoma Medical Center and Veterans Affairs Medical Center between 2008 and 2011 for a free general health screen. Of the 5,713 veterans who presented for medical care, 1,382 screened positive for combat-related TBI and were referred to the TBI clinic for specialty evaluation.

Dr. Couch and his colleagues reported on the first 500 patients evaluated in this program, all of whom underwent a second screen with a physician or a physician’s assistant and were subsequently confirmed to have combat-related TBI. The screen involved queries about the mechanism of injury, such as a blast, fall, assault, motor vehicle accident, or a combination of factors.

Patients completed the Beck Depression Inventory and answered questions about the frequency and intensity of each of their symptoms, which were scored on a five-point scale ranging from none to very severe. The symptoms were chosen to represent the major characteristics of postconcussion syndrome and included headache, dizziness, difficulty with balance, poor coordination, difficulty with decisions, and depression. The investigators evaluated the data by comparing symptom occurrence for the one- to four-year and five- to eight-year groups within each cohort.

Long-Term Impact
Results showed no significant difference in the occurrence or intensity of symptoms between patients who had a TBI within the past two years and those who experienced TBI three to eight years earlier.

After examining the prevalence of severe or very severe intensity symptom levels, the investigators found that 48% of patients had headache, 11% had dizziness, 11% had difficulty with balance, 20% had poor coordination, and 35% had difficulty making decisions. According to scores on the Beck Depression Inventory, 65% of veterans were not depressed, though 34% were mildly to moderately depressed, and 1% were severely depressed.

None of the six symptoms associated with postconcussion syndrome improved during the eight-year period. Of the six symptoms, there was a statistically significant tendency for depression to increase from the one- to four-year cohorts to the five- to eight-year cohorts, as well as an overall tendency for all symptoms to worsen from one to four years and five to eight years after TBI.

 However, this tendency was not statistically significant for symptoms other than depression, and  it was marginally significant for poor coordination.

“The study indicates that TBI while deployed may have significant, long-term consequences for the injured subject,” commented Dr. Couch. Based on the data, he suggested that veterans with postconcussion syndrome resulting from TBI may require follow-up and continual psychiatric and medical care for as long as—and possibly more than—eight years after the injury.

Dr. Couch anticipates more research in this population of patients. “The possibility of late deterioration of neurologic and mental function is an issue that will require further attention and study,” he said.   

To read an accompanying commentary, please click here.

LOS ANGELES—Veterans with traumatic brain injury (TBI) do not show improvement in symptoms of postconcussion syndrome after eight years of follow-up, researchers reported at the 54th Annual Scientific Meeting of the American Headache Society.

“More attention must be focused on recognition and treatment of this syndrome in this group of individuals who are in the prime years of their lives,” said James R. Couch, MD, PhD, Professor of Neurology at the University of Oklahoma Medical Center and Veterans Affairs Medical Center in Oklahoma City, and his colleagues.

Evaluating Veterans With TBI
In this retrospective study, the investigators evaluated data from veterans who served between 2002 and 2010 and were seen at the Oklahoma Medical Center and Veterans Affairs Medical Center between 2008 and 2011 for a free general health screen. Of the 5,713 veterans who presented for medical care, 1,382 screened positive for combat-related TBI and were referred to the TBI clinic for specialty evaluation.

Dr. Couch and his colleagues reported on the first 500 patients evaluated in this program, all of whom underwent a second screen with a physician or a physician’s assistant and were subsequently confirmed to have combat-related TBI. The screen involved queries about the mechanism of injury, such as a blast, fall, assault, motor vehicle accident, or a combination of factors.

Patients completed the Beck Depression Inventory and answered questions about the frequency and intensity of each of their symptoms, which were scored on a five-point scale ranging from none to very severe. The symptoms were chosen to represent the major characteristics of postconcussion syndrome and included headache, dizziness, difficulty with balance, poor coordination, difficulty with decisions, and depression. The investigators evaluated the data by comparing symptom occurrence for the one- to four-year and five- to eight-year groups within each cohort.

Long-Term Impact
Results showed no significant difference in the occurrence or intensity of symptoms between patients who had a TBI within the past two years and those who experienced TBI three to eight years earlier.

After examining the prevalence of severe or very severe intensity symptom levels, the investigators found that 48% of patients had headache, 11% had dizziness, 11% had difficulty with balance, 20% had poor coordination, and 35% had difficulty making decisions. According to scores on the Beck Depression Inventory, 65% of veterans were not depressed, though 34% were mildly to moderately depressed, and 1% were severely depressed.

None of the six symptoms associated with postconcussion syndrome improved during the eight-year period. Of the six symptoms, there was a statistically significant tendency for depression to increase from the one- to four-year cohorts to the five- to eight-year cohorts, as well as an overall tendency for all symptoms to worsen from one to four years and five to eight years after TBI.

 However, this tendency was not statistically significant for symptoms other than depression, and  it was marginally significant for poor coordination.

“The study indicates that TBI while deployed may have significant, long-term consequences for the injured subject,” commented Dr. Couch. Based on the data, he suggested that veterans with postconcussion syndrome resulting from TBI may require follow-up and continual psychiatric and medical care for as long as—and possibly more than—eight years after the injury.

Dr. Couch anticipates more research in this population of patients. “The possibility of late deterioration of neurologic and mental function is an issue that will require further attention and study,” he said.   

To read an accompanying commentary, please click here.

LOS ANGELES—Veterans with traumatic brain injury (TBI) do not show improvement in symptoms of postconcussion syndrome after eight years of follow-up, researchers reported at the 54th Annual Scientific Meeting of the American Headache Society.

“More attention must be focused on recognition and treatment of this syndrome in this group of individuals who are in the prime years of their lives,” said James R. Couch, MD, PhD, Professor of Neurology at the University of Oklahoma Medical Center and Veterans Affairs Medical Center in Oklahoma City, and his colleagues.

Evaluating Veterans With TBI
In this retrospective study, the investigators evaluated data from veterans who served between 2002 and 2010 and were seen at the Oklahoma Medical Center and Veterans Affairs Medical Center between 2008 and 2011 for a free general health screen. Of the 5,713 veterans who presented for medical care, 1,382 screened positive for combat-related TBI and were referred to the TBI clinic for specialty evaluation.

Dr. Couch and his colleagues reported on the first 500 patients evaluated in this program, all of whom underwent a second screen with a physician or a physician’s assistant and were subsequently confirmed to have combat-related TBI. The screen involved queries about the mechanism of injury, such as a blast, fall, assault, motor vehicle accident, or a combination of factors.

Patients completed the Beck Depression Inventory and answered questions about the frequency and intensity of each of their symptoms, which were scored on a five-point scale ranging from none to very severe. The symptoms were chosen to represent the major characteristics of postconcussion syndrome and included headache, dizziness, difficulty with balance, poor coordination, difficulty with decisions, and depression. The investigators evaluated the data by comparing symptom occurrence for the one- to four-year and five- to eight-year groups within each cohort.

Long-Term Impact
Results showed no significant difference in the occurrence or intensity of symptoms between patients who had a TBI within the past two years and those who experienced TBI three to eight years earlier.

After examining the prevalence of severe or very severe intensity symptom levels, the investigators found that 48% of patients had headache, 11% had dizziness, 11% had difficulty with balance, 20% had poor coordination, and 35% had difficulty making decisions. According to scores on the Beck Depression Inventory, 65% of veterans were not depressed, though 34% were mildly to moderately depressed, and 1% were severely depressed.

None of the six symptoms associated with postconcussion syndrome improved during the eight-year period. Of the six symptoms, there was a statistically significant tendency for depression to increase from the one- to four-year cohorts to the five- to eight-year cohorts, as well as an overall tendency for all symptoms to worsen from one to four years and five to eight years after TBI.

 However, this tendency was not statistically significant for symptoms other than depression, and  it was marginally significant for poor coordination.

“The study indicates that TBI while deployed may have significant, long-term consequences for the injured subject,” commented Dr. Couch. Based on the data, he suggested that veterans with postconcussion syndrome resulting from TBI may require follow-up and continual psychiatric and medical care for as long as—and possibly more than—eight years after the injury.

Dr. Couch anticipates more research in this population of patients. “The possibility of late deterioration of neurologic and mental function is an issue that will require further attention and study,” he said.   

To read an accompanying commentary, please click here.

BOSTON—Prolonged exposure therapy is associated with less improvement in symptoms of insomnia and post-traumatic stress disorder (PTSD) among patients with traumatic brain injury (TBI) than among patients without TBI. By the end of therapy, nightmare intensity had increased and total sleep time had decreased from baseline among patients with TBI, according to research presented at the 26th Annual Meeting of the Associated Professional Sleep Societies.

Jessica L. Beltran, a community health program representative at the University of California, San Diego, and colleagues studied 48 veterans diagnosed with PTSD and insomnia. Participants’ mean age was approximately 35, and seven were female. The researchers categorized the patients into a TBI group (25 patients) and a non-TBI group (23 patients) after screening. All subjects kept daily sleep diaries that included information about total sleep time, sleep efficiency, sleep latency, number of awakenings, wake after sleep onset, and nightmare rate and intensity.

In addition, the investigators administered several psychiatric questionnaires to the patients at baseline, including the Insomnia Severity Index, Clinician-Administered PTSD Scale (CAPS), PTSD Checklist Stressor Specific (PCL-S), and Patient Health Questionnaire (PHQ-9). After the participants had undergone prolonged exposure therapy, the researchers administered the questionnaires again. Baseline and post-therapy variables were analyzed with an independent samples t-test.

Ms. Beltran observed no statistically significant differences in sleep-diary variables and questionnaire scores between the TBI group and the non-TBI group at baseline. After treatment, mean nightmare intensity increased from approximately 6 to approximately 7 (on a 10-point scale) in the TBI group, compared with a decrease from about 6 to about 4.5 in the non-TBI group. Mean total sleep time decreased from 350 minutes to 325 minutes in the TBI group, compared with an increase from 350 minutes to 400 minutes for the non-TBI group.

For patients in the TBI group, mean CAPS score decreased from 80 to 70 after therapy, compared with a decrease from 75 to 50 for the non-TBI group. These scores indicated that the TBI group still had severe PTSD after therapy. Mean PHQ-9 score decreased from 15 to 14 for the TBI group, compared with a decrease from 17 to 7 for the non-TBI group. Patients with TBI “might benefit from a combination of multiple therapies that address their specific needs—for instance, more support during the in vivo component of prolonged exposure therapy, as well as a greater focus on cognitive difficulties,” said Ms. Beltran.   

BOSTON—Prolonged exposure therapy is associated with less improvement in symptoms of insomnia and post-traumatic stress disorder (PTSD) among patients with traumatic brain injury (TBI) than among patients without TBI. By the end of therapy, nightmare intensity had increased and total sleep time had decreased from baseline among patients with TBI, according to research presented at the 26th Annual Meeting of the Associated Professional Sleep Societies.

Jessica L. Beltran, a community health program representative at the University of California, San Diego, and colleagues studied 48 veterans diagnosed with PTSD and insomnia. Participants’ mean age was approximately 35, and seven were female. The researchers categorized the patients into a TBI group (25 patients) and a non-TBI group (23 patients) after screening. All subjects kept daily sleep diaries that included information about total sleep time, sleep efficiency, sleep latency, number of awakenings, wake after sleep onset, and nightmare rate and intensity.

In addition, the investigators administered several psychiatric questionnaires to the patients at baseline, including the Insomnia Severity Index, Clinician-Administered PTSD Scale (CAPS), PTSD Checklist Stressor Specific (PCL-S), and Patient Health Questionnaire (PHQ-9). After the participants had undergone prolonged exposure therapy, the researchers administered the questionnaires again. Baseline and post-therapy variables were analyzed with an independent samples t-test.

Ms. Beltran observed no statistically significant differences in sleep-diary variables and questionnaire scores between the TBI group and the non-TBI group at baseline. After treatment, mean nightmare intensity increased from approximately 6 to approximately 7 (on a 10-point scale) in the TBI group, compared with a decrease from about 6 to about 4.5 in the non-TBI group. Mean total sleep time decreased from 350 minutes to 325 minutes in the TBI group, compared with an increase from 350 minutes to 400 minutes for the non-TBI group.

For patients in the TBI group, mean CAPS score decreased from 80 to 70 after therapy, compared with a decrease from 75 to 50 for the non-TBI group. These scores indicated that the TBI group still had severe PTSD after therapy. Mean PHQ-9 score decreased from 15 to 14 for the TBI group, compared with a decrease from 17 to 7 for the non-TBI group. Patients with TBI “might benefit from a combination of multiple therapies that address their specific needs—for instance, more support during the in vivo component of prolonged exposure therapy, as well as a greater focus on cognitive difficulties,” said Ms. Beltran.   

BOSTON—Prolonged exposure therapy is associated with less improvement in symptoms of insomnia and post-traumatic stress disorder (PTSD) among patients with traumatic brain injury (TBI) than among patients without TBI. By the end of therapy, nightmare intensity had increased and total sleep time had decreased from baseline among patients with TBI, according to research presented at the 26th Annual Meeting of the Associated Professional Sleep Societies.

Jessica L. Beltran, a community health program representative at the University of California, San Diego, and colleagues studied 48 veterans diagnosed with PTSD and insomnia. Participants’ mean age was approximately 35, and seven were female. The researchers categorized the patients into a TBI group (25 patients) and a non-TBI group (23 patients) after screening. All subjects kept daily sleep diaries that included information about total sleep time, sleep efficiency, sleep latency, number of awakenings, wake after sleep onset, and nightmare rate and intensity.

In addition, the investigators administered several psychiatric questionnaires to the patients at baseline, including the Insomnia Severity Index, Clinician-Administered PTSD Scale (CAPS), PTSD Checklist Stressor Specific (PCL-S), and Patient Health Questionnaire (PHQ-9). After the participants had undergone prolonged exposure therapy, the researchers administered the questionnaires again. Baseline and post-therapy variables were analyzed with an independent samples t-test.

Ms. Beltran observed no statistically significant differences in sleep-diary variables and questionnaire scores between the TBI group and the non-TBI group at baseline. After treatment, mean nightmare intensity increased from approximately 6 to approximately 7 (on a 10-point scale) in the TBI group, compared with a decrease from about 6 to about 4.5 in the non-TBI group. Mean total sleep time decreased from 350 minutes to 325 minutes in the TBI group, compared with an increase from 350 minutes to 400 minutes for the non-TBI group.

For patients in the TBI group, mean CAPS score decreased from 80 to 70 after therapy, compared with a decrease from 75 to 50 for the non-TBI group. These scores indicated that the TBI group still had severe PTSD after therapy. Mean PHQ-9 score decreased from 15 to 14 for the TBI group, compared with a decrease from 17 to 7 for the non-TBI group. Patients with TBI “might benefit from a combination of multiple therapies that address their specific needs—for instance, more support during the in vivo component of prolonged exposure therapy, as well as a greater focus on cognitive difficulties,” said Ms. Beltran.   

Fewer patients receiving amantadine remained in a vegetative state compared with patients receiving placebo.

Patients with post-traumatic disorders of consciousness who received amantadine hydrochloride experienced a more rapid rate of functional recovery than those treated with a placebo, according to an article published in the March 1 New England Journal of Medicine. The benefit of the drug was evident in patients diagnosed with a vegetative or minimally conscious state at baseline, regardless of when they were enrolled in the trial.

Fewer patients who received amantadine, a drug used to treat Parkinson’s disease, remained in a vegetative state, compared with patients who received placebo, according to Joseph T. Giacino, PhD, Director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital and Associate Professor at Harvard Medical School in Boston. In addition, a greater percentage of patients receiving amantadine met key behavioral milestones for recovery (eg, consistent following of commands and object recognition) by the end of the treatment period, compared with the control group. Treatment did not increase patients’ risk of adverse medical events.

After patients stopped receiving amantadine, their level of improvement continued to increase, albeit at a significantly slower rate. Two weeks after treatment ended, the disability scores of the experimental and control groups were similar.

Treating Post-Traumatic Disorders of Consciousness
Dr. Giacino and his colleagues conducted a prospective, double-blind, randomized trial to evaluate the effectiveness of amantadine in helping patients with post-traumatic trauma recover from a vegetative or minimally conscious state. The study followed 184 patients at 11 clinical sites in three countries.

Eligible patients had experienced traumatic brain injury four to 16 weeks before enrollment, and they were receiving care at in-patient facilities. Participants had disability rating scores (DRS) greater than 11, could not follow commands, and could not engage in functional communication. Nearly 87% of patients were white, and approximately 72% were male.

After randomization, the experimental group received 100 mg of amantadine twice daily for 14 days. The dose was increased to 150 mg twice daily at week three, and to 200 mg twice daily at week four for any patient in the group whose DRS had not improved by two points from baseline. After four weeks, treatment ceased, but DRS scores continued to be assessed for two additional weeks. The control group received a placebo for four weeks.

Amantadine May Shorten In-Patient Stays
“We conclude that amantadine is effective in accelerating the pace of recovery during acute rehabilitation in patients with prolonged post-traumatic disturbances in consciousness,” said Dr. Giacino. “The favorable neurobehavioral effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attentional functions.”

The researchers limited the length of the treatment period for practical and ethical reasons. Therefore, the study results leave open the question of whether amantadine improves patients’ long-term outcome or accelerates recovery to the end point that an untreated patient would reach. “In view of health care cost constraints and declining lengths of stay for in-patient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance,” said Dr. Giacino. Future studies should identify which patients are likely to respond to amantadine, the effective dose, and the optimal duration of treatment, he concluded.   

Fewer patients receiving amantadine remained in a vegetative state compared with patients receiving placebo.

Patients with post-traumatic disorders of consciousness who received amantadine hydrochloride experienced a more rapid rate of functional recovery than those treated with a placebo, according to an article published in the March 1 New England Journal of Medicine. The benefit of the drug was evident in patients diagnosed with a vegetative or minimally conscious state at baseline, regardless of when they were enrolled in the trial.

Fewer patients who received amantadine, a drug used to treat Parkinson’s disease, remained in a vegetative state, compared with patients who received placebo, according to Joseph T. Giacino, PhD, Director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital and Associate Professor at Harvard Medical School in Boston. In addition, a greater percentage of patients receiving amantadine met key behavioral milestones for recovery (eg, consistent following of commands and object recognition) by the end of the treatment period, compared with the control group. Treatment did not increase patients’ risk of adverse medical events.

After patients stopped receiving amantadine, their level of improvement continued to increase, albeit at a significantly slower rate. Two weeks after treatment ended, the disability scores of the experimental and control groups were similar.

Treating Post-Traumatic Disorders of Consciousness
Dr. Giacino and his colleagues conducted a prospective, double-blind, randomized trial to evaluate the effectiveness of amantadine in helping patients with post-traumatic trauma recover from a vegetative or minimally conscious state. The study followed 184 patients at 11 clinical sites in three countries.

Eligible patients had experienced traumatic brain injury four to 16 weeks before enrollment, and they were receiving care at in-patient facilities. Participants had disability rating scores (DRS) greater than 11, could not follow commands, and could not engage in functional communication. Nearly 87% of patients were white, and approximately 72% were male.

After randomization, the experimental group received 100 mg of amantadine twice daily for 14 days. The dose was increased to 150 mg twice daily at week three, and to 200 mg twice daily at week four for any patient in the group whose DRS had not improved by two points from baseline. After four weeks, treatment ceased, but DRS scores continued to be assessed for two additional weeks. The control group received a placebo for four weeks.

Amantadine May Shorten In-Patient Stays
“We conclude that amantadine is effective in accelerating the pace of recovery during acute rehabilitation in patients with prolonged post-traumatic disturbances in consciousness,” said Dr. Giacino. “The favorable neurobehavioral effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attentional functions.”

The researchers limited the length of the treatment period for practical and ethical reasons. Therefore, the study results leave open the question of whether amantadine improves patients’ long-term outcome or accelerates recovery to the end point that an untreated patient would reach. “In view of health care cost constraints and declining lengths of stay for in-patient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance,” said Dr. Giacino. Future studies should identify which patients are likely to respond to amantadine, the effective dose, and the optimal duration of treatment, he concluded.   

Fewer patients receiving amantadine remained in a vegetative state compared with patients receiving placebo.

Patients with post-traumatic disorders of consciousness who received amantadine hydrochloride experienced a more rapid rate of functional recovery than those treated with a placebo, according to an article published in the March 1 New England Journal of Medicine. The benefit of the drug was evident in patients diagnosed with a vegetative or minimally conscious state at baseline, regardless of when they were enrolled in the trial.

Fewer patients who received amantadine, a drug used to treat Parkinson’s disease, remained in a vegetative state, compared with patients who received placebo, according to Joseph T. Giacino, PhD, Director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital and Associate Professor at Harvard Medical School in Boston. In addition, a greater percentage of patients receiving amantadine met key behavioral milestones for recovery (eg, consistent following of commands and object recognition) by the end of the treatment period, compared with the control group. Treatment did not increase patients’ risk of adverse medical events.

After patients stopped receiving amantadine, their level of improvement continued to increase, albeit at a significantly slower rate. Two weeks after treatment ended, the disability scores of the experimental and control groups were similar.

Treating Post-Traumatic Disorders of Consciousness
Dr. Giacino and his colleagues conducted a prospective, double-blind, randomized trial to evaluate the effectiveness of amantadine in helping patients with post-traumatic trauma recover from a vegetative or minimally conscious state. The study followed 184 patients at 11 clinical sites in three countries.

Eligible patients had experienced traumatic brain injury four to 16 weeks before enrollment, and they were receiving care at in-patient facilities. Participants had disability rating scores (DRS) greater than 11, could not follow commands, and could not engage in functional communication. Nearly 87% of patients were white, and approximately 72% were male.

After randomization, the experimental group received 100 mg of amantadine twice daily for 14 days. The dose was increased to 150 mg twice daily at week three, and to 200 mg twice daily at week four for any patient in the group whose DRS had not improved by two points from baseline. After four weeks, treatment ceased, but DRS scores continued to be assessed for two additional weeks. The control group received a placebo for four weeks.

Amantadine May Shorten In-Patient Stays
“We conclude that amantadine is effective in accelerating the pace of recovery during acute rehabilitation in patients with prolonged post-traumatic disturbances in consciousness,” said Dr. Giacino. “The favorable neurobehavioral effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attentional functions.”

The researchers limited the length of the treatment period for practical and ethical reasons. Therefore, the study results leave open the question of whether amantadine improves patients’ long-term outcome or accelerates recovery to the end point that an untreated patient would reach. “In view of health care cost constraints and declining lengths of stay for in-patient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance,” said Dr. Giacino. Future studies should identify which patients are likely to respond to amantadine, the effective dose, and the optimal duration of treatment, he concluded.   

Adolescent girls with TBI may have an increased risk of headache one year after injury compared with controls, according to investigators.

SAVANNAH, GA—Children who experience traumatic brain injury (TBI) are at an increased risk for headache three months later—but for most children, this risk returns to normal one year after injury, researchers reported at the 40th Annual Meeting of the Child Neurology Society.

“The association between pediatric TBI and headache is significant overall and for girls and adolescents following mild TBI, as well as for younger children following moderate/severe TBI,” said Heidi K. Blume, MD, Assistant Professor of Neurology at Seattle Children’s Hospital and the University of Washington, Seattle.

TBI Versus Arm Injury
To determine whether pediatric TBI is associated with long-term headache, the investigators compared headache prevalence in children with TBI with that in children with an arm injury, who served as controls. They also examined age- and sex-related differences in headache frequency following mild and moderate/severe TBI. The study was open to all patients ages 5 to 17 who were treated for a TBI or an arm fracture in one of 10 study hospitals. At baseline, the researchers interviewed a parent/guardian of each child, and at three and 12 months, they conducted follow-up interviews with parents and adolescents ages 14 and older.

In the follow-up interviews, parents were asked to “rate any headache pain by indicating the child’s headache on average in the last week” on a scale of 0 to 10. Adolescents were asked to indicate how much they were bothered by headaches in the past week, as well as to rate their headache pain during the past week on a scale of 0 to 10 and on the Wong-Baker FACES scale.

The investigators defined “headache” as a pain score of 1 or more. They defined “serious headache” as a pain score of 5 or more on the parent surveys and as “bothered a lot,” a score of 5 or more, or report of C-F headache on the FACES scale in the adolescent surveys. The CDC Mild TBI Work Group report and patients’ Glasgow Coma Scale scores after injury were used to define mild, moderate, and severe TBI. Patients ages 5 to 12 were defined as children, and patients ages 13 to 17 were defined as adolescents.

A Three-Month Association
The study included 649 patients: 441 with mild TBI, 71 with moderate/severe TBI, and 137 with arm injury.
At three months, headache prevalence was significantly higher in patients with mild TBI than in controls among the overall cohort (43% vs 26.2%), adolescents (46.4% vs 25%), and girls (58.8% vs 23.8%). In addition, headache prevalence was higher in patients with moderate/severe TBI than in controls among younger children (60% vs 27%). For girls, serious headache was significantly more frequent after mild TBI than after arm injury, and for young children, serious headache was significantly more frequent after moderate/serious TBI than after arm injury. “The prevalence of headache increased with age in girls with mild TBI but not in boys or controls of either sex,” the researchers added.

In the three-month adolescent survey, 55% of girls with mild TBI versus 23% of control girls reported serious headache. In addition, 32% of girls with mild TBI versus 8% of control girls reported that they were “bothered a lot” by headache, and 64% of girls with mild TBI versus 11% of control girls indicated C-F on the FACES scale. However, there were no significant associations between mild TBI and headache for adolescent boys or between moderate/severe TBI and headache for adolescents of either sex.

At 12 months, headache prevalence was not significantly associated with mild TBI or moderate/severe TBI. However, serious headache was more common among girls with mild TBI than among control girls (27% vs 10%).

In the 12-month adolescent survey, girls with mild TBI reported more headaches than control girls on all questions, but the differences did not reach statistical significance. There were similar trends for girls with moderate/severe TBI.

“Adolescent girls with TBI may have an increased risk of headache one year after injury compared to controls,” the researchers concluded. “The epidemiology of headache following pediatric TBI appears to share some features with primary headache disorders such as migraine.

Adolescent girls with TBI may have an increased risk of headache one year after injury compared with controls, according to investigators.

SAVANNAH, GA—Children who experience traumatic brain injury (TBI) are at an increased risk for headache three months later—but for most children, this risk returns to normal one year after injury, researchers reported at the 40th Annual Meeting of the Child Neurology Society.

“The association between pediatric TBI and headache is significant overall and for girls and adolescents following mild TBI, as well as for younger children following moderate/severe TBI,” said Heidi K. Blume, MD, Assistant Professor of Neurology at Seattle Children’s Hospital and the University of Washington, Seattle.

TBI Versus Arm Injury
To determine whether pediatric TBI is associated with long-term headache, the investigators compared headache prevalence in children with TBI with that in children with an arm injury, who served as controls. They also examined age- and sex-related differences in headache frequency following mild and moderate/severe TBI. The study was open to all patients ages 5 to 17 who were treated for a TBI or an arm fracture in one of 10 study hospitals. At baseline, the researchers interviewed a parent/guardian of each child, and at three and 12 months, they conducted follow-up interviews with parents and adolescents ages 14 and older.

In the follow-up interviews, parents were asked to “rate any headache pain by indicating the child’s headache on average in the last week” on a scale of 0 to 10. Adolescents were asked to indicate how much they were bothered by headaches in the past week, as well as to rate their headache pain during the past week on a scale of 0 to 10 and on the Wong-Baker FACES scale.

The investigators defined “headache” as a pain score of 1 or more. They defined “serious headache” as a pain score of 5 or more on the parent surveys and as “bothered a lot,” a score of 5 or more, or report of C-F headache on the FACES scale in the adolescent surveys. The CDC Mild TBI Work Group report and patients’ Glasgow Coma Scale scores after injury were used to define mild, moderate, and severe TBI. Patients ages 5 to 12 were defined as children, and patients ages 13 to 17 were defined as adolescents.

A Three-Month Association
The study included 649 patients: 441 with mild TBI, 71 with moderate/severe TBI, and 137 with arm injury.
At three months, headache prevalence was significantly higher in patients with mild TBI than in controls among the overall cohort (43% vs 26.2%), adolescents (46.4% vs 25%), and girls (58.8% vs 23.8%). In addition, headache prevalence was higher in patients with moderate/severe TBI than in controls among younger children (60% vs 27%). For girls, serious headache was significantly more frequent after mild TBI than after arm injury, and for young children, serious headache was significantly more frequent after moderate/serious TBI than after arm injury. “The prevalence of headache increased with age in girls with mild TBI but not in boys or controls of either sex,” the researchers added.

In the three-month adolescent survey, 55% of girls with mild TBI versus 23% of control girls reported serious headache. In addition, 32% of girls with mild TBI versus 8% of control girls reported that they were “bothered a lot” by headache, and 64% of girls with mild TBI versus 11% of control girls indicated C-F on the FACES scale. However, there were no significant associations between mild TBI and headache for adolescent boys or between moderate/severe TBI and headache for adolescents of either sex.

At 12 months, headache prevalence was not significantly associated with mild TBI or moderate/severe TBI. However, serious headache was more common among girls with mild TBI than among control girls (27% vs 10%).

In the 12-month adolescent survey, girls with mild TBI reported more headaches than control girls on all questions, but the differences did not reach statistical significance. There were similar trends for girls with moderate/severe TBI.

“Adolescent girls with TBI may have an increased risk of headache one year after injury compared to controls,” the researchers concluded. “The epidemiology of headache following pediatric TBI appears to share some features with primary headache disorders such as migraine.

Adolescent girls with TBI may have an increased risk of headache one year after injury compared with controls, according to investigators.

SAVANNAH, GA—Children who experience traumatic brain injury (TBI) are at an increased risk for headache three months later—but for most children, this risk returns to normal one year after injury, researchers reported at the 40th Annual Meeting of the Child Neurology Society.

“The association between pediatric TBI and headache is significant overall and for girls and adolescents following mild TBI, as well as for younger children following moderate/severe TBI,” said Heidi K. Blume, MD, Assistant Professor of Neurology at Seattle Children’s Hospital and the University of Washington, Seattle.

TBI Versus Arm Injury
To determine whether pediatric TBI is associated with long-term headache, the investigators compared headache prevalence in children with TBI with that in children with an arm injury, who served as controls. They also examined age- and sex-related differences in headache frequency following mild and moderate/severe TBI. The study was open to all patients ages 5 to 17 who were treated for a TBI or an arm fracture in one of 10 study hospitals. At baseline, the researchers interviewed a parent/guardian of each child, and at three and 12 months, they conducted follow-up interviews with parents and adolescents ages 14 and older.

In the follow-up interviews, parents were asked to “rate any headache pain by indicating the child’s headache on average in the last week” on a scale of 0 to 10. Adolescents were asked to indicate how much they were bothered by headaches in the past week, as well as to rate their headache pain during the past week on a scale of 0 to 10 and on the Wong-Baker FACES scale.

The investigators defined “headache” as a pain score of 1 or more. They defined “serious headache” as a pain score of 5 or more on the parent surveys and as “bothered a lot,” a score of 5 or more, or report of C-F headache on the FACES scale in the adolescent surveys. The CDC Mild TBI Work Group report and patients’ Glasgow Coma Scale scores after injury were used to define mild, moderate, and severe TBI. Patients ages 5 to 12 were defined as children, and patients ages 13 to 17 were defined as adolescents.

A Three-Month Association
The study included 649 patients: 441 with mild TBI, 71 with moderate/severe TBI, and 137 with arm injury.
At three months, headache prevalence was significantly higher in patients with mild TBI than in controls among the overall cohort (43% vs 26.2%), adolescents (46.4% vs 25%), and girls (58.8% vs 23.8%). In addition, headache prevalence was higher in patients with moderate/severe TBI than in controls among younger children (60% vs 27%). For girls, serious headache was significantly more frequent after mild TBI than after arm injury, and for young children, serious headache was significantly more frequent after moderate/serious TBI than after arm injury. “The prevalence of headache increased with age in girls with mild TBI but not in boys or controls of either sex,” the researchers added.

In the three-month adolescent survey, 55% of girls with mild TBI versus 23% of control girls reported serious headache. In addition, 32% of girls with mild TBI versus 8% of control girls reported that they were “bothered a lot” by headache, and 64% of girls with mild TBI versus 11% of control girls indicated C-F on the FACES scale. However, there were no significant associations between mild TBI and headache for adolescent boys or between moderate/severe TBI and headache for adolescents of either sex.

At 12 months, headache prevalence was not significantly associated with mild TBI or moderate/severe TBI. However, serious headache was more common among girls with mild TBI than among control girls (27% vs 10%).

In the 12-month adolescent survey, girls with mild TBI reported more headaches than control girls on all questions, but the differences did not reach statistical significance. There were similar trends for girls with moderate/severe TBI.

“Adolescent girls with TBI may have an increased risk of headache one year after injury compared to controls,” the researchers concluded. “The epidemiology of headache following pediatric TBI appears to share some features with primary headache disorders such as migraine.