Traumatic Brain Injury

Inefficient sleep appears to be associated with impairment on tasks requiring higher levels of cognitive processing in war veterans with mild to moderate TBI.

MINNEAPOLIS—Insomnia and other types of sleep disturbance may play a significant role in cognitive deficits, psychiatric symptoms, and recovery of normal performance among war veterans with mild to moderate traumatic brain injury (TBI), according to research presented at the 25th Anniversary Meeting of the Associated Professional Sleep Societies.
“Levels of sleep disturbance among war veterans exceeded the general population prevalence,” reported Henry J. Orff, PhD, of the Department of Psychiatry, University of California, San Diego, and colleagues. “Poor sleep is a pervasive complaint in veterans with mild to moderate TBI.”
Dr. Orff’s group conducted retrospective chart reviews of 300 veterans from the wars in Iraq and Afghanistan regarding their clinical sleep, as well as their psychiatric and neuropsychologic test data.
The mean age of participants was 32, and their mean education was 13.5 years. Each veteran had a mean of two TBIs, with a mean longest loss of consciousness of 16 minutes and a mean longest length of posttraumatic amnesia of 137 minutes; 86.5% of all TBIs were mild, and 13.5% were moderate. The mechanisms of injury included blast-related TBI (25.6%), blunt force TBI (38.4%), and both blast and blunt force mechanisms (36%).
Eighty-five percent of the veterans reported sleep disturbance as measured by the scores on item #16 of the Beck Depression Inventory, a question that addresses changes in sleeping patterns from normal in the past week. In addition, 71% of the sample reported getting less sleep. In a subset of 86 veterans who were administered the Pittsburgh Sleep Quality Inventory (PSQI), 100% reported clinically significant sleep disturbance (PSQI global score >5). Furthermore, self-reported sleep latencies averaged 54 minutes, total sleep times averaged 5.4 hours, and sleep efficiencies averaged 77% in this sample.
Depressive symptoms were significantly correlated with a host of sleep complaints, including poorer sleep quality, longer sleep latencies, shorter sleep times, lower sleep efficiencies, more use of medications, and greater daytime dysfunction. Postconcussive symptoms were correlated with poorer sleep quality, shorter sleep duration, and greater self-reported daytime dysfunction.
“Overall, the results suggest that poor sleep in this population may have ramifications for performance on tasks requiring higher levels of cognitive processing, such as executive tasks with a timed component, while having less  impact on more basic cognitive tasks, such as those involving attention and verbal memory,” stated Dr. Orff and colleagues.

Inefficient sleep appears to be associated with impairment on tasks requiring higher levels of cognitive processing in war veterans with mild to moderate TBI.

MINNEAPOLIS—Insomnia and other types of sleep disturbance may play a significant role in cognitive deficits, psychiatric symptoms, and recovery of normal performance among war veterans with mild to moderate traumatic brain injury (TBI), according to research presented at the 25th Anniversary Meeting of the Associated Professional Sleep Societies.
“Levels of sleep disturbance among war veterans exceeded the general population prevalence,” reported Henry J. Orff, PhD, of the Department of Psychiatry, University of California, San Diego, and colleagues. “Poor sleep is a pervasive complaint in veterans with mild to moderate TBI.”
Dr. Orff’s group conducted retrospective chart reviews of 300 veterans from the wars in Iraq and Afghanistan regarding their clinical sleep, as well as their psychiatric and neuropsychologic test data.
The mean age of participants was 32, and their mean education was 13.5 years. Each veteran had a mean of two TBIs, with a mean longest loss of consciousness of 16 minutes and a mean longest length of posttraumatic amnesia of 137 minutes; 86.5% of all TBIs were mild, and 13.5% were moderate. The mechanisms of injury included blast-related TBI (25.6%), blunt force TBI (38.4%), and both blast and blunt force mechanisms (36%).
Eighty-five percent of the veterans reported sleep disturbance as measured by the scores on item #16 of the Beck Depression Inventory, a question that addresses changes in sleeping patterns from normal in the past week. In addition, 71% of the sample reported getting less sleep. In a subset of 86 veterans who were administered the Pittsburgh Sleep Quality Inventory (PSQI), 100% reported clinically significant sleep disturbance (PSQI global score >5). Furthermore, self-reported sleep latencies averaged 54 minutes, total sleep times averaged 5.4 hours, and sleep efficiencies averaged 77% in this sample.
Depressive symptoms were significantly correlated with a host of sleep complaints, including poorer sleep quality, longer sleep latencies, shorter sleep times, lower sleep efficiencies, more use of medications, and greater daytime dysfunction. Postconcussive symptoms were correlated with poorer sleep quality, shorter sleep duration, and greater self-reported daytime dysfunction.
“Overall, the results suggest that poor sleep in this population may have ramifications for performance on tasks requiring higher levels of cognitive processing, such as executive tasks with a timed component, while having less  impact on more basic cognitive tasks, such as those involving attention and verbal memory,” stated Dr. Orff and colleagues.

Inefficient sleep appears to be associated with impairment on tasks requiring higher levels of cognitive processing in war veterans with mild to moderate TBI.

MINNEAPOLIS—Insomnia and other types of sleep disturbance may play a significant role in cognitive deficits, psychiatric symptoms, and recovery of normal performance among war veterans with mild to moderate traumatic brain injury (TBI), according to research presented at the 25th Anniversary Meeting of the Associated Professional Sleep Societies.
“Levels of sleep disturbance among war veterans exceeded the general population prevalence,” reported Henry J. Orff, PhD, of the Department of Psychiatry, University of California, San Diego, and colleagues. “Poor sleep is a pervasive complaint in veterans with mild to moderate TBI.”
Dr. Orff’s group conducted retrospective chart reviews of 300 veterans from the wars in Iraq and Afghanistan regarding their clinical sleep, as well as their psychiatric and neuropsychologic test data.
The mean age of participants was 32, and their mean education was 13.5 years. Each veteran had a mean of two TBIs, with a mean longest loss of consciousness of 16 minutes and a mean longest length of posttraumatic amnesia of 137 minutes; 86.5% of all TBIs were mild, and 13.5% were moderate. The mechanisms of injury included blast-related TBI (25.6%), blunt force TBI (38.4%), and both blast and blunt force mechanisms (36%).
Eighty-five percent of the veterans reported sleep disturbance as measured by the scores on item #16 of the Beck Depression Inventory, a question that addresses changes in sleeping patterns from normal in the past week. In addition, 71% of the sample reported getting less sleep. In a subset of 86 veterans who were administered the Pittsburgh Sleep Quality Inventory (PSQI), 100% reported clinically significant sleep disturbance (PSQI global score >5). Furthermore, self-reported sleep latencies averaged 54 minutes, total sleep times averaged 5.4 hours, and sleep efficiencies averaged 77% in this sample.
Depressive symptoms were significantly correlated with a host of sleep complaints, including poorer sleep quality, longer sleep latencies, shorter sleep times, lower sleep efficiencies, more use of medications, and greater daytime dysfunction. Postconcussive symptoms were correlated with poorer sleep quality, shorter sleep duration, and greater self-reported daytime dysfunction.
“Overall, the results suggest that poor sleep in this population may have ramifications for performance on tasks requiring higher levels of cognitive processing, such as executive tasks with a timed component, while having less  impact on more basic cognitive tasks, such as those involving attention and verbal memory,” stated Dr. Orff and colleagues.

Older adults with TBI should be monitored for signs of cognitive impairment, researchers advise.

PARIS—Older veterans with traumatic brain injury (TBI) have more than a twofold increased risk for dementia, according to research presented at the 2011 Alzheimer’s Association International Conference.
Kristine Yaffe, MD, Professor of Psychiatry, Neurology, and Epidemiology at the University of California, San Francisco and Director of the Memory Disorders Program at the San Francisco VA Medical center, and colleagues reviewed medical records of 281,540 US veterans. All participants were ages 55 or older and received care through the Veterans Health Administration, had at least one inpatient or outpatient visit from 1997 to 2000 and a follow-up between 2001 and 2007, and did not have a dementia diagnosis at the start of the study. The investigators searched the database for TBI and dementia diagnoses and investigated whether TBI of any type was associated with greater risk of dementia, while taking into account demographics and other medical conditions, including psychiatric disorders.
The risk of dementia was 15.3% in those with a TBI diagnosis, compared with 6.8% in those without a TBI diagnosis, the researchers reported. The adjusted hazard ratio for incident dementia in those with any TBI diagnosis was 2.3 for the risk of developing dementia over seven years and was significant for all TBI types. Approximately 2% of older veterans had a TBI diagnosis during the study period.
“This issue is important, because TBI is very common,” said Dr. Yaffe. “About 1.7 million people experience a TBI each year in the US, primarily due to falls and car crashes. TBI is also referred to as the ‘signature wound’ of the conflicts in Iraq and Afghanistan, where TBI accounts for 22% of casualties overall and 59% of blast-related injuries.
“The data suggest that TBI in older veterans may predispose them toward symptomatic dementia, and they raise concern about the potential long-term consequences of TBI in younger veterans,” she said.
The researchers suggest that there are several potential mechanisms by which TBI could increase dementia risk. TBI is associated with swelling of axons, which is accompanied by accumulation of proteins, including beta-amyloid.
According to the investigators, amyloid plaques similar to those found in the brains of patients with Alzheimer’s disease are present in up to 30% of TBI patients who do not survive their injuries, regardless of age. It is possible that these injuries result in the death of axons and neurons, even after a single TBI. Loss of axons and neurons could result in earlier manifestation of Alzheimer’s disease symptoms.
“Our findings raise hope that early treatment and rehabilitation following TBI may help prevent long-term consequences such as dementia,” Dr. Yaffe said. “They also suggest that older adults who experience a TBI should be monitored for signs of cognitive impairment following their injuries.”

Older adults with TBI should be monitored for signs of cognitive impairment, researchers advise.

PARIS—Older veterans with traumatic brain injury (TBI) have more than a twofold increased risk for dementia, according to research presented at the 2011 Alzheimer’s Association International Conference.
Kristine Yaffe, MD, Professor of Psychiatry, Neurology, and Epidemiology at the University of California, San Francisco and Director of the Memory Disorders Program at the San Francisco VA Medical center, and colleagues reviewed medical records of 281,540 US veterans. All participants were ages 55 or older and received care through the Veterans Health Administration, had at least one inpatient or outpatient visit from 1997 to 2000 and a follow-up between 2001 and 2007, and did not have a dementia diagnosis at the start of the study. The investigators searched the database for TBI and dementia diagnoses and investigated whether TBI of any type was associated with greater risk of dementia, while taking into account demographics and other medical conditions, including psychiatric disorders.
The risk of dementia was 15.3% in those with a TBI diagnosis, compared with 6.8% in those without a TBI diagnosis, the researchers reported. The adjusted hazard ratio for incident dementia in those with any TBI diagnosis was 2.3 for the risk of developing dementia over seven years and was significant for all TBI types. Approximately 2% of older veterans had a TBI diagnosis during the study period.
“This issue is important, because TBI is very common,” said Dr. Yaffe. “About 1.7 million people experience a TBI each year in the US, primarily due to falls and car crashes. TBI is also referred to as the ‘signature wound’ of the conflicts in Iraq and Afghanistan, where TBI accounts for 22% of casualties overall and 59% of blast-related injuries.
“The data suggest that TBI in older veterans may predispose them toward symptomatic dementia, and they raise concern about the potential long-term consequences of TBI in younger veterans,” she said.
The researchers suggest that there are several potential mechanisms by which TBI could increase dementia risk. TBI is associated with swelling of axons, which is accompanied by accumulation of proteins, including beta-amyloid.
According to the investigators, amyloid plaques similar to those found in the brains of patients with Alzheimer’s disease are present in up to 30% of TBI patients who do not survive their injuries, regardless of age. It is possible that these injuries result in the death of axons and neurons, even after a single TBI. Loss of axons and neurons could result in earlier manifestation of Alzheimer’s disease symptoms.
“Our findings raise hope that early treatment and rehabilitation following TBI may help prevent long-term consequences such as dementia,” Dr. Yaffe said. “They also suggest that older adults who experience a TBI should be monitored for signs of cognitive impairment following their injuries.”

Older adults with TBI should be monitored for signs of cognitive impairment, researchers advise.

PARIS—Older veterans with traumatic brain injury (TBI) have more than a twofold increased risk for dementia, according to research presented at the 2011 Alzheimer’s Association International Conference.
Kristine Yaffe, MD, Professor of Psychiatry, Neurology, and Epidemiology at the University of California, San Francisco and Director of the Memory Disorders Program at the San Francisco VA Medical center, and colleagues reviewed medical records of 281,540 US veterans. All participants were ages 55 or older and received care through the Veterans Health Administration, had at least one inpatient or outpatient visit from 1997 to 2000 and a follow-up between 2001 and 2007, and did not have a dementia diagnosis at the start of the study. The investigators searched the database for TBI and dementia diagnoses and investigated whether TBI of any type was associated with greater risk of dementia, while taking into account demographics and other medical conditions, including psychiatric disorders.
The risk of dementia was 15.3% in those with a TBI diagnosis, compared with 6.8% in those without a TBI diagnosis, the researchers reported. The adjusted hazard ratio for incident dementia in those with any TBI diagnosis was 2.3 for the risk of developing dementia over seven years and was significant for all TBI types. Approximately 2% of older veterans had a TBI diagnosis during the study period.
“This issue is important, because TBI is very common,” said Dr. Yaffe. “About 1.7 million people experience a TBI each year in the US, primarily due to falls and car crashes. TBI is also referred to as the ‘signature wound’ of the conflicts in Iraq and Afghanistan, where TBI accounts for 22% of casualties overall and 59% of blast-related injuries.
“The data suggest that TBI in older veterans may predispose them toward symptomatic dementia, and they raise concern about the potential long-term consequences of TBI in younger veterans,” she said.
The researchers suggest that there are several potential mechanisms by which TBI could increase dementia risk. TBI is associated with swelling of axons, which is accompanied by accumulation of proteins, including beta-amyloid.
According to the investigators, amyloid plaques similar to those found in the brains of patients with Alzheimer’s disease are present in up to 30% of TBI patients who do not survive their injuries, regardless of age. It is possible that these injuries result in the death of axons and neurons, even after a single TBI. Loss of axons and neurons could result in earlier manifestation of Alzheimer’s disease symptoms.
“Our findings raise hope that early treatment and rehabilitation following TBI may help prevent long-term consequences such as dementia,” Dr. Yaffe said. “They also suggest that older adults who experience a TBI should be monitored for signs of cognitive impairment following their injuries.”

A tool used for evaluating mild traumatic brain injury in service members may not be sensitive enough in the absence of further evaluation, according to study results.

HONOLULU—One of the Department of Defense’s (DoD’s) tests for evaluating traumatic brain injury (TBI) in service members may be insufficiently sensitive when used by itself, according to study results presented at the 63rd Annual Meeting of the American Academy of Neurology.
“The bottom line is that there is no one test for determining who is able or unable to return to the fight after a concussion that is reliable, free of confounding factors, reproducible, and possible for a combat medic to administer on the battlefield,” COL Richard Young, MD, of the University of Connecticut School of Medicine, told Neurology Reviews.
Dr. Young and Kevin Scott, MD, Associate Professor of Neurology at the Pennsylvania State College of Medicine in Hershey, compared the effects of combat TBI and noncombat TBI by evaluating a cohort of 42 service members, 28 of whom had combat TBI exposure and 14 of whom had noncombat TBI exposure. One of the tests used in their evaluations was the Military Acute Concussion Evaluation (MACE), which the DoD has used as a TBI screening tool since 2006. The researchers found that while there was a trend toward worse MACE scores in patients with combat TBI compared with noncombat TBI (19.7 vs 27.4), the difference did not meet statistical significance.
These results suggest that “the MACE, in isolation, is likely not sensitive enough to stratify patients or differentiate between the two [types of injury] for the purposes of management in the setting of a forward unit without easy access to higher-level medical care (eg, neurologists),” said Dr. Scott. “It provides useful data for any individual soldier to follow their recovery or lack thereof, but is best used in combination” with further evaluations. He noted, however, that the study sample was not large enough to provide definitive statistical conclusions.
Challenges of Military Evaluations
The DoD’s evidence-based guidelines for evaluating nonpenetrating TBI, which has been called the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom, are still a “work in progress,” said Dr. Scott. “With the focus on these types of injury, today’s soldiers have significantly better protection and better medical care that emphasizes early assessment and prevention of cumulative damage. Outcome measures often take time to be developed, and I think there will be a lot learned with respect to the value of medications, counseling, rehabilitation, and timing of imaging.”
At present, the best method of determining when a service member can return to duty is a careful neurologic examination, Dr. Young added. “The neurologic evaluation can best evaluate the nature of the injury, the results of cognitive testing, the service member’s degree of psychological stress, the MACE results, the prior educational status, and imaging results (if available). However, there is often no neurologist in theatre, or, only at one base. To obtain a neurologic assessment often necessitates sending the service member to Landstuhl Regional Medical Center [in Germany], with a turnaround time of two to three weeks.
“I know of no research regarding when soldiers are returned to duty,” he continued. “Current doctrine is to remove soldiers from action after a head injury.
Return to duty is a commander’s decision (the physician makes a recommendation to the commander; the commander decides) and is often dictated by the operational needs of the mission. In addition, some soldiers return to duty immediately without seeking medical attention, much as high school football players ‘shake off’ a TBI and return to play without informing their coaches of a concussion.”
Both MACE and the Automated Neuropsychological Assessment Metrics, a computerized assessment that the DoD uses to evaluate TBI, lack specificity and sensitivity, according to Dr. Young. He added that there are additional problems with using these assessments to evaluate deployed soldiers.
“There is a paucity of information about the MACE and its usefulness in the field,” said Dr. Young. “However, the MACE is identical to the Acute Sports Concussion Examination (ASCE), which is used by trainers to evaluate football players and others engaging in contact sports. Scores on the ASCE decline significantly following a concussion, but they may return to baseline within 24 hours. One of the major problems with mild TBI in Iraq is that it may be days before the service member can seek medical attention. By that time, the MACE results may be less reliable.”
Dr. Young said that his experience with service members deployed in Iraq suggests that preexisting cognitive issues may hinder the accuracy of TBI evaluations. “Several soldiers at the Joint Base Balad TBI clinic performed particularly poorly on the mathematics section of the ANAM or the entire test,” he said. “The psychologist at the TBI clinic referred these patients to me for neurologic evaluation. He and I agreed that the soldiers’ poor performance on the ANAM was due to pre-existing cognitive issues—in all likelihood, unrelated to their head injury.”
He added that ANAM is unavailable in Iraq outside of Joint Base Balad and that many service members do not have a baseline ANAM with which a post-TBI ANAM can be compared.
Combat TBI Versus Noncombat TBI
Drs. Young and Scott found some differences between injured service members depending on whether they had combat or noncombat TBI. All of the combat injuries were caused by improvised explosive devices, while the causes of noncombat injuries included falls, motor vehicle accidents, and sports.
Patients with combat TBI were significantly more likely than those with noncombat TBI to experience memory loss (44% vs 13%) and tinnitus (44% vs 6%). Headache, the most common symptom both in combat TBI and in noncombat TBI, was more common in the former injury (70% vs 50%), though the difference was not statistically significant. Patients with combat TBI also showed a nonsignificant trend toward concentration problems (43% vs 14%).
These differences may have been due to a greater severity of injury with combat TBI and to a greater lapse of time before evaluation in noncombat TBI, said Dr. Young. “It is possible that this lapse of time allowed the headache/concentration problems in the noncombat TBI to begin to resolve,” he said. He added that further research is needed to determine whether the circumstances surrounding a TBI play an important role in the injury, which could result in different outcomes for similar injuries depending on whether they occurred on the battlefield.

A tool used for evaluating mild traumatic brain injury in service members may not be sensitive enough in the absence of further evaluation, according to study results.

HONOLULU—One of the Department of Defense’s (DoD’s) tests for evaluating traumatic brain injury (TBI) in service members may be insufficiently sensitive when used by itself, according to study results presented at the 63rd Annual Meeting of the American Academy of Neurology.
“The bottom line is that there is no one test for determining who is able or unable to return to the fight after a concussion that is reliable, free of confounding factors, reproducible, and possible for a combat medic to administer on the battlefield,” COL Richard Young, MD, of the University of Connecticut School of Medicine, told Neurology Reviews.
Dr. Young and Kevin Scott, MD, Associate Professor of Neurology at the Pennsylvania State College of Medicine in Hershey, compared the effects of combat TBI and noncombat TBI by evaluating a cohort of 42 service members, 28 of whom had combat TBI exposure and 14 of whom had noncombat TBI exposure. One of the tests used in their evaluations was the Military Acute Concussion Evaluation (MACE), which the DoD has used as a TBI screening tool since 2006. The researchers found that while there was a trend toward worse MACE scores in patients with combat TBI compared with noncombat TBI (19.7 vs 27.4), the difference did not meet statistical significance.
These results suggest that “the MACE, in isolation, is likely not sensitive enough to stratify patients or differentiate between the two [types of injury] for the purposes of management in the setting of a forward unit without easy access to higher-level medical care (eg, neurologists),” said Dr. Scott. “It provides useful data for any individual soldier to follow their recovery or lack thereof, but is best used in combination” with further evaluations. He noted, however, that the study sample was not large enough to provide definitive statistical conclusions.
Challenges of Military Evaluations
The DoD’s evidence-based guidelines for evaluating nonpenetrating TBI, which has been called the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom, are still a “work in progress,” said Dr. Scott. “With the focus on these types of injury, today’s soldiers have significantly better protection and better medical care that emphasizes early assessment and prevention of cumulative damage. Outcome measures often take time to be developed, and I think there will be a lot learned with respect to the value of medications, counseling, rehabilitation, and timing of imaging.”
At present, the best method of determining when a service member can return to duty is a careful neurologic examination, Dr. Young added. “The neurologic evaluation can best evaluate the nature of the injury, the results of cognitive testing, the service member’s degree of psychological stress, the MACE results, the prior educational status, and imaging results (if available). However, there is often no neurologist in theatre, or, only at one base. To obtain a neurologic assessment often necessitates sending the service member to Landstuhl Regional Medical Center [in Germany], with a turnaround time of two to three weeks.
“I know of no research regarding when soldiers are returned to duty,” he continued. “Current doctrine is to remove soldiers from action after a head injury.
Return to duty is a commander’s decision (the physician makes a recommendation to the commander; the commander decides) and is often dictated by the operational needs of the mission. In addition, some soldiers return to duty immediately without seeking medical attention, much as high school football players ‘shake off’ a TBI and return to play without informing their coaches of a concussion.”
Both MACE and the Automated Neuropsychological Assessment Metrics, a computerized assessment that the DoD uses to evaluate TBI, lack specificity and sensitivity, according to Dr. Young. He added that there are additional problems with using these assessments to evaluate deployed soldiers.
“There is a paucity of information about the MACE and its usefulness in the field,” said Dr. Young. “However, the MACE is identical to the Acute Sports Concussion Examination (ASCE), which is used by trainers to evaluate football players and others engaging in contact sports. Scores on the ASCE decline significantly following a concussion, but they may return to baseline within 24 hours. One of the major problems with mild TBI in Iraq is that it may be days before the service member can seek medical attention. By that time, the MACE results may be less reliable.”
Dr. Young said that his experience with service members deployed in Iraq suggests that preexisting cognitive issues may hinder the accuracy of TBI evaluations. “Several soldiers at the Joint Base Balad TBI clinic performed particularly poorly on the mathematics section of the ANAM or the entire test,” he said. “The psychologist at the TBI clinic referred these patients to me for neurologic evaluation. He and I agreed that the soldiers’ poor performance on the ANAM was due to pre-existing cognitive issues—in all likelihood, unrelated to their head injury.”
He added that ANAM is unavailable in Iraq outside of Joint Base Balad and that many service members do not have a baseline ANAM with which a post-TBI ANAM can be compared.
Combat TBI Versus Noncombat TBI
Drs. Young and Scott found some differences between injured service members depending on whether they had combat or noncombat TBI. All of the combat injuries were caused by improvised explosive devices, while the causes of noncombat injuries included falls, motor vehicle accidents, and sports.
Patients with combat TBI were significantly more likely than those with noncombat TBI to experience memory loss (44% vs 13%) and tinnitus (44% vs 6%). Headache, the most common symptom both in combat TBI and in noncombat TBI, was more common in the former injury (70% vs 50%), though the difference was not statistically significant. Patients with combat TBI also showed a nonsignificant trend toward concentration problems (43% vs 14%).
These differences may have been due to a greater severity of injury with combat TBI and to a greater lapse of time before evaluation in noncombat TBI, said Dr. Young. “It is possible that this lapse of time allowed the headache/concentration problems in the noncombat TBI to begin to resolve,” he said. He added that further research is needed to determine whether the circumstances surrounding a TBI play an important role in the injury, which could result in different outcomes for similar injuries depending on whether they occurred on the battlefield.

A tool used for evaluating mild traumatic brain injury in service members may not be sensitive enough in the absence of further evaluation, according to study results.

HONOLULU—One of the Department of Defense’s (DoD’s) tests for evaluating traumatic brain injury (TBI) in service members may be insufficiently sensitive when used by itself, according to study results presented at the 63rd Annual Meeting of the American Academy of Neurology.
“The bottom line is that there is no one test for determining who is able or unable to return to the fight after a concussion that is reliable, free of confounding factors, reproducible, and possible for a combat medic to administer on the battlefield,” COL Richard Young, MD, of the University of Connecticut School of Medicine, told Neurology Reviews.
Dr. Young and Kevin Scott, MD, Associate Professor of Neurology at the Pennsylvania State College of Medicine in Hershey, compared the effects of combat TBI and noncombat TBI by evaluating a cohort of 42 service members, 28 of whom had combat TBI exposure and 14 of whom had noncombat TBI exposure. One of the tests used in their evaluations was the Military Acute Concussion Evaluation (MACE), which the DoD has used as a TBI screening tool since 2006. The researchers found that while there was a trend toward worse MACE scores in patients with combat TBI compared with noncombat TBI (19.7 vs 27.4), the difference did not meet statistical significance.
These results suggest that “the MACE, in isolation, is likely not sensitive enough to stratify patients or differentiate between the two [types of injury] for the purposes of management in the setting of a forward unit without easy access to higher-level medical care (eg, neurologists),” said Dr. Scott. “It provides useful data for any individual soldier to follow their recovery or lack thereof, but is best used in combination” with further evaluations. He noted, however, that the study sample was not large enough to provide definitive statistical conclusions.
Challenges of Military Evaluations
The DoD’s evidence-based guidelines for evaluating nonpenetrating TBI, which has been called the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom, are still a “work in progress,” said Dr. Scott. “With the focus on these types of injury, today’s soldiers have significantly better protection and better medical care that emphasizes early assessment and prevention of cumulative damage. Outcome measures often take time to be developed, and I think there will be a lot learned with respect to the value of medications, counseling, rehabilitation, and timing of imaging.”
At present, the best method of determining when a service member can return to duty is a careful neurologic examination, Dr. Young added. “The neurologic evaluation can best evaluate the nature of the injury, the results of cognitive testing, the service member’s degree of psychological stress, the MACE results, the prior educational status, and imaging results (if available). However, there is often no neurologist in theatre, or, only at one base. To obtain a neurologic assessment often necessitates sending the service member to Landstuhl Regional Medical Center [in Germany], with a turnaround time of two to three weeks.
“I know of no research regarding when soldiers are returned to duty,” he continued. “Current doctrine is to remove soldiers from action after a head injury.
Return to duty is a commander’s decision (the physician makes a recommendation to the commander; the commander decides) and is often dictated by the operational needs of the mission. In addition, some soldiers return to duty immediately without seeking medical attention, much as high school football players ‘shake off’ a TBI and return to play without informing their coaches of a concussion.”
Both MACE and the Automated Neuropsychological Assessment Metrics, a computerized assessment that the DoD uses to evaluate TBI, lack specificity and sensitivity, according to Dr. Young. He added that there are additional problems with using these assessments to evaluate deployed soldiers.
“There is a paucity of information about the MACE and its usefulness in the field,” said Dr. Young. “However, the MACE is identical to the Acute Sports Concussion Examination (ASCE), which is used by trainers to evaluate football players and others engaging in contact sports. Scores on the ASCE decline significantly following a concussion, but they may return to baseline within 24 hours. One of the major problems with mild TBI in Iraq is that it may be days before the service member can seek medical attention. By that time, the MACE results may be less reliable.”
Dr. Young said that his experience with service members deployed in Iraq suggests that preexisting cognitive issues may hinder the accuracy of TBI evaluations. “Several soldiers at the Joint Base Balad TBI clinic performed particularly poorly on the mathematics section of the ANAM or the entire test,” he said. “The psychologist at the TBI clinic referred these patients to me for neurologic evaluation. He and I agreed that the soldiers’ poor performance on the ANAM was due to pre-existing cognitive issues—in all likelihood, unrelated to their head injury.”
He added that ANAM is unavailable in Iraq outside of Joint Base Balad and that many service members do not have a baseline ANAM with which a post-TBI ANAM can be compared.
Combat TBI Versus Noncombat TBI
Drs. Young and Scott found some differences between injured service members depending on whether they had combat or noncombat TBI. All of the combat injuries were caused by improvised explosive devices, while the causes of noncombat injuries included falls, motor vehicle accidents, and sports.
Patients with combat TBI were significantly more likely than those with noncombat TBI to experience memory loss (44% vs 13%) and tinnitus (44% vs 6%). Headache, the most common symptom both in combat TBI and in noncombat TBI, was more common in the former injury (70% vs 50%), though the difference was not statistically significant. Patients with combat TBI also showed a nonsignificant trend toward concentration problems (43% vs 14%).
These differences may have been due to a greater severity of injury with combat TBI and to a greater lapse of time before evaluation in noncombat TBI, said Dr. Young. “It is possible that this lapse of time allowed the headache/concentration problems in the noncombat TBI to begin to resolve,” he said. He added that further research is needed to determine whether the circumstances surrounding a TBI play an important role in the injury, which could result in different outcomes for similar injuries depending on whether they occurred on the battlefield.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

Nearly two-thirds of patients experience metabolic crisis after traumatic brain injury, even after receiving successful standard fluid resuscitation treatment.

SAN DIEGO—Early metabolic crisis is common after traumatic brain injury and may be more common if certain physiologic factors are present, researchers reported at the Society of Critical Care Medicine’s 40th Critical Care Congress.

Nathan R. Stein, a student from the Department of Bioengineering at the University of California, Los Angeles; David L. McArthur, PhD, from the Department of Neurosurgery; and Paul Vespa, MD, FCCM, from the Departments of Neurology and Neurosurgery at UCLA, performed cerebral microdialysis of normal-appearing white matter in 41 patients (33 men) with severe traumatic brain injury. They collected data for the first week after injury; in total, 5,723 hourly samples were analyzed.

Within the first 48 hours after injury, 66.85% of the participants had experienced metabolic crisis, defined as glucose concentrations less than 0.8 mmol/L and a lactate/pyruvate ratio higher than 40.

Standard Resuscitation Does Not Prevent Metabolic Crisis
Patients underwent standard fluid resuscitation protocol using saline and norepinephrine titrations for two hours to maintain central venous pressure and mean arterial pressure at safe levels. Although 93% of patients received successful resuscitation, a majority of patients experienced metabolic crisis for an average duration of 19.54 hours during the initial 48 hours after the injury.

“Our research suggests that successful fluid resuscitation in the first two days after a traumatic brain injury does not reduce the incidence of metabolic crisis,” Mr. Stein told Neurology Reviews.

Low brain glucose occurred in 92.68% of patients at an average of 82.79% of the total time of metabolic crisis, while elevated lactate/pyruvate ratio occurred in 70.73% of patients at an average of 43.95% of the time.

Triggers for Metabolic Crisis
Mr. Stein’s group also identified certain physiologic factors that may increase the risk for, and duration of, metabolic crisis, including intracranial pressure more than 20 mm Hg, blood glucose lower than 110 mg/dL, and fever higher than 38°C. Treating one or more of these conditions helped correct metabolic crisis.

“Despite being able to correct the metabolic crisis in more than 60% of patients over the next four days, the initial trauma’s deleterious effects on brain metabolism seem to persist for the first few days following injury,” Mr. Stein added.

“We will now turn to looking at how early treatment of specific physiologic triggers … within the first few hours postinjury may reduce the duration or severity of the initial metabolic crisis, and see if treatments, such as higher blood glucose goals or therapeutic hypothermia, help correct the metabolic crisis sooner,” he concluded.

Nearly two-thirds of patients experience metabolic crisis after traumatic brain injury, even after receiving successful standard fluid resuscitation treatment.

SAN DIEGO—Early metabolic crisis is common after traumatic brain injury and may be more common if certain physiologic factors are present, researchers reported at the Society of Critical Care Medicine’s 40th Critical Care Congress.

Nathan R. Stein, a student from the Department of Bioengineering at the University of California, Los Angeles; David L. McArthur, PhD, from the Department of Neurosurgery; and Paul Vespa, MD, FCCM, from the Departments of Neurology and Neurosurgery at UCLA, performed cerebral microdialysis of normal-appearing white matter in 41 patients (33 men) with severe traumatic brain injury. They collected data for the first week after injury; in total, 5,723 hourly samples were analyzed.

Within the first 48 hours after injury, 66.85% of the participants had experienced metabolic crisis, defined as glucose concentrations less than 0.8 mmol/L and a lactate/pyruvate ratio higher than 40.

Standard Resuscitation Does Not Prevent Metabolic Crisis
Patients underwent standard fluid resuscitation protocol using saline and norepinephrine titrations for two hours to maintain central venous pressure and mean arterial pressure at safe levels. Although 93% of patients received successful resuscitation, a majority of patients experienced metabolic crisis for an average duration of 19.54 hours during the initial 48 hours after the injury.

“Our research suggests that successful fluid resuscitation in the first two days after a traumatic brain injury does not reduce the incidence of metabolic crisis,” Mr. Stein told Neurology Reviews.

Low brain glucose occurred in 92.68% of patients at an average of 82.79% of the total time of metabolic crisis, while elevated lactate/pyruvate ratio occurred in 70.73% of patients at an average of 43.95% of the time.

Triggers for Metabolic Crisis
Mr. Stein’s group also identified certain physiologic factors that may increase the risk for, and duration of, metabolic crisis, including intracranial pressure more than 20 mm Hg, blood glucose lower than 110 mg/dL, and fever higher than 38°C. Treating one or more of these conditions helped correct metabolic crisis.

“Despite being able to correct the metabolic crisis in more than 60% of patients over the next four days, the initial trauma’s deleterious effects on brain metabolism seem to persist for the first few days following injury,” Mr. Stein added.

“We will now turn to looking at how early treatment of specific physiologic triggers … within the first few hours postinjury may reduce the duration or severity of the initial metabolic crisis, and see if treatments, such as higher blood glucose goals or therapeutic hypothermia, help correct the metabolic crisis sooner,” he concluded.

Nearly two-thirds of patients experience metabolic crisis after traumatic brain injury, even after receiving successful standard fluid resuscitation treatment.

SAN DIEGO—Early metabolic crisis is common after traumatic brain injury and may be more common if certain physiologic factors are present, researchers reported at the Society of Critical Care Medicine’s 40th Critical Care Congress.

Nathan R. Stein, a student from the Department of Bioengineering at the University of California, Los Angeles; David L. McArthur, PhD, from the Department of Neurosurgery; and Paul Vespa, MD, FCCM, from the Departments of Neurology and Neurosurgery at UCLA, performed cerebral microdialysis of normal-appearing white matter in 41 patients (33 men) with severe traumatic brain injury. They collected data for the first week after injury; in total, 5,723 hourly samples were analyzed.

Within the first 48 hours after injury, 66.85% of the participants had experienced metabolic crisis, defined as glucose concentrations less than 0.8 mmol/L and a lactate/pyruvate ratio higher than 40.

Standard Resuscitation Does Not Prevent Metabolic Crisis
Patients underwent standard fluid resuscitation protocol using saline and norepinephrine titrations for two hours to maintain central venous pressure and mean arterial pressure at safe levels. Although 93% of patients received successful resuscitation, a majority of patients experienced metabolic crisis for an average duration of 19.54 hours during the initial 48 hours after the injury.

“Our research suggests that successful fluid resuscitation in the first two days after a traumatic brain injury does not reduce the incidence of metabolic crisis,” Mr. Stein told Neurology Reviews.

Low brain glucose occurred in 92.68% of patients at an average of 82.79% of the total time of metabolic crisis, while elevated lactate/pyruvate ratio occurred in 70.73% of patients at an average of 43.95% of the time.

Triggers for Metabolic Crisis
Mr. Stein’s group also identified certain physiologic factors that may increase the risk for, and duration of, metabolic crisis, including intracranial pressure more than 20 mm Hg, blood glucose lower than 110 mg/dL, and fever higher than 38°C. Treating one or more of these conditions helped correct metabolic crisis.

“Despite being able to correct the metabolic crisis in more than 60% of patients over the next four days, the initial trauma’s deleterious effects on brain metabolism seem to persist for the first few days following injury,” Mr. Stein added.

“We will now turn to looking at how early treatment of specific physiologic triggers … within the first few hours postinjury may reduce the duration or severity of the initial metabolic crisis, and see if treatments, such as higher blood glucose goals or therapeutic hypothermia, help correct the metabolic crisis sooner,” he concluded.

SAN ANTONIO—Recent Department of Defense (DoD) studies indicate that exposure to varying intensities of explosive blast is associated with varying levels of traumatic brain injury (TBI), according to research presented at the 64th Annual Meeting of the American Epilepsy Society.

Colonel Geoffrey Ling, MD, PhD, a Program Manager at the DoD’s Defense Advanced Research Projects Agency (DARPA) and Chairman of the Neurology Department and Director of the Division of Critical Care Medicine at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, made one of several presentations on how the DoD and the Department of Veterans Affairs (VA) have responded to TBI from blast injury. This injury has been called the signature wound of Operation Enduring Freedom and Operation Iraqi Freedom. Other speakers discussed the DoD’s new policies regarding the evaluation and management of mild TBI and the VA’s efforts to cope with an expected increase in TBI-related epilepsy among veterans.

Different Blasts, Different Injuries

DARPA has been working on a large research program to explore the mechanisms of blast injury for the last year and a half, said Dr. Ling. The program’s animal model arm exposed pigs, rats, and primates to very low-level bomb explosions and used such measures as gait analyses and angiograms to determine the blasts’ effects. Its clinical arm studied Marines who were exposed to bomb explosions as part of their training regimen and who were given neurobehavioral testing, fMRIs, and sleep studies.

“We have learned that there are three levels of TBI associated with blast in these preclinical models,” Dr. Ling said. “The subjects can actually withstand exposure if the blast is about 20 pounds per square inch (PPI). At about 20 to 40 PPI, however, you start seeing neuroinflammatory changes that can persist for days or weeks, particularly at the higher levels of inflammation. They resolve over time, but they can lead to some neurocognitive degeneration at the higher levels and are associated with increasing transient neurologic deficits—primarily, gait and early cognitive changes. Moderate TBI occurs at roughly 50 to 75 PSI and is associated with functional deficits that are much more persistent. And with severe TBI, you see widespread process breakdown of large amounts of tissue and vasospasm.”

A More Proactive Approach

In addition to its ongoing research efforts, the DoD recently has adopted a much more proactive approach to the evaluation and management of concussion, said Commander Jack W. Tsao, MD, DPhil, FAAN, Director of the Traumatic Brain Injury Programs for the US Navy Bureau of Medicine and Surgery and Associate Professor of Neurology and Neuroscience at Uniformed Services University of the Health Sciences.

“Prior to June 21, 2010, the DoD expected personnel to come forward to their commander and say, ‘Hey, I think I may have a concussion. I don’t think I can fight,’” he said. “Well, service members didn’t come forward. Or their attitude was, ‘Hey, it probably wasn’t a concussion. I’m going to tough it out.’’”

In contrast, the new policy is a “culture shift” and requires service members who experience certain events that might have caused a concussion to undergo a medical evaluation, a minimum rest period, and medical clearance before returning to duty. The DoD’s new concussion examination is based on the one used by the National Football League (Standard Assessment of Concussion), takes less than 10 minutes to perform, and can be administered by non-neurologists.

When a service member is diagnosed with concussion, providers implement a treatment plan that usually consists of rest, Dr. Tsao said. Before the service member can return to duty, he or she must undergo exertional testing to determine whether exercise leads to cognitive impairment, headaches, or visual disturbances. In addition, service members who experience a loss of consciousness after a head injury have to go to a combat hospital, where they generally receive a CAT scan.

“The DoD’s algorithms further define what happens if you have more than one concussion,” Dr. Tsao added. “If you have a second concussion within 12 months, resolution of clinical symptoms followed by additional rest days is required. If you have a third concussion, you are not only restricted from sports and other activities where you may be reconcussed, but you also receive a comprehensive evaluation before you’re allowed to return to duty. The comprehensive evaluation is an examination by a neurologist and includes neuropsychologic testing and functional testing. There are three possible outcomes—you are returned to full duty, you return to duty with operational restrictions, or they send you home.”

Veterans and Posttraumatic Epilepsy

The VA is expecting a huge wave of posttraumatic epilepsy among its patients, according to Karen L. Parko, MD, Director of the Epilepsy Center at the San Francisco VA Medical Center, Chair of the National VA Epilepsy Centers of Excellence in San Francisco, and Associate Professor of Neurology at the University of California at San Francisco.

“There are guesses and estimates, because we now know there were 190,000 TBIs in service members since fiscal year 2000, but how many of those are going to eventually develop epilepsy we don’t know,” said Dr. Parko. “There’s a mathematical formula that’s used in the military to predict epilepsy from TBI, but no one thinks that formula is going to be applicable in this case, because the injuries are usually mild and the injury type is usually blast.” She added that while 50% of service members with penetrating missile TBI can be expected to develop epilepsy, only 12% of TBIs in service members fall into this category.

In 2008, Congress moved to prepare for the expected increase by mandating the establishment of the VA Epilepsy Centers of Excellence Network. At present, 15 VA Epilepsy Centers of Excellence have been geographically set up based on regional veteran populations. The centers have surgical capability and are grouped into four regions, each of which has its own polytrauma center.

“The network’s goal is to provide a high quality of care to veterans across the United States,” Dr. Parko said. “When you reintegrate into civilian life, no matter where you decide to live, you should be able to receive very high-level epilepsy care, up to and including surgery.”

—Jack Baney

SAN ANTONIO—Recent Department of Defense (DoD) studies indicate that exposure to varying intensities of explosive blast is associated with varying levels of traumatic brain injury (TBI), according to research presented at the 64th Annual Meeting of the American Epilepsy Society.

Colonel Geoffrey Ling, MD, PhD, a Program Manager at the DoD’s Defense Advanced Research Projects Agency (DARPA) and Chairman of the Neurology Department and Director of the Division of Critical Care Medicine at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, made one of several presentations on how the DoD and the Department of Veterans Affairs (VA) have responded to TBI from blast injury. This injury has been called the signature wound of Operation Enduring Freedom and Operation Iraqi Freedom. Other speakers discussed the DoD’s new policies regarding the evaluation and management of mild TBI and the VA’s efforts to cope with an expected increase in TBI-related epilepsy among veterans.

Different Blasts, Different Injuries

DARPA has been working on a large research program to explore the mechanisms of blast injury for the last year and a half, said Dr. Ling. The program’s animal model arm exposed pigs, rats, and primates to very low-level bomb explosions and used such measures as gait analyses and angiograms to determine the blasts’ effects. Its clinical arm studied Marines who were exposed to bomb explosions as part of their training regimen and who were given neurobehavioral testing, fMRIs, and sleep studies.

“We have learned that there are three levels of TBI associated with blast in these preclinical models,” Dr. Ling said. “The subjects can actually withstand exposure if the blast is about 20 pounds per square inch (PPI). At about 20 to 40 PPI, however, you start seeing neuroinflammatory changes that can persist for days or weeks, particularly at the higher levels of inflammation. They resolve over time, but they can lead to some neurocognitive degeneration at the higher levels and are associated with increasing transient neurologic deficits—primarily, gait and early cognitive changes. Moderate TBI occurs at roughly 50 to 75 PSI and is associated with functional deficits that are much more persistent. And with severe TBI, you see widespread process breakdown of large amounts of tissue and vasospasm.”

A More Proactive Approach

In addition to its ongoing research efforts, the DoD recently has adopted a much more proactive approach to the evaluation and management of concussion, said Commander Jack W. Tsao, MD, DPhil, FAAN, Director of the Traumatic Brain Injury Programs for the US Navy Bureau of Medicine and Surgery and Associate Professor of Neurology and Neuroscience at Uniformed Services University of the Health Sciences.

“Prior to June 21, 2010, the DoD expected personnel to come forward to their commander and say, ‘Hey, I think I may have a concussion. I don’t think I can fight,’” he said. “Well, service members didn’t come forward. Or their attitude was, ‘Hey, it probably wasn’t a concussion. I’m going to tough it out.’’”

In contrast, the new policy is a “culture shift” and requires service members who experience certain events that might have caused a concussion to undergo a medical evaluation, a minimum rest period, and medical clearance before returning to duty. The DoD’s new concussion examination is based on the one used by the National Football League (Standard Assessment of Concussion), takes less than 10 minutes to perform, and can be administered by non-neurologists.

When a service member is diagnosed with concussion, providers implement a treatment plan that usually consists of rest, Dr. Tsao said. Before the service member can return to duty, he or she must undergo exertional testing to determine whether exercise leads to cognitive impairment, headaches, or visual disturbances. In addition, service members who experience a loss of consciousness after a head injury have to go to a combat hospital, where they generally receive a CAT scan.

“The DoD’s algorithms further define what happens if you have more than one concussion,” Dr. Tsao added. “If you have a second concussion within 12 months, resolution of clinical symptoms followed by additional rest days is required. If you have a third concussion, you are not only restricted from sports and other activities where you may be reconcussed, but you also receive a comprehensive evaluation before you’re allowed to return to duty. The comprehensive evaluation is an examination by a neurologist and includes neuropsychologic testing and functional testing. There are three possible outcomes—you are returned to full duty, you return to duty with operational restrictions, or they send you home.”

Veterans and Posttraumatic Epilepsy

The VA is expecting a huge wave of posttraumatic epilepsy among its patients, according to Karen L. Parko, MD, Director of the Epilepsy Center at the San Francisco VA Medical Center, Chair of the National VA Epilepsy Centers of Excellence in San Francisco, and Associate Professor of Neurology at the University of California at San Francisco.

“There are guesses and estimates, because we now know there were 190,000 TBIs in service members since fiscal year 2000, but how many of those are going to eventually develop epilepsy we don’t know,” said Dr. Parko. “There’s a mathematical formula that’s used in the military to predict epilepsy from TBI, but no one thinks that formula is going to be applicable in this case, because the injuries are usually mild and the injury type is usually blast.” She added that while 50% of service members with penetrating missile TBI can be expected to develop epilepsy, only 12% of TBIs in service members fall into this category.

In 2008, Congress moved to prepare for the expected increase by mandating the establishment of the VA Epilepsy Centers of Excellence Network. At present, 15 VA Epilepsy Centers of Excellence have been geographically set up based on regional veteran populations. The centers have surgical capability and are grouped into four regions, each of which has its own polytrauma center.

“The network’s goal is to provide a high quality of care to veterans across the United States,” Dr. Parko said. “When you reintegrate into civilian life, no matter where you decide to live, you should be able to receive very high-level epilepsy care, up to and including surgery.”

—Jack Baney

SAN ANTONIO—Recent Department of Defense (DoD) studies indicate that exposure to varying intensities of explosive blast is associated with varying levels of traumatic brain injury (TBI), according to research presented at the 64th Annual Meeting of the American Epilepsy Society.

Colonel Geoffrey Ling, MD, PhD, a Program Manager at the DoD’s Defense Advanced Research Projects Agency (DARPA) and Chairman of the Neurology Department and Director of the Division of Critical Care Medicine at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, made one of several presentations on how the DoD and the Department of Veterans Affairs (VA) have responded to TBI from blast injury. This injury has been called the signature wound of Operation Enduring Freedom and Operation Iraqi Freedom. Other speakers discussed the DoD’s new policies regarding the evaluation and management of mild TBI and the VA’s efforts to cope with an expected increase in TBI-related epilepsy among veterans.

Different Blasts, Different Injuries

DARPA has been working on a large research program to explore the mechanisms of blast injury for the last year and a half, said Dr. Ling. The program’s animal model arm exposed pigs, rats, and primates to very low-level bomb explosions and used such measures as gait analyses and angiograms to determine the blasts’ effects. Its clinical arm studied Marines who were exposed to bomb explosions as part of their training regimen and who were given neurobehavioral testing, fMRIs, and sleep studies.

“We have learned that there are three levels of TBI associated with blast in these preclinical models,” Dr. Ling said. “The subjects can actually withstand exposure if the blast is about 20 pounds per square inch (PPI). At about 20 to 40 PPI, however, you start seeing neuroinflammatory changes that can persist for days or weeks, particularly at the higher levels of inflammation. They resolve over time, but they can lead to some neurocognitive degeneration at the higher levels and are associated with increasing transient neurologic deficits—primarily, gait and early cognitive changes. Moderate TBI occurs at roughly 50 to 75 PSI and is associated with functional deficits that are much more persistent. And with severe TBI, you see widespread process breakdown of large amounts of tissue and vasospasm.”

A More Proactive Approach

In addition to its ongoing research efforts, the DoD recently has adopted a much more proactive approach to the evaluation and management of concussion, said Commander Jack W. Tsao, MD, DPhil, FAAN, Director of the Traumatic Brain Injury Programs for the US Navy Bureau of Medicine and Surgery and Associate Professor of Neurology and Neuroscience at Uniformed Services University of the Health Sciences.

“Prior to June 21, 2010, the DoD expected personnel to come forward to their commander and say, ‘Hey, I think I may have a concussion. I don’t think I can fight,’” he said. “Well, service members didn’t come forward. Or their attitude was, ‘Hey, it probably wasn’t a concussion. I’m going to tough it out.’’”

In contrast, the new policy is a “culture shift” and requires service members who experience certain events that might have caused a concussion to undergo a medical evaluation, a minimum rest period, and medical clearance before returning to duty. The DoD’s new concussion examination is based on the one used by the National Football League (Standard Assessment of Concussion), takes less than 10 minutes to perform, and can be administered by non-neurologists.

When a service member is diagnosed with concussion, providers implement a treatment plan that usually consists of rest, Dr. Tsao said. Before the service member can return to duty, he or she must undergo exertional testing to determine whether exercise leads to cognitive impairment, headaches, or visual disturbances. In addition, service members who experience a loss of consciousness after a head injury have to go to a combat hospital, where they generally receive a CAT scan.

“The DoD’s algorithms further define what happens if you have more than one concussion,” Dr. Tsao added. “If you have a second concussion within 12 months, resolution of clinical symptoms followed by additional rest days is required. If you have a third concussion, you are not only restricted from sports and other activities where you may be reconcussed, but you also receive a comprehensive evaluation before you’re allowed to return to duty. The comprehensive evaluation is an examination by a neurologist and includes neuropsychologic testing and functional testing. There are three possible outcomes—you are returned to full duty, you return to duty with operational restrictions, or they send you home.”

Veterans and Posttraumatic Epilepsy

The VA is expecting a huge wave of posttraumatic epilepsy among its patients, according to Karen L. Parko, MD, Director of the Epilepsy Center at the San Francisco VA Medical Center, Chair of the National VA Epilepsy Centers of Excellence in San Francisco, and Associate Professor of Neurology at the University of California at San Francisco.

“There are guesses and estimates, because we now know there were 190,000 TBIs in service members since fiscal year 2000, but how many of those are going to eventually develop epilepsy we don’t know,” said Dr. Parko. “There’s a mathematical formula that’s used in the military to predict epilepsy from TBI, but no one thinks that formula is going to be applicable in this case, because the injuries are usually mild and the injury type is usually blast.” She added that while 50% of service members with penetrating missile TBI can be expected to develop epilepsy, only 12% of TBIs in service members fall into this category.

In 2008, Congress moved to prepare for the expected increase by mandating the establishment of the VA Epilepsy Centers of Excellence Network. At present, 15 VA Epilepsy Centers of Excellence have been geographically set up based on regional veteran populations. The centers have surgical capability and are grouped into four regions, each of which has its own polytrauma center.

“The network’s goal is to provide a high quality of care to veterans across the United States,” Dr. Parko said. “When you reintegrate into civilian life, no matter where you decide to live, you should be able to receive very high-level epilepsy care, up to and including surgery.”

—Jack Baney

Out-of-hospital administration of hypertonic fluids following severe traumatic brain injury (TBI) offers no additional benefits over normal saline in patients who are not in hypovolemic shock, according to a report in the October 6 JAMA. In a double-blind, randomized, placebo-controlled multi-center trial of patients 15 and older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less, subjects received a single 250-mL bolus of either hypertonic saline with dextran (7.5% saline/6% dextran 70), hypertonic saline (7.5% saline), or normal saline (0.9% saline). Six-month data, which were available for 1,087 of the 1,282 patients enrolled in the study, showed no difference in neurologic outcome and no significant differences in disability by treatment group. Survival rates at 28 days were 74.3% in the hypertonic/dextran group, 75.7% in the hypertonic group, and 75.1% with normal saline.

Out-of-hospital administration of hypertonic fluids following severe traumatic brain injury (TBI) offers no additional benefits over normal saline in patients who are not in hypovolemic shock, according to a report in the October 6 JAMA. In a double-blind, randomized, placebo-controlled multi-center trial of patients 15 and older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less, subjects received a single 250-mL bolus of either hypertonic saline with dextran (7.5% saline/6% dextran 70), hypertonic saline (7.5% saline), or normal saline (0.9% saline). Six-month data, which were available for 1,087 of the 1,282 patients enrolled in the study, showed no difference in neurologic outcome and no significant differences in disability by treatment group. Survival rates at 28 days were 74.3% in the hypertonic/dextran group, 75.7% in the hypertonic group, and 75.1% with normal saline.

Out-of-hospital administration of hypertonic fluids following severe traumatic brain injury (TBI) offers no additional benefits over normal saline in patients who are not in hypovolemic shock, according to a report in the October 6 JAMA. In a double-blind, randomized, placebo-controlled multi-center trial of patients 15 and older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less, subjects received a single 250-mL bolus of either hypertonic saline with dextran (7.5% saline/6% dextran 70), hypertonic saline (7.5% saline), or normal saline (0.9% saline). Six-month data, which were available for 1,087 of the 1,282 patients enrolled in the study, showed no difference in neurologic outcome and no significant differences in disability by treatment group. Survival rates at 28 days were 74.3% in the hypertonic/dextran group, 75.7% in the hypertonic group, and 75.1% with normal saline.

Stroke After Cardiac Surgery and Role of Carotid Stenosis
Combining carotid and cardiac procedures is neither necessary nor effective in reducing postoperative stroke in patients with asymptomatic carotid stenosis, according to a study in the September Archives of Neurology. Researchers found no direct causal relationship between significant carotid stenosis and postoperative stroke in patients who underwent cardiac operations.

Yuebing Li, MD, PhD, and colleagues at Lehigh Valley Hospital and Health Network in Allentown, Pennsylvania, reviewed data of 4,335 patients receiving nonurgent coronary artery bypass grafting (CABG) and/or aortic valve replacement between July 2001 and December 2006. Prior to surgery, 3,942 patients were evaluated for carotid stenosis using high-resolution sonography, 239 (6.1%) of whom were identified as having significant carotid stenosis.

A total of 76 patients (1.8%) had a clinically definitive stroke following surgery. Of those, 18 patients had significant carotid stenosis (23.7%). Although stroke was more common in individuals with carotid stenosis than in those without (7.5% vs 1.8%), 14 of the 18 strokes “occurred outside the territory of diseased carotid artery,” the study authors noted. Furthermore, the majority (76.3%) of postoperative strokes occurred in individuals without carotid disease, and 60% of the strokes were not confined to a single carotid artery.

“According to clinical data, in 94.7% of patients, stroke occurred without direct correlation to significant carotid stenosis,” the study authors wrote. “This study strongly suggests there is no direct causal relationship between postoperative stroke and severe carotid stenosis.”

In a related editorial, Louis R. Caplan, MD, Professor of Neurology at Harvard Medical School in Boston, commented on the neurologic complications of elective coronary artery surgery. “Processes that include checklists and time-outs during which the team reviews findings and strategies have led to reduced medical errors and improved outcomes,” Dr. Caplan wrote. “I suggest that patients and preoperative information should be reviewed before surgery by a team approach that includes a cardiologist who will observe the patients throughout their hospitalization and the cardiac surgeon who will perform the operation.”
Li Y, Walicki D, Mathiesen C, et al. Strokes after cardiac surgery and relationship to carotid stenosis. Arch Neurol. 2009;66(9):1091-1096.
Caplan LR. Translating what is known about neurological complications of coronary artery bypass graft surgery into action. Arch Neurol. 2009;66(9):1062-1064.

CT Scans in Children With Head Injury
Researchers have identified guidelines for accurately predicting children at very low risk of clinically important traumatic brain injuries (TBI), for whom CT scans should be avoided, as reported in the September 15 online Lancet. Nathan Kuppermann, MD, of the University of California-Davis School of Medicine in Sacramento, and colleagues analyzed 42,412 children with head trauma in 25 North American emergency departments, and derived and validated age-specific prediction rules for clinically important TBI. Application of these rules, the investigators believe, could limit CT use, protecting children from unnecessary radiation risks.

Dr. Kuppermann’s group, the Pediatric Emergency Care Applied Research Network, identified the following algorithms with 100% and 99.95% negative predictive value for clinically important TBI, respectively:

• For children younger than 2, normal mental status, no scalp hematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 seconds, nonsevere injury mechanism, no palpable skull fracture, and acting normally according to the parents.
• For children 2 and older, normal mental status, no loss of consciousness, no vomiting, nonsevere injury mechanism, no signs of basilar skull fracture, and no severe headache.

“Data to guide clinical decision making for children with head trauma are urgently needed because head trauma is common and CT use is increasing,” the study authors commented. “Children sustaining minor head trauma infrequently have TBI and rarely need neurosurgery. The small risk of clinically important TBI should be balanced against the risks of ionizing radiation of CTs.”

“Kuppermann and colleagues remind us that the rules are meant to inform clinical decision making, not to replace it,” Patricia C. Parkin, MD, and Jonathon L. Maguire, MD, of the Division of Pediatric Medicine and the Pediatric Outcomes Research Team at the Hospital for Sick Children in Toronto, wrote in an accompanying comment. “The next challenge for evidence-based medicine is knowledge translation. Decision aids might provide structured presentations of options and outcomes.”
Kuppermann N, Holmes JF, Dayan PS, et al. Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study. Lancet. 2009 Sep 14; [Epub ahead of print].
Parkin PC, Maguire JL. Clinically important head injuries after head trauma in children. Lancet. 2009 Sep 14; [Epub ahead of print].

Parent-of-Origin Effects in MS
The greater female-to-male ratio in patients with multiple sclerosis (MS) appears to be more strongly related to the mother, a study published in the August 25 Neurology reported. This maternal parent-of-origin effect, previously seen in studies of half-siblings and avuncular pairs, was found in offspring from a Caucasian mother and North American Aboriginal father.

S.V. Ramagopalan, DPhil, of the Wellcome Trust Centre for Human Genetics at the University of Oxford, UK, and colleagues examined 30,000 MS cases from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) and identified 58 individuals with one Caucasian parent and one North American Aboriginal parent. Of these, 27 had a Caucasian mother and 31 had a North American Aboriginal mother. Although the total number of affected offspring was similar in the two mating types studied, the sex ratio differed. Female-to-male sex ratio was 7:1 for patients with MS who had a Caucasian mother, compared with a 2:1 ratio for those with a Caucasian father.

“A parent-of-origin effect (maternal) has been repeatedly observed in MS, based on studies of half-siblings, sibships including dizygotic twins, a large extended Dutch pedigree, and avuncular pairs, as well as timing of birth effect,” the study authors noted. “The comparison of offspring from interracial matings is a novel method of analysis to look for parent of origin effects.

“The data from this study hint at an intriguing possibility that the observed female preponderance of MS could result from environmental factors acting upon mothers to differentially affect MS risk more in female than in male offspring,” the researchers pointed out.

In a related editorial, John W. Rose, MD, commented that this study “illustrated the continued potential of the CCPGSMS to address interesting questions related to the disease.… By evaluating a small set of MS patients with a Caucasian parent and a Native Aboriginal American parent, the investigators were able to assess parental effects on the disease,” he continued. “The susceptibility to disease is presumed to be predominantly introduced by the Caucasian parent based on previous investigations. In this admixture study, the results demonstrate a maternal effect which strongly influences the sex ratio of offspring affected by MS, linking these two classes of gender differences in MS.”
Ramagopalan SV, Yee IM, Dyment DA, et al. Parent-of-origin effect in multiple sclerosis: observations from interracial matings. Neurology. 2009;73(8):602-605.
Rose JW. Multiple sclerosis: evidence of maternal effects and an increasing incidence in women. Neurology. 2009;73(8):578-579.

Stroke After Cardiac Surgery and Role of Carotid Stenosis
Combining carotid and cardiac procedures is neither necessary nor effective in reducing postoperative stroke in patients with asymptomatic carotid stenosis, according to a study in the September Archives of Neurology. Researchers found no direct causal relationship between significant carotid stenosis and postoperative stroke in patients who underwent cardiac operations.

Yuebing Li, MD, PhD, and colleagues at Lehigh Valley Hospital and Health Network in Allentown, Pennsylvania, reviewed data of 4,335 patients receiving nonurgent coronary artery bypass grafting (CABG) and/or aortic valve replacement between July 2001 and December 2006. Prior to surgery, 3,942 patients were evaluated for carotid stenosis using high-resolution sonography, 239 (6.1%) of whom were identified as having significant carotid stenosis.

A total of 76 patients (1.8%) had a clinically definitive stroke following surgery. Of those, 18 patients had significant carotid stenosis (23.7%). Although stroke was more common in individuals with carotid stenosis than in those without (7.5% vs 1.8%), 14 of the 18 strokes “occurred outside the territory of diseased carotid artery,” the study authors noted. Furthermore, the majority (76.3%) of postoperative strokes occurred in individuals without carotid disease, and 60% of the strokes were not confined to a single carotid artery.

“According to clinical data, in 94.7% of patients, stroke occurred without direct correlation to significant carotid stenosis,” the study authors wrote. “This study strongly suggests there is no direct causal relationship between postoperative stroke and severe carotid stenosis.”

In a related editorial, Louis R. Caplan, MD, Professor of Neurology at Harvard Medical School in Boston, commented on the neurologic complications of elective coronary artery surgery. “Processes that include checklists and time-outs during which the team reviews findings and strategies have led to reduced medical errors and improved outcomes,” Dr. Caplan wrote. “I suggest that patients and preoperative information should be reviewed before surgery by a team approach that includes a cardiologist who will observe the patients throughout their hospitalization and the cardiac surgeon who will perform the operation.”
Li Y, Walicki D, Mathiesen C, et al. Strokes after cardiac surgery and relationship to carotid stenosis. Arch Neurol. 2009;66(9):1091-1096.
Caplan LR. Translating what is known about neurological complications of coronary artery bypass graft surgery into action. Arch Neurol. 2009;66(9):1062-1064.

CT Scans in Children With Head Injury
Researchers have identified guidelines for accurately predicting children at very low risk of clinically important traumatic brain injuries (TBI), for whom CT scans should be avoided, as reported in the September 15 online Lancet. Nathan Kuppermann, MD, of the University of California-Davis School of Medicine in Sacramento, and colleagues analyzed 42,412 children with head trauma in 25 North American emergency departments, and derived and validated age-specific prediction rules for clinically important TBI. Application of these rules, the investigators believe, could limit CT use, protecting children from unnecessary radiation risks.

Dr. Kuppermann’s group, the Pediatric Emergency Care Applied Research Network, identified the following algorithms with 100% and 99.95% negative predictive value for clinically important TBI, respectively:

• For children younger than 2, normal mental status, no scalp hematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 seconds, nonsevere injury mechanism, no palpable skull fracture, and acting normally according to the parents.
• For children 2 and older, normal mental status, no loss of consciousness, no vomiting, nonsevere injury mechanism, no signs of basilar skull fracture, and no severe headache.

“Data to guide clinical decision making for children with head trauma are urgently needed because head trauma is common and CT use is increasing,” the study authors commented. “Children sustaining minor head trauma infrequently have TBI and rarely need neurosurgery. The small risk of clinically important TBI should be balanced against the risks of ionizing radiation of CTs.”

“Kuppermann and colleagues remind us that the rules are meant to inform clinical decision making, not to replace it,” Patricia C. Parkin, MD, and Jonathon L. Maguire, MD, of the Division of Pediatric Medicine and the Pediatric Outcomes Research Team at the Hospital for Sick Children in Toronto, wrote in an accompanying comment. “The next challenge for evidence-based medicine is knowledge translation. Decision aids might provide structured presentations of options and outcomes.”
Kuppermann N, Holmes JF, Dayan PS, et al. Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study. Lancet. 2009 Sep 14; [Epub ahead of print].
Parkin PC, Maguire JL. Clinically important head injuries after head trauma in children. Lancet. 2009 Sep 14; [Epub ahead of print].

Parent-of-Origin Effects in MS
The greater female-to-male ratio in patients with multiple sclerosis (MS) appears to be more strongly related to the mother, a study published in the August 25 Neurology reported. This maternal parent-of-origin effect, previously seen in studies of half-siblings and avuncular pairs, was found in offspring from a Caucasian mother and North American Aboriginal father.

S.V. Ramagopalan, DPhil, of the Wellcome Trust Centre for Human Genetics at the University of Oxford, UK, and colleagues examined 30,000 MS cases from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) and identified 58 individuals with one Caucasian parent and one North American Aboriginal parent. Of these, 27 had a Caucasian mother and 31 had a North American Aboriginal mother. Although the total number of affected offspring was similar in the two mating types studied, the sex ratio differed. Female-to-male sex ratio was 7:1 for patients with MS who had a Caucasian mother, compared with a 2:1 ratio for those with a Caucasian father.

“A parent-of-origin effect (maternal) has been repeatedly observed in MS, based on studies of half-siblings, sibships including dizygotic twins, a large extended Dutch pedigree, and avuncular pairs, as well as timing of birth effect,” the study authors noted. “The comparison of offspring from interracial matings is a novel method of analysis to look for parent of origin effects.

“The data from this study hint at an intriguing possibility that the observed female preponderance of MS could result from environmental factors acting upon mothers to differentially affect MS risk more in female than in male offspring,” the researchers pointed out.

In a related editorial, John W. Rose, MD, commented that this study “illustrated the continued potential of the CCPGSMS to address interesting questions related to the disease.… By evaluating a small set of MS patients with a Caucasian parent and a Native Aboriginal American parent, the investigators were able to assess parental effects on the disease,” he continued. “The susceptibility to disease is presumed to be predominantly introduced by the Caucasian parent based on previous investigations. In this admixture study, the results demonstrate a maternal effect which strongly influences the sex ratio of offspring affected by MS, linking these two classes of gender differences in MS.”
Ramagopalan SV, Yee IM, Dyment DA, et al. Parent-of-origin effect in multiple sclerosis: observations from interracial matings. Neurology. 2009;73(8):602-605.
Rose JW. Multiple sclerosis: evidence of maternal effects and an increasing incidence in women. Neurology. 2009;73(8):578-579.

Stroke After Cardiac Surgery and Role of Carotid Stenosis
Combining carotid and cardiac procedures is neither necessary nor effective in reducing postoperative stroke in patients with asymptomatic carotid stenosis, according to a study in the September Archives of Neurology. Researchers found no direct causal relationship between significant carotid stenosis and postoperative stroke in patients who underwent cardiac operations.

Yuebing Li, MD, PhD, and colleagues at Lehigh Valley Hospital and Health Network in Allentown, Pennsylvania, reviewed data of 4,335 patients receiving nonurgent coronary artery bypass grafting (CABG) and/or aortic valve replacement between July 2001 and December 2006. Prior to surgery, 3,942 patients were evaluated for carotid stenosis using high-resolution sonography, 239 (6.1%) of whom were identified as having significant carotid stenosis.

A total of 76 patients (1.8%) had a clinically definitive stroke following surgery. Of those, 18 patients had significant carotid stenosis (23.7%). Although stroke was more common in individuals with carotid stenosis than in those without (7.5% vs 1.8%), 14 of the 18 strokes “occurred outside the territory of diseased carotid artery,” the study authors noted. Furthermore, the majority (76.3%) of postoperative strokes occurred in individuals without carotid disease, and 60% of the strokes were not confined to a single carotid artery.

“According to clinical data, in 94.7% of patients, stroke occurred without direct correlation to significant carotid stenosis,” the study authors wrote. “This study strongly suggests there is no direct causal relationship between postoperative stroke and severe carotid stenosis.”

In a related editorial, Louis R. Caplan, MD, Professor of Neurology at Harvard Medical School in Boston, commented on the neurologic complications of elective coronary artery surgery. “Processes that include checklists and time-outs during which the team reviews findings and strategies have led to reduced medical errors and improved outcomes,” Dr. Caplan wrote. “I suggest that patients and preoperative information should be reviewed before surgery by a team approach that includes a cardiologist who will observe the patients throughout their hospitalization and the cardiac surgeon who will perform the operation.”
Li Y, Walicki D, Mathiesen C, et al. Strokes after cardiac surgery and relationship to carotid stenosis. Arch Neurol. 2009;66(9):1091-1096.
Caplan LR. Translating what is known about neurological complications of coronary artery bypass graft surgery into action. Arch Neurol. 2009;66(9):1062-1064.

CT Scans in Children With Head Injury
Researchers have identified guidelines for accurately predicting children at very low risk of clinically important traumatic brain injuries (TBI), for whom CT scans should be avoided, as reported in the September 15 online Lancet. Nathan Kuppermann, MD, of the University of California-Davis School of Medicine in Sacramento, and colleagues analyzed 42,412 children with head trauma in 25 North American emergency departments, and derived and validated age-specific prediction rules for clinically important TBI. Application of these rules, the investigators believe, could limit CT use, protecting children from unnecessary radiation risks.

Dr. Kuppermann’s group, the Pediatric Emergency Care Applied Research Network, identified the following algorithms with 100% and 99.95% negative predictive value for clinically important TBI, respectively:

• For children younger than 2, normal mental status, no scalp hematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 seconds, nonsevere injury mechanism, no palpable skull fracture, and acting normally according to the parents.
• For children 2 and older, normal mental status, no loss of consciousness, no vomiting, nonsevere injury mechanism, no signs of basilar skull fracture, and no severe headache.

“Data to guide clinical decision making for children with head trauma are urgently needed because head trauma is common and CT use is increasing,” the study authors commented. “Children sustaining minor head trauma infrequently have TBI and rarely need neurosurgery. The small risk of clinically important TBI should be balanced against the risks of ionizing radiation of CTs.”

“Kuppermann and colleagues remind us that the rules are meant to inform clinical decision making, not to replace it,” Patricia C. Parkin, MD, and Jonathon L. Maguire, MD, of the Division of Pediatric Medicine and the Pediatric Outcomes Research Team at the Hospital for Sick Children in Toronto, wrote in an accompanying comment. “The next challenge for evidence-based medicine is knowledge translation. Decision aids might provide structured presentations of options and outcomes.”
Kuppermann N, Holmes JF, Dayan PS, et al. Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study. Lancet. 2009 Sep 14; [Epub ahead of print].
Parkin PC, Maguire JL. Clinically important head injuries after head trauma in children. Lancet. 2009 Sep 14; [Epub ahead of print].

Parent-of-Origin Effects in MS
The greater female-to-male ratio in patients with multiple sclerosis (MS) appears to be more strongly related to the mother, a study published in the August 25 Neurology reported. This maternal parent-of-origin effect, previously seen in studies of half-siblings and avuncular pairs, was found in offspring from a Caucasian mother and North American Aboriginal father.

S.V. Ramagopalan, DPhil, of the Wellcome Trust Centre for Human Genetics at the University of Oxford, UK, and colleagues examined 30,000 MS cases from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) and identified 58 individuals with one Caucasian parent and one North American Aboriginal parent. Of these, 27 had a Caucasian mother and 31 had a North American Aboriginal mother. Although the total number of affected offspring was similar in the two mating types studied, the sex ratio differed. Female-to-male sex ratio was 7:1 for patients with MS who had a Caucasian mother, compared with a 2:1 ratio for those with a Caucasian father.

“A parent-of-origin effect (maternal) has been repeatedly observed in MS, based on studies of half-siblings, sibships including dizygotic twins, a large extended Dutch pedigree, and avuncular pairs, as well as timing of birth effect,” the study authors noted. “The comparison of offspring from interracial matings is a novel method of analysis to look for parent of origin effects.

“The data from this study hint at an intriguing possibility that the observed female preponderance of MS could result from environmental factors acting upon mothers to differentially affect MS risk more in female than in male offspring,” the researchers pointed out.

In a related editorial, John W. Rose, MD, commented that this study “illustrated the continued potential of the CCPGSMS to address interesting questions related to the disease.… By evaluating a small set of MS patients with a Caucasian parent and a Native Aboriginal American parent, the investigators were able to assess parental effects on the disease,” he continued. “The susceptibility to disease is presumed to be predominantly introduced by the Caucasian parent based on previous investigations. In this admixture study, the results demonstrate a maternal effect which strongly influences the sex ratio of offspring affected by MS, linking these two classes of gender differences in MS.”
Ramagopalan SV, Yee IM, Dyment DA, et al. Parent-of-origin effect in multiple sclerosis: observations from interracial matings. Neurology. 2009;73(8):602-605.
Rose JW. Multiple sclerosis: evidence of maternal effects and an increasing incidence in women. Neurology. 2009;73(8):578-579.