Traumatic Brain Injury

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.

SEATTLE—Insomnia is significantly more prevalent among patients with mild traumatic brain injury (TBI) than in the general population, according to research presented at the 23rd Annual Meeting of the Associated Professional Sleep Societies. Other nighttime sleep problems and excessive daytime sleepiness are also strongly associated with mild TBI, reported Michael B. Russo, MD, and colleagues.

Because TBI may disrupt various components of the sleep/wake regulatory network, the investigators had hypothesized that patients with TBI would have a high incidence of insomnia and other sleep-related problems. Dr. Russo’s group reviewed medical records of 35 patients (30 males; mean age, 30) with mild TBI; 20 subjects were military service members. All patients had attended a military neurology clinic for sleep-related complaints, and no patients had had insomnia before incurring a head injury.

The researchers found that 31 patients (89%) had insomnia, compared with an estimated rate of 10% in the general adult population. In addition, 27 patients had sleep-onset insomnia, 30 had difficulty staying asleep, 15 awakened throughout the night, and 11 awakened in the early morning. Furthermore, 23 patients had more than one type of insomnia, according to Dr. Russo, Colonel, Medical Corps, US Army, Tripler Army Medical Center in Honolulu.

The investigators also found that 34 patients had a sleep/wake-related problem and that 31 had excessive daytime sleepiness. Sleep/wake-related problems were defined as having daytime dysfunction associated with not being able to fall asleep, feeling restless at night, having nightmares, awakening at night, awakening in the early morning, and having excessive daytime sleepiness. Excessive daytime sleepiness was defined as having direct complaints, naps, and decreased social and work performance due to sleepiness.

“We suggest that screening for insomnia and sleep/wake-related problems be considered in all patients suspected of having mild TBI,” said Dr. Russo.

NR

—Colby Stong

SEATTLE—Insomnia is significantly more prevalent among patients with mild traumatic brain injury (TBI) than in the general population, according to research presented at the 23rd Annual Meeting of the Associated Professional Sleep Societies. Other nighttime sleep problems and excessive daytime sleepiness are also strongly associated with mild TBI, reported Michael B. Russo, MD, and colleagues.

Because TBI may disrupt various components of the sleep/wake regulatory network, the investigators had hypothesized that patients with TBI would have a high incidence of insomnia and other sleep-related problems. Dr. Russo’s group reviewed medical records of 35 patients (30 males; mean age, 30) with mild TBI; 20 subjects were military service members. All patients had attended a military neurology clinic for sleep-related complaints, and no patients had had insomnia before incurring a head injury.

The researchers found that 31 patients (89%) had insomnia, compared with an estimated rate of 10% in the general adult population. In addition, 27 patients had sleep-onset insomnia, 30 had difficulty staying asleep, 15 awakened throughout the night, and 11 awakened in the early morning. Furthermore, 23 patients had more than one type of insomnia, according to Dr. Russo, Colonel, Medical Corps, US Army, Tripler Army Medical Center in Honolulu.

The investigators also found that 34 patients had a sleep/wake-related problem and that 31 had excessive daytime sleepiness. Sleep/wake-related problems were defined as having daytime dysfunction associated with not being able to fall asleep, feeling restless at night, having nightmares, awakening at night, awakening in the early morning, and having excessive daytime sleepiness. Excessive daytime sleepiness was defined as having direct complaints, naps, and decreased social and work performance due to sleepiness.

“We suggest that screening for insomnia and sleep/wake-related problems be considered in all patients suspected of having mild TBI,” said Dr. Russo.

NR

—Colby Stong

SEATTLE—Insomnia is significantly more prevalent among patients with mild traumatic brain injury (TBI) than in the general population, according to research presented at the 23rd Annual Meeting of the Associated Professional Sleep Societies. Other nighttime sleep problems and excessive daytime sleepiness are also strongly associated with mild TBI, reported Michael B. Russo, MD, and colleagues.

Because TBI may disrupt various components of the sleep/wake regulatory network, the investigators had hypothesized that patients with TBI would have a high incidence of insomnia and other sleep-related problems. Dr. Russo’s group reviewed medical records of 35 patients (30 males; mean age, 30) with mild TBI; 20 subjects were military service members. All patients had attended a military neurology clinic for sleep-related complaints, and no patients had had insomnia before incurring a head injury.

The researchers found that 31 patients (89%) had insomnia, compared with an estimated rate of 10% in the general adult population. In addition, 27 patients had sleep-onset insomnia, 30 had difficulty staying asleep, 15 awakened throughout the night, and 11 awakened in the early morning. Furthermore, 23 patients had more than one type of insomnia, according to Dr. Russo, Colonel, Medical Corps, US Army, Tripler Army Medical Center in Honolulu.

The investigators also found that 34 patients had a sleep/wake-related problem and that 31 had excessive daytime sleepiness. Sleep/wake-related problems were defined as having daytime dysfunction associated with not being able to fall asleep, feeling restless at night, having nightmares, awakening at night, awakening in the early morning, and having excessive daytime sleepiness. Excessive daytime sleepiness was defined as having direct complaints, naps, and decreased social and work performance due to sleepiness.

“We suggest that screening for insomnia and sleep/wake-related problems be considered in all patients suspected of having mild TBI,” said Dr. Russo.

NR

—Colby Stong

SEATTLE—A new, more reliable, efficient, and valid classification system for traumatic brain injury (TBI) is under development, with the goal of driving more focused research and individualized therapy for patients with head injury, reported Geoffrey Manley, MD, PhD, at the 61st Annual Meeting of the American Academy of Neurology.

Problems With the Current Classification System
TBI classification is “still a symptoms-based classification system,” said Dr. Manley, Professor of Neurosurgery at the University of California, San Francisco, and Chief of Neurosurgery at San Francisco General Hospital.

In fact, Dr. Manley argued, “we probably had a better classification system for head injury 200 years ago than we have today.” In the beginning of the 18th century, autopsies became more routine and many disease conditions, including head injuries, started to be classified based on pathoanatomic features. At that time, TBI was classified as follows: commotio (ie, concussion), contusio (ie, bruising of the brain, contusions), and compresio (ie, compressive injuries such as subdural and epidural hematomas). Today, “we classify TBI as mild, moderate, and severe, and that’s based upon the Glasgow Coma Score (GCS),” said Dr. Manley. “I think that, pathoanatomically, we’re looking at a much more heterogeneous disease process than just mild, moderate, and severe.”

As an example of the insufficiency of classifying TBI based solely on GCS score, Dr. Manley described the case of a 56-year-old executive. The patient fell and was found to have a GCS of 15. “The residents thought he was doing fine, because the day after the injury he’s showing two fingers, he seems to be conversing just fine,” stated Dr. Manley. However, the patient had an orbitofrontal lesion, and at 12-month follow-up he was found to be impulsive, unemployed, and divorced. “So I don’t think this was a mild head injury for this guy,” said Dr. Manley. “We don’t consider this lesion mild just because this patient had a GCS of 14 or 15. We look at this kind of injury, and we say, ‘This is someone who’s going to have social dysregulation in the future.’”

Dr. Manley suggested that because the GCS does not provide information about the pathophysiologic mechanisms behind neurologic deficits, a more multidimensional classification system is needed to develop more targeted treatment and improve outcomes. Cancer, for example, is classified using a multidimensional system. “It’s really the pinnacle of disease classification. It’s a mixture of anatomy, physiology, metabolomics, immunology, and genetically defined diseases,” said Dr. Manley. “We didn’t get as far as we did with cancer by saying ‘You’ve got mild cancer,’ ‘You’ve got moderate cancer,’ and ‘You’re on death’s door.’”

Workshop Recommendations
In October 2007, the NINDS, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to discuss the limitations of using the GCS for classification of TBI and the need to develop a more pathoanatomic-based classification system. The organizing committee was cochaired by Dr. Manley, and their recommendations were published in the July 2008 Journal of Neurotrauma.

In order to begin to reclassify TBI, “we really have to restructure the field from the ground up,” said Dr. Manley. “We need to define a common set of demographic data elements so that we’re all collecting the same kind of information across studies, whether they’re funded by the NIH, whether they’re funded by the Department of Defense, whether this is just a study that you’re going to get funded out of your individual funds at your own department. We should all be collecting the same demographic data.”

Dr. Manley emphasized the need for agreement on outcome measures. “We have to do more in terms of getting better outcome measures that define the disabilities that these patients have.” He also suggested that imaging requirements should be better defined. When doing CT and MRI scans, he said, the same kind of sequences should be used so that films can be compared from site to site and across different studies.

Lastly, Dr. Manley recommended defining requirements for genomics and proteomics. Setting standards for collecting, processing, and sorting is essential for investigating biomarkers, he said.

New Horizons in TBI Research
Dr. Manley noted that in the upcoming months, “diffusion tensor imaging … is going to be very important. We’ve been doing a lot of work with magnetoencephalography and looking at things like functional connectivity…. It’s not where the lesion is, but how it affects the connectivity in the brain.”

Higher resolution imaging will also be studied. “We’ve been doing a lot of scanning of our [TBI] patients on our new 7-Tesla magnet … and it’s just absolutely amazing, the structural images,” Dr. Manley commented.

“The other thing that I think we really need to improve upon is medical informatics,” said Dr. Manley, noting that better clinical decision-making tools are needed to assist clinicians who do not focus solely on TBI. “Most importantly, I think we need a prospective, multivariate TBI database. I’m not sure we even know what TBI is in 2009. Almost everything we do as clinicians is based on what we learned from the Traumatic Coma Data Bank, which contains patient data collected over 25 years ago,” said Dr. Manley. Prospective observational studies across the entire TBI injury spectrum will require 1,000 to 2,000 patients, rather than 20 to 30, to develop a clearer picture of TBI and help to focus future research and clinical efforts.

In March 2009, a total of 49 institutions and government agencies, including the NIH, National Institute on Disability and Rehabilitation Reasearch, Defense Centers of Excellence, Defense and Veterans Brain Injury Center, Veterans Affairs, and other stakeholders, organized a consensus conference in Washington, DC to discuss these issues. “What I hope you’ll see by the end of the year is a series of white papers that essentially outline what these common data elements are for TBI demographics, neuroimaging, biomarkers, outcome, and assessment of psychological health. The vision is to provide the tools to standardize data collection to improve TBI research and clinical care.”

SEATTLE—A new, more reliable, efficient, and valid classification system for traumatic brain injury (TBI) is under development, with the goal of driving more focused research and individualized therapy for patients with head injury, reported Geoffrey Manley, MD, PhD, at the 61st Annual Meeting of the American Academy of Neurology.

Problems With the Current Classification System
TBI classification is “still a symptoms-based classification system,” said Dr. Manley, Professor of Neurosurgery at the University of California, San Francisco, and Chief of Neurosurgery at San Francisco General Hospital.

In fact, Dr. Manley argued, “we probably had a better classification system for head injury 200 years ago than we have today.” In the beginning of the 18th century, autopsies became more routine and many disease conditions, including head injuries, started to be classified based on pathoanatomic features. At that time, TBI was classified as follows: commotio (ie, concussion), contusio (ie, bruising of the brain, contusions), and compresio (ie, compressive injuries such as subdural and epidural hematomas). Today, “we classify TBI as mild, moderate, and severe, and that’s based upon the Glasgow Coma Score (GCS),” said Dr. Manley. “I think that, pathoanatomically, we’re looking at a much more heterogeneous disease process than just mild, moderate, and severe.”

As an example of the insufficiency of classifying TBI based solely on GCS score, Dr. Manley described the case of a 56-year-old executive. The patient fell and was found to have a GCS of 15. “The residents thought he was doing fine, because the day after the injury he’s showing two fingers, he seems to be conversing just fine,” stated Dr. Manley. However, the patient had an orbitofrontal lesion, and at 12-month follow-up he was found to be impulsive, unemployed, and divorced. “So I don’t think this was a mild head injury for this guy,” said Dr. Manley. “We don’t consider this lesion mild just because this patient had a GCS of 14 or 15. We look at this kind of injury, and we say, ‘This is someone who’s going to have social dysregulation in the future.’”

Dr. Manley suggested that because the GCS does not provide information about the pathophysiologic mechanisms behind neurologic deficits, a more multidimensional classification system is needed to develop more targeted treatment and improve outcomes. Cancer, for example, is classified using a multidimensional system. “It’s really the pinnacle of disease classification. It’s a mixture of anatomy, physiology, metabolomics, immunology, and genetically defined diseases,” said Dr. Manley. “We didn’t get as far as we did with cancer by saying ‘You’ve got mild cancer,’ ‘You’ve got moderate cancer,’ and ‘You’re on death’s door.’”

Workshop Recommendations
In October 2007, the NINDS, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to discuss the limitations of using the GCS for classification of TBI and the need to develop a more pathoanatomic-based classification system. The organizing committee was cochaired by Dr. Manley, and their recommendations were published in the July 2008 Journal of Neurotrauma.

In order to begin to reclassify TBI, “we really have to restructure the field from the ground up,” said Dr. Manley. “We need to define a common set of demographic data elements so that we’re all collecting the same kind of information across studies, whether they’re funded by the NIH, whether they’re funded by the Department of Defense, whether this is just a study that you’re going to get funded out of your individual funds at your own department. We should all be collecting the same demographic data.”

Dr. Manley emphasized the need for agreement on outcome measures. “We have to do more in terms of getting better outcome measures that define the disabilities that these patients have.” He also suggested that imaging requirements should be better defined. When doing CT and MRI scans, he said, the same kind of sequences should be used so that films can be compared from site to site and across different studies.

Lastly, Dr. Manley recommended defining requirements for genomics and proteomics. Setting standards for collecting, processing, and sorting is essential for investigating biomarkers, he said.

New Horizons in TBI Research
Dr. Manley noted that in the upcoming months, “diffusion tensor imaging … is going to be very important. We’ve been doing a lot of work with magnetoencephalography and looking at things like functional connectivity…. It’s not where the lesion is, but how it affects the connectivity in the brain.”

Higher resolution imaging will also be studied. “We’ve been doing a lot of scanning of our [TBI] patients on our new 7-Tesla magnet … and it’s just absolutely amazing, the structural images,” Dr. Manley commented.

“The other thing that I think we really need to improve upon is medical informatics,” said Dr. Manley, noting that better clinical decision-making tools are needed to assist clinicians who do not focus solely on TBI. “Most importantly, I think we need a prospective, multivariate TBI database. I’m not sure we even know what TBI is in 2009. Almost everything we do as clinicians is based on what we learned from the Traumatic Coma Data Bank, which contains patient data collected over 25 years ago,” said Dr. Manley. Prospective observational studies across the entire TBI injury spectrum will require 1,000 to 2,000 patients, rather than 20 to 30, to develop a clearer picture of TBI and help to focus future research and clinical efforts.

In March 2009, a total of 49 institutions and government agencies, including the NIH, National Institute on Disability and Rehabilitation Reasearch, Defense Centers of Excellence, Defense and Veterans Brain Injury Center, Veterans Affairs, and other stakeholders, organized a consensus conference in Washington, DC to discuss these issues. “What I hope you’ll see by the end of the year is a series of white papers that essentially outline what these common data elements are for TBI demographics, neuroimaging, biomarkers, outcome, and assessment of psychological health. The vision is to provide the tools to standardize data collection to improve TBI research and clinical care.”

SEATTLE—A new, more reliable, efficient, and valid classification system for traumatic brain injury (TBI) is under development, with the goal of driving more focused research and individualized therapy for patients with head injury, reported Geoffrey Manley, MD, PhD, at the 61st Annual Meeting of the American Academy of Neurology.

Problems With the Current Classification System
TBI classification is “still a symptoms-based classification system,” said Dr. Manley, Professor of Neurosurgery at the University of California, San Francisco, and Chief of Neurosurgery at San Francisco General Hospital.

In fact, Dr. Manley argued, “we probably had a better classification system for head injury 200 years ago than we have today.” In the beginning of the 18th century, autopsies became more routine and many disease conditions, including head injuries, started to be classified based on pathoanatomic features. At that time, TBI was classified as follows: commotio (ie, concussion), contusio (ie, bruising of the brain, contusions), and compresio (ie, compressive injuries such as subdural and epidural hematomas). Today, “we classify TBI as mild, moderate, and severe, and that’s based upon the Glasgow Coma Score (GCS),” said Dr. Manley. “I think that, pathoanatomically, we’re looking at a much more heterogeneous disease process than just mild, moderate, and severe.”

As an example of the insufficiency of classifying TBI based solely on GCS score, Dr. Manley described the case of a 56-year-old executive. The patient fell and was found to have a GCS of 15. “The residents thought he was doing fine, because the day after the injury he’s showing two fingers, he seems to be conversing just fine,” stated Dr. Manley. However, the patient had an orbitofrontal lesion, and at 12-month follow-up he was found to be impulsive, unemployed, and divorced. “So I don’t think this was a mild head injury for this guy,” said Dr. Manley. “We don’t consider this lesion mild just because this patient had a GCS of 14 or 15. We look at this kind of injury, and we say, ‘This is someone who’s going to have social dysregulation in the future.’”

Dr. Manley suggested that because the GCS does not provide information about the pathophysiologic mechanisms behind neurologic deficits, a more multidimensional classification system is needed to develop more targeted treatment and improve outcomes. Cancer, for example, is classified using a multidimensional system. “It’s really the pinnacle of disease classification. It’s a mixture of anatomy, physiology, metabolomics, immunology, and genetically defined diseases,” said Dr. Manley. “We didn’t get as far as we did with cancer by saying ‘You’ve got mild cancer,’ ‘You’ve got moderate cancer,’ and ‘You’re on death’s door.’”

Workshop Recommendations
In October 2007, the NINDS, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to discuss the limitations of using the GCS for classification of TBI and the need to develop a more pathoanatomic-based classification system. The organizing committee was cochaired by Dr. Manley, and their recommendations were published in the July 2008 Journal of Neurotrauma.

In order to begin to reclassify TBI, “we really have to restructure the field from the ground up,” said Dr. Manley. “We need to define a common set of demographic data elements so that we’re all collecting the same kind of information across studies, whether they’re funded by the NIH, whether they’re funded by the Department of Defense, whether this is just a study that you’re going to get funded out of your individual funds at your own department. We should all be collecting the same demographic data.”

Dr. Manley emphasized the need for agreement on outcome measures. “We have to do more in terms of getting better outcome measures that define the disabilities that these patients have.” He also suggested that imaging requirements should be better defined. When doing CT and MRI scans, he said, the same kind of sequences should be used so that films can be compared from site to site and across different studies.

Lastly, Dr. Manley recommended defining requirements for genomics and proteomics. Setting standards for collecting, processing, and sorting is essential for investigating biomarkers, he said.

New Horizons in TBI Research
Dr. Manley noted that in the upcoming months, “diffusion tensor imaging … is going to be very important. We’ve been doing a lot of work with magnetoencephalography and looking at things like functional connectivity…. It’s not where the lesion is, but how it affects the connectivity in the brain.”

Higher resolution imaging will also be studied. “We’ve been doing a lot of scanning of our [TBI] patients on our new 7-Tesla magnet … and it’s just absolutely amazing, the structural images,” Dr. Manley commented.

“The other thing that I think we really need to improve upon is medical informatics,” said Dr. Manley, noting that better clinical decision-making tools are needed to assist clinicians who do not focus solely on TBI. “Most importantly, I think we need a prospective, multivariate TBI database. I’m not sure we even know what TBI is in 2009. Almost everything we do as clinicians is based on what we learned from the Traumatic Coma Data Bank, which contains patient data collected over 25 years ago,” said Dr. Manley. Prospective observational studies across the entire TBI injury spectrum will require 1,000 to 2,000 patients, rather than 20 to 30, to develop a clearer picture of TBI and help to focus future research and clinical efforts.

In March 2009, a total of 49 institutions and government agencies, including the NIH, National Institute on Disability and Rehabilitation Reasearch, Defense Centers of Excellence, Defense and Veterans Brain Injury Center, Veterans Affairs, and other stakeholders, organized a consensus conference in Washington, DC to discuss these issues. “What I hope you’ll see by the end of the year is a series of white papers that essentially outline what these common data elements are for TBI demographics, neuroimaging, biomarkers, outcome, and assessment of psychological health. The vision is to provide the tools to standardize data collection to improve TBI research and clinical care.”

NASHVILLE—Therapeutic hypothermia is being used with increasing frequency to treat patients with neurologic injury from conditions such as stroke, cardiac arrest, and traumatic brain injury (TBI). “Induced hypothermia can sometimes be risky, but it’s potentially highly rewarding,” said Kees H. Polderman, MD, PhD, at the Society of Critical Care Medicine’s 38th Critical Care Congress. Effective use of hypothermia is strongly dependent on the quality of other aspects of ICU care; therefore, he recommended that clinicians give careful attention to all of these factors.

When interpreting findings from studies examining therapeutic hypothermia, “you should always look at where it’s being performed, the context in which this treatment is taking place, and what other aspects of care are similar to your own and which ones are different; then you can assess if you can reproduce those results in your own center, or if you need to adapt your policy a bit,” commented Dr. Polderman, Professor in Intensive Care Medicine at the Department of Critical Care, University of Pittsburgh Medical Center.

Goals of Therapeutic Hypothermia
Stroke, cardiac arrest, and, to a lesser extent, TBI are characterized by ischemia and reperfusion injury. After a period of ischemia, a series of destructive processes takes place in the injured cells of the brain. “The damage is ongoing while the patient is in your ICU or your emergency room,” said Dr. Polderman.

Therefore, the first goal of treatment with hypothermia is to try to limit this injury. “Hypothermia acts as a sort of blanket therapy,” he said. “It can interrupt every single one of these harmful processes, in contrast to many other therapies that we’ve tried in the past.”

Another goal is to treat brain edema, which may also play a role in some disease states—TBI being one example. For patients with brain edema, the approach to treatment is slightly different, requiring a longer period of cooling.

Controlling Brain Temperature
When using hypothermia for patients with neurologic injury, physicians should do their best to prevent fever, Dr. Polderman advised. “Most of our patients in the neurocritical care units develop fever at some point in their ICU stay. The more severe the injury, the more likely the chance that [the patient] will develop fever,” he said.

Fever is associated with longer length of stay, worse neurologic outcome, and higher mortality. In two studies involving patients with subarachnoid hemorrhage and intracerebral hemorrhage, researchers reported that even a minimal elevation in temperature to slightly greater than 37.5°C—not considered a real fever by some—had a significant adverse effect on outcome.

One explanation for this could be that brain temperature exceeds core temperature. “The destructive processes triggered by ischemia generate heat. Local brain edema makes it difficult to get rid of the excess heat, and this leads to overheating of the brain,” explained Dr. Polderman. “So fever after neurologic injury seems to be extremely harmful, and hypothermia seems to be really protective.”

Proven Efficacy
Three randomized controlled trials have assessed neurologic outcome in patients who underwent therapeutic hypothermia following witnessed cardiac arrest, with significant improvement seen in patients treated with hypothermia across all three studies, said Dr. Polderman. In addition, a number of nonrandomized studies have reported good outcomes following treatment with induced hypothermia.

Dr. Polderman and his colleagues conducted a prospective, multicenter study in which 64 patients with witnessed cardiac arrest underwent therapeutic hypothermia. The results have not yet been published as a full paper. In this study, 60% of patients with ventricular tachycardia/ventricular fibrillation (VT/VF) had a good neurologic outcome (defined as return to their home situation with no or only minimal neurologic impairment). In addition, 50% of patients with an initial rhythm of asystole who reached the hospital alive also had a good neurologic outcome.

“We should lose the pessimism surrounding patients with witnessed cardiac arrest, because the good outcome rates can be better than 50% in this category of patients when hypothermia has been used,” commented Dr. Polderman. “We need to get the cardiologist to do the appropriate intervention, even when the patient is comatose. We need to promote bystander CPR, because the chances of this therapy helping the patient are much better if basic CPR has been performed.”

Some studies have also reported good outcome following therapeutic cooling in patients with severe TBI. Meta-analyses have reported a 22% to 48% reduction in the risk for adverse neurologic outcome in patients with severe TBI treated with therapeutic hypothermia, although not all these differences were statistically significant.

However, the treatment looks highly promising, according to Dr. Polderman. He pointed out for comparison that data on the use of barbiturates and mannitol do not show any benefit on neurologic outcome in patients with TBI.

Cooling in the Right Context
Although hypothermia has beneficial effects on neurologic outcome, “a treatment can only be effective if the other aspects of intensive care are good,” cautioned Dr. Polderman. Therefore, “context matters. It’s not just about cooling.”

When using hypothermia, temperature should be lowered rapidly, but rewarming should be done very slowly, noted Dr. Polderman. “If you do it rapidly, you could lose some or all of the protective effects of hypothermia,” he warned.

In addition, physicians should consider other aspects of ICU treatment, such as prevention of hypo- and hypercapnia, electrolyte disorders, hyperglycemia, and hypoglycemia. “All these things matter, and they may make all the difference,” he said. “Without getting that right, hypothermia can be an ineffective or even dangerous therapy.”

“The idea of context applies even more strongly to areas like severe TBI,” he asserted. “Speed and duration of cooling are important.” For patients with TBI who receive hypothermia, longer duration of cooling (ie, greater than 48 hours) and slow rewarming protocols are associated with better outcome. He noted that one way to determine the optimal duration of cooling in individual patients is to measure intracranial pressure. Intracranial pressure is both a marker of ongoing brain injury and a potential cause of additional injury.

“The use of hypothermia is not risk-free. There are severe side effects, which we should take into account, but the good news is that these can be fairly easily managed,” concluded Dr. Polderman.   

NASHVILLE—Therapeutic hypothermia is being used with increasing frequency to treat patients with neurologic injury from conditions such as stroke, cardiac arrest, and traumatic brain injury (TBI). “Induced hypothermia can sometimes be risky, but it’s potentially highly rewarding,” said Kees H. Polderman, MD, PhD, at the Society of Critical Care Medicine’s 38th Critical Care Congress. Effective use of hypothermia is strongly dependent on the quality of other aspects of ICU care; therefore, he recommended that clinicians give careful attention to all of these factors.

When interpreting findings from studies examining therapeutic hypothermia, “you should always look at where it’s being performed, the context in which this treatment is taking place, and what other aspects of care are similar to your own and which ones are different; then you can assess if you can reproduce those results in your own center, or if you need to adapt your policy a bit,” commented Dr. Polderman, Professor in Intensive Care Medicine at the Department of Critical Care, University of Pittsburgh Medical Center.

Goals of Therapeutic Hypothermia
Stroke, cardiac arrest, and, to a lesser extent, TBI are characterized by ischemia and reperfusion injury. After a period of ischemia, a series of destructive processes takes place in the injured cells of the brain. “The damage is ongoing while the patient is in your ICU or your emergency room,” said Dr. Polderman.

Therefore, the first goal of treatment with hypothermia is to try to limit this injury. “Hypothermia acts as a sort of blanket therapy,” he said. “It can interrupt every single one of these harmful processes, in contrast to many other therapies that we’ve tried in the past.”

Another goal is to treat brain edema, which may also play a role in some disease states—TBI being one example. For patients with brain edema, the approach to treatment is slightly different, requiring a longer period of cooling.

Controlling Brain Temperature
When using hypothermia for patients with neurologic injury, physicians should do their best to prevent fever, Dr. Polderman advised. “Most of our patients in the neurocritical care units develop fever at some point in their ICU stay. The more severe the injury, the more likely the chance that [the patient] will develop fever,” he said.

Fever is associated with longer length of stay, worse neurologic outcome, and higher mortality. In two studies involving patients with subarachnoid hemorrhage and intracerebral hemorrhage, researchers reported that even a minimal elevation in temperature to slightly greater than 37.5°C—not considered a real fever by some—had a significant adverse effect on outcome.

One explanation for this could be that brain temperature exceeds core temperature. “The destructive processes triggered by ischemia generate heat. Local brain edema makes it difficult to get rid of the excess heat, and this leads to overheating of the brain,” explained Dr. Polderman. “So fever after neurologic injury seems to be extremely harmful, and hypothermia seems to be really protective.”

Proven Efficacy
Three randomized controlled trials have assessed neurologic outcome in patients who underwent therapeutic hypothermia following witnessed cardiac arrest, with significant improvement seen in patients treated with hypothermia across all three studies, said Dr. Polderman. In addition, a number of nonrandomized studies have reported good outcomes following treatment with induced hypothermia.

Dr. Polderman and his colleagues conducted a prospective, multicenter study in which 64 patients with witnessed cardiac arrest underwent therapeutic hypothermia. The results have not yet been published as a full paper. In this study, 60% of patients with ventricular tachycardia/ventricular fibrillation (VT/VF) had a good neurologic outcome (defined as return to their home situation with no or only minimal neurologic impairment). In addition, 50% of patients with an initial rhythm of asystole who reached the hospital alive also had a good neurologic outcome.

“We should lose the pessimism surrounding patients with witnessed cardiac arrest, because the good outcome rates can be better than 50% in this category of patients when hypothermia has been used,” commented Dr. Polderman. “We need to get the cardiologist to do the appropriate intervention, even when the patient is comatose. We need to promote bystander CPR, because the chances of this therapy helping the patient are much better if basic CPR has been performed.”

Some studies have also reported good outcome following therapeutic cooling in patients with severe TBI. Meta-analyses have reported a 22% to 48% reduction in the risk for adverse neurologic outcome in patients with severe TBI treated with therapeutic hypothermia, although not all these differences were statistically significant.

However, the treatment looks highly promising, according to Dr. Polderman. He pointed out for comparison that data on the use of barbiturates and mannitol do not show any benefit on neurologic outcome in patients with TBI.

Cooling in the Right Context
Although hypothermia has beneficial effects on neurologic outcome, “a treatment can only be effective if the other aspects of intensive care are good,” cautioned Dr. Polderman. Therefore, “context matters. It’s not just about cooling.”

When using hypothermia, temperature should be lowered rapidly, but rewarming should be done very slowly, noted Dr. Polderman. “If you do it rapidly, you could lose some or all of the protective effects of hypothermia,” he warned.

In addition, physicians should consider other aspects of ICU treatment, such as prevention of hypo- and hypercapnia, electrolyte disorders, hyperglycemia, and hypoglycemia. “All these things matter, and they may make all the difference,” he said. “Without getting that right, hypothermia can be an ineffective or even dangerous therapy.”

“The idea of context applies even more strongly to areas like severe TBI,” he asserted. “Speed and duration of cooling are important.” For patients with TBI who receive hypothermia, longer duration of cooling (ie, greater than 48 hours) and slow rewarming protocols are associated with better outcome. He noted that one way to determine the optimal duration of cooling in individual patients is to measure intracranial pressure. Intracranial pressure is both a marker of ongoing brain injury and a potential cause of additional injury.

“The use of hypothermia is not risk-free. There are severe side effects, which we should take into account, but the good news is that these can be fairly easily managed,” concluded Dr. Polderman.   

NASHVILLE—Therapeutic hypothermia is being used with increasing frequency to treat patients with neurologic injury from conditions such as stroke, cardiac arrest, and traumatic brain injury (TBI). “Induced hypothermia can sometimes be risky, but it’s potentially highly rewarding,” said Kees H. Polderman, MD, PhD, at the Society of Critical Care Medicine’s 38th Critical Care Congress. Effective use of hypothermia is strongly dependent on the quality of other aspects of ICU care; therefore, he recommended that clinicians give careful attention to all of these factors.

When interpreting findings from studies examining therapeutic hypothermia, “you should always look at where it’s being performed, the context in which this treatment is taking place, and what other aspects of care are similar to your own and which ones are different; then you can assess if you can reproduce those results in your own center, or if you need to adapt your policy a bit,” commented Dr. Polderman, Professor in Intensive Care Medicine at the Department of Critical Care, University of Pittsburgh Medical Center.

Goals of Therapeutic Hypothermia
Stroke, cardiac arrest, and, to a lesser extent, TBI are characterized by ischemia and reperfusion injury. After a period of ischemia, a series of destructive processes takes place in the injured cells of the brain. “The damage is ongoing while the patient is in your ICU or your emergency room,” said Dr. Polderman.

Therefore, the first goal of treatment with hypothermia is to try to limit this injury. “Hypothermia acts as a sort of blanket therapy,” he said. “It can interrupt every single one of these harmful processes, in contrast to many other therapies that we’ve tried in the past.”

Another goal is to treat brain edema, which may also play a role in some disease states—TBI being one example. For patients with brain edema, the approach to treatment is slightly different, requiring a longer period of cooling.

Controlling Brain Temperature
When using hypothermia for patients with neurologic injury, physicians should do their best to prevent fever, Dr. Polderman advised. “Most of our patients in the neurocritical care units develop fever at some point in their ICU stay. The more severe the injury, the more likely the chance that [the patient] will develop fever,” he said.

Fever is associated with longer length of stay, worse neurologic outcome, and higher mortality. In two studies involving patients with subarachnoid hemorrhage and intracerebral hemorrhage, researchers reported that even a minimal elevation in temperature to slightly greater than 37.5°C—not considered a real fever by some—had a significant adverse effect on outcome.

One explanation for this could be that brain temperature exceeds core temperature. “The destructive processes triggered by ischemia generate heat. Local brain edema makes it difficult to get rid of the excess heat, and this leads to overheating of the brain,” explained Dr. Polderman. “So fever after neurologic injury seems to be extremely harmful, and hypothermia seems to be really protective.”

Proven Efficacy
Three randomized controlled trials have assessed neurologic outcome in patients who underwent therapeutic hypothermia following witnessed cardiac arrest, with significant improvement seen in patients treated with hypothermia across all three studies, said Dr. Polderman. In addition, a number of nonrandomized studies have reported good outcomes following treatment with induced hypothermia.

Dr. Polderman and his colleagues conducted a prospective, multicenter study in which 64 patients with witnessed cardiac arrest underwent therapeutic hypothermia. The results have not yet been published as a full paper. In this study, 60% of patients with ventricular tachycardia/ventricular fibrillation (VT/VF) had a good neurologic outcome (defined as return to their home situation with no or only minimal neurologic impairment). In addition, 50% of patients with an initial rhythm of asystole who reached the hospital alive also had a good neurologic outcome.

“We should lose the pessimism surrounding patients with witnessed cardiac arrest, because the good outcome rates can be better than 50% in this category of patients when hypothermia has been used,” commented Dr. Polderman. “We need to get the cardiologist to do the appropriate intervention, even when the patient is comatose. We need to promote bystander CPR, because the chances of this therapy helping the patient are much better if basic CPR has been performed.”

Some studies have also reported good outcome following therapeutic cooling in patients with severe TBI. Meta-analyses have reported a 22% to 48% reduction in the risk for adverse neurologic outcome in patients with severe TBI treated with therapeutic hypothermia, although not all these differences were statistically significant.

However, the treatment looks highly promising, according to Dr. Polderman. He pointed out for comparison that data on the use of barbiturates and mannitol do not show any benefit on neurologic outcome in patients with TBI.

Cooling in the Right Context
Although hypothermia has beneficial effects on neurologic outcome, “a treatment can only be effective if the other aspects of intensive care are good,” cautioned Dr. Polderman. Therefore, “context matters. It’s not just about cooling.”

When using hypothermia, temperature should be lowered rapidly, but rewarming should be done very slowly, noted Dr. Polderman. “If you do it rapidly, you could lose some or all of the protective effects of hypothermia,” he warned.

In addition, physicians should consider other aspects of ICU treatment, such as prevention of hypo- and hypercapnia, electrolyte disorders, hyperglycemia, and hypoglycemia. “All these things matter, and they may make all the difference,” he said. “Without getting that right, hypothermia can be an ineffective or even dangerous therapy.”

“The idea of context applies even more strongly to areas like severe TBI,” he asserted. “Speed and duration of cooling are important.” For patients with TBI who receive hypothermia, longer duration of cooling (ie, greater than 48 hours) and slow rewarming protocols are associated with better outcome. He noted that one way to determine the optimal duration of cooling in individual patients is to measure intracranial pressure. Intracranial pressure is both a marker of ongoing brain injury and a potential cause of additional injury.

“The use of hypothermia is not risk-free. There are severe side effects, which we should take into account, but the good news is that these can be fairly easily managed,” concluded Dr. Polderman.   

STOWE, VT—US soldiers who have sustained a mild head injury have an increased risk for chronic posttraumatic headaches, which typically involve moderate to severe migraine-like pain and functional impairment, according to Jay Erickson, MD, PhD. Soldiers with posttraumatic headache are also likely to have a high burden of psychiatric comorbidity and sleep disturbance, he reported at the Headache Cooperative of New England’s 19th Annual Headache Symposium.

Among 5,000 soldiers who returned from deployment to Fort Lewis, Washington, in the summer of 2008, Dr. Erickson and colleagues found that 19% had had a concussion, and more than 90% of this group reported having headaches during the previous three months. About a third of the soldiers had headache onset within one week of head trauma, which meets the definition of a posttraumatic headache per the International Classification of Headache Disorders, Second Edition (ICHD-2).

“A mild head injury is a concussion,” noted Dr. Erickson, Lieutenant Colonel, US Army Medical Corps, and Director of the Neurology Residency Program at Madigan Army Medical Center (MAMC) in Tacoma, Washington. “To have a concussion, you don’t necessarily need to have a loss of consciousness.”

Evaluating and Treating Posttraumatic Headache
Dr. Erickson and colleagues conducted an observational, longitudinal study of 189 soldiers with chronic posttraumatic headaches secondary to mild head injury. The soldiers underwent a standardized clinical evaluation at baseline and were followed up three months later. The examination included a headache questionnaire and use of the Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT)-6, Posttraumatic Syndrome Checklist, and Patient Health Questionnaire (PHQ)-9.

The patients (96% male; mean age, 27) had had a mild head injury while deployed—80% had a mild head injury related to a blast exposure, while others had blunt trauma, a motor vehicle accident, a fall, injury due to fighting, and other accidents. Two-thirds had a concussion with loss of consciousness. About 52% had multiple concussions, and the average number of concussions per soldier was 2.2. The average time from headache onset until the soldiers were evaluated by Dr. Erickson’s group was 16.9 months, and half had had headaches for more than a year. “For many of them, this has been a very chronic process,” said Dr. Erickson.

Two-thirds of participants had moderate pain accompanying their headache, and 24% had severe headaches. Per the ICHD-2 criteria, 96% of these headaches would be classified as migraine-type headaches. In contrast, Lew et al found that 28% of posttraumatic headaches in civilians were migraine-like.

On average, the soldiers had a mean of 16 headache days per month, and half had 15 or more headache days per month during the previous three months. About 72% of the soldiers had severe disability from their headache, per MIDAS scores. Participants had used their acute medications, on average, 12 days per month.

“One-third used acute analgesics for 15 or more days per month and therefore had possible medication-overuse headache,” said Dr. Erickson. Two-thirds of the soldiers had inadequate headache relief with their acute medication, defined as complete or nearly complete relief of head pain within two hours of taking the medication and enabling the individual to return to normal activities.

Psychiatric Comorbidity
According to the PTSD Symptom Checklist, 41% of soldiers screened positive for PTSD, and an additional 21% were in the indeterminate range for PTSD. One-third screened positive for depression on the PHQ-9 scale, and 82% reported moderate or severe difficulty sleeping. Most (71%) reported regular nightmares. “We definitely try to address and treat these comorbid sleep conditions as well as the comorbid psychiatric conditions,” said Dr. Erickson. A number also reported cognitive symptoms, such as decreased concentration, memory impairment, and slowed thinking. “In my experience, the cognitive symptoms are  mostly related to sleep deprivation, anxiety, depression, medications, and alcohol,” noted Dr. Erickson. “Little of this is actually due to the traumatic injury to their brain.”

Treatment Recommendations
Thus far, no randomized controlled trials have been conducted regarding treatment for posttraumatic headache. However, the Defense and Veterans Brain Injury Coalition has developed treatment guidelines, and the Department of Defense has mandated screening for traumatic brain injury in all soldiers returning from deployment. For prophylactic agents in individuals with posttraumatic headache, the coalition recommends amitriptyline, propranolol, topiramate, or gabapentin. For acute therapies, it recommends NSAIDs, triptans, and then cautious use of combination analgesics, as well as trying to avoid narcotics.

Dr. Erickson and colleagues have prescribed triptans to three-quarters of soldiers and NSAIDs to 18% as acute headache medication. As for prophylactic therapies, the researchers have prescribed a tricyclic antidepressant to about half of soldiers, followed by topiramate, propranolol, and valproate. Nonpharmacologic treatment approaches, such as behavioral health, headache education class, and biofeedback therapy, have also been recommended by Dr. Erickson’s group.

“In this population at baseline, 20% were using an acute medication that provided adequate relief,” said Dr. Erickson. “With our treatments, we got that up to 64%.” About 79% of soldiers who were given a triptan reported having adequate two-hour headache relief, compared with 29% who were taking a nontriptan. “This provides evidence that triptans are effective in this population,” he added. “It also helps support the idea that in many of these [cases], the headache itself is a migraine or something very similar to a migraine.”

The response to prophylactic therapies for posttraumatic headache has been “disappointing,” however, said Dr. Erickson. “We don’t seem to have a robust response in terms of headache frequency in the short term,” he commented. “In comparison, if you look at patients with nontraumatic migraine in our clinic, we get a pretty robust response with the initial prophylactic agent. Likewise, patients with nontraumatic migraine who have PTSD also seem to have a pretty good response to prophylactic therapy. So traumatic migraine doesn’t seem to respond the same as nontraumatic migraine. Disability scores do decrease between baseline and follow-up, and I think this is largely related to the effectiveness of acute medications. The triptan is effective, so [soldiers] are less disabled from their headache attacks. If we were able to reduce headache frequency, then I would expect their disability to drop even further.

“Trying to treat their headache in isolation is not going to be as successful as trying to identify all of the problems that are contributing to it,” he continued. “It is important to follow these patients maybe a little bit more closely than you would a typical migraine patient, knowing that the response to prophylactic therapies is not quite as robust. I believe that these patients are going to need more adjustments of their treatment. Finally, I think patient education and expectations for recovery are key in this population.”

STOWE, VT—US soldiers who have sustained a mild head injury have an increased risk for chronic posttraumatic headaches, which typically involve moderate to severe migraine-like pain and functional impairment, according to Jay Erickson, MD, PhD. Soldiers with posttraumatic headache are also likely to have a high burden of psychiatric comorbidity and sleep disturbance, he reported at the Headache Cooperative of New England’s 19th Annual Headache Symposium.

Among 5,000 soldiers who returned from deployment to Fort Lewis, Washington, in the summer of 2008, Dr. Erickson and colleagues found that 19% had had a concussion, and more than 90% of this group reported having headaches during the previous three months. About a third of the soldiers had headache onset within one week of head trauma, which meets the definition of a posttraumatic headache per the International Classification of Headache Disorders, Second Edition (ICHD-2).

“A mild head injury is a concussion,” noted Dr. Erickson, Lieutenant Colonel, US Army Medical Corps, and Director of the Neurology Residency Program at Madigan Army Medical Center (MAMC) in Tacoma, Washington. “To have a concussion, you don’t necessarily need to have a loss of consciousness.”

Evaluating and Treating Posttraumatic Headache
Dr. Erickson and colleagues conducted an observational, longitudinal study of 189 soldiers with chronic posttraumatic headaches secondary to mild head injury. The soldiers underwent a standardized clinical evaluation at baseline and were followed up three months later. The examination included a headache questionnaire and use of the Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT)-6, Posttraumatic Syndrome Checklist, and Patient Health Questionnaire (PHQ)-9.

The patients (96% male; mean age, 27) had had a mild head injury while deployed—80% had a mild head injury related to a blast exposure, while others had blunt trauma, a motor vehicle accident, a fall, injury due to fighting, and other accidents. Two-thirds had a concussion with loss of consciousness. About 52% had multiple concussions, and the average number of concussions per soldier was 2.2. The average time from headache onset until the soldiers were evaluated by Dr. Erickson’s group was 16.9 months, and half had had headaches for more than a year. “For many of them, this has been a very chronic process,” said Dr. Erickson.

Two-thirds of participants had moderate pain accompanying their headache, and 24% had severe headaches. Per the ICHD-2 criteria, 96% of these headaches would be classified as migraine-type headaches. In contrast, Lew et al found that 28% of posttraumatic headaches in civilians were migraine-like.

On average, the soldiers had a mean of 16 headache days per month, and half had 15 or more headache days per month during the previous three months. About 72% of the soldiers had severe disability from their headache, per MIDAS scores. Participants had used their acute medications, on average, 12 days per month.

“One-third used acute analgesics for 15 or more days per month and therefore had possible medication-overuse headache,” said Dr. Erickson. Two-thirds of the soldiers had inadequate headache relief with their acute medication, defined as complete or nearly complete relief of head pain within two hours of taking the medication and enabling the individual to return to normal activities.

Psychiatric Comorbidity
According to the PTSD Symptom Checklist, 41% of soldiers screened positive for PTSD, and an additional 21% were in the indeterminate range for PTSD. One-third screened positive for depression on the PHQ-9 scale, and 82% reported moderate or severe difficulty sleeping. Most (71%) reported regular nightmares. “We definitely try to address and treat these comorbid sleep conditions as well as the comorbid psychiatric conditions,” said Dr. Erickson. A number also reported cognitive symptoms, such as decreased concentration, memory impairment, and slowed thinking. “In my experience, the cognitive symptoms are  mostly related to sleep deprivation, anxiety, depression, medications, and alcohol,” noted Dr. Erickson. “Little of this is actually due to the traumatic injury to their brain.”

Treatment Recommendations
Thus far, no randomized controlled trials have been conducted regarding treatment for posttraumatic headache. However, the Defense and Veterans Brain Injury Coalition has developed treatment guidelines, and the Department of Defense has mandated screening for traumatic brain injury in all soldiers returning from deployment. For prophylactic agents in individuals with posttraumatic headache, the coalition recommends amitriptyline, propranolol, topiramate, or gabapentin. For acute therapies, it recommends NSAIDs, triptans, and then cautious use of combination analgesics, as well as trying to avoid narcotics.

Dr. Erickson and colleagues have prescribed triptans to three-quarters of soldiers and NSAIDs to 18% as acute headache medication. As for prophylactic therapies, the researchers have prescribed a tricyclic antidepressant to about half of soldiers, followed by topiramate, propranolol, and valproate. Nonpharmacologic treatment approaches, such as behavioral health, headache education class, and biofeedback therapy, have also been recommended by Dr. Erickson’s group.

“In this population at baseline, 20% were using an acute medication that provided adequate relief,” said Dr. Erickson. “With our treatments, we got that up to 64%.” About 79% of soldiers who were given a triptan reported having adequate two-hour headache relief, compared with 29% who were taking a nontriptan. “This provides evidence that triptans are effective in this population,” he added. “It also helps support the idea that in many of these [cases], the headache itself is a migraine or something very similar to a migraine.”

The response to prophylactic therapies for posttraumatic headache has been “disappointing,” however, said Dr. Erickson. “We don’t seem to have a robust response in terms of headache frequency in the short term,” he commented. “In comparison, if you look at patients with nontraumatic migraine in our clinic, we get a pretty robust response with the initial prophylactic agent. Likewise, patients with nontraumatic migraine who have PTSD also seem to have a pretty good response to prophylactic therapy. So traumatic migraine doesn’t seem to respond the same as nontraumatic migraine. Disability scores do decrease between baseline and follow-up, and I think this is largely related to the effectiveness of acute medications. The triptan is effective, so [soldiers] are less disabled from their headache attacks. If we were able to reduce headache frequency, then I would expect their disability to drop even further.

“Trying to treat their headache in isolation is not going to be as successful as trying to identify all of the problems that are contributing to it,” he continued. “It is important to follow these patients maybe a little bit more closely than you would a typical migraine patient, knowing that the response to prophylactic therapies is not quite as robust. I believe that these patients are going to need more adjustments of their treatment. Finally, I think patient education and expectations for recovery are key in this population.”

STOWE, VT—US soldiers who have sustained a mild head injury have an increased risk for chronic posttraumatic headaches, which typically involve moderate to severe migraine-like pain and functional impairment, according to Jay Erickson, MD, PhD. Soldiers with posttraumatic headache are also likely to have a high burden of psychiatric comorbidity and sleep disturbance, he reported at the Headache Cooperative of New England’s 19th Annual Headache Symposium.

Among 5,000 soldiers who returned from deployment to Fort Lewis, Washington, in the summer of 2008, Dr. Erickson and colleagues found that 19% had had a concussion, and more than 90% of this group reported having headaches during the previous three months. About a third of the soldiers had headache onset within one week of head trauma, which meets the definition of a posttraumatic headache per the International Classification of Headache Disorders, Second Edition (ICHD-2).

“A mild head injury is a concussion,” noted Dr. Erickson, Lieutenant Colonel, US Army Medical Corps, and Director of the Neurology Residency Program at Madigan Army Medical Center (MAMC) in Tacoma, Washington. “To have a concussion, you don’t necessarily need to have a loss of consciousness.”

Evaluating and Treating Posttraumatic Headache
Dr. Erickson and colleagues conducted an observational, longitudinal study of 189 soldiers with chronic posttraumatic headaches secondary to mild head injury. The soldiers underwent a standardized clinical evaluation at baseline and were followed up three months later. The examination included a headache questionnaire and use of the Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT)-6, Posttraumatic Syndrome Checklist, and Patient Health Questionnaire (PHQ)-9.

The patients (96% male; mean age, 27) had had a mild head injury while deployed—80% had a mild head injury related to a blast exposure, while others had blunt trauma, a motor vehicle accident, a fall, injury due to fighting, and other accidents. Two-thirds had a concussion with loss of consciousness. About 52% had multiple concussions, and the average number of concussions per soldier was 2.2. The average time from headache onset until the soldiers were evaluated by Dr. Erickson’s group was 16.9 months, and half had had headaches for more than a year. “For many of them, this has been a very chronic process,” said Dr. Erickson.

Two-thirds of participants had moderate pain accompanying their headache, and 24% had severe headaches. Per the ICHD-2 criteria, 96% of these headaches would be classified as migraine-type headaches. In contrast, Lew et al found that 28% of posttraumatic headaches in civilians were migraine-like.

On average, the soldiers had a mean of 16 headache days per month, and half had 15 or more headache days per month during the previous three months. About 72% of the soldiers had severe disability from their headache, per MIDAS scores. Participants had used their acute medications, on average, 12 days per month.

“One-third used acute analgesics for 15 or more days per month and therefore had possible medication-overuse headache,” said Dr. Erickson. Two-thirds of the soldiers had inadequate headache relief with their acute medication, defined as complete or nearly complete relief of head pain within two hours of taking the medication and enabling the individual to return to normal activities.

Psychiatric Comorbidity
According to the PTSD Symptom Checklist, 41% of soldiers screened positive for PTSD, and an additional 21% were in the indeterminate range for PTSD. One-third screened positive for depression on the PHQ-9 scale, and 82% reported moderate or severe difficulty sleeping. Most (71%) reported regular nightmares. “We definitely try to address and treat these comorbid sleep conditions as well as the comorbid psychiatric conditions,” said Dr. Erickson. A number also reported cognitive symptoms, such as decreased concentration, memory impairment, and slowed thinking. “In my experience, the cognitive symptoms are  mostly related to sleep deprivation, anxiety, depression, medications, and alcohol,” noted Dr. Erickson. “Little of this is actually due to the traumatic injury to their brain.”

Treatment Recommendations
Thus far, no randomized controlled trials have been conducted regarding treatment for posttraumatic headache. However, the Defense and Veterans Brain Injury Coalition has developed treatment guidelines, and the Department of Defense has mandated screening for traumatic brain injury in all soldiers returning from deployment. For prophylactic agents in individuals with posttraumatic headache, the coalition recommends amitriptyline, propranolol, topiramate, or gabapentin. For acute therapies, it recommends NSAIDs, triptans, and then cautious use of combination analgesics, as well as trying to avoid narcotics.

Dr. Erickson and colleagues have prescribed triptans to three-quarters of soldiers and NSAIDs to 18% as acute headache medication. As for prophylactic therapies, the researchers have prescribed a tricyclic antidepressant to about half of soldiers, followed by topiramate, propranolol, and valproate. Nonpharmacologic treatment approaches, such as behavioral health, headache education class, and biofeedback therapy, have also been recommended by Dr. Erickson’s group.

“In this population at baseline, 20% were using an acute medication that provided adequate relief,” said Dr. Erickson. “With our treatments, we got that up to 64%.” About 79% of soldiers who were given a triptan reported having adequate two-hour headache relief, compared with 29% who were taking a nontriptan. “This provides evidence that triptans are effective in this population,” he added. “It also helps support the idea that in many of these [cases], the headache itself is a migraine or something very similar to a migraine.”

The response to prophylactic therapies for posttraumatic headache has been “disappointing,” however, said Dr. Erickson. “We don’t seem to have a robust response in terms of headache frequency in the short term,” he commented. “In comparison, if you look at patients with nontraumatic migraine in our clinic, we get a pretty robust response with the initial prophylactic agent. Likewise, patients with nontraumatic migraine who have PTSD also seem to have a pretty good response to prophylactic therapy. So traumatic migraine doesn’t seem to respond the same as nontraumatic migraine. Disability scores do decrease between baseline and follow-up, and I think this is largely related to the effectiveness of acute medications. The triptan is effective, so [soldiers] are less disabled from their headache attacks. If we were able to reduce headache frequency, then I would expect their disability to drop even further.

“Trying to treat their headache in isolation is not going to be as successful as trying to identify all of the problems that are contributing to it,” he continued. “It is important to follow these patients maybe a little bit more closely than you would a typical migraine patient, knowing that the response to prophylactic therapies is not quite as robust. I believe that these patients are going to need more adjustments of their treatment. Finally, I think patient education and expectations for recovery are key in this population.”