Traumatic Brain Injury

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

WASHINGTON, DC—Football helmet add-ons such as outer soft-shell layers, spray treatments, helmet pads, and fiber sheets may not significantly help lower the risk of concussions in athletes, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “Our study suggests that despite many products targeted at reducing concussions in players, there is no magic concussion prevention product on the market at this time,” said study author John Lloyd, PhD, of BRAINS, a company in San Antonio, Florida.

Researchers modified the standard drop test system, approved by the National Operating Committee on Standards for Athletic Equipment, by using a crash test dummy head and neck to more realistically simulate head impact. Sensors were placed in the dummy’s head to measure linear and angular rotational responses to helmet impacts at 10, 12, and 14 miles per hour.

Using this device, BRAINS researchers evaluated four football helmet add-ons: Guardian Cap, UnEqual Technologies’ Concussion Reduction Technology, Shockstrips, and Helmet Glide. Riddell Revolution Speed and Xenith X1 football helmets were outfitted with each of these add-ons and impacted five times from drop heights of 1.0, 1.5, and 2.0 meters. Linear acceleration, angular velocity, and angular accelerations of the head were measured in response to impacts.

The study found that compared with helmets without the add-ons, those fitted with the Guardian Cap, Concussion Reduction Technology, and Shockstrips reduced linear accelerations by about 11%, but only reduced angular accelerations by 2%, while Helmet Glide was shown to have no effect.

“These findings are important because angular accelerations are believed to be the major biomechanical forces involved in concussion,” said Dr. Lloyd. “Few add-on products have undergone even basic biomechanical evaluation. Hopefully, our research will lead to more rigorous testing of helmets and add-ons.”

The study was supported by BRAINS and the Seeing Stars Foundation.

WASHINGTON, DC—Football helmet add-ons such as outer soft-shell layers, spray treatments, helmet pads, and fiber sheets may not significantly help lower the risk of concussions in athletes, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “Our study suggests that despite many products targeted at reducing concussions in players, there is no magic concussion prevention product on the market at this time,” said study author John Lloyd, PhD, of BRAINS, a company in San Antonio, Florida.

Researchers modified the standard drop test system, approved by the National Operating Committee on Standards for Athletic Equipment, by using a crash test dummy head and neck to more realistically simulate head impact. Sensors were placed in the dummy’s head to measure linear and angular rotational responses to helmet impacts at 10, 12, and 14 miles per hour.

Using this device, BRAINS researchers evaluated four football helmet add-ons: Guardian Cap, UnEqual Technologies’ Concussion Reduction Technology, Shockstrips, and Helmet Glide. Riddell Revolution Speed and Xenith X1 football helmets were outfitted with each of these add-ons and impacted five times from drop heights of 1.0, 1.5, and 2.0 meters. Linear acceleration, angular velocity, and angular accelerations of the head were measured in response to impacts.

The study found that compared with helmets without the add-ons, those fitted with the Guardian Cap, Concussion Reduction Technology, and Shockstrips reduced linear accelerations by about 11%, but only reduced angular accelerations by 2%, while Helmet Glide was shown to have no effect.

“These findings are important because angular accelerations are believed to be the major biomechanical forces involved in concussion,” said Dr. Lloyd. “Few add-on products have undergone even basic biomechanical evaluation. Hopefully, our research will lead to more rigorous testing of helmets and add-ons.”

The study was supported by BRAINS and the Seeing Stars Foundation.

WASHINGTON, DC—Football helmet add-ons such as outer soft-shell layers, spray treatments, helmet pads, and fiber sheets may not significantly help lower the risk of concussions in athletes, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “Our study suggests that despite many products targeted at reducing concussions in players, there is no magic concussion prevention product on the market at this time,” said study author John Lloyd, PhD, of BRAINS, a company in San Antonio, Florida.

Researchers modified the standard drop test system, approved by the National Operating Committee on Standards for Athletic Equipment, by using a crash test dummy head and neck to more realistically simulate head impact. Sensors were placed in the dummy’s head to measure linear and angular rotational responses to helmet impacts at 10, 12, and 14 miles per hour.

Using this device, BRAINS researchers evaluated four football helmet add-ons: Guardian Cap, UnEqual Technologies’ Concussion Reduction Technology, Shockstrips, and Helmet Glide. Riddell Revolution Speed and Xenith X1 football helmets were outfitted with each of these add-ons and impacted five times from drop heights of 1.0, 1.5, and 2.0 meters. Linear acceleration, angular velocity, and angular accelerations of the head were measured in response to impacts.

The study found that compared with helmets without the add-ons, those fitted with the Guardian Cap, Concussion Reduction Technology, and Shockstrips reduced linear accelerations by about 11%, but only reduced angular accelerations by 2%, while Helmet Glide was shown to have no effect.

“These findings are important because angular accelerations are believed to be the major biomechanical forces involved in concussion,” said Dr. Lloyd. “Few add-on products have undergone even basic biomechanical evaluation. Hopefully, our research will lead to more rigorous testing of helmets and add-ons.”

The study was supported by BRAINS and the Seeing Stars Foundation.

Cerebral blood flow recovery could be a biomarker of outcomes in athletes following concussion, according to an imaging study published online ahead of print March 2 in JAMA Neurology. “To our knowledge, this study provides the first prospective evidence of reduced cerebral blood flow and subsequent recovery following concussion in a homogeneous sample of collegiate football athletes and also demonstrates the potential of quantified cerebral blood flow as an objective biomarker for concussion,” said lead author Timothy B. Meier, PhD, and his research colleagues. According to the investigators, the resolution of cerebral blood flow abnormalities closely mirrors that of previous reports from the animal literature and shows real-world validity for predicting outcome following concussion.

Dr. Meier, of the Mind Research Network/Lovelace Biomedical and Environmental Research Institute in Albuquerque, and colleagues enrolled 44 collegiate football athletes in a mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging. The study was conducted from March 2012 to December 2013.

Of the 44 football players, 17 were concussed and had serial imaging performed approximately one day, one week, and one month postconcussion. The study also included 27 healthy football players who served as a control group. All athletes reported no premorbid mood disorders, anxiety disorders, substance abuse, or alcohol abuse.

Arterial spin labeling MRI was used to collect voxelwise relative cerebral blood flow data at each visit. Neuropsychiatric evaluations and a brief cognitive screen also were performed at all three time points (ie, one day, one week, and one month). Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome (ie, number of days withheld from competition).

Cognitive (ie, simple reaction time) and neuropsychiatric symptoms at one day postconcussion resolved at either one week postinjury or one month postinjury. Imaging data suggested cross-sectional (ie, healthy vs concussed athletes) and longitudinal (ie, one day and one week vs one month postinjury) evidence of cerebral blood flow recovery in the right insular and superior temporal cortex. The researchers also found that cerebral blood flow in the dorsal midinsular cortex was decreased at one month postinjury in slower-to-recover athletes and was inversely related to the magnitude of initial psychiatric symptoms, as rated on the Hamilton Depression Scale and the Hamilton Anxiety Scale.

“The current results suggest that regional cerebral blood flow may provide an objective biomarker for tracking both normal and potentially pathologic recovery from concussion,” the researchers concluded.

Future studies identifying the time course of metabolic dysfunction following concussion and its relationship to cerebral blood flow are crucial to characterize the physiologic effect of concussion, according to the investigators. “Specifically, the cerebral metabolic rate of glucose, the cerebral metabolic rate of oxygen, and cerebral blood flow are tightly coupled in health, but become dysregulated following mild traumatic brain injury.”

—Glenn S. Williams

Cerebral blood flow recovery could be a biomarker of outcomes in athletes following concussion, according to an imaging study published online ahead of print March 2 in JAMA Neurology. “To our knowledge, this study provides the first prospective evidence of reduced cerebral blood flow and subsequent recovery following concussion in a homogeneous sample of collegiate football athletes and also demonstrates the potential of quantified cerebral blood flow as an objective biomarker for concussion,” said lead author Timothy B. Meier, PhD, and his research colleagues. According to the investigators, the resolution of cerebral blood flow abnormalities closely mirrors that of previous reports from the animal literature and shows real-world validity for predicting outcome following concussion.

Dr. Meier, of the Mind Research Network/Lovelace Biomedical and Environmental Research Institute in Albuquerque, and colleagues enrolled 44 collegiate football athletes in a mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging. The study was conducted from March 2012 to December 2013.

Of the 44 football players, 17 were concussed and had serial imaging performed approximately one day, one week, and one month postconcussion. The study also included 27 healthy football players who served as a control group. All athletes reported no premorbid mood disorders, anxiety disorders, substance abuse, or alcohol abuse.

Arterial spin labeling MRI was used to collect voxelwise relative cerebral blood flow data at each visit. Neuropsychiatric evaluations and a brief cognitive screen also were performed at all three time points (ie, one day, one week, and one month). Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome (ie, number of days withheld from competition).

Cognitive (ie, simple reaction time) and neuropsychiatric symptoms at one day postconcussion resolved at either one week postinjury or one month postinjury. Imaging data suggested cross-sectional (ie, healthy vs concussed athletes) and longitudinal (ie, one day and one week vs one month postinjury) evidence of cerebral blood flow recovery in the right insular and superior temporal cortex. The researchers also found that cerebral blood flow in the dorsal midinsular cortex was decreased at one month postinjury in slower-to-recover athletes and was inversely related to the magnitude of initial psychiatric symptoms, as rated on the Hamilton Depression Scale and the Hamilton Anxiety Scale.

“The current results suggest that regional cerebral blood flow may provide an objective biomarker for tracking both normal and potentially pathologic recovery from concussion,” the researchers concluded.

Future studies identifying the time course of metabolic dysfunction following concussion and its relationship to cerebral blood flow are crucial to characterize the physiologic effect of concussion, according to the investigators. “Specifically, the cerebral metabolic rate of glucose, the cerebral metabolic rate of oxygen, and cerebral blood flow are tightly coupled in health, but become dysregulated following mild traumatic brain injury.”

—Glenn S. Williams

Cerebral blood flow recovery could be a biomarker of outcomes in athletes following concussion, according to an imaging study published online ahead of print March 2 in JAMA Neurology. “To our knowledge, this study provides the first prospective evidence of reduced cerebral blood flow and subsequent recovery following concussion in a homogeneous sample of collegiate football athletes and also demonstrates the potential of quantified cerebral blood flow as an objective biomarker for concussion,” said lead author Timothy B. Meier, PhD, and his research colleagues. According to the investigators, the resolution of cerebral blood flow abnormalities closely mirrors that of previous reports from the animal literature and shows real-world validity for predicting outcome following concussion.

Dr. Meier, of the Mind Research Network/Lovelace Biomedical and Environmental Research Institute in Albuquerque, and colleagues enrolled 44 collegiate football athletes in a mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging. The study was conducted from March 2012 to December 2013.

Of the 44 football players, 17 were concussed and had serial imaging performed approximately one day, one week, and one month postconcussion. The study also included 27 healthy football players who served as a control group. All athletes reported no premorbid mood disorders, anxiety disorders, substance abuse, or alcohol abuse.

Arterial spin labeling MRI was used to collect voxelwise relative cerebral blood flow data at each visit. Neuropsychiatric evaluations and a brief cognitive screen also were performed at all three time points (ie, one day, one week, and one month). Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome (ie, number of days withheld from competition).

Cognitive (ie, simple reaction time) and neuropsychiatric symptoms at one day postconcussion resolved at either one week postinjury or one month postinjury. Imaging data suggested cross-sectional (ie, healthy vs concussed athletes) and longitudinal (ie, one day and one week vs one month postinjury) evidence of cerebral blood flow recovery in the right insular and superior temporal cortex. The researchers also found that cerebral blood flow in the dorsal midinsular cortex was decreased at one month postinjury in slower-to-recover athletes and was inversely related to the magnitude of initial psychiatric symptoms, as rated on the Hamilton Depression Scale and the Hamilton Anxiety Scale.

“The current results suggest that regional cerebral blood flow may provide an objective biomarker for tracking both normal and potentially pathologic recovery from concussion,” the researchers concluded.

Future studies identifying the time course of metabolic dysfunction following concussion and its relationship to cerebral blood flow are crucial to characterize the physiologic effect of concussion, according to the investigators. “Specifically, the cerebral metabolic rate of glucose, the cerebral metabolic rate of oxygen, and cerebral blood flow are tightly coupled in health, but become dysregulated following mild traumatic brain injury.”

—Glenn S. Williams

BALTIMORE—A common molecule may prolong cell survival in patients with serious neurologic conditions, according to research presented at the 59th Annual Meeting of the Biophysical Society. “The present findings could provide a new lead compound for the development of drug therapies for necrosis-related diseases such as traumatic brain injury [TBI], stroke, and myocardial infarction—conditions for which no effective drug-based treatments are currently available [that work by blocking necrosis],” said Abraham H. Parola, MSc, a Professor of Biophysical Chemistry at Ben-Gurion University of the Negev in Beer-Sheva, Israel. Prof. Parola is a visiting professor of Biophysical Chemistry and Director of Natural Sciences at New York University Shanghai.

Stroke, heart attack, and TBI are separate diseases with certain shared pathologies that achieve a common end—cell death and human injury due to hypoxia. In these diseases, a lack of blood supply to affected tissues begins a signaling pathway that ultimately halts the production of energy-releasing adenosine triphosphate (ATP) molecules, which ultimately leads to cell death.

By employing derivatives of humanin, a naturally occurring peptide encoded in the genome of cellular mitochondria, researchers are working to interrupt this process, buying precious time for tissues whose cellular mechanisms have ceased to function.

The humanin derivatives work by counteracting the decrease in ATP levels caused by necrosis. The researchers tested the effectiveness of the humanin analogues AGA(C8R)-HNG17 and AGA-HNG by treating neuronal cells with these peptides prior to exposure to a necrotic agent. Results showed that humanin analogues reduced necrosis.

Prof. Parola’s previous work dealt with membrane dynamics and the mechanism of action of antiangiogenesis drugs, which starve malignant tumor growths by preventing the supply of nutrients and oxygen to the fast-growing tissue. Prof. Parola also has studied various other biophysical and molecular medicine and diagnostic topics.

“A recent paper published by our group suggested the involvement of cardiolipin [a phospholipid in inner mitochondrial membranes] in the necrotic process,” Prof. Parola said. “During this work, we stumbled upon humanin, were intrigued by its antiapoptotic effect, and extended it to [an] antinecrotic effect.”

Prof. Parola and his colleagues also performed in vivo studies by treating mice with TBI with an HNG17 analogue, which successfully reduced cranial fluid buildup and lowered the mice’s motor impairment severity scores.

As the peptides Prof. Parola and his colleagues used are derivatives of naturally occurring humanin, an ideal treatment might involve a drug delivery system with the HNG17 as the lead compound. The delivery process would be aided by the peptides’ ability to penetrate the cell membrane without the use of additional reagents.

Future work for this research team will include further exploration of ischemic activity in liver cirrhosis, as induced by acetaminophen activity, in addition to a search for a synergistic effect between humanin and other antinecrotic agents, such as protease inhibitors, to increase the clinical potential of humanin.

BALTIMORE—A common molecule may prolong cell survival in patients with serious neurologic conditions, according to research presented at the 59th Annual Meeting of the Biophysical Society. “The present findings could provide a new lead compound for the development of drug therapies for necrosis-related diseases such as traumatic brain injury [TBI], stroke, and myocardial infarction—conditions for which no effective drug-based treatments are currently available [that work by blocking necrosis],” said Abraham H. Parola, MSc, a Professor of Biophysical Chemistry at Ben-Gurion University of the Negev in Beer-Sheva, Israel. Prof. Parola is a visiting professor of Biophysical Chemistry and Director of Natural Sciences at New York University Shanghai.

Stroke, heart attack, and TBI are separate diseases with certain shared pathologies that achieve a common end—cell death and human injury due to hypoxia. In these diseases, a lack of blood supply to affected tissues begins a signaling pathway that ultimately halts the production of energy-releasing adenosine triphosphate (ATP) molecules, which ultimately leads to cell death.

By employing derivatives of humanin, a naturally occurring peptide encoded in the genome of cellular mitochondria, researchers are working to interrupt this process, buying precious time for tissues whose cellular mechanisms have ceased to function.

The humanin derivatives work by counteracting the decrease in ATP levels caused by necrosis. The researchers tested the effectiveness of the humanin analogues AGA(C8R)-HNG17 and AGA-HNG by treating neuronal cells with these peptides prior to exposure to a necrotic agent. Results showed that humanin analogues reduced necrosis.

Prof. Parola’s previous work dealt with membrane dynamics and the mechanism of action of antiangiogenesis drugs, which starve malignant tumor growths by preventing the supply of nutrients and oxygen to the fast-growing tissue. Prof. Parola also has studied various other biophysical and molecular medicine and diagnostic topics.

“A recent paper published by our group suggested the involvement of cardiolipin [a phospholipid in inner mitochondrial membranes] in the necrotic process,” Prof. Parola said. “During this work, we stumbled upon humanin, were intrigued by its antiapoptotic effect, and extended it to [an] antinecrotic effect.”

Prof. Parola and his colleagues also performed in vivo studies by treating mice with TBI with an HNG17 analogue, which successfully reduced cranial fluid buildup and lowered the mice’s motor impairment severity scores.

As the peptides Prof. Parola and his colleagues used are derivatives of naturally occurring humanin, an ideal treatment might involve a drug delivery system with the HNG17 as the lead compound. The delivery process would be aided by the peptides’ ability to penetrate the cell membrane without the use of additional reagents.

Future work for this research team will include further exploration of ischemic activity in liver cirrhosis, as induced by acetaminophen activity, in addition to a search for a synergistic effect between humanin and other antinecrotic agents, such as protease inhibitors, to increase the clinical potential of humanin.

BALTIMORE—A common molecule may prolong cell survival in patients with serious neurologic conditions, according to research presented at the 59th Annual Meeting of the Biophysical Society. “The present findings could provide a new lead compound for the development of drug therapies for necrosis-related diseases such as traumatic brain injury [TBI], stroke, and myocardial infarction—conditions for which no effective drug-based treatments are currently available [that work by blocking necrosis],” said Abraham H. Parola, MSc, a Professor of Biophysical Chemistry at Ben-Gurion University of the Negev in Beer-Sheva, Israel. Prof. Parola is a visiting professor of Biophysical Chemistry and Director of Natural Sciences at New York University Shanghai.

Stroke, heart attack, and TBI are separate diseases with certain shared pathologies that achieve a common end—cell death and human injury due to hypoxia. In these diseases, a lack of blood supply to affected tissues begins a signaling pathway that ultimately halts the production of energy-releasing adenosine triphosphate (ATP) molecules, which ultimately leads to cell death.

By employing derivatives of humanin, a naturally occurring peptide encoded in the genome of cellular mitochondria, researchers are working to interrupt this process, buying precious time for tissues whose cellular mechanisms have ceased to function.

The humanin derivatives work by counteracting the decrease in ATP levels caused by necrosis. The researchers tested the effectiveness of the humanin analogues AGA(C8R)-HNG17 and AGA-HNG by treating neuronal cells with these peptides prior to exposure to a necrotic agent. Results showed that humanin analogues reduced necrosis.

Prof. Parola’s previous work dealt with membrane dynamics and the mechanism of action of antiangiogenesis drugs, which starve malignant tumor growths by preventing the supply of nutrients and oxygen to the fast-growing tissue. Prof. Parola also has studied various other biophysical and molecular medicine and diagnostic topics.

“A recent paper published by our group suggested the involvement of cardiolipin [a phospholipid in inner mitochondrial membranes] in the necrotic process,” Prof. Parola said. “During this work, we stumbled upon humanin, were intrigued by its antiapoptotic effect, and extended it to [an] antinecrotic effect.”

Prof. Parola and his colleagues also performed in vivo studies by treating mice with TBI with an HNG17 analogue, which successfully reduced cranial fluid buildup and lowered the mice’s motor impairment severity scores.

As the peptides Prof. Parola and his colleagues used are derivatives of naturally occurring humanin, an ideal treatment might involve a drug delivery system with the HNG17 as the lead compound. The delivery process would be aided by the peptides’ ability to penetrate the cell membrane without the use of additional reagents.

Future work for this research team will include further exploration of ischemic activity in liver cirrhosis, as induced by acetaminophen activity, in addition to a search for a synergistic effect between humanin and other antinecrotic agents, such as protease inhibitors, to increase the clinical potential of humanin.