References

2016

Blennow, K; Brody, D L; Kochanek, P M; Levin, H; McKee, A; Ribbers, G M; Yaffe, K; Zetterberg, H

Traumatic brain injuries Journal Article

In: Nature Reviews Disease Primers, vol. 2, 2016.

Abstract | Links | BibTeX | Tags: amyloid beta protein, Article, axonal injury, biological marker, BIOPHYSICS, blood, brain, BRAIN damage, cerebrospinal fluid, Chronic traumatic encephalopathy, computer assisted tomography, disease severity, endocrine disease, heredity, human, molecular pathology, neuropathology, nonhuman, nuclear magnetic resonance imaging, Pathophysiology, positron emission tomography, postconcussion syndrome, priority journal, protein aggregation, quality of life, screening, tau protein, traumatic brain injury

@article{Blennow2016,

title = {Traumatic brain injuries},

author = {Blennow, K and Brody, D L and Kochanek, P M and Levin, H and McKee, A and Ribbers, G M and Yaffe, K and Zetterberg, H},

doi = {10.1038/nrdp.2016.84},

year  = {2016},

date = {2016-01-01},

journal = {Nature Reviews Disease Primers},

volume = {2},

abstract = {Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury-the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators. © 2016 Macmillan Publishers Limited, part of Springer Nature.},

keywords = {amyloid beta protein, Article, axonal injury, biological marker, BIOPHYSICS, blood, brain, BRAIN damage, cerebrospinal fluid, Chronic traumatic encephalopathy, computer assisted tomography, disease severity, endocrine disease, heredity, human, molecular pathology, neuropathology, nonhuman, nuclear magnetic resonance imaging, Pathophysiology, positron emission tomography, postconcussion syndrome, priority journal, protein aggregation, quality of life, screening, tau protein, traumatic brain injury},

pubstate = {published},

tppubtype = {article}

}

Beiske, K K; Kostov, K H; Kostov, H

Rhythmic midtemporal discharge in a youth during light sleep Journal Article

In: Neurodiagnostic Journal, vol. 56, no. 1, pp. 32–36, 2016.

Abstract | Links | BibTeX | Tags: Adolescent, Article, Automobile Driving, Benign EEG pattern, car driving, case report, case reports, complication, computer assisted tomography, Concussion, Craniocerebral Trauma, drowsiness, EEG pattern, electroencephalogram, Electroencephalography, Epilepsy, epileptic discharge, febrile convulsion, football, Functional Laterality, head injury, hemispheric dominance, human, Humans, hyperventilation, Injuries, Light sleep, Male, neuroimaging, neurologic examination, nuclear magnetic resonance imaging, Pathophysiology, Patient treatment, Rhythmic midtemporal discharge, RMTD, SLEEP, Sleep research, spike wave, temporal lobe, temporal lobe epilepsy, theta rhythm, tonic clonic seizure, unconsciousness, wakefulness

Papa, L; Brophy, G M; Welch, R D; Lewis, L M; Braga, C F; Tan, C N; Ameli, N J; Lopez, M A; Haeussler, C A; Mendez Giordano, D I; Silvestri, S; Giordano, P; Weber, K D; Hill-Pryor, C; Hack, D C

Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury Journal Article

In: JAMA Neurology, vol. 73, no. 5, pp. 551–560, 2016.

Abstract | Links | BibTeX | Tags: adult, aged, American Indian, amnesia, area under the curve, Article, Asian, assault, bicycle, Black person, blood sampling, blunt trauma, brain concussion, Caucasian, cohort analysis, computer assisted tomography, controlled study, diagnostic accuracy, diagnostic test accuracy study, disorientation, emergency ward, falling, Female, Glasgow Coma Scale, glial fibrillary acidic protein, Hispanic, human, limit of detection, limit of quantitation, major clinical study, Male, mild to moderate traumatic brain injury, neurosurgery, pedestrian, priority journal, prospective study, sport injury, traffic accident, traumatic brain injury, traumatic intracranial lesion, ubiquitin, ubiquitin carboxy terminal hydrolase L1, unclassified drug, unconsciousness, very elderly

@article{Papa2016a,

title = {Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury},

author = {Papa, L and Brophy, G M and Welch, R D and Lewis, L M and Braga, C F and Tan, C N and Ameli, N J and Lopez, M A and Haeussler, C A and {Mendez Giordano}, D I and Silvestri, S and Giordano, P and Weber, K D and Hill-Pryor, C and Hack, D C},

doi = {10.1001/jamaneurol.2016.0039},

year  = {2016},

date = {2016-01-01},

journal = {JAMA Neurology},

volume = {73},

number = {5},

pages = {551--560},

abstract = {Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice. Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. Design, Setting, and Participants: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury. Main Outcomes and Measures: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention. Results: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0%[362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95%CI, 0.69-0.77) to 0.94 (95%CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95%CI, 0.02-0.50) to 0.67 (95%CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95%CI, 0.67-0.92) to 0.97 (95%CI, 0.93-1.00)for GFAP and 0.31 (95%CI, 0-0.63) to 0.77 (95%CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95%CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95%CI, 0-1.00) to 0.92 (95%CI, 0.83-1.00). Conclusions and Relevance: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period. © Copyright 2016 American Medical Association. All rights reserved.},

keywords = {adult, aged, American Indian, amnesia, area under the curve, Article, Asian, assault, bicycle, Black person, blood sampling, blunt trauma, brain concussion, Caucasian, cohort analysis, computer assisted tomography, controlled study, diagnostic accuracy, diagnostic test accuracy study, disorientation, emergency ward, falling, Female, Glasgow Coma Scale, glial fibrillary acidic protein, Hispanic, human, limit of detection, limit of quantitation, major clinical study, Male, mild to moderate traumatic brain injury, neurosurgery, pedestrian, priority journal, prospective study, sport injury, traffic accident, traumatic brain injury, traumatic intracranial lesion, ubiquitin, ubiquitin carboxy terminal hydrolase L1, unclassified drug, unconsciousness, very elderly},

pubstate = {published},

tppubtype = {article}

}

Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice. Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. Design, Setting, and Participants: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury. Main Outcomes and Measures: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention. Results: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0%[362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95%CI, 0.69-0.77) to 0.94 (95%CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95%CI, 0.02-0.50) to 0.67 (95%CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95%CI, 0.67-0.92) to 0.97 (95%CI, 0.93-1.00)for GFAP and 0.31 (95%CI, 0-0.63) to 0.77 (95%CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95%CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95%CI, 0-1.00) to 0.92 (95%CI, 0.83-1.00). Conclusions and Relevance: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period. © Copyright 2016 American Medical Association. All rights reserved.

2015

Morgan, C D; Zuckerman, S L; King, L E; Beaird, S E; Sills, A K; Solomon, G S

Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging Journal Article

In: Child's Nervous System, vol. 31, no. 12, pp. 2305–2309, 2015.

Abstract | Links | BibTeX | Tags: Adolescent, arachnoid cyst, Article, brain, Brain Injury, Child, Computed tomography (CT) neuroimaging, computer assisted tomography, Computer-Assisted, Concussion, cost effectiveness analysis, cost utility analysis, DECISION making, diagnostic value, DSM-IV, Female, human, Humans, image processing, Magnetic Resonance Imaging, Magnetic resonance imaging (MRI), major clinical study, Male, mild traumatic brain injury, neuroimaging, neurosurgery, nuclear magnetic resonance, nuclear magnetic resonance imaging, pathology, Post-Concussion Syndrome, postconcussion syndrome, Preschool, preschool child, priority journal, Radiography, Retrospective Studies, retrospective study, Sports, STATISTICS, Tomography, traumatic brain injury, X ray, X-Ray Computed

@article{Morgan2015,

title = {Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging},

author = {Morgan, C D and Zuckerman, S L and King, L E and Beaird, S E and Sills, A K and Solomon, G S},

doi = {10.1007/s00381-015-2916-y},

year  = {2015},

date = {2015-01-01},

journal = {Child's Nervous System},

volume = {31},

number = {12},

pages = {2305--2309},

abstract = {Purpose: Approximately 90% of concussions are transient, with symptoms resolving within 10\textendash14 days. However, a minority of patients remain symptomatic several months post-injury, a condition known as post-concussion syndrome (PCS). The treatment of these patients can be challenging. The goal of our study was to assess the utility and cost-effectiveness of neurologic imaging two or more weeks post-injury in a cohort of youth with PCS. Methods: We conducted a retrospective study of 52 pediatric patients with persistent post-concussion symptoms after 3 months. We collected demographics and neuroimaging results obtained greater than 2 weeks post-concussion. Neuroimaging ordered in the first 2 weeks post-concussion was excluded, except to determine the rate of re-imaging. Descriptive statistics and corresponding cost data were collected. Results: Of 52 patients with PCS, 23/52 (44 %) had neuroimaging at least 2 weeks after the initial injury, for a total of 32 diagnostic studies. In summary, 1/19 MRIs (5.3 %), 1/8 CTs (13 %), and 0/5 x-rays (0 %) yielded significant positive findings, none of which altered clinical management. Chronic phase neuroimaging estimated costs from these 52 pediatric patients totaled $129,025. We estimate the cost to identify a single positive finding was $21,000 for head CT and $104,500 for brain MRI. Conclusions: In this cohort of pediatric PCS patients, brain imaging in the chronic phase (defined as more than 2 weeks after concussion) was pursued in almost half the study sample, had low diagnostic yield, and had poor cost-effectiveness. Based on these results, outpatient management of pediatric patients with long-term post-concussive symptoms should rarely include repeat neuroimaging beyond the acute phase. © 2015, Springer-Verlag Berlin Heidelberg.},

keywords = {Adolescent, arachnoid cyst, Article, brain, Brain Injury, Child, Computed tomography (CT) neuroimaging, computer assisted tomography, Computer-Assisted, Concussion, cost effectiveness analysis, cost utility analysis, DECISION making, diagnostic value, DSM-IV, Female, human, Humans, image processing, Magnetic Resonance Imaging, Magnetic resonance imaging (MRI), major clinical study, Male, mild traumatic brain injury, neuroimaging, neurosurgery, nuclear magnetic resonance, nuclear magnetic resonance imaging, pathology, Post-Concussion Syndrome, postconcussion syndrome, Preschool, preschool child, priority journal, Radiography, Retrospective Studies, retrospective study, Sports, STATISTICS, Tomography, traumatic brain injury, X ray, X-Ray Computed},

pubstate = {published},

tppubtype = {article}

}

Phillips, S; Woessner, D

Sports-Related Traumatic Brain Injury Journal Article

In: Primary Care - Clinics in Office Practice, vol. 42, no. 2, pp. 243–248, 2015.

Abstract | Links | BibTeX | Tags: Anxiety, Athletic Injuries, attention deficit disorder, balance disorder, Balance Error Scoring System, benzodiazepine derivative, beta adrenergic receptor blocking agent, body equilibrium, brain concussion, Brain Injuries, clinical assessment tool, computer assisted tomography, Concussion, coordination disorder, depression, Dizziness, drowsiness, evaluation and follow up, headache, human, Humans, irritability, meclozine, memory disorder, mental concentration, Mild TBI guidelines, mild traumatic brain injury, mood change, mTBI, nausea, NFL Sideline Concussion Assessment Tool, nuclear magnetic resonance imaging, paracetamol, personal hygiene, postconcussion syndrome, Postconcussive syndrome, Primary Health Care, priority journal, procedures, recurrent disease, rest, Review, scoring system, Sideline Concussion Assessment Tool 3, Sideline concussion assessment tool 3 (SCAT3), sleep disorder, Sport, sport injury, Sports, Sports-related, Tomography, traumatic brain injury, tricyclic antidepressant agent, VERTIGO, visual disorder, vomiting, X-Ray Computed

@article{Phillips2015b,

title = {Sports-Related Traumatic Brain Injury},

author = {Phillips, S and Woessner, D},

doi = {10.1016/j.pop.2015.01.010},

year  = {2015},

date = {2015-01-01},

journal = {Primary Care - Clinics in Office Practice},

volume = {42},

number = {2},

pages = {243--248},

abstract = {Concussions have garnered more attention in the medical literature, media, and social media. As such, in the nomenclature according to the Centers for Disease Control and Prevention, the term concussion has been supplanted by the term mild traumatic brain injury. Current numbers indicate that 1.7 million TBIs are documented annually, with estimates around 3 million annually (173,285 sports- and recreation-related TBIs among children and adolescents). The Sideline Concussion Assessment Tool 3 and the NFL Sideline Concussion Assessment Tool are commonly used sideline tools. © 2015 Elsevier Inc.},

keywords = {Anxiety, Athletic Injuries, attention deficit disorder, balance disorder, Balance Error Scoring System, benzodiazepine derivative, beta adrenergic receptor blocking agent, body equilibrium, brain concussion, Brain Injuries, clinical assessment tool, computer assisted tomography, Concussion, coordination disorder, depression, Dizziness, drowsiness, evaluation and follow up, headache, human, Humans, irritability, meclozine, memory disorder, mental concentration, Mild TBI guidelines, mild traumatic brain injury, mood change, mTBI, nausea, NFL Sideline Concussion Assessment Tool, nuclear magnetic resonance imaging, paracetamol, personal hygiene, postconcussion syndrome, Postconcussive syndrome, Primary Health Care, priority journal, procedures, recurrent disease, rest, Review, scoring system, Sideline Concussion Assessment Tool 3, Sideline concussion assessment tool 3 (SCAT3), sleep disorder, Sport, sport injury, Sports, Sports-related, Tomography, traumatic brain injury, tricyclic antidepressant agent, VERTIGO, visual disorder, vomiting, X-Ray Computed},

pubstate = {published},

tppubtype = {article}

}

Stone Jr., M E; Safadjou, S; Farber, B; Velazco, N; Man, J; Reddy, S H; Todor, R; Teperman, S

Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population Journal Article

In: Journal of Trauma and Acute Care Surgery, vol. 79, no. 1, pp. 147–151, 2015.

Abstract | Links | BibTeX | Tags: Adolescent, adult, aged, Alcoholic Intoxication, amnesia, Article, assessment of humans, brain concussion, Brain Injuries, clinical assessment tool, computer assisted tomography, Concussion screening, Confounding Factors (Epidemiology), controlled study, DATA analysis, Demography, diagnostic test accuracy study, Dizziness, emergency health service, Female, Head, headache, hospital admission, human, Humans, injury severity, irritability, major clinical study, Male, middle aged, mild traumatic brain injury, Military Acute Concussion Evaluation, military medicine, nausea and vomiting, predictive value, priority journal, quality control, receiver operating characteristic, ROC Curve, screening test, Sensitivity and Specificity, traumatic brain injury, unconsciousness, Urban Population, visual disorder, Young Adult

@article{StoneJr.2015,

title = {Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population},

author = {{Stone Jr.}, M E and Safadjou, S and Farber, B and Velazco, N and Man, J and Reddy, S H and Todor, R and Teperman, S},

doi = {10.1097/TA.0000000000000679},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Trauma and Acute Care Surgery},

volume = {79},

number = {1},

pages = {147--151},

abstract = {BACKGROUND: Mild traumatic brain injury (mTBI) constitutes 75% of more than 1.5 million traumatic brain injuries annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian trauma is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in sports injury. As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian trauma population. METHODS: From June 2013 to May 2014, patients 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I trauma center. Patients with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as loss of consciousness and/or posttraumatic amnesia; concussed patients were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. RESULTS: There were 84 concussions and 30 nonconcussed patients. Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed patients. Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. CONCLUSION: The MACE showed a lower mean score for individuals with concussion, defined by loss of consciousness and/or posttraumatic amnesia. However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian trauma population. LEVEL OF EVIDENCE: Diagnostic study, level II. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.},

keywords = {Adolescent, adult, aged, Alcoholic Intoxication, amnesia, Article, assessment of humans, brain concussion, Brain Injuries, clinical assessment tool, computer assisted tomography, Concussion screening, Confounding Factors (Epidemiology), controlled study, DATA analysis, Demography, diagnostic test accuracy study, Dizziness, emergency health service, Female, Head, headache, hospital admission, human, Humans, injury severity, irritability, major clinical study, Male, middle aged, mild traumatic brain injury, Military Acute Concussion Evaluation, military medicine, nausea and vomiting, predictive value, priority journal, quality control, receiver operating characteristic, ROC Curve, screening test, Sensitivity and Specificity, traumatic brain injury, unconsciousness, Urban Population, visual disorder, Young Adult},

pubstate = {published},

tppubtype = {article}

}

BACKGROUND: Mild traumatic brain injury (mTBI) constitutes 75% of more than 1.5 million traumatic brain injuries annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian trauma is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in sports injury. As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian trauma population. METHODS: From June 2013 to May 2014, patients 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I trauma center. Patients with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as loss of consciousness and/or posttraumatic amnesia; concussed patients were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. RESULTS: There were 84 concussions and 30 nonconcussed patients. Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed patients. Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. CONCLUSION: The MACE showed a lower mean score for individuals with concussion, defined by loss of consciousness and/or posttraumatic amnesia. However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian trauma population. LEVEL OF EVIDENCE: Diagnostic study, level II. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Rapp, P E; Keyser, D O; Albano, A; Hernandez, R; Gibson, D B; Zambon, R A; David Hairston, W; Hughes, J D; Krystal, A; Nichols, A S

Traumatic brain injury detection using electrophysiological methods Journal Article

In: Frontiers in Human Neuroscience, vol. 9, no. FEB, 2015.

Abstract | Links | BibTeX | Tags: Article, brain electrophysiology, computer assisted tomography, Concussion, connectome, diagnostic accuracy, EEG, electroencephalogram, Electroencephalography, event related potential, Event-Related Potentials, evidence based medicine, executive function, human, intermethod comparison, latent period, neuroimaging, neuropathology, Non-linear dynamical analysis, nuclear magnetic resonance imaging, QEEG, Signal Processing, traumatic brain injury

@article{Rapp2015,

title = {Traumatic brain injury detection using electrophysiological methods},

author = {Rapp, P E and Keyser, D O and Albano, A and Hernandez, R and Gibson, D B and Zambon, R A and {David Hairston}, W and Hughes, J D and Krystal, A and Nichols, A S},

doi = {10.3389/fnhum.2015.00011},

year  = {2015},

date = {2015-01-01},

journal = {Frontiers in Human Neuroscience},

volume = {9},

number = {FEB},

abstract = {Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI).This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3)The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in qEEG evaluations of TBI must be interpreted with care. High specificities have been reported in carefully constructed clinical studies in which healthy controls were compared against a carefully selected TBI population. The published literature indicates, however, that similar abnormalities in qEEG measures are observed in other neuropsychiatric disorders. While it may be possible to distinguish a clinical patient from a healthy control participant with this technology, these measures are unlikely to discriminate between, for example, major depressive disorder, bipolar disorder, or TBI. The specificities observed in these clinical studies may well be lost in real world clinical practice. (5)The absence of specificity does not preclude clinical utility. The possibility of use as a longitudinal measure of treatment response remains. However, efficacy as a longitudinal clinical measure does require acceptable test-retest reliability. To date, very few test-retest reliability studies have been published with qEEG data obtained from TBI patients or from healthy controls. This is a particular concern because high variability is a known characteristic of the injured central nervous system. © 2015 Rapp, Keyser , Albano, Hernandez, Gibson, Zambon, Hairston, Hughes, Krystal and Nichols.},

keywords = {Article, brain electrophysiology, computer assisted tomography, Concussion, connectome, diagnostic accuracy, EEG, electroencephalogram, Electroencephalography, event related potential, Event-Related Potentials, evidence based medicine, executive function, human, intermethod comparison, latent period, neuroimaging, neuropathology, Non-linear dynamical analysis, nuclear magnetic resonance imaging, QEEG, Signal Processing, traumatic brain injury},

pubstate = {published},

tppubtype = {article}

}

Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI).This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3)The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in qEEG evaluations of TBI must be interpreted with care. High specificities have been reported in carefully constructed clinical studies in which healthy controls were compared against a carefully selected TBI population. The published literature indicates, however, that similar abnormalities in qEEG measures are observed in other neuropsychiatric disorders. While it may be possible to distinguish a clinical patient from a healthy control participant with this technology, these measures are unlikely to discriminate between, for example, major depressive disorder, bipolar disorder, or TBI. The specificities observed in these clinical studies may well be lost in real world clinical practice. (5)The absence of specificity does not preclude clinical utility. The possibility of use as a longitudinal measure of treatment response remains. However, efficacy as a longitudinal clinical measure does require acceptable test-retest reliability. To date, very few test-retest reliability studies have been published with qEEG data obtained from TBI patients or from healthy controls. This is a particular concern because high variability is a known characteristic of the injured central nervous system. © 2015 Rapp, Keyser , Albano, Hernandez, Gibson, Zambon, Hairston, Hughes, Krystal and Nichols.

Reference Search

Blennow, K; Brody, D L; Kochanek, P M; Levin, H; McKee, A; Ribbers, G M; Yaffe, K; Zetterberg, H

Traumatic brain injuries Journal Article

In: Nature Reviews Disease Primers, vol. 2, 2016.

Abstract | Links | BibTeX

Beiske, K K; Kostov, K H; Kostov, H

Rhythmic midtemporal discharge in a youth during light sleep Journal Article

In: Neurodiagnostic Journal, vol. 56, no. 1, pp. 32–36, 2016.

Abstract | Links | BibTeX

Papa, L; Brophy, G M; Welch, R D; Lewis, L M; Braga, C F; Tan, C N; Ameli, N J; Lopez, M A; Haeussler, C A; Mendez Giordano, D I; Silvestri, S; Giordano, P; Weber, K D; Hill-Pryor, C; Hack, D C

Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury Journal Article

In: JAMA Neurology, vol. 73, no. 5, pp. 551–560, 2016.

Abstract | Links | BibTeX

@article{Papa2016a,

title = {Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury},

author = {Papa, L and Brophy, G M and Welch, R D and Lewis, L M and Braga, C F and Tan, C N and Ameli, N J and Lopez, M A and Haeussler, C A and {Mendez Giordano}, D I and Silvestri, S and Giordano, P and Weber, K D and Hill-Pryor, C and Hack, D C},

doi = {10.1001/jamaneurol.2016.0039},

year  = {2016},

date = {2016-01-01},

journal = {JAMA Neurology},

volume = {73},

number = {5},

pages = {551--560},

abstract = {Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice. Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. Design, Setting, and Participants: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury. Main Outcomes and Measures: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention. Results: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0%[362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95%CI, 0.69-0.77) to 0.94 (95%CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95%CI, 0.02-0.50) to 0.67 (95%CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95%CI, 0.67-0.92) to 0.97 (95%CI, 0.93-1.00)for GFAP and 0.31 (95%CI, 0-0.63) to 0.77 (95%CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95%CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95%CI, 0-1.00) to 0.92 (95%CI, 0.83-1.00). Conclusions and Relevance: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period. © Copyright 2016 American Medical Association. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Morgan, C D; Zuckerman, S L; King, L E; Beaird, S E; Sills, A K; Solomon, G S

Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging Journal Article

In: Child's Nervous System, vol. 31, no. 12, pp. 2305–2309, 2015.

Abstract | Links | BibTeX

@article{Morgan2015,

title = {Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging},

author = {Morgan, C D and Zuckerman, S L and King, L E and Beaird, S E and Sills, A K and Solomon, G S},

doi = {10.1007/s00381-015-2916-y},

year  = {2015},

date = {2015-01-01},

journal = {Child's Nervous System},

volume = {31},

number = {12},

pages = {2305--2309},

abstract = {Purpose: Approximately 90% of concussions are transient, with symptoms resolving within 10\textendash14 days. However, a minority of patients remain symptomatic several months post-injury, a condition known as post-concussion syndrome (PCS). The treatment of these patients can be challenging. The goal of our study was to assess the utility and cost-effectiveness of neurologic imaging two or more weeks post-injury in a cohort of youth with PCS. Methods: We conducted a retrospective study of 52 pediatric patients with persistent post-concussion symptoms after 3 months. We collected demographics and neuroimaging results obtained greater than 2 weeks post-concussion. Neuroimaging ordered in the first 2 weeks post-concussion was excluded, except to determine the rate of re-imaging. Descriptive statistics and corresponding cost data were collected. Results: Of 52 patients with PCS, 23/52 (44 %) had neuroimaging at least 2 weeks after the initial injury, for a total of 32 diagnostic studies. In summary, 1/19 MRIs (5.3 %), 1/8 CTs (13 %), and 0/5 x-rays (0 %) yielded significant positive findings, none of which altered clinical management. Chronic phase neuroimaging estimated costs from these 52 pediatric patients totaled $129,025. We estimate the cost to identify a single positive finding was $21,000 for head CT and $104,500 for brain MRI. Conclusions: In this cohort of pediatric PCS patients, brain imaging in the chronic phase (defined as more than 2 weeks after concussion) was pursued in almost half the study sample, had low diagnostic yield, and had poor cost-effectiveness. Based on these results, outpatient management of pediatric patients with long-term post-concussive symptoms should rarely include repeat neuroimaging beyond the acute phase. © 2015, Springer-Verlag Berlin Heidelberg.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Phillips, S; Woessner, D

Sports-Related Traumatic Brain Injury Journal Article

In: Primary Care - Clinics in Office Practice, vol. 42, no. 2, pp. 243–248, 2015.

Abstract | Links | BibTeX

Stone Jr., M E; Safadjou, S; Farber, B; Velazco, N; Man, J; Reddy, S H; Todor, R; Teperman, S

Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population Journal Article

In: Journal of Trauma and Acute Care Surgery, vol. 79, no. 1, pp. 147–151, 2015.

Abstract | Links | BibTeX

@article{StoneJr.2015,

title = {Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population},

author = {{Stone Jr.}, M E and Safadjou, S and Farber, B and Velazco, N and Man, J and Reddy, S H and Todor, R and Teperman, S},

doi = {10.1097/TA.0000000000000679},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Trauma and Acute Care Surgery},

volume = {79},

number = {1},

pages = {147--151},

abstract = {BACKGROUND: Mild traumatic brain injury (mTBI) constitutes 75% of more than 1.5 million traumatic brain injuries annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian trauma is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in sports injury. As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian trauma population. METHODS: From June 2013 to May 2014, patients 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I trauma center. Patients with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as loss of consciousness and/or posttraumatic amnesia; concussed patients were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. RESULTS: There were 84 concussions and 30 nonconcussed patients. Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed patients. Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. CONCLUSION: The MACE showed a lower mean score for individuals with concussion, defined by loss of consciousness and/or posttraumatic amnesia. However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian trauma population. LEVEL OF EVIDENCE: Diagnostic study, level II. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Rapp, P E; Keyser, D O; Albano, A; Hernandez, R; Gibson, D B; Zambon, R A; David Hairston, W; Hughes, J D; Krystal, A; Nichols, A S

Traumatic brain injury detection using electrophysiological methods Journal Article

In: Frontiers in Human Neuroscience, vol. 9, no. FEB, 2015.

Abstract | Links | BibTeX

@article{Rapp2015,

title = {Traumatic brain injury detection using electrophysiological methods},

author = {Rapp, P E and Keyser, D O and Albano, A and Hernandez, R and Gibson, D B and Zambon, R A and {David Hairston}, W and Hughes, J D and Krystal, A and Nichols, A S},

doi = {10.3389/fnhum.2015.00011},

year  = {2015},

date = {2015-01-01},

journal = {Frontiers in Human Neuroscience},

volume = {9},

number = {FEB},

abstract = {Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI).This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3)The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in qEEG evaluations of TBI must be interpreted with care. High specificities have been reported in carefully constructed clinical studies in which healthy controls were compared against a carefully selected TBI population. The published literature indicates, however, that similar abnormalities in qEEG measures are observed in other neuropsychiatric disorders. While it may be possible to distinguish a clinical patient from a healthy control participant with this technology, these measures are unlikely to discriminate between, for example, major depressive disorder, bipolar disorder, or TBI. The specificities observed in these clinical studies may well be lost in real world clinical practice. (5)The absence of specificity does not preclude clinical utility. The possibility of use as a longitudinal measure of treatment response remains. However, efficacy as a longitudinal clinical measure does require acceptable test-retest reliability. To date, very few test-retest reliability studies have been published with qEEG data obtained from TBI patients or from healthy controls. This is a particular concern because high variability is a known characteristic of the injured central nervous system. © 2015 Rapp, Keyser , Albano, Hernandez, Gibson, Zambon, Hairston, Hughes, Krystal and Nichols.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Most Referenced Keywords

Show all

2016

Blennow, K; Brody, D L; Kochanek, P M; Levin, H; McKee, A; Ribbers, G M; Yaffe, K; Zetterberg, H

Traumatic brain injuries Journal Article

In: Nature Reviews Disease Primers, vol. 2, 2016.

@article{Blennow2016,

title = {Traumatic brain injuries},

author = {Blennow, K and Brody, D L and Kochanek, P M and Levin, H and McKee, A and Ribbers, G M and Yaffe, K and Zetterberg, H},

doi = {10.1038/nrdp.2016.84},

year  = {2016},

date = {2016-01-01},

journal = {Nature Reviews Disease Primers},

volume = {2},

abstract = {Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury-the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators. © 2016 Macmillan Publishers Limited, part of Springer Nature.},

keywords = {amyloid beta protein, Article, axonal injury, biological marker, BIOPHYSICS, blood, brain, BRAIN damage, cerebrospinal fluid, Chronic traumatic encephalopathy, computer assisted tomography, disease severity, endocrine disease, heredity, human, molecular pathology, neuropathology, nonhuman, nuclear magnetic resonance imaging, Pathophysiology, positron emission tomography, postconcussion syndrome, priority journal, protein aggregation, quality of life, screening, tau protein, traumatic brain injury},

pubstate = {published},

tppubtype = {article}

}

Beiske, K K; Kostov, K H; Kostov, H

Rhythmic midtemporal discharge in a youth during light sleep Journal Article

In: Neurodiagnostic Journal, vol. 56, no. 1, pp. 32–36, 2016.

Papa, L; Brophy, G M; Welch, R D; Lewis, L M; Braga, C F; Tan, C N; Ameli, N J; Lopez, M A; Haeussler, C A; Mendez Giordano, D I; Silvestri, S; Giordano, P; Weber, K D; Hill-Pryor, C; Hack, D C

Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury Journal Article

In: JAMA Neurology, vol. 73, no. 5, pp. 551–560, 2016.

@article{Papa2016a,

title = {Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury},

author = {Papa, L and Brophy, G M and Welch, R D and Lewis, L M and Braga, C F and Tan, C N and Ameli, N J and Lopez, M A and Haeussler, C A and {Mendez Giordano}, D I and Silvestri, S and Giordano, P and Weber, K D and Hill-Pryor, C and Hack, D C},

doi = {10.1001/jamaneurol.2016.0039},

year  = {2016},

date = {2016-01-01},

journal = {JAMA Neurology},

volume = {73},

number = {5},

pages = {551--560},

abstract = {Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice. Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. Design, Setting, and Participants: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury. Main Outcomes and Measures: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention. Results: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0%[362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95%CI, 0.69-0.77) to 0.94 (95%CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95%CI, 0.02-0.50) to 0.67 (95%CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95%CI, 0.67-0.92) to 0.97 (95%CI, 0.93-1.00)for GFAP and 0.31 (95%CI, 0-0.63) to 0.77 (95%CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95%CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95%CI, 0-1.00) to 0.92 (95%CI, 0.83-1.00). Conclusions and Relevance: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period. © Copyright 2016 American Medical Association. All rights reserved.},

keywords = {adult, aged, American Indian, amnesia, area under the curve, Article, Asian, assault, bicycle, Black person, blood sampling, blunt trauma, brain concussion, Caucasian, cohort analysis, computer assisted tomography, controlled study, diagnostic accuracy, diagnostic test accuracy study, disorientation, emergency ward, falling, Female, Glasgow Coma Scale, glial fibrillary acidic protein, Hispanic, human, limit of detection, limit of quantitation, major clinical study, Male, mild to moderate traumatic brain injury, neurosurgery, pedestrian, priority journal, prospective study, sport injury, traffic accident, traumatic brain injury, traumatic intracranial lesion, ubiquitin, ubiquitin carboxy terminal hydrolase L1, unclassified drug, unconsciousness, very elderly},

pubstate = {published},

tppubtype = {article}

}

2015

Morgan, C D; Zuckerman, S L; King, L E; Beaird, S E; Sills, A K; Solomon, G S

Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging Journal Article

In: Child's Nervous System, vol. 31, no. 12, pp. 2305–2309, 2015.

@article{Morgan2015,

title = {Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging},

author = {Morgan, C D and Zuckerman, S L and King, L E and Beaird, S E and Sills, A K and Solomon, G S},

doi = {10.1007/s00381-015-2916-y},

year  = {2015},

date = {2015-01-01},

journal = {Child's Nervous System},

volume = {31},

number = {12},

pages = {2305--2309},

abstract = {Purpose: Approximately 90% of concussions are transient, with symptoms resolving within 10\textendash14 days. However, a minority of patients remain symptomatic several months post-injury, a condition known as post-concussion syndrome (PCS). The treatment of these patients can be challenging. The goal of our study was to assess the utility and cost-effectiveness of neurologic imaging two or more weeks post-injury in a cohort of youth with PCS. Methods: We conducted a retrospective study of 52 pediatric patients with persistent post-concussion symptoms after 3 months. We collected demographics and neuroimaging results obtained greater than 2 weeks post-concussion. Neuroimaging ordered in the first 2 weeks post-concussion was excluded, except to determine the rate of re-imaging. Descriptive statistics and corresponding cost data were collected. Results: Of 52 patients with PCS, 23/52 (44 %) had neuroimaging at least 2 weeks after the initial injury, for a total of 32 diagnostic studies. In summary, 1/19 MRIs (5.3 %), 1/8 CTs (13 %), and 0/5 x-rays (0 %) yielded significant positive findings, none of which altered clinical management. Chronic phase neuroimaging estimated costs from these 52 pediatric patients totaled $129,025. We estimate the cost to identify a single positive finding was $21,000 for head CT and $104,500 for brain MRI. Conclusions: In this cohort of pediatric PCS patients, brain imaging in the chronic phase (defined as more than 2 weeks after concussion) was pursued in almost half the study sample, had low diagnostic yield, and had poor cost-effectiveness. Based on these results, outpatient management of pediatric patients with long-term post-concussive symptoms should rarely include repeat neuroimaging beyond the acute phase. © 2015, Springer-Verlag Berlin Heidelberg.},

keywords = {Adolescent, arachnoid cyst, Article, brain, Brain Injury, Child, Computed tomography (CT) neuroimaging, computer assisted tomography, Computer-Assisted, Concussion, cost effectiveness analysis, cost utility analysis, DECISION making, diagnostic value, DSM-IV, Female, human, Humans, image processing, Magnetic Resonance Imaging, Magnetic resonance imaging (MRI), major clinical study, Male, mild traumatic brain injury, neuroimaging, neurosurgery, nuclear magnetic resonance, nuclear magnetic resonance imaging, pathology, Post-Concussion Syndrome, postconcussion syndrome, Preschool, preschool child, priority journal, Radiography, Retrospective Studies, retrospective study, Sports, STATISTICS, Tomography, traumatic brain injury, X ray, X-Ray Computed},

pubstate = {published},

tppubtype = {article}

}

Phillips, S; Woessner, D

Sports-Related Traumatic Brain Injury Journal Article

In: Primary Care - Clinics in Office Practice, vol. 42, no. 2, pp. 243–248, 2015.

@article{Phillips2015b,

title = {Sports-Related Traumatic Brain Injury},

author = {Phillips, S and Woessner, D},

doi = {10.1016/j.pop.2015.01.010},

year  = {2015},

date = {2015-01-01},

journal = {Primary Care - Clinics in Office Practice},

volume = {42},

number = {2},

pages = {243--248},

abstract = {Concussions have garnered more attention in the medical literature, media, and social media. As such, in the nomenclature according to the Centers for Disease Control and Prevention, the term concussion has been supplanted by the term mild traumatic brain injury. Current numbers indicate that 1.7 million TBIs are documented annually, with estimates around 3 million annually (173,285 sports- and recreation-related TBIs among children and adolescents). The Sideline Concussion Assessment Tool 3 and the NFL Sideline Concussion Assessment Tool are commonly used sideline tools. © 2015 Elsevier Inc.},

keywords = {Anxiety, Athletic Injuries, attention deficit disorder, balance disorder, Balance Error Scoring System, benzodiazepine derivative, beta adrenergic receptor blocking agent, body equilibrium, brain concussion, Brain Injuries, clinical assessment tool, computer assisted tomography, Concussion, coordination disorder, depression, Dizziness, drowsiness, evaluation and follow up, headache, human, Humans, irritability, meclozine, memory disorder, mental concentration, Mild TBI guidelines, mild traumatic brain injury, mood change, mTBI, nausea, NFL Sideline Concussion Assessment Tool, nuclear magnetic resonance imaging, paracetamol, personal hygiene, postconcussion syndrome, Postconcussive syndrome, Primary Health Care, priority journal, procedures, recurrent disease, rest, Review, scoring system, Sideline Concussion Assessment Tool 3, Sideline concussion assessment tool 3 (SCAT3), sleep disorder, Sport, sport injury, Sports, Sports-related, Tomography, traumatic brain injury, tricyclic antidepressant agent, VERTIGO, visual disorder, vomiting, X-Ray Computed},

pubstate = {published},

tppubtype = {article}

}

Stone Jr., M E; Safadjou, S; Farber, B; Velazco, N; Man, J; Reddy, S H; Todor, R; Teperman, S

Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population Journal Article

In: Journal of Trauma and Acute Care Surgery, vol. 79, no. 1, pp. 147–151, 2015.

@article{StoneJr.2015,

title = {Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population},

author = {{Stone Jr.}, M E and Safadjou, S and Farber, B and Velazco, N and Man, J and Reddy, S H and Todor, R and Teperman, S},

doi = {10.1097/TA.0000000000000679},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Trauma and Acute Care Surgery},

volume = {79},

number = {1},

pages = {147--151},

abstract = {BACKGROUND: Mild traumatic brain injury (mTBI) constitutes 75% of more than 1.5 million traumatic brain injuries annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian trauma is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in sports injury. As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian trauma population. METHODS: From June 2013 to May 2014, patients 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I trauma center. Patients with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as loss of consciousness and/or posttraumatic amnesia; concussed patients were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. RESULTS: There were 84 concussions and 30 nonconcussed patients. Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed patients. Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. CONCLUSION: The MACE showed a lower mean score for individuals with concussion, defined by loss of consciousness and/or posttraumatic amnesia. However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian trauma population. LEVEL OF EVIDENCE: Diagnostic study, level II. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.},

keywords = {Adolescent, adult, aged, Alcoholic Intoxication, amnesia, Article, assessment of humans, brain concussion, Brain Injuries, clinical assessment tool, computer assisted tomography, Concussion screening, Confounding Factors (Epidemiology), controlled study, DATA analysis, Demography, diagnostic test accuracy study, Dizziness, emergency health service, Female, Head, headache, hospital admission, human, Humans, injury severity, irritability, major clinical study, Male, middle aged, mild traumatic brain injury, Military Acute Concussion Evaluation, military medicine, nausea and vomiting, predictive value, priority journal, quality control, receiver operating characteristic, ROC Curve, screening test, Sensitivity and Specificity, traumatic brain injury, unconsciousness, Urban Population, visual disorder, Young Adult},

pubstate = {published},

tppubtype = {article}

}

Rapp, P E; Keyser, D O; Albano, A; Hernandez, R; Gibson, D B; Zambon, R A; David Hairston, W; Hughes, J D; Krystal, A; Nichols, A S

Traumatic brain injury detection using electrophysiological methods Journal Article

In: Frontiers in Human Neuroscience, vol. 9, no. FEB, 2015.

@article{Rapp2015,

title = {Traumatic brain injury detection using electrophysiological methods},

author = {Rapp, P E and Keyser, D O and Albano, A and Hernandez, R and Gibson, D B and Zambon, R A and {David Hairston}, W and Hughes, J D and Krystal, A and Nichols, A S},

doi = {10.3389/fnhum.2015.00011},

year  = {2015},

date = {2015-01-01},

journal = {Frontiers in Human Neuroscience},

volume = {9},

number = {FEB},

abstract = {Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI).This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3)The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in qEEG evaluations of TBI must be interpreted with care. High specificities have been reported in carefully constructed clinical studies in which healthy controls were compared against a carefully selected TBI population. The published literature indicates, however, that similar abnormalities in qEEG measures are observed in other neuropsychiatric disorders. While it may be possible to distinguish a clinical patient from a healthy control participant with this technology, these measures are unlikely to discriminate between, for example, major depressive disorder, bipolar disorder, or TBI. The specificities observed in these clinical studies may well be lost in real world clinical practice. (5)The absence of specificity does not preclude clinical utility. The possibility of use as a longitudinal measure of treatment response remains. However, efficacy as a longitudinal clinical measure does require acceptable test-retest reliability. To date, very few test-retest reliability studies have been published with qEEG data obtained from TBI patients or from healthy controls. This is a particular concern because high variability is a known characteristic of the injured central nervous system. © 2015 Rapp, Keyser , Albano, Hernandez, Gibson, Zambon, Hairston, Hughes, Krystal and Nichols.},

keywords = {Article, brain electrophysiology, computer assisted tomography, Concussion, connectome, diagnostic accuracy, EEG, electroencephalogram, Electroencephalography, event related potential, Event-Related Potentials, evidence based medicine, executive function, human, intermethod comparison, latent period, neuroimaging, neuropathology, Non-linear dynamical analysis, nuclear magnetic resonance imaging, QEEG, Signal Processing, traumatic brain injury},

pubstate = {published},

tppubtype = {article}

}

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