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
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}
}
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}
}
Mitsis, E M; Riggio, S; Kostakoglu, L; Dickstein, D L; Machac, J; Delman, B; Goldstein, M; Jennings, D; D'Antonio, E; Martin, J; Naidich, T P; Aloysi, A; Fernandez, C; Seibyl, J; DeKosky, S T; Elder, G A; Marek, K; Gordon, W; Hof, P R; Sano, M; Gandy, S
In: Translational Psychiatry, vol. 4, no. 9, 2014.
Abstract | Links | BibTeX | Tags: adult, aged, amyloid plaque, arachnoid cyst, Article, case report, Chronic Traumatic Encephalopathy florbetapir f 18, Concussion, diagnostic accuracy, eye movement, football, frontotemporal dementia, head injury, human, injury severity, ligand binding, Male, memory disorder, middle aged, molecular imaging, motor dysfunction, muscle tone, personality disorder, positron emission tomography, short term memory, subdural hematoma, tauopathy, traumatic brain injury
@article{Mitsis2014,
title = {Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: Studies of a retired NFL player and of a man with FTD and a severe head injury},
author = {Mitsis, E M and Riggio, S and Kostakoglu, L and Dickstein, D L and Machac, J and Delman, B and Goldstein, M and Jennings, D and D'Antonio, E and Martin, J and Naidich, T P and Aloysi, A and Fernandez, C and Seibyl, J and DeKosky, S T and Elder, G A and Marek, K and Gordon, W and Hof, P R and Sano, M and Gandy, S},
url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84918535750\&partnerID=40\&md5=704b918a7429432cbd631e703c44eb63},
doi = {10.1038/tp.2014.91},
year = {2014},
date = {2014-01-01},
journal = {Translational Psychiatry},
volume = {4},
number = {9},
abstract = {Single, severe traumatic brain injury (TBI) which elevates CNS amyloid, increases the risk of Alzheimer's disease (AD); while repetitive concussive and subconcussive events as observed in athletes and military personnel, may increase the risk of chronic traumatic encephalopathy (CTE). We describe two clinical cases, one with a history of multiple concussions during a career in the National Football League (NFL) and the second with frontotemporal dementia and a single, severe TBI. Both patients presented with cognitive decline and underwent [18F]-Florbetapir positron emission tomography (PET) imaging for amyloid plaques; the retired NFL player also underwent [18F]-T807 PET imaging, a new ligand binding to tau, the main constituent of neurofibrillary tangles (NFT). Case 1, the former NFL player, was 71 years old when he presented with memory impairment and a clinical profile highly similar to AD. [18F]-Florbetapir PET imaging was negative, essentially excluding AD as a diagnosis. CTE was suspected clinically, and [18F]-T807 PET imaging revealed striatal and nigral [18F]-T807 retention consistent with the presence of tauopathy. Case 2 was a 56- year-old man with personality changes and cognitive decline who had sustained a fall complicated by a subdural hematoma. At 1 year post injury, [18F]-Florbetapir PET imaging was negative for an AD pattern of amyloid accumulation in this subject. Focal [18F]- Florbetapir retention was noted at the site of impact. In case 1, amyloid imaging provided improved diagnostic accuracy where standard clinical and laboratory criteria were inadequate. In that same case, tau imaging with [18F]-T807 revealed a subcortical tauopathy that we interpret as a novel form of CTE with a distribution of tauopathy that mimics, to some extent, that of progressive supranuclear palsy (PSP), despite a clinical presentation of amnesia without any movement disorder complaints or signs. A key distinguishing feature is that our patient presented with hippocampal involvement, which is more frequently seen in CTE than in PSP. In case 2, focal [18F]-Florbetapir retention at the site of injury in an otherwise negative scan suggests focal amyloid aggregation. In each of these complex cases, a combination of [18F]-fluorodeoxyglucose, [18F]-Florbetapir and/or [18F]-T807 PET molecular imaging improved the accuracy of diagnosis and prevented inappropriate interventions. © 2014 Macmillan Publishers Limited.},
keywords = {adult, aged, amyloid plaque, arachnoid cyst, Article, case report, Chronic Traumatic Encephalopathy florbetapir f 18, Concussion, diagnostic accuracy, eye movement, football, frontotemporal dementia, head injury, human, injury severity, ligand binding, Male, memory disorder, middle aged, molecular imaging, motor dysfunction, muscle tone, personality disorder, positron emission tomography, short term memory, subdural hematoma, tauopathy, traumatic brain injury},
pubstate = {published},
tppubtype = {article}
}
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
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 = {},
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 = {},
pubstate = {published},
tppubtype = {article}
}
Mitsis, E M; Riggio, S; Kostakoglu, L; Dickstein, D L; Machac, J; Delman, B; Goldstein, M; Jennings, D; D'Antonio, E; Martin, J; Naidich, T P; Aloysi, A; Fernandez, C; Seibyl, J; DeKosky, S T; Elder, G A; Marek, K; Gordon, W; Hof, P R; Sano, M; Gandy, S
In: Translational Psychiatry, vol. 4, no. 9, 2014.
@article{Mitsis2014,
title = {Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: Studies of a retired NFL player and of a man with FTD and a severe head injury},
author = {Mitsis, E M and Riggio, S and Kostakoglu, L and Dickstein, D L and Machac, J and Delman, B and Goldstein, M and Jennings, D and D'Antonio, E and Martin, J and Naidich, T P and Aloysi, A and Fernandez, C and Seibyl, J and DeKosky, S T and Elder, G A and Marek, K and Gordon, W and Hof, P R and Sano, M and Gandy, S},
url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84918535750\&partnerID=40\&md5=704b918a7429432cbd631e703c44eb63},
doi = {10.1038/tp.2014.91},
year = {2014},
date = {2014-01-01},
journal = {Translational Psychiatry},
volume = {4},
number = {9},
abstract = {Single, severe traumatic brain injury (TBI) which elevates CNS amyloid, increases the risk of Alzheimer's disease (AD); while repetitive concussive and subconcussive events as observed in athletes and military personnel, may increase the risk of chronic traumatic encephalopathy (CTE). We describe two clinical cases, one with a history of multiple concussions during a career in the National Football League (NFL) and the second with frontotemporal dementia and a single, severe TBI. Both patients presented with cognitive decline and underwent [18F]-Florbetapir positron emission tomography (PET) imaging for amyloid plaques; the retired NFL player also underwent [18F]-T807 PET imaging, a new ligand binding to tau, the main constituent of neurofibrillary tangles (NFT). Case 1, the former NFL player, was 71 years old when he presented with memory impairment and a clinical profile highly similar to AD. [18F]-Florbetapir PET imaging was negative, essentially excluding AD as a diagnosis. CTE was suspected clinically, and [18F]-T807 PET imaging revealed striatal and nigral [18F]-T807 retention consistent with the presence of tauopathy. Case 2 was a 56- year-old man with personality changes and cognitive decline who had sustained a fall complicated by a subdural hematoma. At 1 year post injury, [18F]-Florbetapir PET imaging was negative for an AD pattern of amyloid accumulation in this subject. Focal [18F]- Florbetapir retention was noted at the site of impact. In case 1, amyloid imaging provided improved diagnostic accuracy where standard clinical and laboratory criteria were inadequate. In that same case, tau imaging with [18F]-T807 revealed a subcortical tauopathy that we interpret as a novel form of CTE with a distribution of tauopathy that mimics, to some extent, that of progressive supranuclear palsy (PSP), despite a clinical presentation of amnesia without any movement disorder complaints or signs. A key distinguishing feature is that our patient presented with hippocampal involvement, which is more frequently seen in CTE than in PSP. In case 2, focal [18F]-Florbetapir retention at the site of injury in an otherwise negative scan suggests focal amyloid aggregation. In each of these complex cases, a combination of [18F]-fluorodeoxyglucose, [18F]-Florbetapir and/or [18F]-T807 PET molecular imaging improved the accuracy of diagnosis and prevented inappropriate interventions. © 2014 Macmillan Publishers Limited.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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
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}
}
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}
}
Mitsis, E M; Riggio, S; Kostakoglu, L; Dickstein, D L; Machac, J; Delman, B; Goldstein, M; Jennings, D; D'Antonio, E; Martin, J; Naidich, T P; Aloysi, A; Fernandez, C; Seibyl, J; DeKosky, S T; Elder, G A; Marek, K; Gordon, W; Hof, P R; Sano, M; Gandy, S
In: Translational Psychiatry, vol. 4, no. 9, 2014.
Abstract | Links | BibTeX | Tags: adult, aged, amyloid plaque, arachnoid cyst, Article, case report, Chronic Traumatic Encephalopathy florbetapir f 18, Concussion, diagnostic accuracy, eye movement, football, frontotemporal dementia, head injury, human, injury severity, ligand binding, Male, memory disorder, middle aged, molecular imaging, motor dysfunction, muscle tone, personality disorder, positron emission tomography, short term memory, subdural hematoma, tauopathy, traumatic brain injury
@article{Mitsis2014,
title = {Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: Studies of a retired NFL player and of a man with FTD and a severe head injury},
author = {Mitsis, E M and Riggio, S and Kostakoglu, L and Dickstein, D L and Machac, J and Delman, B and Goldstein, M and Jennings, D and D'Antonio, E and Martin, J and Naidich, T P and Aloysi, A and Fernandez, C and Seibyl, J and DeKosky, S T and Elder, G A and Marek, K and Gordon, W and Hof, P R and Sano, M and Gandy, S},
url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84918535750\&partnerID=40\&md5=704b918a7429432cbd631e703c44eb63},
doi = {10.1038/tp.2014.91},
year = {2014},
date = {2014-01-01},
journal = {Translational Psychiatry},
volume = {4},
number = {9},
abstract = {Single, severe traumatic brain injury (TBI) which elevates CNS amyloid, increases the risk of Alzheimer's disease (AD); while repetitive concussive and subconcussive events as observed in athletes and military personnel, may increase the risk of chronic traumatic encephalopathy (CTE). We describe two clinical cases, one with a history of multiple concussions during a career in the National Football League (NFL) and the second with frontotemporal dementia and a single, severe TBI. Both patients presented with cognitive decline and underwent [18F]-Florbetapir positron emission tomography (PET) imaging for amyloid plaques; the retired NFL player also underwent [18F]-T807 PET imaging, a new ligand binding to tau, the main constituent of neurofibrillary tangles (NFT). Case 1, the former NFL player, was 71 years old when he presented with memory impairment and a clinical profile highly similar to AD. [18F]-Florbetapir PET imaging was negative, essentially excluding AD as a diagnosis. CTE was suspected clinically, and [18F]-T807 PET imaging revealed striatal and nigral [18F]-T807 retention consistent with the presence of tauopathy. Case 2 was a 56- year-old man with personality changes and cognitive decline who had sustained a fall complicated by a subdural hematoma. At 1 year post injury, [18F]-Florbetapir PET imaging was negative for an AD pattern of amyloid accumulation in this subject. Focal [18F]- Florbetapir retention was noted at the site of impact. In case 1, amyloid imaging provided improved diagnostic accuracy where standard clinical and laboratory criteria were inadequate. In that same case, tau imaging with [18F]-T807 revealed a subcortical tauopathy that we interpret as a novel form of CTE with a distribution of tauopathy that mimics, to some extent, that of progressive supranuclear palsy (PSP), despite a clinical presentation of amnesia without any movement disorder complaints or signs. A key distinguishing feature is that our patient presented with hippocampal involvement, which is more frequently seen in CTE than in PSP. In case 2, focal [18F]-Florbetapir retention at the site of injury in an otherwise negative scan suggests focal amyloid aggregation. In each of these complex cases, a combination of [18F]-fluorodeoxyglucose, [18F]-Florbetapir and/or [18F]-T807 PET molecular imaging improved the accuracy of diagnosis and prevented inappropriate interventions. © 2014 Macmillan Publishers Limited.},
keywords = {adult, aged, amyloid plaque, arachnoid cyst, Article, case report, Chronic Traumatic Encephalopathy florbetapir f 18, Concussion, diagnostic accuracy, eye movement, football, frontotemporal dementia, head injury, human, injury severity, ligand binding, Male, memory disorder, middle aged, molecular imaging, motor dysfunction, muscle tone, personality disorder, positron emission tomography, short term memory, subdural hematoma, tauopathy, traumatic brain injury},
pubstate = {published},
tppubtype = {article}
}