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1
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Varanoske AN, McClung HL, Sepowitz JJ, Halagarda CJ, Farina EK, Berryman CE, Lieberman HR, McClung JP, Pasiakos SM, Philip Karl J. Stress and the gut-brain axis: Cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability following severe physical and psychological stress. Brain Behav Immun 2022; 101:383-393. [PMID: 35131441 DOI: 10.1016/j.bbi.2022.02.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/13/2022] [Accepted: 02/01/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Physical and psychological stress alter gut-brain axis activity, potentially causing intestinal barrier dysfunction that may, in turn, induce cognitive and mood impairments through exacerbated inflammation and blood brain barrier (BBB) permeability. These interactions are commonly studied in animals or artificial laboratory environments. However, military survival training provides an alternative and unique human model for studying the impacts of severe physical and psychological stress on the gut-brain axis in a realistic environment. PURPOSE To determine changes in intestinal barrier and BBB permeability during stressful military survival training and identify relationships between those changes and markers of stress, inflammation, cognitive performance, and mood state. MATERIALS AND METHODS Seventy-one male U.S. Marines (25.2 ± 2.6 years) were studied during Survival, Evasion, Resistance, and Escape (SERE) training. Measurements were conducted on day 2 of the 10-day classroom phase of training (PRE), following completion of the 7.5-day field-based simulation phase of the training (POST), and following a 27-day recovery period (REC). Fat-free mass (FFM) was measured to assess the overall physiologic impact of the training. Biomarkers of intestinal permeability (liposaccharide-binding protein [LBP]) and BBB permeability (S100 calcium-binding protein B [S100B]), stress (cortisol, dehydroepiandrosterone sulfate [DHEA-S] epinephrine, norepinephrine) and inflammation (interleukin-6 [IL-6], high-sensitivity C-reactive protein [hsCRP]) were measured in blood. Cognitive performance was assessed by psychomotor vigilance (PVT) and grammatical reasoning (GR) tests, and mood state by the Profile of Mood States (total mood disturbance; TMD), General Anxiety Disorder-7 (GAD-7), and Patient Health (PHQ-9) questionnaires. RESULTS FFM, psychomotor vigilance, and LBP decreased from PRE to POST, while TMD, anxiety, and depression scores, and S100B, DHEA-S, IL-6, norepinephrine, and epinephrine concentrations all increased (all p ≤ 0.01). Increases in DHEA-S were associated with decreases in body mass (p = 0.015). Decreases in FFM were associated with decreases in LBP concentrations (p = 0.015), and both decreases in FFM and LBP were associated with increases in TMD and depression scores (all p < 0.05) but not with changes in cognitive performance. Conversely, increases in S100B concentrations were associated with decreases in psychomotor vigilance (p < 0.05) but not with changes in mood state or LBP concentrations. CONCLUSIONS Evidence of increased intestinal permeability was not observed in this military survival training-based model of severe physical and psychological stress. However, increased BBB permeability was associated with stress and cognitive decline, while FFM loss was associated with mood disturbance, suggesting that distinct mechanisms may contribute to decrements in cognitive performance and mood state during the severe physical and psychological stress experienced during military survival training.
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Affiliation(s)
- Alyssa N Varanoske
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, USA
| | - Holly L McClung
- Biophysics and Biomedical Modeling Division, USARIEM, Natick, MA, USA
| | - John J Sepowitz
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA
| | | | - Emily K Farina
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA
| | - Claire E Berryman
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, USA; Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA
| | - Harris R Lieberman
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA
| | - James P McClung
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA
| | | | - J Philip Karl
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA.
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2
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Slavoaca D, Birle C, Stan A, Tatomir A, Popa O, Rosu P, Vulcan AM, Chira D, Livint Popa L, Dina C, Vacaras V, Strilciuc S, Vos P. Prediction of Neurocognitive Outcome after Moderate-Severe Traumatic Brain Injury Using Serum Neuron-Specific Enolase and S100 biomarkers. J Med Life 2020; 13:306-313. [PMID: 33072201 PMCID: PMC7550145 DOI: 10.25122/jml-2020-0147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Seric biomarkers have been tested in a large number of studies on traumatic brain injuries (TBI) patients in order to predict severity, especially related to the short-term outcome. However, TBI patients have a high risk of developing long-term complications such as physical disability, cognitive impairment, psychiatric pathology, epilepsy, and others. The aim of this study was to assess the correlation between protein biomarkers S100 and neuron-specific enolase (NSE) and neurocognitive status at 10- and 90-days post-injury. Both biomarkers were tested in the first 4h and after 72h post-injury in 62 patients with moderate-severe TBI. The patients were evaluated by a series of neurocognitive tests: Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale-Extended (GOSE), The Mini-Mental State Examination (MMSE), Processing Speed Index (PSI), and Stroop Test, at 10 and 90 days post-injury and supplementary by the Hospital Anxiety and Depression Scale at 90 days. For evaluating the whole neurocognitive status instead of every scale separately, we used Structural Equation Modeling (SEM), while for anxiety and depressive symptoms, we used multiple regression analyses. SEM showed that NSE values at 4 hours were significant predictors of the cognitive status at 10 (p=0.034) and 90 days (p= 0.023). Also, there were found significant correlations between NSE at 4h and the anxiety level. This study demonstrated a significant correlation between NSE at 4h and short and medium-term neuropsychological outcomes, which recommends using this biomarker for selecting patients with a higher risk of cognitive dysfunction.
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Affiliation(s)
- Dana Slavoaca
- Department of Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania
| | - Codruta Birle
- Department of Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania
| | - Adina Stan
- Department of Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania
| | - Alexandru Tatomir
- Department of Neurology, University of Maryland, School of Medicine, Baltimore, United States of America
| | - Oana Popa
- Neurology Clinic, Cluj Emergency County Hospital, Cluj-Napoca, Romania
| | - Paula Rosu
- Neurology Clinic, Cluj Emergency County Hospital, Cluj-Napoca, Romania
| | - Ana-Maria Vulcan
- Neurology Clinic, Cluj Emergency County Hospital, Cluj-Napoca, Romania
| | - Diana Chira
- "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania
| | - Livia Livint Popa
- Department of Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania
| | - Constantin Dina
- Department of Radiology, "Ovidius" University, Faculty of Medicine, Constanta, Romania
| | - Vitalie Vacaras
- Department of Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania.,Neurology Clinic, Cluj Emergency County Hospital, Cluj-Napoca, Romania
| | - Stefan Strilciuc
- Department of Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania
| | - Pieter Vos
- Department of Neurology, Slingeland Hospital, Doetinchem, The Netherlands
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3
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Hellewell SC, Beaton CS, Welton T, Grieve SM. Characterizing the Risk of Depression Following Mild Traumatic Brain Injury: A Meta-Analysis of the Literature Comparing Chronic mTBI to Non-mTBI Populations. Front Neurol 2020; 11:350. [PMID: 32508733 PMCID: PMC7248359 DOI: 10.3389/fneur.2020.00350] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 04/08/2020] [Indexed: 12/11/2022] Open
Abstract
Objective: Mild traumatic brain injury (mTBI) is associated with depressed mood acutely post-injury, but there is little evidence regarding long-term depression. The aim of this study was to determine the odds ratio (OR) of depression chronically following mTBI. Methods: We searched Medline (PubMed), ProQuest, and Web of Science from date of database creation to January 23, 2019, for eligible studies examining depression at least 6 months post-injury in adult subjects with mTBI of any etiology, including civilians and military. Three authors independently reviewed titles and abstracts for study eligibility. Data were extracted and collated by two investigators. Risk of bias was assessed with the SIGN methodology. Study data were pooled using random-effects meta-analysis. The primary exposure was mTBI, and the primary outcome was depression. Secondary exploratory variables were time of assessment, age at injury, age at assessment, sex, and etiology. Results: We included 47 cross-sectional studies (n = 25,103 mTBI and 29,982 control), 26 cohort studies (n = 70,119 mTBI, 262,034 control), four prospective observational studies (n = 1,058 mTBI and 733 control), two prospective longitudinal studies (n = 119 mTBI, 81 control), two case-control studies (n = 56 mTBI, 56 control), and one randomized controlled trial (n = 252 mTBI, 3,214 control). mTBI was associated with a 3.29-fold increased risk of depression (OR 3.29, 95% CI 2.68–4.03, I2 = 96%). The OR for depression did not change when subjects were assessed at 6–12 months (OR 2.43, 1.45–4.07), years 1–2 (OR 4.12, 2.10–8.07); 2–10 (OR 3.28, 2.42–4.46), or 10+ (OR 3.42, 1.51–7.77). Similar risk of depression was sustained across different age at injury (<25: OR 2.26, 1.82–2.81; 25–35: OR 4.67, 3.06–7.14; >35: OR 2.69, 1.42–5.10) and different age at assessment (<40 years: OR 3.14, 2.48–3.99; >40 years: OR 4.57, 2.54–8.24). Female sex had a non-significant increase in OR (OR 19.97, 2.39–166.93) compared to male (OR 3.0, 2.33–3.86). mTBI etiology had no impact on depression. Conclusions: Those experiencing mTBI are more than three times more likely to experience depression compared to those without a history of mTBI, and this risk remains decades beyond the mTBI event. Future longitudinal studies are needed to identify and mitigate this risk.
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Affiliation(s)
- Sarah C Hellewell
- Imaging and Phenotyping Laboratory, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Caerwen S Beaton
- Imaging and Phenotyping Laboratory, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Thomas Welton
- Imaging and Phenotyping Laboratory, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Stuart M Grieve
- Imaging and Phenotyping Laboratory, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.,Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Department of Radiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Singla A, Leineweber B, Monteith S, Oskouian RJ, Tubbs RS. The anatomy of concussion and chronic traumatic encephalopathy: A comprehensive review. Clin Anat 2018; 32:310-318. [DOI: 10.1002/ca.23313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 11/09/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Amit Singla
- Swedish Neuroscience Institute; Seattle Washington
| | | | | | | | - R. Shane Tubbs
- Seattle Science Foundation; Seattle Washington
- Department of Anatomical Sciences; St. Georges University; St. Georges Grenada
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Rogatzki MJ, Keuler SA, Harris AE, Ringgenberg SW, Breckenridge RE, White JL, Baker JS. Response of protein S100B to playing American football, lifting weights, and treadmill running. Scand J Med Sci Sports 2018; 28:2505-2514. [DOI: 10.1111/sms.13297] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 08/20/2018] [Accepted: 09/06/2018] [Indexed: 01/30/2023]
Affiliation(s)
- Matthew J. Rogatzki
- Department of Health and Exercise Science; Appalachian State University; Boone North Carolina
| | - Sydney A. Keuler
- Department of Health and Human Performance; University of Wisconsin-Platteville; Platteville Wisconsin
| | - Abigail E. Harris
- Department of Health and Human Performance; University of Wisconsin-Platteville; Platteville Wisconsin
- Palmer College of Chiropractic; Port Orange Florida
| | - Scott W. Ringgenberg
- Department of Health and Human Performance; University of Wisconsin-Platteville; Platteville Wisconsin
| | | | | | - Julien S. Baker
- Institute of Clinical Exercise and Health Sciences, School of Science and Sport; University of the West of Scotland; Hamilton UK
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Mercier E, Tardif PA, Cameron PA, Batomen Kuimi BL, Émond M, Moore L, Mitra B, Frenette J, De Guise E, Ouellet MC, Bordeleau M, Le Sage N. Prognostic Value of S-100β Protein for Prediction of Post-Concussion Symptoms after a Mild Traumatic Brain Injury: Systematic Review and Meta-Analysis. J Neurotrauma 2018; 35:609-622. [PMID: 28969486 DOI: 10.1089/neu.2017.5013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms after a mild traumatic brain injury (mTBI). A search strategy was submitted to seven databases from their inception to October 2016. Individual patient data were requested. Cohort studies evaluating the association between S-100β protein level and post-concussion symptoms assessed at least seven days after the mTBI were considered. Outcomes were dichotomized as persistent (≥3 months) or early (≥7 days <3 months). Our search strategy yielded 23,298 citations of which 29 studies including between seven and 223 patients (n = 2505) were included. Post-concussion syndrome (PCS) (16 studies) and neuropsychological symptoms (9 studies) were the most frequently assessed outcomes. The odds of having persistent PCS (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.34-1.12, p = 0.11, I2 0% [n = five studies]) in patients with an elevated S-100β protein serum level were not significantly different from those of patients with normal values while the odds of having early PCS (OR 1.67, 95% CI: 0.98-2.85, p = 0.06, I2 38% [n = five studies]) were close to statistical significance. Similarly, having an elevated S-100β protein serum level was not associated with the odds of returning to work at six months (OR 2.31, 95% CI: 0.50-10.64, p = 0.28, I2 22% [n = two studies]). Overall risk of bias was considered moderate. Results suggest that the prognostic biomarker S-100β protein has a low clinical value to identify patients at risk of persistent post-concussion symptoms. Variability in injury to S-100ß protein sample time, mTBI populations, and outcomes assessed could potentially explain the lack of association and needs further evaluation.
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Affiliation(s)
- Eric Mercier
- 1 Département de Médecine Familiale et Médecine d'Urgence, Faculté de Médecine, Université Laval , Québec, Canada .,2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada .,3 Emergency and Trauma Centre, The Alfred Hospital , Alfred Health, Australia .,4 School of Public Health and Preventive Medicine, Monash University , Melbourne, Victoria, Australia
| | - Pier-Alexandre Tardif
- 2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada
| | - Peter A Cameron
- 3 Emergency and Trauma Centre, The Alfred Hospital , Alfred Health, Australia .,4 School of Public Health and Preventive Medicine, Monash University , Melbourne, Victoria, Australia .,5 National Trauma Research Institute , The Alfred Hospital, Melbourne, Victoria, Australia
| | - Brice Lionel Batomen Kuimi
- 2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada
| | - Marcel Émond
- 1 Département de Médecine Familiale et Médecine d'Urgence, Faculté de Médecine, Université Laval , Québec, Canada .,6 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Vieillissement, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada
| | - Lynne Moore
- 2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada .,6 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Vieillissement, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada .,7 Département de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval , Québec, Canada
| | - Biswadev Mitra
- 3 Emergency and Trauma Centre, The Alfred Hospital , Alfred Health, Australia .,4 School of Public Health and Preventive Medicine, Monash University , Melbourne, Victoria, Australia .,5 National Trauma Research Institute , The Alfred Hospital, Melbourne, Victoria, Australia
| | - Jérôme Frenette
- 8 Centre de Recherche et Centre Hospitalier Universitaire de Québec , Québec, Canada
| | - Elaine De Guise
- 9 Research-Institute, McGill University Health Centre , Montreal, Québec, Canada .,10 Centre de recherche interdisciplinaire en réadaptation du Montréal métropolitain (CRIR), Montréal , Québec, Canada
| | - Marie-Christine Ouellet
- 2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada .,8 Centre de Recherche et Centre Hospitalier Universitaire de Québec , Québec, Canada
| | - Martine Bordeleau
- 2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada
| | - Natalie Le Sage
- 1 Département de Médecine Familiale et Médecine d'Urgence, Faculté de Médecine, Université Laval , Québec, Canada .,2 Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval , Québec, Canada
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Jones A, Jarvis P. Review of the potential use of blood neuro-biomarkers in the diagnosis of mild traumatic brain injury. Clin Exp Emerg Med 2017; 4:121-127. [PMID: 29026884 PMCID: PMC5635461 DOI: 10.15441/ceem.17.226] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 05/05/2017] [Accepted: 05/29/2017] [Indexed: 01/11/2023] Open
Abstract
Head injury is a common presenting complaint amongst emergency department patients. To date, there has been no widespread utilization of neuro-biomarkers to aid the diagnosis of traumatic brain injury. This review article explores which neuro-biomarkers could be used in the emergency department in aiding the clinical diagnosis of mild traumatic brain injury. Based on the available evidence, the most promising neuro-biomarkers appear to be Glial fibrillary acidic protein (GFAP) and Ubiquitin C-Terminal Hydrolase Isozyme L1 (UCH-L1) as these show significant rises in peripheral blood levels shortly after injury and these have been demonstrated to correlate with long-term clinical outcomes. Treatment strategies for minor traumatic brain injury in the emergency department setting are not well developed. The introduction of blood neuro-biomarkers could reduce unnecessary radiation exposure and provide an opportunity to improve the care of this patient group.
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Affiliation(s)
- Alastair Jones
- Department of Emergency Medicine, Bradford Royal Infirmary, Bradford, UK
| | - Paul Jarvis
- Global Medical Affairs, Abbott Point of Care, Princeton, NJ, USA
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8
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Mercier E, Tardif PA, Emond M, Ouellet MC, de Guise É, Mitra B, Cameron P, Le Sage N. Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review. BMJ Open 2017; 7:e017848. [PMID: 28963310 PMCID: PMC5623519 DOI: 10.1136/bmjopen-2017-017848] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Mild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI. DATA SOURCES Searches of MEDLINE, Embase, CENTRAL, CINAHL, Web of Science, PsycBITE and PsycINFO up to October 2016. DATA SELECTION AND EXTRACTION Two reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS A total of 23 298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurological disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous traumatic brain injury (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was postconcussion syndrome using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI. CONCLUSIONS Most studies have recruited samples that are not representative and generalisable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict postconcussion symptoms.
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Affiliation(s)
- Eric Mercier
- Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval, Quebec, Canada
- Département de Médecine Familiale et Médecine d’Urgence, Faculté de Médecine, Université Laval, Quebec, Canada
- Emergency and Trauma Centre, The Alfred Hospital, Alfred Health, Melbourne, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Pier-Alexandre Tardif
- Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval, Quebec, Canada
| | - Marcel Emond
- Département de Médecine Familiale et Médecine d’Urgence, Faculté de Médecine, Université Laval, Quebec, Canada
- Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Vieillissement, Centre de recherche du CHU de Québec, Université Laval, Quebec, Canada
| | - Marie-Christine Ouellet
- Centre Interdisciplinaire de Recherche en Réadaptation et Intégration Sociale (CIRRIS), Quebec, Canada
| | - Élaine de Guise
- Research-Institute, McGill University Health Centre, Quebec, Canada
- Centre de recherche interdisciplinaire en réadaptation du Montréal métropolitain (CRIR), Quebec, Canada
| | - Biswadev Mitra
- Emergency and Trauma Centre, The Alfred Hospital, Alfred Health, Melbourne, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- National Trauma Research Institute, The Alfred Hospital, Melbourne, Victoria, Australia
| | - Peter Cameron
- Emergency and Trauma Centre, The Alfred Hospital, Alfred Health, Melbourne, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- National Trauma Research Institute, The Alfred Hospital, Melbourne, Victoria, Australia
| | - Natalie Le Sage
- Axe Santé des Populations et Pratiques Optimales en Santé, Unité de recherche en Traumatologie - Urgence - Soins Intensifs, Centre de recherche du CHU de Québec, Université Laval, Quebec, Canada
- Département de Médecine Familiale et Médecine d’Urgence, Faculté de Médecine, Université Laval, Quebec, Canada
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Abstract
Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.
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10
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Sahu S, Nag DS, Swain A, Samaddar DP. Biochemical changes in the injured brain. World J Biol Chem 2017; 8:21-31. [PMID: 28289516 PMCID: PMC5329711 DOI: 10.4331/wjbc.v8.i1.21] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 10/23/2016] [Accepted: 12/13/2016] [Indexed: 02/05/2023] Open
Abstract
Brain metabolism is an energy intensive phenomenon involving a wide spectrum of chemical intermediaries. Various injury states have a detrimental effect on the biochemical processes involved in the homeostatic and electrophysiological properties of the brain. The biochemical markers of brain injury are a recent addition in the armamentarium of neuro-clinicians and are being increasingly used in the routine management of neuro-pathological entities such as traumatic brain injury, stroke, subarachnoid haemorrhage and intracranial space occupying lesions. These markers are increasingly being used in assessing severity as well as in predicting the prognostic course of neuro-pathological lesions. S-100 protein, neuron specific enolase, creatinine phosphokinase isoenzyme BB and myelin basic protein are some of the biochemical markers which have been proven to have prognostic and clinical value in the brain injury. While S-100, glial fibrillary acidic protein and ubiquitin C terminal hydrolase are early biomarkers of neuronal injury and have the potential to aid in clinical decision-making in the initial management of patients presenting with an acute neuronal crisis, the other biomarkers are of value in predicting long-term complications and prognosis in such patients. In recent times cerebral microdialysis has established itself as a novel way of monitoring brain tissue biochemical metabolites such as glucose, lactate, pyruvate, glutamate and glycerol while small non-coding RNAs have presented themselves as potential markers of brain injury for future.
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Jeon YT, Kim BG, Park YH, Sohn HM, Kim J, Kim SC, An SS, Kim S. Postoperative cognitive changes after total knee arthroplasty under regional anesthesia. Medicine (Baltimore) 2016; 95:e5635. [PMID: 28033253 PMCID: PMC5207549 DOI: 10.1097/md.0000000000005635] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The type of postoperative cognitive decline after surgery under spinal anesthesia is unknown. We investigated the type of postoperative cognitive decline after total knee arthroplasty (TKA). Neuropsychological testing was conducted and the changes in cerebrospinal fluid (CSF) biomarkers after surgery were evaluated. METHODS Fifteen patients who required bilateral TKA at a 1-week interval under spinal anesthesia were included. Neuropsychological tests were performed twice, once the day before the first operation and just before the second operation (usually 1 week after the first test) to determine cognitive decline. Validated neuropsychological tests were used to examine 4 types of cognitive decline: memory, frontal-executive, language-semantic, and others. Concentrations of CSF amyloid peptide, tau protein, and S100B were measured twice during spinal anesthesia at a 1-week interval. The patients showed poor performance in frontal-executive function (forward digit span, semantic fluency, letter-phonemic fluency, and Stroop color reading) at the second compared to the first neuropsychological assessment. RESULTS S100B concentration decreased significantly 1 week after the operation compared to the basal value (638 ± 178 vs 509 ± 167 pg/mL) (P = 0.019). Amyloid protein β1-42, total tau, and phosphorylated tau concentrations tended to decrease but the changes were not significant. CONCLUSION Our results suggest that frontal-executive function declined 1 week after TKA under spinal anesthesia. The CSF biomarker analysis indicated that TKA under regional anesthesia might not cause neuronal damage.
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Affiliation(s)
- Young-Tae Jeon
- Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Byung-Gun Kim
- Department of Anesthesiology and Pain Medicine, Inha University School of Medicine, Inha University Hospital
| | - Young Ho Park
- Department of Neurology, Seoul National University College of Medicine, Seoul
- Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam
| | - Hye-Min Sohn
- Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Jungeun Kim
- Department of Neurology, Seoul National University College of Medicine, Seoul
- Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam
| | - Seung Chan Kim
- College of BioNano technology, Gacheon University, South Korea
| | - Seong Soo An
- College of BioNano technology, Gacheon University, South Korea
| | - SangYun Kim
- Department of Neurology, Seoul National University College of Medicine, Seoul
- Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam
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S100B protein and neuron-specific enolase as predictors of cognitive dysfunction after coronary artery bypass graft surgery. Eur J Anaesthesiol 2016; 33:681-9. [DOI: 10.1097/eja.0000000000000450] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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13
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Williams VB, Danan IJ. A Historical Perspective on Sports Concussion: Where We Have Been and Where We Are Going. Curr Pain Headache Rep 2016; 20:43. [DOI: 10.1007/s11916-016-0569-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Rappold T, Laflam A, Hori D, Brown C, Brandt J, Mintz CD, Sieber F, Gottschalk A, Yenokyan G, Everett A, Hogue CW. Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery. Br J Anaesth 2016; 116:83-9. [PMID: 26675953 DOI: 10.1093/bja/aev415] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Postoperative cognitive dysfunction (POCD) is common after non-cardiac surgery, but the mechanism is unclear. We hypothesized that decrements in cognition 1 month after non-cardiac surgery would be associated with evidence of brain injury detected by elevation of plasma concentrations of S100β, neuron-specific enolase (NSE), and/or the brain-specific protein glial fibrillary acid protein (GFAP). METHODS One hundred and forty-nine patients undergoing shoulder surgery underwent neuropsychological testing before and then 1 month after surgery. Plasma was collected before and after anaesthesia. We determined the relationship between plasma biomarker concentrations and individual neuropsychological test results and a composite cognitive functioning score (mean Z-score). RESULTS POCD (≥-1.5 sd decrement in Z-score from baseline) was present in 10.1% of patients 1 month after surgery. There was a negative relationship between higher plasma GFAP concentrations and lower postoperative composite Z-scores {estimated slope=-0.14 [95% confidence interval (CI) -0.24 to -0.04], P=0.005} and change from baseline in postoperative scores on the Rey Complex Figure Test copy trial (P=0.021), delayed recall trial (P=0.010), and the Symbol Digit Modalities Test (P=0.004) after adjustment for age, sex, history of hypertension and diabetes. A similar relationship was not observed with S100β or NSE concentrations. CONCLUSIONS Decline in cognition 1 month after shoulder surgery is associated with brain cellular injury as demonstrated by elevated plasma GFAP concentrations.
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Affiliation(s)
- T Rappold
- Medical Student, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - A Laflam
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - D Hori
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - C Brown
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - J Brandt
- Departments of Psychiatry and Behavioral Sciences and Neurology, Johns Hopkins University School of Medicine and the Department of Mental Health, Bloomberg School of Public Health, Baltimore, MD, USA
| | - C D Mintz
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - F Sieber
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - A Gottschalk
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - G Yenokyan
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - A Everett
- Department of Pediatrics, Johns Hopkins University School of Medicine, Johns Hopkins Children's Center, Baltimore, MD, USA
| | - C W Hogue
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans, Zayed 6208B, Baltimore, MD 21287, USA
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Kulbe JR, Geddes JW. Current status of fluid biomarkers in mild traumatic brain injury. Exp Neurol 2016; 275 Pt 3:334-352. [PMID: 25981889 PMCID: PMC4699183 DOI: 10.1016/j.expneurol.2015.05.004] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 05/05/2015] [Accepted: 05/08/2015] [Indexed: 01/07/2023]
Abstract
Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. Athletes and military personnel are at great risk for repeat injury which can result in second impact syndrome or chronic traumatic encephalopathy. An objective and quantifiable measure, such as a serum biomarker, is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments, and would further elucidate mTBI pathophysiology. The majority of TBI biomarker research focuses on severe TBI with few studies specific to mild injury. Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers.
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Affiliation(s)
- Jacqueline R Kulbe
- Spinal Cord and Brain Injury Research Center, College of Medicine, University of Kentucky, Lexington, KY, 40536-0509, USA,; Department of Anatomy and Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, 40536-0509, USA
| | - James W Geddes
- Spinal Cord and Brain Injury Research Center, College of Medicine, University of Kentucky, Lexington, KY, 40536-0509, USA,; Department of Anatomy and Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, 40536-0509, USA.
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Shoulder surgery in the beach chair position is associated with diminished cerebral autoregulation but no differences in postoperative cognition or brain injury biomarker levels compared with supine positioning: the anesthesia patient safety foundation beach chair study. Anesth Analg 2015; 120:176-185. [PMID: 25268397 DOI: 10.1213/ane.0000000000000455] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Although controversial, failing to consider the gravitational effects of head elevation on cerebral perfusion is speculated to increase susceptibility to rare, but devastating, neurologic complications after shoulder surgery in the beach chair position (BCP). We hypothesized that patients in the BCP have diminished cerebral blood flow autoregulation than those who undergo surgery in the lateral decubitus position (LDP). A secondary aim was to examine whether there is a relationship between patient positioning during surgery and postoperative cognition or serum brain injury biomarker levels. METHODS Patients undergoing shoulder surgery in the BCP (n = 109) or LDP (n = 109) had mean arterial blood pressure (MAP) and regional cerebral oxygen saturation (rScO2) monitored with near-infrared spectroscopy. A continuous, moving Pearson correlation coefficient was calculated between MAP and rScO2, generating the variable cerebral oximetry index (COx). When MAP is in the autoregulated range, COx approaches zero because there is no correlation between cerebral blood flow and arterial blood pressure. In contrast, when MAP is below the limit of autoregulation, COx is higher because there is a direct relationship between lower arterial blood pressure and lower cerebral blood flow. Thus, diminished autoregulation would be manifest as higher COx. Psychometric testing was performed before surgery and then 7 to 10 days and 4 to 6 weeks after surgery. A composite cognitive outcome was determined as the Z-score. Serum S100β, neuron-specific enolase, and glial fibrillary acidic protein were measured at baseline, after surgery, and on postoperative day 1. RESULTS After adjusting for age and history of hypertension, COx (P = 0.035) was higher and rScO2 lower (P < 0.0001) in the BCP group than in the LDP group. After adjusting for baseline composite cognitive outcome, there was no difference in Z-score 7 to 10 days (P = 0.530) or 4 to 6 weeks (P = 0.202) after surgery between the BCP and the LDP groups. There was no difference in serum biomarker levels between the 2 position groups CONCLUSIONS : Compared with patients in the LDP, patients undergoing shoulder surgery in the BCP are more likely to have higher COx indicating diminished cerebral autoregulation and lower rScO2. There were no differences in the composite cognitive outcome between the BCP and the LDP groups after surgery after accounting for baseline Z-score.
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Heidari K, Asadollahi S, Jamshidian M, Abrishamchi SN, Nouroozi M. Prediction of neuropsychological outcome after mild traumatic brain injury using clinical parameters, serum S100B protein and findings on computed tomography. Brain Inj 2014; 29:33-40. [DOI: 10.3109/02699052.2014.948068] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Kamran Heidari
- Department of Emergency Medicine, Loghman Hakim Hospital,
| | | | - Morteza Jamshidian
- Department of Emergency Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shohreh Nasiri Abrishamchi
- Department of Emergency Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Nouroozi
- Department of Emergency Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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Mondello S, Schmid K, Berger RP, Kobeissy F, Italiano D, Jeromin A, Hayes RL, Tortella FC, Buki A. The challenge of mild traumatic brain injury: role of biochemical markers in diagnosis of brain damage. Med Res Rev 2013; 34:503-31. [PMID: 23813922 DOI: 10.1002/med.21295] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
During the past decade there has been an increasing recognition of the incidence of mild traumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficits that may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteria for mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detect brain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss the current research on serum biomarkers for mTBI including their rationale and diagnostic performances. Sensitive and specific biomarkers reflecting brain injury can provide important information regarding TBI pathophysiology and serve as candidate markers for predicting abnormal computed tomography findings and/or the development of residual deficits in patients who sustain an mTBI. We also outline the roles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and military injuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emerging proteomics-based strategies for identifying novel markers will be discussed.
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Affiliation(s)
- Stefania Mondello
- Department of Neurosciences, University of Messina, 98125, Messina, Italy
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Papa L, Robinson G, Oli M, Pineda J, Demery J, Brophy G, Robicsek SA, Gabrielli A, Robertson CS, Wang KK, Hayes RL. Use of biomarkers for diagnosis and management of traumatic brain injury patients. ACTA ACUST UNITED AC 2013; 2:937-45. [PMID: 23495867 DOI: 10.1517/17530059.2.8.937] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Advances in the understanding of human biochemistry and physiology have provided insight into new pathways by which we can understand traumatic brain injury (TBI). Increased sophistication of laboratory techniques and developments in the field of proteomics has led to the discovery and rapid detection of new biomarkers not previously available. OBJECTIVE To review recent advances in biomarker research for traumatic brain injury, describe the features of the ideal biomarker and to explore the potential role of these biomarkers in improving clinical management of brain injured patients. METHODS Through a literature review of recent research on TBI biomarkers and through experience with TBI research, important elements of biomarker development are described together with potential applications to patient care. CONCLUSIONS TBI biomarkers could have a significant impact on patient care by assisting in the diagnosis, risk stratification and management of TBI. Biomarkers could provide major opportunities for the conduct of clinical research, including confirmation of injury mechanism(s) and drug target identification. Continuing studies by the authors' group are now being conducted to elucidate more fully the relationships between new biomarkers and severity of injury and clinical outcomes in all severities of TBI patients.
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Affiliation(s)
- Linda Papa
- Director of Academic Clinical Research Orlando Regional Medical Center, Department of Emergency Medicine, 86 W. Underwood (S-200), Orlando, FL 32806, USA +1 407 237 6329 ; +1 407 649 3083 ;
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Leis AA, Stokic DS, Petzold A. Glial S100B is elevated in serum across the spectrum of west nile virus infection. Muscle Nerve 2012; 45:826-30. [DOI: 10.1002/mus.23241] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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LI YC, XI CH, AN YF, DONG WH, ZHOU M. Perioperative inflammatory response and protein S-100β concentrations - relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand 2012; 56:595-600. [PMID: 22224444 DOI: 10.1111/j.1399-6576.2011.02616.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2011] [Indexed: 11/29/2022]
Abstract
BACKGROUND One major concern in about one third of elder patients after total hip-replacement surgery is post-operative cognitive dysfunction (POCD). Previous studies have suggested that cognitive impairment is accompanied with changes in serum S-100β protein (S-100β) and inflammatory markers. Thus, the aim of the current study was to investigate the value of serum S-100β and interleukin(IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), and C-reactive protein (CRP) in reflecting POCD after total hip-replacement surgery. METHODS Forty-two elderly patients were enrolled, and 37 patients completed the follow-up. Serum S-100β protein and IL-1β, IL-6, TNF-α, and CRP were determined pre-operatively, as well as 1 h and 6 h post-operatively. Neuropsychological tests were performed pre-operatively, as well as on day 1, 3, and 7 post-operatively. RESULTS Seventeen (45.9%, 17/37) patients developed POCD 1 day after surgery, and three (8.1%, 3/37) developed POCD 7 days after surgery. [Correction added after publication 7 February 2012: in the preceding sentence (54.1%, 17/37) was corrected to (45.9%, 17/37)]. Patients with POCD 1 day after surgery had significantly higher serum levels of IL-6 at 6 h (135 ± 32 pg/ml vs. 91 ± 29 pg/ml, P < 0.05) and S-100β at 1 h (1872 ± 385 pg/ml vs. 1289 ± 143 pg/ml, P < 0.05. No significant post-operative change was detected in levels of TNF-α, IL-1, or CRP. CONCLUSION The serum levels of pro-inflammatory marker IL-6 and S-100β protein increased after total hip-replacement in elderly patients, and such increase may serve as predicting parameters for the occurrence of POCD.
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Affiliation(s)
- Y-C. LI
- Department of Anesthesiology; the Sixth People's Hospital Affiliated to Shanghai Jiaotong University; Shanghai; China
| | - C-H. XI
- Department of Anesthesiology; the Sixth People's Hospital Affiliated to Shanghai Jiaotong University; Shanghai; China
| | - Y-F. AN
- Department of Anesthesiology; the Sixth People's Hospital Affiliated to Shanghai Jiaotong University; Shanghai; China
| | - W-H. DONG
- Department of Anesthesiology; the Sixth People's Hospital Affiliated to Shanghai Jiaotong University; Shanghai; China
| | - M. ZHOU
- Department of Anesthesiology; the Sixth People's Hospital Affiliated to Shanghai Jiaotong University; Shanghai; China
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Finnoff JT, Jelsing EJ, Smith J. Biomarkers, genetics, and risk factors for concussion. PM R 2012; 3:S452-9. [PMID: 22035689 DOI: 10.1016/j.pmrj.2011.07.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Accepted: 07/29/2011] [Indexed: 10/15/2022]
Abstract
It is estimated that between 1.6 and 3.8 million concussions occur annually in the United States. Although frequently regarded as benign, concussions can lead to multiple different adverse outcomes, including prolonged postconcussive symptoms, chronic traumatic encephalopathy, cognitive impairment, early onset dementia, movement disorders, psychiatric disorders, motor neuron disease, and even death. Therefore it is important to identify individuals with concussion to provide appropriate medical care and minimize adverse outcomes. Furthermore, it is important to identify individuals who are predisposed to sustaining a concussion or to having an adverse outcome after concussion. This article will discuss the current research on serum biomarkers for concussion, genetic influence on concussion, risk factors associated with concussion predisposition and poor outcome, and practical suggestions for the application of this information in clinical practice.
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Affiliation(s)
- Jonathan T Finnoff
- Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Mayo Clinic Sports Medicine Center, 200 First St SW, Rochester, MN 55905, USA.
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Wiesmann M, Steinmeier E, Magerkurth O, Linn J, Gottmann D, Missler U. Outcome prediction in traumatic brain injury: comparison of neurological status, CT findings, and blood levels of S100B and GFAP. Acta Neurol Scand 2010; 121:178-85. [PMID: 19804476 DOI: 10.1111/j.1600-0404.2009.01196.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To investigate the predictive value of early serum levels of S100B and glial fibrillary acidic protein (GFAP) in traumatic brain injury. METHODS Sixty patients admitted within 24 h of trauma were included. Neurological status on admission (Glasgow Coma Scale), initial cranial computed tomography (CCT) studies (Marshall Computed Tomographic Classification), and outcome after 6 months (Glasgow Outcome Scale) were evaluated. S100B and GFAP levels were determined on admission and 24 h after trauma. RESULTS Blood levels of S100B and GFAP were elevated following head trauma and quantitatively reflected the severity of trauma. S100B levels after 24 h and on admission were of higher predictive value than CCT findings or clinical examination. GFAP, but not S100B levels rapidly declined after trauma. CONCLUSIONS Blood levels of S100B and GFAP indicate the severity of brain damage and are correlated with neurological prognosis after trauma. Both methods can yield additional prognostic information if combined with clinical and CCT findings.
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Affiliation(s)
- M Wiesmann
- Department of Neuroradiology, University of Munich, Munich, Germany.
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Himanen L, Portin R, Tenovuo O, Taiminen T, Koponen S, Hiekkanen H, Helenius H. Attention and depressive symptoms in chronic phase after traumatic brain injury. Brain Inj 2009; 23:220-7. [PMID: 19205958 DOI: 10.1080/02699050902748323] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To study whether attention deficits differ between TBI (traumatic brain injury) patients with and without depressive symptoms. METHOD The study group (n = 61, mean age = 59 years) consisted of symptomatic TBI patients injured on average 30 years earlier. They were studied with a broad range of attention tasks including computerized methods. The patients were divided into those with depressive symptoms (n = 32) and those without (n = 29), according to the short form of the Beck depression scale with a cut-off score of 5. In addition, a diagnosis of major depression was applied according to the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) (n = 6). The groups with depression or depressive symptoms were compared with the non-depressed TBI patients and with an age- and education-matched healthy control group (n = 31). RESULTS Cognitive methods that require flexibility (Trail making B, Card sorting, Word fluency) and working memory (Subtraction test) were sensitive to discriminate TBI patients without depressive symptoms from the control subjects (p < 0.001). Only a few methods were able to discriminate the TBI patients with depressive symptoms from those without (p < 0.001 for Simple reaction time, p < 0.003 for Vigilance test). The depressed TBI patients (assessed by SCAN) did not differ from the non-depressed TBI patients in attention functions. CONCLUSIONS The results suggest that problems in complex attention processing are more specific to TBI, while slowness in simple psychomotor speed and impaired sustained attention may be mostly related to depressive symptoms in patients with chronic TBI sequelae.
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Affiliation(s)
- Leena Himanen
- Department of Neurology, Turku University Hospital, Turku, Finland.
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Müller K, Ingebrigtsen T, Wilsgaard T, Wikran G, Fagerheim T, Romner B, Waterloo K. Prediction of time trends in recovery of cognitive function after mild head injury. Neurosurgery 2009; 64:698-704; discussion 704. [PMID: 19349827 DOI: 10.1227/01.neu.0000340978.42892.78] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE To investigate relations between predictors and outcomes, and especially to identify predictors influencing the time trend in recovery after mild traumatic brain injury. METHODS We included 59 patients with mild head injury in a prospective study. They underwent comprehensive assessment with neurological and neuroradiological examinations, serum S-100B analysis, and apolipoprotein E (APOE) genotyping. Neuropsychological testing was performed before and 6 months after discharge. Linear mixed models were used to assess associations between baseline predictors and neurocognitive performance and its change. RESULTS A Glasgow Coma Scale score of less than 15, traumatic brain injury demonstrated with computed tomography, magnetic resonance imaging, and serum S-100B greater than 0.14 microg/L predicted impaired cognitive performance both at baseline and after 6 months; APOE genotype did not. There was significant improvement of performance after 6 months. APOE-epsilon4 genotype was the only independent factor significantly predicting less improvement. CONCLUSION The presence of the APOE-epsilon4 allele predicts less recovery of cognitive function after mild head injury.
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Affiliation(s)
- Kay Müller
- Department of Neurosurgery, University Hospital of North Norway, Tromsø, Norway.
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Hergenroeder GW, Redell JB, Moore AN, Dash PK. Biomarkers in the clinical diagnosis and management of traumatic brain injury. Mol Diagn Ther 2009; 12:345-58. [PMID: 19035622 DOI: 10.1007/bf03256301] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Traumatic brain injury (TBI) is the leading cause of death and disability among young adults. Numerous safety improvements in the workplace, the addition of airbags to vehicles, and the enforcement of speed limits have all helped to reduce the incidence and severity of head trauma. While improvements in emergency response times and acute care have increased TBI survivability, this has heightened the necessity for developing reliable methods to identify patients at risk of developing secondary pathologies. At present, the primary clinical indicators for the presence of brain injury are the Glasgow Coma Scale (GCS), pupil reactivity, and head computed tomography (CT). While these indices have proven useful for stratifying the magnitude and extent of brain damage, they have limited utility for predicting adverse secondary events or detecting subtle damage. Biomarkers, reflecting a biological response to injury or disease, have proven useful for the diagnosis of many pathological conditions including cancer, heart failure, infection, and genetic disorders. For TBI, several proteins synthesized in astroglial cells or neurons have been proposed as potential biomarkers. These proteins include the BB isozyme of creatine kinase (CK-BB, predominant in brain), glial fibrilary acidic protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), and S100B.The presence of these biomarkers in the cerebrospinal fluid and serum of patients with moderate-to-severe TBI, and their correlation with outcome, suggest that they may have utility as surrogate markers in clinical trials. In addition, many of these markers have been found to be sensitive indicators of injury, and therefore may have the potential to diagnose persons with mild TBI. In addition to biomarkers that correlate with long-term outcome, a few studies have identified prognostic biomarkers for secondary injury that may be useful in individualizing patient management.
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Affiliation(s)
- Georgene W Hergenroeder
- Vivian L. Smith Center for Neurological Research, Departments of Neurobiology and Anatomy, Neurosurgery, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
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27
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Neurochemical approaches of cerebrospinal fluid diagnostics in neurodegenerative diseases. Methods 2008; 44:289-98. [DOI: 10.1016/j.ymeth.2007.06.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2007] [Accepted: 06/20/2007] [Indexed: 12/12/2022] Open
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Bloomfield SM, McKinney J, Smith L, Brisman J. Reliability of S100B in predicting severity of central nervous system injury. Neurocrit Care 2007; 6:121-38. [PMID: 17522796 DOI: 10.1007/s12028-007-0008-x] [Citation(s) in RCA: 145] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
S100B is a protein biomarker that reflects CNS injury. It can be measured in the CSF or serum with readily available immunoassay kits. The excellent sensitivity of S100B has enabled it to confirm the existence of subtle brain injury in patients with mild head trauma, strokes, and after successful resuscitation from cardiopulmonary arrest. The extent of S100B elevation has been found to be useful in predicting clinical outcome after brain injury. Elevations of S100B above certain threshold levels might be able to reliably predict brain death or mortality. A normal S100B level reliably predicts the absence of significant CNS injury. The specificity of S100B levels as a reflection of CNS injury is compromised by the findings that extra-cranial injuries can lead to elevations in the absence of brain injury. This potential problem can most likely be avoided by measuring serial S100B levels along with other biomarkers and carefully noting peripheral injuries. Serum markers GFAP and NSE are both more specific for CNS injury and have little to no extra-cranial sources. Sustained elevations of S100B over 24 h along with elevations of GFAP and NSE can more reliably predict the extent of brain injury and clinical outcomes. In the future, S100B measurements might reliably predict secondary brain injury and enable physicians to initiate therapeutic interventions in a timelier manner. S100B levels have been shown to rise hours to days before changes in ICP, neurological examinations, and neuroimaging tests. S100B levels may also be used to monitor the efficacy of treatments.
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Affiliation(s)
- Stephen M Bloomfield
- New Jersey Neuroscience, Institute JFK Hospital and Medical Center, Edison, NJ 08818, USA.
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Carstairs JR, Shores EA. The macquarie university neuropsychological normative study (MUNNS): Rationale and methodology. AUSTRALIAN PSYCHOLOGIST 2007. [DOI: 10.1080/00050060008257466] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Watt SE, Shores EA, Baguley IJ, Dorsch N, Fearnside MR. Protein S-100 and neuropsychological functioning following severe traumatic brain injury. Brain Inj 2007; 20:1007-17. [PMID: 17060133 DOI: 10.1080/02699050600909698] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
PRIMARY OBJECTIVE To examine the relationship between serum concentrations of protein S-100beta and neuropsychological functioning following severe traumatic brain injury. DESIGN Matched control group. METHODS Blood samples were taken within 12 hours of injury and then daily up to 7 days post-injury (n=23). Within 2 weeks of emerging from post-traumatic amnesia (PTA), participants completed a battery of neuropsychological measures. These results were compared with a matched sample of healthy controls. RESULTS Early measurement of S-100 not only reflected overall brain injury severity, but also related to neuropsychological deficits, with higher serum concentrations associated with poorer performance across most cognitive domains. PTA duration, measured by the Westmead PTA Scale, was found to be the strongest predictor of S-100 concentration (R2=0.59, p<0.001). CONCLUSIONS These findings show that measurement of serum protein S-100 may further aid in the identification of individuals with severe TBI who are likely to experience cognitive difficulties.
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Affiliation(s)
- Sharon E Watt
- Department of Psychology, Macquarie University, and Brain Injury Rehabilitation Service, Department of Neurosurgery, Westmead Hospital, New South Wales, Australia
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31
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Naeimi ZS, Weinhofer A, Sarahrudi K, Heinz T, Vécsei V. Predictive value of S-100B protein and neuron specific-enolase as markers of traumatic brain damage in clinical use. Brain Inj 2007; 20:463-8. [PMID: 16716992 DOI: 10.1080/02699050600664418] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
OBJECTIVE S-100B and NSE proteins are considered to be neurobiochemical markers for the brain damage. The aim of this study was to consider the diagnostic and prognostic validity of the initial serum levels of S-100B and NSE in clinical use. METHODS Forty-five patients with traumatic brain injury were included in this prospective study. Neurologic examination and CCT-scan were performed. S-100B and NSE were analysed. Patients were divided in two groups depending on the severity of injury. RESULTS The results showed a significant difference between the S-100B serum concentration and the two groups-minor head injuries and severe head injuries. A statistically significant correlation was observed between an increase of S-100B and NSE serum values and a cerebral pathological finding in CT scans. CONCLUSION The clear correlation between S-100B and NSE serum concentrations and CCT findings does not validate both markers as an independent predictor of diagnosis and prognosis of brain injury.
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Affiliation(s)
- Zahra S Naeimi
- Department of Traumatology, Medical University Vienna, Austria.
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Townend W, Ingebrigtsen T. Head injury outcome prediction: a role for protein S-100B? Injury 2006; 37:1098-108. [PMID: 17070812 DOI: 10.1016/j.injury.2006.07.014] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2006] [Accepted: 07/12/2006] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Prediction of the likely outcome of head injury from the outset would allow early rehabilitation to be targeted at those with most to gain. Clinical evaluation of a head injured patient may be confounded by intoxicants such as alcohol. Imaging modalities are insensitive (CT) or impractical (MR) for screening populations of such patients. A peripheral marker that reflected the extent of brain injury might offer an objective indication of likely adverse sequelae. This review evaluates the evidence for Protein S-100B as such a marker. METHODS A search of published literature revealed 18 studies designed to evaluate the relation between serum S-100B and measures of outcome after head injury. RESULTS A cut-off point of 2.5microg/L is related to dependent disability in those presenting with low conscious level, and may be a specific test for this. There appears to be a relation between initial serum S-100B concentration and measures of disability as well as post-concussion symptoms for those with seemingly mild injuries. There does not appear to be a relation between S-100B and measures of neuropsychological performance. CONCLUSION Patients with high levels of S-100B at initial assessment (>2.5microg/L) may represent a high risk group for disability after head trauma.
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Affiliation(s)
- Will Townend
- Emergency Department, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, UK.
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Meares S, Shores EA, Batchelor J, Baguley IJ, Chapman J, Gurka J, Marosszeky JE. The relationship of psychological and cognitive factors and opioids in the development of the postconcussion syndrome in general trauma patients with mild traumatic brain injury. J Int Neuropsychol Soc 2006; 12:792-801. [PMID: 17064443 DOI: 10.1017/s1355617706060978] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2006] [Revised: 07/07/2006] [Accepted: 07/07/2006] [Indexed: 11/07/2022]
Abstract
The relationship of psychological and cognitive factors in the development of the postconcussion syndrome (PCS) following mild uncomplicated traumatic brain injury (mTBI) has received little study. This may be because of the widely held belief that neurological factors are the cause of early PCS symptoms, whereas psychological factors are responsible for enduring symptoms. To further understand these relationships, the association between PCS and neuropsychological and psychological outcome was investigated in 122 general trauma patients, many of whom had orthopedic injuries, around 5 days following mTBI. Apart from verbal fluency, participants with a PCS did not differ in their performances on neuropsychological measures compared to those without a PCS. Individuals with a PCS reported significantly more psychological symptoms. Large effect sizes present on the psychological measures showed that the difference between participants with a PCS and without was greater on psychological than on neuropsychological measures. Analyses also revealed a relationship between opioid analgesia and depression, anxiety and stress, and opioids and reduced learning. The results suggest that psychological factors are present much earlier than has previously been considered in the development of the PCS.
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Affiliation(s)
- Susanne Meares
- Department of Psychology, Macquarie University, New South Wales, Australia
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Begaz T, Kyriacou DN, Segal J, Bazarian JJ. Serum biochemical markers for post-concussion syndrome in patients with mild traumatic brain injury. J Neurotrauma 2006; 23:1201-10. [PMID: 16928178 DOI: 10.1089/neu.2006.23.1201] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Mild traumatic brain injury (MTBI) is a major public health problem in the United States. A significant subset of MTBI patients develop persistent and distressing neurological, cognitive, and behavioral symptoms, known as the post-concussion syndrome (PCS). To date, multiple studies have assessed the relationship between brain-related proteins found in the serum at the time of injury, and the development of PCS. We conducted a systematic review of prospective cohort studies that assessed the ability of serum biochemical markers to predict PCS after MTBI. A total of 11 studies assessing three different potential biochemical markers of PCS--S100 proteins, neuron-specific enolase (NSE), and cleaved Tau protein (CTP)--met selection criteria. Of these markers, S100 appeared to be the best researched. We conclude that no biomarker has consistently demonstrated the ability to predict PCS after MTBI. A combination of clinical factors in conjunction with biochemical markers may be necessary to develop a comprehensive decision rule that more accurately predicts PCS after MTBI.
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Affiliation(s)
- Tomer Begaz
- Department of Emergency Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
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Bazarian JJ, Zemlan FP, Mookerjee S, Stigbrand T. Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild traumatic brain injury. Brain Inj 2006; 20:759-65. [PMID: 16809208 DOI: 10.1080/02699050500488207] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PRIMARY OBJECTIVE To determine the relationship of serum S-100B and C-tau levels to long-term outcome after mild traumatic brain injury (mild TBI). RESEARCH DESIGN A prospective study of 35 mild TBI subjects presenting to the emergency department. METHODS AND PROCEDURES Six hour serum S-100B and C-tau levels compared to 3-month Rivermead Post Concussion Questionnaire (RPCQ) scores and post-concussive syndrome (PCS). MAIN OUTCOMES AND RESULTS The linear correlation between marker levels and RPCQ scores was weak (S-100B: r = 0.071, C-tau: r = -0.21). There was no statistically significant correlation between marker levels and 3-month PCS (S-100B: AUC = 0.589, 95%CI. 038, 0.80; C-tau: AUC = 0.634, 95%CI 0.43, 0.84). The sensitivity of these markers ranged from 43.8-56.3% and the specificity from 35.7-71.4%. CONCLUSIONS Initial serum S-100B and C-tau levels appear to be poor predictors of 3-month outcome after mild TBI.
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Affiliation(s)
- Jeffrey J Bazarian
- Department of Emergency Medicine, University of Rochester School of Medicine, Rochester, New York 14472, USA.
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Inglese M, Grossman RI, Diller L, Babb JS, Gonen O, Silver JMA, Rusinek H. Clinical significance of dilated Virchow-Robin spaces in mild traumatic brain injury. Brain Inj 2006; 20:15-21. [PMID: 16403696 DOI: 10.1080/02699050500309593] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
PRIMARY OBJECTIVE To investigate the relationship between the number of dilated Virchow-Robin spaces (VRS) and neurocognitive findings in patients with traumatic brain injury (TBI). RESEARCH DESIGN Thirty-eight patients with TBI and 21 controls were studied. METHODS AND PROCEDURES Fifteen patients underwent MRI within a mean interval of 5.4 (range 1-12) days from the brain injury and 23 after an average period of 5.5 (range 0.2-31) years. All subjects were examined with a battery of 13 neuropsychological tests (NP). MAIN OUTCOMES AND RESULTS The average number of VRS was significantly higher in patients than in controls. There were no significant differences between patients and controls in terms of NP tests. The number of VRS showed a significant inverse correlation with processing speed and a positive correlation with visual perceptual of attention only in patients studied within a short delay of trauma. CONCLUSIONS VRS are not directly associated to neurocognitive findings, suggesting that they may represent a result of the shear-strain injury.
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Affiliation(s)
- Matilde Inglese
- Department of Radiology, New York University School of Medicine, NY 10016, USA.
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Bulut M, Koksal O, Dogan S, Bolca N, Ozguc H, Korfali E, Ilcol YO, Parklak M. Tau protein as a serum marker of brain damage in mild traumatic brain injury: preliminary results. Adv Ther 2006; 23:12-22. [PMID: 16644603 DOI: 10.1007/bf02850342] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The objective of this study was to investigate the diagnostic value of serum tau protein in determining the severity of traumatic brain injury in patients with mild traumatic brain injury (mTBI) and high-risk patients. Adult patients who presented to our emergency department (ED) with mTBI over 1 year were prospectively enrolled. Patients underwent cranial computed tomography (CT) and were subdivided into high- and low-risk groups, according to the probability of resultant intracranial injury. Serum tau levels of 60 patients and 20 healthy volunteers, who served as a control group, were measured. The mean age of the 60 patients (45 males, 15 females) was 32.5 years (range, 15-66 y). Mean Glasgow Coma Scale (GCS) score was 14+/-0.6. CT scans demonstrated intracranial injury in 11 patients (18.3%) and depressed fracture in 4 patients (6.7%). Serum tau levels of patients (188+/-210 pg/mL), compared with those of controls (86+/-48 pg/mL), were relatively higher; however, differences were not statistically significant (P=.445). Also, serum tau levels of high-risk patients (307+/-246 pg/mL) were significantly higher than those of low-risk patients (77+/-61 pg/mL) (P=.001). A total of 48 patients (80%) were accessible for follow-up after 6 months. Postconcussive syndrome was observed in 8 patients, 5 of whom had serum tau protein levels that were higher than those of the other 3 patients. However, no statistically significant difference was observed (P>.05). Investigators of the present study noted that serum tau levels in patients with mTBI were increased. Therefore, it is believed that this biomarker may prove helpful in identifying high-risk patients with mTBI. However, additional studies are needed to establish the diagnostic value of serum tau in detecting traumatic brain injury in patients with mTBI.
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Affiliation(s)
- M Bulut
- Department of Emergency Medicine, Uludag University Medical School, Bursa, Turkey
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Is increased serum S-100 protein concentration a marker of metastasis in malignant melanoma? A four-year experience report. EUROPEAN JOURNAL OF PLASTIC SURGERY 2005. [DOI: 10.1007/s00238-004-0696-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Stapert S, de Kruijk J, Houx P, Menheere P, Twijnstra A, Jolles J. S-100B Concentration Is Not Related to Neurocognitive Performance in the First Month after Mild Traumatic Brain Injury. Eur Neurol 2004; 53:22-6. [PMID: 15677870 DOI: 10.1159/000083678] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2004] [Indexed: 11/19/2022]
Abstract
The serum concentration of S-100B is reported to reflect the severity of brain damage. The purpose of this study was to determine whether elevated serum S-100B concentrations were related to neuropsychological test performance of patients in the subacute phase of recovery from mild traumatic brain injury (TBI). S-100B concentrations were measured in blood samples taken within 6 h after TBI. Serum S-100B was estimated using an immunoluminometric assay. Cognitive speed and memory were assessed with neuropsychological tests at a median of 13 days (range 7-21 days) after injury. The two groups, formed on a median split of initial serum S-100B concentrations (>or<0.22 microg/l) did not differ in age or education. The neuropsychological performance of the TBI patients was also compared with that of a healthy control group. Cognitive speed and memory performance of mild TBI patients were inferior compared to those of healthy subjects. There were no significant differences within the TBI group when serum S-100B concentration was taken into consideration. The findings suggest that serum S-100B levels after mild TBI are not predictive of neuropsychological performance in the subacute stage of recovery.
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Affiliation(s)
- Sven Stapert
- Department of Psychology, Institute Brain & Behaviour, Maastricht University, Maastricht, The Netherlands.
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Vos PE, Lamers KJB, Hendriks JCM, van Haaren M, Beems T, Zimmerman C, van Geel W, de Reus H, Biert J, Verbeek MM. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 2004; 62:1303-10. [PMID: 15111666 DOI: 10.1212/01.wnl.0000120550.00643.dc] [Citation(s) in RCA: 276] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To study the ability of glial (glial fibrillary acidic protein [GFAP] and S100b) and neuronal (neuron specific enolase [NSE]) protein levels in peripheral blood to predict outcome after severe traumatic brain injury. METHODS Eighty-five patients with severe traumatic brain injury (admission Glasgow Coma Score [GCS] < or = 8) were included. Blood samples taken at the time of hospital admission were analyzed for S100b, GFAP, and NSE. Data collected included demographic and clinical variables. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months post injury. RESULTS The median serum levels of S100b, GFAP, and NSE were raised 18.3 fold (S100b), 4.6 fold (GFAP), and twofold (NSE) compared to normal reference values. S100b, GFAP, and NSE serum levels correlated significantly with the injury severity score and CT findings but not with age, sex, or GCS. S100b, GFAP, and NSE levels were significantly higher in patients who died or had a poor outcome 6 months post injury than in those who were alive or had good outcome. S100b level >1.13 microg/L was the strongest predictor of death with 100% discrimination, but GFAP (>1.5 microg/L) and NSE (>21.7 microg/L) levels also strongly predicted death (adjusted odds ratios 5.82 [for GFAP] and 3.91 [for NSE]). S100b, GFAP, and NSE all strongly predicted poor outcome (adjusted odds ratios 5.12 [S100b], 8.82 [GFAP], and 3.95 [NSE]). CONCLUSIONS These results suggest that determination of serum levels of glial and neuronal proteins may add to the clinical assessment of the primary damage and prediction of outcome after severe traumatic brain injury.
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Affiliation(s)
- P E Vos
- Department of Neurology, University Medical Centre Nijmegen, The Netherlands.
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Pelinka LE, Jafarmadar M, Redl H, Bahrami S. NEURON-SPECIFIC-ENOLASE IS INCREASED IN PLASMA AFTER HEMORRHAGIC SHOCK AND AFTER BILATERAL FEMUR FRACTURE WITHOUT TRAUMATIC BRAIN INJURY IN THE RAT. Shock 2004; 22:88-91. [PMID: 15201708 DOI: 10.1097/01.shk.0000130157.34382.3f] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Neuron-specific enolase (NSE) is an acknowledged marker of traumatic brain injury. Several markers originally considered reliable in the setting of traumatic brain injury have been challenged after having been studied more extensively. The aim of our experimental study was to determine whether NSE is a reliable marker of traumatic brain injury early after trauma. Hemorrhagic shock was achieved by bleeding anesthetized rats to a mean arterial pressure (MAP) of 30-35 mmHg through a femoral catheter until incipient decompensation. MAP was maintained at 30-35 mmHg until 40% of shed blood had been administered as Ringer's solution and was then increased and maintained at 40-45 mmHg for 40 min by further administration of Ringer's solution, mimicking the phase of inadequate preclinical resuscitation. Blood samples were drawn at the end of the 40-min period of inadequate resuscitation. Femur fracture was achieved in anesthetized rats by bilateral application of forceps. Blood samples were drawn 30 and 60 min after fracture. Hemorrhagic shock caused NSE increase versus laboratory controls at the end of inadequate resuscitation (P < 0.01). Bilateral femur fracture caused NSE increase versus laboratory controls 30 min after fracture, which was significant 60 min after fracture (P < 0.01). During femur fracture, MAP remained at a level that is not associated with shock in rats. Our findings show for the first time that NSE increases after hemorrhagic shock as well as after femur fracture without hemorrhagic shock in rats. From a clinical point of view, these findings indicate that NSE cannot be considered a reliable marker of traumatic brain injury early after trauma in cases associated with hemorrhagic shock and/or femur fracture.
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Affiliation(s)
- Linda E Pelinka
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology and Research Center of the Worker's Compensation Board (AUVA), Vienna, Austria.
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Ucar T, Baykal A, Akyuz M, Dosemeci L, Toptas B. Comparison of Serum and Cerebrospinal Fluid Protein S-100b Levels After Severe Head Injury and Their Prognostic Importance. ACTA ACUST UNITED AC 2004; 57:95-8. [PMID: 15284555 DOI: 10.1097/01.ta.0000071352.95491.75] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND This study aimed to compare serum and cerebrospinal fluid (CSF) S-100b protein levels after a severe head injury. The changes in serum S-100b and CSF S-100b concentrations were investigated as indicators of brain damage for patients suffering from severe head injuries. METHODS The sample included 48 patients with Glasgow Coma Scale scores of 8 or below who had been admitted to the authors' emergency service soon after their severe head injury occurred. Both blood and CSF samples were taken within 1 to 11 hours after admission, then 24, 48, and 72 hours after the injury. Samples of CSF were taken using a ventricular catheter. The outcome was evaluated 6 to 9 months after hospital discharge using the Glasgow Outcome Scale. RESULTS The overall mean serum S-100b concentration was 3.5 +/- 6.4 among the patients with unfavorable outcomes and 1.3 +/- 2.5 among those with favorable outcomes. These results were not statistically significant (p > 0.05). The overall mean CSF S-100b concentration was 62.2 +/- 21.8 among the patients with unfavorable outcomes and 21.8 +/- 17.7 among those with favorable outcomes. These results, however, were statistically significant (p < 0.05). CONCLUSION The results show that CSF S-100b levels clearly are superior to serum S-100b levels for predicting outcome after severe head injury.
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Affiliation(s)
- Tanju Ucar
- Department of Neurosurgery, University of Akdeniz School of Medicine, Antalya, Turkey.
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Savola O, Pyhtinen J, Leino TK, Siitonen S, Niemelä O, Hillbom M. Effects of Head and Extracranial Injuries on Serum Protein S100B Levels in Trauma Patients. ACTA ACUST UNITED AC 2004; 56:1229-34; discussion 1234. [PMID: 15211130 DOI: 10.1097/01.ta.0000096644.08735.72] [Citation(s) in RCA: 164] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND Serum protein S100B determinations have been recently suggested as markers of traumatic brain injury. However, little is known about the effects of extracranial injuries on S100B levels in trauma patients. METHODS We studied 224 patients with head trauma (54 of whom also had extracranial injuries), 155 patients with various types of extracranial injuries, and 8 healthy pilots exposed to high Gz forces. The head trauma patients had either no brain injury (n = 35), mild brain injury (n = 165), or moderate to severe brain injury (n = 24). The extracranial injuries were divided into small and large injuries. Serum protein S100B levels were determined from samples taken within 6 hours after the trauma event. RESULTS The head trauma patients had a significantly higher median S100B (0.17 microg/L) than the patients with extracranial injuries (0.07 microg/L) (p < 0.001). Serum S100B levels also correlated with the severity of brain injury (p < 0.001), the highest values occurring in the patients with moderate to severe brain injury (1.27 microg/L). However, large extracranial injuries also elevated S100B levels (0.35 microg/L), whereas small extracranial injuries in the absence of head trauma did not significantly affect S100B levels (0.07 microg/L). Above the cutoff level of 0.13 microg/L, there were 61% of the head trauma patients and 26% of those with extracranial injuries (Pearson chi test, p < 0.001). However, only 4% of the patients with purely extracranial injuries had a concentration of S100B above the cutoff level of 0.50 microg/L, whereas the head trauma patients with moderate to severe brain injury exceeded this cutoff in 67% of the cases. Exposure to high Gz forces did not influence serum S100B levels in healthy individuals. CONCLUSION We conclude that serum S100B is a sensitive marker of brain injury, which correlates with the severity of the injury. Large extracranial injuries also elevate S100B levels. However, S100B has a high negative predictive power, and the finding of a normal S100B value shortly after trauma should thus exclude significant brain injury with a high accuracy.
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Affiliation(s)
- Olli Savola
- Department of Neurology, Oulu University Hospital, Oulu, Finland.
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Park ES, Park CI, Choi KS, Choi IH, Shin JS. Over-expression of S100B protein in children with cerebral palsy or delayed development. Brain Dev 2004; 26:190-6. [PMID: 15030908 DOI: 10.1016/s0387-7604(03)00126-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2003] [Revised: 05/27/2003] [Accepted: 06/17/2003] [Indexed: 11/24/2022]
Abstract
S100B protein plays a role in promoting the maturation of a variety of neurons in many different CNS regions. Behavioral dysfunction in S100B over-expressed transgenic mice and the chronic elevation of S100B in Down's syndrome and in schizophrenia suggest that S100B over-expression is related to abnormal brain function. Therefore, we believed that the over-expression of S100B protein might be implicated in developmental brain dysfunction. The purpose of this study was to evaluate the serum S100B protein levels in patients with developmental brain dysfunction, such as cerebral palsy and delayed development, and to determine the clinical relevance of serum S100B protein in these patients. The mean values of serum S100B protein were significantly increased in both conditions. Patients with cerebral palsy had a S100B protein level of 3455.8 +/- 5004.6 ng/L and those with delayed development of 2557.0 +/- 2321.0 ng/L, compared with a normal control level of 583.8 +/- 483.0 ng/L (P < 0.05). The over-expression of S100B (defined as the normal mean plus three standard deviations) was found in 47.1% of the total patient group (delayed development (47.5%) and cerebral palsy (47.0%)). The frequency of over-expression was not significantly related to clinical diagnosis, disease severity or to brain MRI findings. However, patients who had periventricular leukomalacia by brain MRI showed a wide range and very high levels of S100B exceeding 10,000 ng/L in some cases. These findings suggest that the pathogenesis implied by the over-expression of S100B protein during brain development may play a role in developmental brain dysfunction.
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Affiliation(s)
- Eun Sook Park
- Department of Rehabilitation Medicine and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 134 Shinchon-dong Seodaemoon-gu, Seoul 120-752, Republic of Korea
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Mathias JL, Beall JA, Bigler ED. Neuropsychological and information processing deficits following mild traumatic brain injury. J Int Neuropsychol Soc 2004; 10:286-97. [PMID: 15012849 DOI: 10.1017/s1355617704102117] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2003] [Revised: 07/16/2003] [Indexed: 11/07/2022]
Abstract
Neuroradiological and neuropathological investigations have found evidence of diffuse brain damage in the frontal and temporal lobes, corpus callosum, and fornices in patients who have sustained a mild traumatic brain injury (TBI). However, neuropsychological assessments of these patients do not typically target many of the subtle information processing deficits that may arise from diffuse damage involving the frontotemporal regions of the brain as well as white matter pathology, including the corpus callosum. Consequently, we have a limited understanding of the deficits that may be attributable to temporary or permanent disruptions to these functional pathways. This study assessed a group of mild TBI patients (N = 40) and a matched control group (N = 40) on a number of standard neuropsychological tests of selective and sustained attention, verbal and non-verbal fluency, and verbal memory. In addition, reaction time (RT) tasks, requiring both the inter- and intra-hemispheric processing of visual and tactile information, were used to assess the functional integrity of the tracts that are likely to be affected by diffuse damage. In the 1st month after sustaining their injury, the mild TBI group demonstrated deficits in attention, non-verbal fluency, and verbal memory. They also demonstrated slower visual and tactile RTs, with the visual RTs of mild TBI patients being more affected by increased task difficulty and the need to transfer information across the corpus callosum, than did their matched controls.
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Affiliation(s)
- Jane L Mathias
- Department of Psychology, University of Adelaide, Adelaide, South Australia.
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Stålnacke BM, Tegner Y, Sojka P. Playing ice hockey and basketball increases serum levels of S-100B in elite players: a pilot study. Clin J Sport Med 2003; 13:292-302. [PMID: 14501312 DOI: 10.1097/00042752-200309000-00004] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To investigate changes in serum concentrations of the biochemical markers of brain damage S-100B and neuron-specific enolase (NSE) in ice hockey and basketball players during games. DESIGN Descriptive clinical research. SETTING Competitive games of the Swedish Elite Ice Hockey League and the Swedish Elite Basketball League. PARTICIPANTS Twenty-six male ice hockey players (from two teams) and 18 basketball players (from two teams). INTERVENTIONS None. MAIN OUTCOME MEASURES S-100B and NSE were analyzed using two-site immunoluminometric assays. The numbers of acceleration/deceleration events were assessed from videotape recordings of the games. Head trauma-related symptoms were monitored 24 hours after the game using the Rivermead Post Concussion Symptoms Questionnaire. RESULTS Changes in serum concentrations of S-100B (postgame - pregame values) were statistically significant after both games (ice hockey, 0.072 +/- 0.108 microg/L, P = 0.00004; basketball, 0.076 +/- 0.091 microg/L, P = 0.001). In basketball, there was a significant correlation between the change in S-100B (postgame-pregame values) and jumps, which were the most frequent acceleration/deceleration (r = 0.706, P = 0.002). For NSE, no statistically significant change in serum concentration was found in either game. For one ice hockey player who experienced concussion during play, S-100B was increased more than for the other players. CONCLUSIONS S-100B was released into the blood of the players as a consequence of game-related activities and events. Analysis of the biochemical brain damage markers (in particular S-100B) seems to have the potential to become a valuable additional tool for assessment of the degree of brain tissue damage in sport-related head trauma and probably for decision making about returning to play.
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Akhtar JI, Spear RM, Senac MO, Peterson BM, Diaz SM. Detection of traumatic brain injury with magnetic resonance imaging and S-100B protein in children, despite normal computed tomography of the brain. Pediatr Crit Care Med 2003; 4:322-6. [PMID: 12831414 DOI: 10.1097/01.pcc.0000075323.47797.b8] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The objective of this study was to obtain data to further define the extent of traumatic brain injury by using S-100B protein and standard noncontrast magnetic resonance imaging with added fluid-attenuated inversion recovery (FLAIR) and gradient echo sequence in children with normal head computed tomography. DESIGN Pilot, single cohort, prospective, clinical diagnostic study. SETTING Pediatric intensive care and intermediate care unit in a tertiary care children's hospital. PATIENTS Children ages 5-18 yrs who sustained traumatic brain injury, had a negative computed tomography of the brain, and were admitted to hospital were eligible for enrollment. INTERVENTIONS Two blood samples were drawn for S-100B protein analysis: the first (t-1) as soon as possible or close to 6 hrs of injury and the second (t-2) close to 12 hrs from the time of injury. A magnetic resonance image of the brain was obtained within 96 hrs of injury. MEASUREMENTS AND MAIN RESULTS Seven of 17 patients (41%) had positive magnetic resonance image. Of the seven patients with positive magnetic resonance image, 100% (seven of seven) had a positive magnetic resonance image with FLAIR sequence, 85% (six of seven) with axial T2 sequence and 50% (three of six) with gradient echo sequence. There was no statistically significant difference in S-100B protein concentrations in patients with a positive magnetic resonance image (n = 7) and those with a negative magnetic resonance image (n = 10; p =.40 at t-1 and p =.13 at t-2). The concentration of S-100B protein was statistically significantly higher in patients with head and other bodily injury (n = 9) compared with isolated head injury (n = 6; p =.018 at t-1 and p =.025 at t-2). Patients with a positive magnetic resonance image had a lower Glasgow Coma Scale score and longer duration of hospital stay. CONCLUSIONS Magnetic resonance imaging seems to be a useful modality to better define the spectrum of brain injury in children with mild head trauma. The addition of S-100B protein measurement does not seem to be useful in this setting.
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Affiliation(s)
- Javed I Akhtar
- Division of Pediatric Critical Care, Children's Hospital, San Diego, CA, USA.
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Rothermundt M, Peters M, Prehn JHM, Arolt V. S100B in brain damage and neurodegeneration. Microsc Res Tech 2003; 60:614-32. [PMID: 12645009 DOI: 10.1002/jemt.10303] [Citation(s) in RCA: 436] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
S100B is a calcium-binding peptide produced mainly by astrocytes that exert paracrine and autocrine effects on neurons and glia. Some knowledge has been acquired from in vitro and in vivo animal experiments to understand S100B's roles in cellular energy metabolism, cytoskeleton modification, cell proliferation, and differentiation. Also, insights have been gained regarding the interaction between S100B and the cerebral immune system, and the regulation of S100B activity through serotonergic transmission. Secreted glial S100B exerts trophic or toxic effects depending on its concentration. At nanomolar concentrations, S100B stimulates neurite outgrowth and enhances survival of neurons during development. In contrast, micromolar levels of extracellular S100B in vitro stimulate the expression of proinflammatory cytokines and induce apoptosis. In animal studies, changes in the cerebral concentration of S100B cause behavioral disturbances and cognitive deficits. In humans, increased S100B has been detected with various clinical conditions. Brain trauma and ischemia is associated with increased S100B concentrations, probably due to the destruction of astrocytes. In neurodegenerative, inflammatory and psychiatric diseases, increased S100B levels may be caused by secreted S100B or release from damaged astrocytes. This review summarizes published findings on S100B regarding human brain damage and neurodegeneration. Findings from in vitro and in vivo animal experiments relevant for human neurodegenerative diseases and brain damage are reviewed together with the results of studies on traumatic, ischemic, and inflammatory brain damage as well as neurodegenerative and psychiatric disorders. Methodological problems are discussed and perspectives for future research are outlined.
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Abstract
A small proportion of patients with mild head injury (MHI) develop post-concussion symptoms (PCSs). We searched simple measures for the early detection of patients who are probable to develop PCSs. We recorded signs and symptoms, history of previous diseases, medications, and lifestyle factors and measured serum protein S-100B on admission in a series of 172 consecutive MHI patients admitted into the emergency room of a general hospital. A modified Rivermead Post-Concussion Symptoms Questionnaire was used to identify the patients with and without PCSs 1 month after the injury. We identified 37 patients with MHI who developed PCSs (22%). Odds ratios (OR) and 95% confidence intervals (CI) after adjustment for possible confounding variables were calculated by logistic regression. Independent early risk factors for PCSs in the MHI patients were skull fracture (OR 8.0, 95% CI 2.6-24.6), serum protein S-100B >/= 0.50 microg/l (OR 5.5, 95% CI 1.6-18.6), dizziness (OR 3.1, 95% CI 1.2-8.0), and headache (OR 2.6, 95% CI 1.0-6.5). Serum protein S-100B proved to be a specific, but not sensitive predictor of PCSs. The presence of skull fracture, elevated serum protein S-100B, dizziness, and headache may help the emergency room physician to identify patients at risk of PCSs and to refer them for further examination and follow-up.
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Affiliation(s)
- O Savola
- Department of Neurology, Oulu University Hospital, Oulu, Finland
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Ingebrigtsen T, Romner B. Biochemical serum markers of traumatic brain injury. THE JOURNAL OF TRAUMA 2002; 52:798-808. [PMID: 11956409 DOI: 10.1097/00005373-200204000-00038] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Tor Ingebrigtsen
- Department of Neurosurgery, Tromsø University Hospital, Tromsø, Norway.
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