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Boscarello T, Boparai R, Samson N, Rodriguez A, Knoblauch T, Vanier C, Snyder T. Neuroimaging findings and balance problems after mild traumatic brain injury: A systematic review protocol. PLoS One 2025; 20:e0307339. [PMID: 39908314 PMCID: PMC11798431 DOI: 10.1371/journal.pone.0307339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 12/13/2024] [Indexed: 02/07/2025] Open
Abstract
OBJECTIVE To systematically review studies relating neuroimaging findings to balance problems resulting from a history of mTBI. INTRODUCTION Mild traumatic brain injury affects 55.9 million people worldwide every year. These injuries can have persistent symptoms such as maintaining balance which can be life-altering. Difficulties maintaining balance persist months or years after a mild traumatic brain injury in >30% of patients. Neuroimaging modalities, including magnetic resonance imaging, diffusion-weighted imaging, functional magnetic resonance imaging, electroencephalography, and magnetoencephalography, have been associated with presentation or persistence of balance difficulties, but no clinical guidelines are currently in place. INCLUSION CRITERIA Studies will include participants of any age or sex who were diagnosed as having mild traumatic brain injury by a medical professional, excluding studies which by design included patients with other conditions diagnosed using neuroimaging findings. There must be at least one post-injury scan from at one or more of the included neuroimaging modalities, and assessment of balance problems. A comparator must be present in the form of either a control group or longitudinal design. METHODS A search will be conducted in Elsevier (Embase), MEDLINE (PubMed), Google Scholar, SportDiscus (EBSCOhost) and ProQuest for studies meeting the inclusion criteria, published 2013-2024, and available in English. Reviews will not be included. The process of study selection, critical assessment, data extraction, and summarizing findings will be conducted by two independent reviewers, with disagreements resolved by a third. The meta-analysis will summarize the strength of association between specific findings related to brain regions using various neuroimaging modalities and the presentation or persistence of balance difficulties. Evidence related to each neuroimaging modality will summarized using the GRADE approach. TRIAL REGISTRATION Systematic review registration number: CRD42024476988.
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Affiliation(s)
- Todd Boscarello
- Reno School of Medicine, University of Nevada, Reno, NV, United States of America
| | - Robby Boparai
- Reno School of Medicine, University of Nevada, Reno, NV, United States of America
| | - Nathan Samson
- Touro University of Nevada, College of Osteopathic Medicine, Henderson, NV, United States of America
| | - Alan Rodriguez
- Touro University of Nevada, College of Osteopathic Medicine, Henderson, NV, United States of America
- IMGEN Research Group, Las Vegas, NV, United States of America
| | - Thomas Knoblauch
- Touro University of Nevada, College of Osteopathic Medicine, Henderson, NV, United States of America
- IMGEN Research Group, Las Vegas, NV, United States of America
| | - Cheryl Vanier
- Touro University of Nevada, College of Osteopathic Medicine, Henderson, NV, United States of America
- IMGEN Research Group, Las Vegas, NV, United States of America
- Touro University Nevada: A JBI Affiliated Group, Henderson, NV, United States of America
| | - Travis Snyder
- Touro University of Nevada, College of Osteopathic Medicine, Henderson, NV, United States of America
- IMGEN Research Group, Las Vegas, NV, United States of America
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Criado-Marrero M, Ravi S, Bhaskar E, Barroso D, Pizzi MA, Williams L, Wellington CL, Febo M, Abisambra JF. Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries in mice. Neuroimage 2024; 298:120764. [PMID: 39089604 PMCID: PMC12083070 DOI: 10.1016/j.neuroimage.2024.120764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/08/2024] [Accepted: 07/29/2024] [Indexed: 08/04/2024] Open
Abstract
Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBI) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI by employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the closed-head impact model of engineered rotational acceleration (CHIMERA) model, we conducted rmTBIs or sham (control) procedures on young (2.5-3-months-old) and aged (22-months-old) male and female mice to model high-risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposhigh-risking effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBI.
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Affiliation(s)
- Marangelie Criado-Marrero
- Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, FL 32610, USA; Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
| | - Sakthivel Ravi
- Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, FL 32610, USA; Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
| | - Ekta Bhaskar
- Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Department of Computer of Information Science and Engineering (CISE), University of Florida, Gainesville, FL 32610, USA
| | - Daylin Barroso
- Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, FL 32610, USA; Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
| | - Michael A Pizzi
- Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Brain Injury Rehabilitation and Neuroresilience (BRAIN) Center University of Florida, Gainesville, FL 32610, USA; Department of Neurology, University of Florida, Gainesville, FL 32610, USA
| | - Lakiesha Williams
- J. Crayton Pruitt Family Department of Biomedical Engineering, Gainesville, FL 32610, USA
| | - Cheryl L Wellington
- Department of Pathology and Laboratory Medicine, Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada
| | - Marcelo Febo
- McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Department of Psychiatry, University of Florida, Gainesville, FL 32610, USA; Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL 32610, USA
| | - Jose Francisco Abisambra
- Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, FL 32610, USA; Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL 32610, USA; Brain Injury Rehabilitation and Neuroresilience (BRAIN) Center University of Florida, Gainesville, FL 32610, USA.
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Frattini D, Rosén N, Wibble T. A Proposed Mechanism for Visual Vertigo: Post-Concussion Patients Have Higher Gain From Visual Input Into Subcortical Gaze Stabilization. Invest Ophthalmol Vis Sci 2024; 65:26. [PMID: 38607620 PMCID: PMC11018265 DOI: 10.1167/iovs.65.4.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 03/20/2024] [Indexed: 04/13/2024] Open
Abstract
Purpose Post-concussion syndrome (PCS) is commonly associated with dizziness and visual motion sensitivity. This case-control study set out to explore altered motion processing in PCS by measuring gaze stabilization as a reflection of the capacity of the brain to integrate motion, and it aimed to uncover mechanisms of injury where invasive subcortical recordings are not feasible. Methods A total of 554 eye movements were analyzed in 10 PCS patients and nine healthy controls across 171 trials. Optokinetic and vestibulo-ocular reflexes were recorded using a head-mounted eye tracker while participants were exposed to visual, vestibular, and visuo-vestibular motion stimulations in the roll plane. Torsional and vergence eye movements were analyzed in terms of slow-phase velocities, gain, nystagmus frequency, and sensory-specific contributions toward gaze stabilization. Results Participants expressed eye-movement responses consistent with expected gaze stabilization; slow phases were fastest for visuo-vestibular trials and slowest for visual stimulations (P < 0.001) and increased with stimulus acceleration (P < 0.001). Concussed patients demonstrated increased gain from visual input to gaze stabilization (P = 0.005), faster slow phases (P = 0.013), earlier nystagmus beats (P = 0.003), and higher relative visual influence over the gaze-stabilizing response (P = 0.001), presenting robust effect sizes despite the limited population size. Conclusions The enhanced neural responsiveness to visual motion in PCS, combined with semi-intact visuo-vestibular integration, presented a subcortical hierarchy for altered gaze stabilization. Drawing on comparable animal trials, findings suggest that concussed patients may suffer from diffuse injuries to inhibiting pathways for optokinetic information, likely early in the visuo-vestibular hierarchy of sensorimotor integration. These findings offer context for common but elusive symptoms, presenting a neurological explanation for motion sensitivity and visual vertigo in PCS.
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Affiliation(s)
- Davide Frattini
- Department of Clinical Neuroscience, Division of Eye and Vision, Marianne Bernadotte Centrum, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Niklas Rosén
- Department of Clinical Neuroscience, Division of Eye and Vision, Marianne Bernadotte Centrum, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Tobias Wibble
- Department of Clinical Neuroscience, Division of Eye and Vision, Marianne Bernadotte Centrum, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden
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Lima Santos JP, Kontos AP, Holland CL, Suss SJ, Stiffler RS, Bitzer HB, Colorito AT, Shaffer M, Skeba A, Iyengar S, Manelis A, Brent D, Shirtcliff EA, Ladouceur CD, Phillips ML, Collins MW, Versace A. The Role of Puberty and Sex on Brain Structure in Adolescents With Anxiety Following Concussion. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2024; 9:285-297. [PMID: 36517369 DOI: 10.1016/j.bpsc.2022.09.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 09/08/2022] [Accepted: 09/13/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Adolescence represents a window of vulnerability for developing psychological symptoms following concussion, especially in girls. Concussion-related lesions in emotion regulation circuits may help explain these symptoms. However, the contribution of sex and pubertal maturation remains unclear. Using the neurite density index (NDI) in emotion regulation tracts (left/right cingulum bundle [CB], forceps minor [FMIN], and left/right uncinate fasciculus), we sought to elucidate these relationships. METHODS No adolescent had a history of anxiety and/or depression. The Screen for Child Anxiety Related Emotional Disorders and Children's Depression Rating Scale were used at scan to assess anxiety and depressive symptoms in 55 concussed adolescents (41.8% girls) and 50 control adolescents with no current/history of concussion (44% girls). We evaluated if a mediation-moderation model including the NDI (mediation) and sex or pubertal status (moderation) could help explain this relationship. RESULTS Relative to control adolescents, concussed adolescents showed higher anxiety (p = .003) and lower NDI, with those at more advanced pubertal maturation showing greater abnormalities in 4 clusters: the left CB frontal (p = .002), right CB frontal (p = .011), FMIN left-sided (p = .003), and FMIN right-sided (p = .003). Across all concussed adolescents, lower NDI in the left CB frontal and FMIN left-sided clusters partially mediated the association between concussion and anxiety, with the CB being specific to female adolescents. These effects did not explain depressive symptoms. CONCLUSIONS Our findings indicate that lower NDI in the CB and FMIN may help explain anxiety following concussion and that adolescents at more advanced (vs less advanced) status of pubertal maturation may be more vulnerable to concussion-related injuries, especially in girls.
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Affiliation(s)
- João Paulo Lima Santos
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Anthony P Kontos
- Department of Orthopaedic Surgery/UPMC Sports Concussion Program, University of Pittsburgh, Pennsylvania
| | - Cynthia L Holland
- Department of Orthopaedic Surgery/UPMC Sports Concussion Program, University of Pittsburgh, Pennsylvania
| | - Stephen J Suss
- Department of Orthopaedic Surgery/UPMC Sports Concussion Program, University of Pittsburgh, Pennsylvania
| | - Richelle S Stiffler
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Hannah B Bitzer
- Department of Psychology, Florida International University, Miami, Florida
| | - Adam T Colorito
- Department of Psychology, Florida International University, Miami, Florida
| | - Madelyn Shaffer
- Department of Psychology, Florida International University, Miami, Florida
| | - Alexander Skeba
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Satish Iyengar
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Anna Manelis
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - David Brent
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychiatry, UPMC Western Psychiatric Hospital, Pittsburgh, Pennsylvania
| | - Elizabeth A Shirtcliff
- Center for Translational Neuroscience and Department of Psychology, University of Oregon, Eugene, Oregon
| | - Cecile D Ladouceur
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Mary L Phillips
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Michael W Collins
- Department of Orthopaedic Surgery/UPMC Sports Concussion Program, University of Pittsburgh, Pennsylvania
| | - Amelia Versace
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Radiology, Magnetic Resonance Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
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Jacquens A, Delmotte PR, Gourbeix C, Farny N, Perret-Liaudet B, Hijazi D, Batisti V, Torkomian G, Cassereau D, Debarle C, Shotar E, Gellman C, Mathon B, Bayen E, Galanaud D, Perlbarg V, Puybasset L, Degos V. MRI volumetry and diffusion tensor imaging for diagnosis and follow-up of late post-traumatic injuries. Ann Phys Rehabil Med 2024; 67:101783. [PMID: 38147704 DOI: 10.1016/j.rehab.2023.101783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 05/02/2023] [Accepted: 05/29/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND Traumatic Brain Injury (TBI) is a major cause of acquired disability and can cause devastating and progressive post-traumatic encephalopathy. TBI is a dynamic condition that continues to evolve over time. A better understanding of the pathophysiology of these late lesions is important for the development of new therapeutic strategies. OBJECTIVES The primary objective was to compare the ability of fluid-attenuated reversion recovery (FLAIR) and diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) markers to identify participants with a Glasgow outcome scale extended (GOS-E) score of 7-8, up to 10 years after their original TBI. The secondary objective was to study the brain regionalization of DTI markers. Finally, we analyzed the evolution of late-developing brain lesions using repeated MRI images, also taken up to 10 years after the TBI. METHODS In this retrospective study, participants were included from a cohort of people hospitalized following a severe TBI. Following their discharge, they were followed-up and clinically assessed, including a DTI-MRI scan, between 2012 and 2016. We performed a cross-sectional analysis on 97 participants at a median (IQR) of 5 years (3-6) post-TBI, and a further post-TBI longitudinal analysis over 10 years on a subpopulation (n = 17) of the cohort. RESULTS Although the area under the curve (AUC) of FLAIR, fractional anisotropy (FA), and mean diffusivity (MD) were not significantly different, only the AUC of FA was statistically greater than 0.5. In addition, only the FA was correlated with clinical outcomes as assessed by GOS-E score (P<10-4). On the cross-sectional analysis, DTI markers allowed study post-TBI white matter lesions by region. In the longitudinal subpopulation analysis, the observed number of brain lesions increased for the first 5 years post-TBI, before stabilizing over the next 5 years. CONCLUSIONS This study has shown for the first time that post-TBI lesions can present in a two-phase evolution. These results must be confirmed in larger studies. French Data Protection Agency (Commission nationale de l'informatique et des libertés; CNIL) study registration no: 1934708v0.
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Affiliation(s)
- Alice Jacquens
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France.
| | - Pierre-Romain Delmotte
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Claire Gourbeix
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Nicolas Farny
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Bérenger Perret-Liaudet
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Dany Hijazi
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Valentine Batisti
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Grégory Torkomian
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Didier Cassereau
- Laboratoire d'Imagerie Biomédicale, Sorbonne Université, 15 rue de l'Ecole de Médecine, 75006, Paris, France; ESPCI, 10 rue Vauquelin, 75005, Paris, France
| | - Clara Debarle
- Physical Medicine and Rehabilitation Department, Centre Hospitalier Saint-Anne, 1 rue Cabanis, GHU Paris psychiatrie et neurosciences, 75014, Paris, France
| | - Eimad Shotar
- Department of Interventional Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France
| | - Celia Gellman
- Icahn School of Medicine at Mount Sinai, NYC Health + Hospitals/Elmhurst, Internal Medicine Residency Program, United States
| | - Bertrand Mathon
- Department of Neurosurgery, APHP - Sorbonne University, La Pitié-Salpêtrière Hospital, 47-83, Boulevard de L'Hôpital, 75651 Cedex 13, Paris, France
| | - Eleonor Bayen
- UGECAM-IdF, groupe hospitalier Pitié-Salpêtrière, service de médecine physique et de réadaptation, Paris France
| | - Damien Galanaud
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neuroradiologie, 75013, Paris, France
| | | | - Louis Puybasset
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France; BRAINTALE SAS, Paris, France
| | - Vincent Degos
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
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Criado-Marrero M, Ravi S, Bhaskar E, Barroso D, Pizzi MA, Williams L, Wellington CL, Febo M, Abisambra JF. Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.25.577316. [PMID: 38328104 PMCID: PMC10849649 DOI: 10.1101/2024.01.25.577316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following repetitive mild traumatic brain injuries (rmTBIs). In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and Neurite Orientation Dispersion and Density Imaging (NODDI). Utilizing the CHIMERA model, we conducted rmTBIs or sham (control) procedures on young (2.5-3 months old) and aged (22-month-old) male and female mice to model high risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposing effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean, radial, axial diffusivity, fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Inflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in aged animals. These findings provide a comprehensive understanding of the intricate interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBIs.
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Vrettou CS, Fragkou PC, Mallios I, Barba C, Giannopoulos C, Gavrielatou E, Dimopoulou I. The Role of Automated Infrared Pupillometry in Traumatic Brain Injury: A Narrative Review. J Clin Med 2024; 13:614. [PMID: 38276120 PMCID: PMC10817296 DOI: 10.3390/jcm13020614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/15/2024] [Accepted: 01/20/2024] [Indexed: 01/27/2024] Open
Abstract
Pupillometry, an integral component of neurological examination, serves to evaluate both pupil size and reactivity. The conventional manual assessment exhibits inherent limitations, thereby necessitating the development of portable automated infrared pupillometers (PAIPs). Leveraging infrared technology, these devices provide an objective assessment, proving valuable in the context of brain injury for the detection of neuro-worsening and the facilitation of patient monitoring. In cases of mild brain trauma particularly, traditional methods face constraints. Conversely, in severe brain trauma scenarios, PAIPs contribute to neuro-prognostication and non-invasive neuromonitoring. Parameters derived from PAIPs exhibit correlations with changes in intracranial pressure. It is important to acknowledge, however, that PAIPs cannot replace invasive intracranial pressure monitoring while their widespread adoption awaits robust support from clinical studies. Ongoing research endeavors delve into the role of PAIPs in managing critical neuro-worsening in brain trauma patients, underscoring the non-invasive monitoring advantages while emphasizing the imperative for further clinical validation. Future advancements in this domain encompass sophisticated pupillary assessment tools and the integration of smartphone applications, emblematic of a continually evolving landscape.
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Affiliation(s)
- Charikleia S. Vrettou
- First Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Medical School, National and Kapodistrian University of Athens, 10676 Athens, Greece (I.D.)
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O’Connell CJ, Brown RS, Peach TM, Traubert OD, Schwierling HC, Notorgiacomo GA, Robson MJ. Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System. Brain Sci 2024; 14:51. [PMID: 38248266 PMCID: PMC10813794 DOI: 10.3390/brainsci14010051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 12/20/2023] [Accepted: 01/02/2024] [Indexed: 01/23/2024] Open
Abstract
Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. This has made therapies for TBI notoriously difficult to develop, and currently, there are no FDA-approved pharmacotherapies specifically for the acute or chronic treatment of TBI. TBI is associated with changes in cognition and can precipitate the onset of debilitating psychiatric disorders like major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Complicating these effects of TBI, FDA-approved pharmacotherapies utilized to treat these disorders often fail to reach the desired level of efficacy in the context of neurotrauma. Although a complicated association, decades of work have linked central serotonin (5-HT) neurotransmission as being involved in the etiology of a myriad of neuropsychiatric disorders, including MDD and GAD. 5-HT is a biogenic monoamine neurotransmitter that is highly conserved across scales of biology. Though the majority of 5-HT is isolated to peripheral sites such as the gastrointestinal (GI) tract, 5-HT neurotransmission within the CNS exerts exquisite control over diverse biological functions, including sleep, appetite and respiration, while simultaneously establishing normal mood, perception, and attention. Although several key studies have begun to elucidate how various forms of neurotrauma impact central 5-HT neurotransmission, a full determination of precisely how TBI disrupts the highly regulated dynamics of 5-HT neuron function and/or 5-HT neurotransmission has yet to be conceptually or experimentally resolved. The purpose of the current review is, therefore, to integrate the disparate bodies of 5-HT and TBI research and synthesize insight into how new combinatorial research regarding 5-HT neurotransmission and TBI may offer an informed perspective into the nature of TBI-induced neuropsychiatric complications.
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Affiliation(s)
- Christopher J. O’Connell
- Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; (C.J.O.); (R.S.B.); (T.M.P.)
| | - Ryan S. Brown
- Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; (C.J.O.); (R.S.B.); (T.M.P.)
| | - Taylor M. Peach
- Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; (C.J.O.); (R.S.B.); (T.M.P.)
| | - Owen D. Traubert
- Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA;
| | - Hana C. Schwierling
- Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; (C.J.O.); (R.S.B.); (T.M.P.)
| | | | - Matthew J. Robson
- Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA; (C.J.O.); (R.S.B.); (T.M.P.)
- Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
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9
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Karvandi E, Helmy A, Kolias AG, Belli A, Ganau M, Gomes C, Grey M, Griffiths M, Griffiths T, Griffiths P, Holliman D, Jenkins P, Jones B, Lawrence T, McLoughlin T, McMahon C, Messahel S, Newton J, Noad R, Raymont V, Sharma K, Sylvester R, Tadmor D, Whitfield P, Wilson M, Woodberry E, Parker M, Hutchinson PJ. Specialist healthcare services for concussion/mild traumatic brain injury in England: a consensus statement using modified Delphi methodology. BMJ Open 2023; 13:e077022. [PMID: 38070886 PMCID: PMC10729241 DOI: 10.1136/bmjopen-2023-077022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 11/14/2023] [Indexed: 12/18/2023] Open
Abstract
OBJECTIVE To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome. DESIGN This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%. SETTING Specialist outpatient services. PARTICIPANTS Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England. PRIMARY OUTCOME MEASURE A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England. RESULTS 55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics. CONCLUSIONS This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.
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Affiliation(s)
- Elika Karvandi
- Department of Neurosurgery, University of Cambridge, Cambridge, UK
| | - Adel Helmy
- Department of Neurosurgery, University of Cambridge, Cambridge, UK
| | - Angelos G Kolias
- Department of Neurosurgery, University of Cambridge, Cambridge, UK
| | - Antonio Belli
- Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Mario Ganau
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Clint Gomes
- Royal Liverpool University Hospital, Liverpool, UK
- UK Sports Institute, Liverpool, UK
| | - Michael Grey
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - Michael Griffiths
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- Department of Paediatric Neurology, Alder-Hey Children's NHS Trust, Liverpool, UK
| | - Timothy Griffiths
- Department of Cognitive Neurology, Newcastle University, Newcastle Upon Tyne, UK
- Institute of Neurology, University College London, London, UK
| | - Philippa Griffiths
- Sunderland & South Tyneside Community Acquired Brain Injury Service, Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Damian Holliman
- Department of Neurosurgery, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - Peter Jenkins
- Wessex Neuroscience Centre, Southampton General Hospital, Southampton, UK
- Imperial College London, London, UK
| | - Ben Jones
- Carnegie Applied Rugby Research (CARR) Centre, Leeds Beckett University-Headingley Campus, Leeds, UK
- England Performance Unit, Rugby Football League Ltd, Leeds, UK
| | - Tim Lawrence
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | | | - Catherine McMahon
- Manchester Centre for Clinical Neurosciences (MCCN), Salford Royal Infirmary, Northern Care Alliance, Liverpool, UK
| | - Shrouk Messahel
- Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK
| | - Joanne Newton
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Rupert Noad
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | | | - Kanchan Sharma
- Department of Neurology, North Bristol NHS Trust, Westbury on Trym, UK
| | - Richard Sylvester
- National Hospital for Neurology and Neurosurgery, London, London, UK
- Institute of Exercise and Health, University College London, London, UK
| | - Daniel Tadmor
- Carnegie School of Sport, Leeds Beckett University, Leeds, UK
- Medical, Leeds Rhinos Rugby League Club, Leeds, UK
| | | | - Mark Wilson
- Imperial College London, London, UK
- Department of Neurosurgery, Imperial College Healthcare NHS Trust, London, UK
| | - Emma Woodberry
- Department of Neuropsychology, University of Cambridge, Cambridge, UK
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10
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Asturias A, Knoblauch T, Rodriguez A, Vanier C, Le Tohic C, Barrett B, Eisenberg M, Gibbert R, Zimmerman L, Parikh S, Nguyen A, Azad S, Germin L, Fazzini E, Snyder T. Diffusion in the corpus callosum predicts persistence of clinical symptoms after mild traumatic brain injury, a multi-scanner study. FRONTIERS IN NEUROIMAGING 2023; 2:1153115. [PMID: 38025312 PMCID: PMC10654678 DOI: 10.3389/fnimg.2023.1153115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 08/23/2023] [Indexed: 12/01/2023]
Abstract
Background Mild traumatic brain injuries (mTBIs) comprise 80% of all TBI, but conventional MRI techniques are often insensitive to the subtle changes and injuries produced in a concussion. Diffusion tensor imaging (DTI) is one of the most sensitive MRI techniques for mTBI studies with outcome and symptom associations described. The corpus callosum (CC) is one of the most studied fiber tracts in TBI and mTBI, but the comprehensive post-mTBI symptom relationship has not fully been explored. Methods This is a retrospective observational study of how quantitative DTI data of the CC and its sub-regions may relate to clinical presentation of symptoms and timing of resolution of symptoms in patients diagnosed with uncomplicated mTBI. DTI and clinical data were obtained retrospectively from 446 (mean age 42 years, range 13-82) civilian patients. From patient medical charts, presentation of the following common post-concussive symptoms was noted: headache, balance issues, cognitive deficits, fatigue, anxiety, depression, and emotional lability. Also recorded was the time between injury and a visit to the physician when improvement or resolution of a particular symptom was reported. FA values from the total CC and 3 subregions of the CC (genu or anterior, mid body, and splenium or posterior) were obtained from hand tracing on the Olea Sphere v3.0 SP12 free-standing workstation. DTI data was obtained from 8 different 3T MRI scanners and harmonized via ComBat harmonization. The statistical models used to explore the association between regional Fractional Anisotropy (FA) values and symptom presentation and time to symptom resolution were logistic regression and interval-censored semi-parametric Cox proportional hazard models, respectively. Subgroups related to age and timing of first scan were also analyzed. Results Patients with the highest FA in the total CC (p = 0.01), anterior CC (p < 0.01), and mid-body CC (p = 0.03), but not the posterior CC (p = 0.91) recovered faster from post-concussive cognitive deficits. Patients with the highest FA in the posterior CC recovered faster from depression (p = 0.04) and emotional lability (p = 0.01). There was no evidence that FA in the CC or any of its sub-regions was associated with symptom presentation or with time to resolution of headache, balance issues, fatigue, or anxiety. Patients with mTBI under 40 had higher FA in the CC and the anterior and mid-body subregions (but not the posterior subregion: p = 1.00) compared to patients 40 or over (p ≤ 0.01). There was no evidence for differences in symptom presentation based on loss of consciousness (LOC) or sex (p ≥ 0.18). Conclusion This study suggests that FA of the CC has diagnostic and prognostic value for clinical assessment of mTBI in a large diverse civilian population, particularly in patients with cognitive symptoms.
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Affiliation(s)
- Alexander Asturias
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
| | - Thomas Knoblauch
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
- School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States
| | - Alan Rodriguez
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
| | - Cheryl Vanier
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
| | - Caroline Le Tohic
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | - Brandon Barrett
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | - Matthew Eisenberg
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | | | - Lennon Zimmerman
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | | | - Anh Nguyen
- Touro University Nevada, Henderson, NV, United States
| | - Sherwin Azad
- MountainView Hospital, HCA Healthcare, Las Vegas, NV, United States
| | - Leo Germin
- Clinical Neurology Specialists, Las Vegas, NV, United States
| | | | - Travis Snyder
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
- MountainView Hospital, HCA Healthcare, Las Vegas, NV, United States
- SimonMed Imaging, Scottsdale, AZ, United States
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11
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Neumann KD, Broshek DK, Newman BT, Druzgal TJ, Kundu BK, Resch JE. Concussion: Beyond the Cascade. Cells 2023; 12:2128. [PMID: 37681861 PMCID: PMC10487087 DOI: 10.3390/cells12172128] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/09/2023] Open
Abstract
Sport concussion affects millions of athletes each year at all levels of sport. Increasing evidence demonstrates clinical and physiological recovery are becoming more divergent definitions, as evidenced by several studies examining blood-based biomarkers of inflammation and imaging studies of the central nervous system (CNS). Recent studies have shown elevated microglial activation in the CNS in active and retired American football players, as well as in active collegiate athletes who were diagnosed with a concussion and returned to sport. These data are supportive of discordance in clinical symptomology and the inflammatory response in the CNS upon symptom resolution. In this review, we will summarize recent advances in the understanding of the inflammatory response associated with sport concussion and broader mild traumatic brain injury, as well as provide an outlook for important research questions to better align clinical and physiological recovery.
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Affiliation(s)
- Kiel D. Neumann
- Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;
| | - Donna K. Broshek
- Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22903, USA;
| | - Benjamin T. Newman
- Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA; (B.T.N.); (T.J.D.); (B.K.K.)
| | - T. Jason Druzgal
- Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA; (B.T.N.); (T.J.D.); (B.K.K.)
| | - Bijoy K. Kundu
- Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA; (B.T.N.); (T.J.D.); (B.K.K.)
| | - Jacob E. Resch
- Department of Kinesiology, University of Virginia, Charlottesville, VA 22903, USA
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12
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Sanchez-Molano J, Blaya MO, Padgett KR, Moreno WJ, Zhao W, Dietrich WD, Bramlett HM. Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes. PLoS One 2023; 18:e0289786. [PMID: 37549175 PMCID: PMC10406285 DOI: 10.1371/journal.pone.0289786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/25/2023] [Indexed: 08/09/2023] Open
Abstract
Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.
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Affiliation(s)
- Juliana Sanchez-Molano
- Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Meghan O. Blaya
- Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Kyle R. Padgett
- Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - William J. Moreno
- Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Weizhao Zhao
- Department of Biomedical Engineering, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - W. Dalton Dietrich
- Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Helen M. Bramlett
- Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America
- Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida, United States of America
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13
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Déry J, Ouellet B, de Guise É, Bussières ÈL, Lamontagne ME. Prognostic factors for persistent symptoms in adults with mild traumatic brain injury: an overview of systematic reviews. Syst Rev 2023; 12:127. [PMID: 37468999 PMCID: PMC10357711 DOI: 10.1186/s13643-023-02284-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 06/26/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Mild traumatic brain injury (mTBI) is an increasing public health problem, because of its persistent symptoms and several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help to guide the prevention of persistent symptoms following mTBI. The prognosis of mTBI has stimulated several empirical primary research papers and many systematic reviews leading to the identification of a wide range of factors. We aim to synthesize these factors to get a better understanding of their breadth and scope. METHODS We conducted an overview of systematic reviews. We searched in databases systematic reviews synthesizing evidence about the prognosis of persistent symptoms after mTBI in the adult population. Two reviewers independently screened all references and selected eligible reviews based on eligibility criteria. They extracted relevant information using an extraction grid. They also rated independently the risk of bias using the ROBIS tool. We synthesized evidence into a comprehensive conceptual map to facilitate the understanding of prognostic factors that have an impact on persistent post-concussion symptoms. RESULTS From the 3857 references retrieved in a database search, we included 25 systematic reviews integrating the results of 312 primary articles published between 1957 and 2019. We examined 35 prognostic factors from the systematics reviews. No single prognostic factor demonstrated convincing and conclusive results. However, age, sex, and multiple concussions showed an affirmatory association with persistent post-concussion outcomes in systematic reviews. CONCLUSION We highlighted the need for a comprehensive picture of prognostic factors related to persistent post-concussion symptoms. We believe that these prognostic factors would guide clinical decisions and research related to prevention and intervention regarding persistent post-concussion symptoms. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020176676.
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Affiliation(s)
- Julien Déry
- School of Rehabilitation Sciences, Université Laval, Pavillon Ferdinand-Vandry, local 2475, 1050, avenue de la Médecine, Québec, QC, G1V 0A6, Canada
- Centre interdisciplinaire de recherche en réadaptation et intégration sociale (Cirris), 525, boul. Wilfrid-Hamel, Québec, QC, G1M 2S8, Canada
| | - Béatrice Ouellet
- School of Rehabilitation Sciences, Université Laval, Pavillon Ferdinand-Vandry, local 2475, 1050, avenue de la Médecine, Québec, QC, G1V 0A6, Canada
- Centre interdisciplinaire de recherche en réadaptation et intégration sociale (Cirris), 525, boul. Wilfrid-Hamel, Québec, QC, G1M 2S8, Canada
| | - Élaine de Guise
- Department of Psychology, Université de Montréal, Montréal, Canada
- Research Institute of the McGill University Health Centre (RI-MUHC), Montréal, Canada
- Centre de recherche interdisciplinaire en réadaptation du Montréal métropolitain (CRIR), Montréal, Canada
| | - Ève-Line Bussières
- Centre interdisciplinaire de recherche en réadaptation et intégration sociale (Cirris), 525, boul. Wilfrid-Hamel, Québec, QC, G1M 2S8, Canada
- Department of Psychology, Université du Québec à Trois-Rivières, 3007 Michel-Sarrazin, 3600 rue Sainte-Marguerite, Trois-Rivières, QC, G9A 5H7, Canada
| | - Marie-Eve Lamontagne
- School of Rehabilitation Sciences, Université Laval, Pavillon Ferdinand-Vandry, local 2475, 1050, avenue de la Médecine, Québec, QC, G1V 0A6, Canada.
- Centre interdisciplinaire de recherche en réadaptation et intégration sociale (Cirris), 525, boul. Wilfrid-Hamel, Québec, QC, G1M 2S8, Canada.
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14
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van Velkinburgh JC, Herbst MD, Casper SM. Diffusion tensor imaging in the courtroom: Distinction between scientific specificity and legally admissible evidence. World J Clin Cases 2023; 11:4477-4497. [PMID: 37469746 PMCID: PMC10353495 DOI: 10.12998/wjcc.v11.i19.4477] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/26/2023] [Accepted: 06/13/2023] [Indexed: 06/30/2023] Open
Abstract
Interest and uptake of science and medicine peer-reviewed literature by readers outside of a paper’s topical subject, field or even discipline is ever-expanding. While the application of knowledge from one field or discipline to others can stimulate innovative solutions to problems facing modern society, it is also fraught with danger for misuse. In the practice of law in the United States, academic papers are submitted to the courts as evidence in personal injury litigation from both the plaintiff (complainant) and defendant. Such transcendence of an academic publication over disciplinary boundaries is immediately met with the challenge of application by a group that inherently lacks in-depth knowledge on the scientific method, the practice of evidence-based medicine, or the publication process as a structured and internationally synthesized process involving peer review and guided by ethical standards and norms. A modern-day example of this is the ongoing conflict between the sensitivity of diffusion tensor imaging (DTI) and the legal standards for admissibility of evidence in litigation cases of mild traumatic brain injury (mTBI). In this review, we amalgamate the peer-reviewed research on DTI in mTBI with the court’s rationale underlying decisions to admit or exclude evidence of DTI abnormalities to support claims of brain injury. We found that the papers which are critical of the use of DTI in the courtroom reflect a primary misunderstanding about how diagnostic biomarkers differ legally from relevant and admissible evidence. The clinical use of DTI to identify white matter abnormalities in the brain at the chronic stage is a valid methodology both clinically as well as forensically, contributes data that may or may not corroborate the existence of white matter damage, and should be admitted into evidence in personal injury trials if supported by a clinician. We also delve into an aspect of science publication and peer review that can be manipulated by scientists and clinicians to publish an opinion piece and misrepresent it as an unbiased, evidence-based, systematic research article in court cases, the decisions of which establish precedence for future cases and have implications on future legislation that will impact the lives of every citizen and erode the integrity of science and medicine practitioners.
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Affiliation(s)
| | - Mark D Herbst
- Diagnostic Radiology, Independent Diagnostic Radiology Inc, St Petersburg, FL 33711, United States
| | - Stewart M Casper
- Personal Injury Law, Casper & DeToledo LLC, Stamford, CT 06905, United States
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15
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Machine learning classification of chronic traumatic brain injury using diffusion tensor imaging and NODDI: A replication and extension study. NEUROIMAGE: REPORTS 2023; 3. [PMID: 37169013 PMCID: PMC10168530 DOI: 10.1016/j.ynirp.2023.100157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Individuals with acute and chronic traumatic brain injury (TBI) are associated with unique white matter (WM) structural abnormalities, including fractional anisotropy (FA) differences. Our research group previously used FA as a feature in a linear support vector machine (SVM) pattern classifier, observing high classification between individuals with and without acute TBI (i.e., an area under the curve [AUC] value of 75.50%). However, it is not known whether FA could similarly classify between individuals with and without history of chronic TBI. Here, we attempted to replicate our previous work with a new sample, investigating whether FA could similarly classify between incarcerated men with (n = 80) and without (n = 80) self-reported history of chronic TBI. Additionally, given limitations associated with FA, including underestimation of FA values in WM tracts containing crossing fibers, we extended upon our previous study by incorporating neurite orientation dispersion and density imaging (NODDI) metrics, including orientation dispersion (ODI) and isotropic volume (Viso). A linear SVM based classification approach, similar to our previous study, was incorporated here to classify between individuals with and without self-reported chronic TBI using FA and NODDI metrics as separate features. Overall classification rates were similar when incorporating FA and NODDI ODI metrics as features (AUC: 82.50%). Additionally, NODDI-based metrics provided the highest sensitivity (ODI: 85.00%) and specificity (Viso: 82.50%) rates. The current study serves as a replication and extension of our previous study, observing that multiple diffusion MRI metrics can reliably classify between individuals with and without self-reported history of chronic TBI.
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16
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Stenberg J, Skandsen T, Gøran Moen K, Vik A, Eikenes L, Håberg AK. Diffusion Tensor and Kurtosis Imaging Findings the First Year following Mild Traumatic Brain Injury. J Neurotrauma 2023; 40:457-471. [PMID: 36305387 PMCID: PMC9986024 DOI: 10.1089/neu.2022.0206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Despite enormous research interest in diffusion tensor imaging and diffusion kurtosis imaging (DTI; DKI) following mild traumatic brain injury (MTBI), it remains unknown how diffusion in white matter evolves post-injury and relates to acute MTBI characteristics. This prospective cohort study aimed to characterize diffusion changes in white matter the first year after MTBI. Patients with MTBI (n = 193) and matched controls (n = 83) underwent 3T magnetic resonance imaging (MRI) within 72 h and 3- and 12-months post-injury. Diffusion data were analyzed in three steps: 1) voxel-wise comparisons between the MTBI and control group were performed with tract-based spatial statistics at each time-point; 2) clusters of significant voxels identified in step 1 above were evaluated longitudinally with mixed-effect models; 3) the MTBI group was divided into: (A) complicated (with macrostructural findings on MRI) and uncomplicated MTBI; (B) long (1-24 h) and short (< 1 h) post-traumatic amnesia (PTA); and (C) other and no other concurrent injuries to investigate if findings in step 1 were driven mainly by aberrant diffusion in patients with a more severe injury. At 72 h, voxel-wise comparisons revealed significantly lower fractional anisotropy (FA) in one tract and significantly lower mean kurtosis (Kmean) in 11 tracts in the MTBI compared with control group. At 3 months, the MTBI group had significantly higher mean diffusivity in eight tracts compared with controls. At 12 months, FA was significantly lower in four tracts and Kmean in 10 tracts in patients with MTBI compared with controls. There was considerable overlap in affected tracts across time, including the corpus callosum, corona radiata, internal and external capsule, and cerebellar peduncles. Longitudinal analyses revealed that the diffusion metrics remained relatively stable throughout the first year after MTBI. The significant group*time interactions identified were driven by changes in the control rather than the MTBI group. Further, differences identified in step 1 did not result from greater diffusion abnormalities in patients with complicated MTBI, long PTA, or other concurrent injuries, as standardized mean differences in diffusion metrics between the groups were small (0.07 ± 0.11) and non-significant. However, follow-up voxel-wise analyses revealed that other concurrent injuries had effects on diffusion metrics, but predominantly in other metrics and at other time-points than the effects observed in the MTBI versus control group analysis. In conclusion, patients with MTBI differed from controls in white matter integrity already 72 h after injury. Diffusion metrics remained relatively stable throughout the first year after MTBI and were not driven by deviating diffusion in patients with a more severe MTBI.
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Affiliation(s)
- Jonas Stenberg
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Toril Skandsen
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Kent Gøran Moen
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Radiology, Vestre Viken Hospital Trust, Drammen Hospital, Drammen, Norway.,Department of Radiology, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger, Norway
| | - Anne Vik
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Neurosurgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Live Eikenes
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Asta K Håberg
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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17
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Liang B, Alosco ML, Armañanzas R, Martin BM, Tripodis Y, Stern RA, Prichep LS. Long-Term Changes in Brain Connectivity Reflected in Quantitative Electrophysiology of Symptomatic Former National Football League Players. J Neurotrauma 2023; 40:309-317. [PMID: 36324216 PMCID: PMC9902050 DOI: 10.1089/neu.2022.0029] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Exposure to repetitive head impacts (RHI) has been associated with long-term disturbances in cognition, mood, and neurobehavioral dysregulation, and reflected in neuroimaging. Distinct patterns of changes in quantitative features of the brain electrical activity (quantitative electroencephalogram [qEEG]) have been demonstrated to be sensitive to brain changes seen in neurodegenerative disorders and in traumatic brain injuries (TBI). While these qEEG biomarkers are highly sensitive at time of injury, the long-term effects of exposure to RHI on brain electrical activity are relatively unexplored. Ten minutes of eyes closed resting EEG data were collected from a frontal and frontotemporal electrode montage (BrainScope Food and Drug Administration-cleared EEG acquisition device), as well as assessments of neuropsychiatric function and age of first exposure (AFE) to American football. A machine learning methodology was used to derive a qEEG-based algorithm to discriminate former National Football League (NFL) players (n = 87, 55.40 ± 7.98 years old) from same-age men without history of RHI (n = 68, 54.94 ± 7.63 years old), and a second algorithm to discriminate former players with AFE <12 years (n = 33) from AFE ≥12 years (n = 54). The algorithm separating NFL retirees from controls had a specificity = 80%, a sensitivity = 60%, and an area under curve (AUC) = 0.75. Within the NFL population, the algorithm separating AFE <12 from AFE ≥12 resulted in a sensitivity = 76%, a specificity = 52%, and an AUC = 0.72. The presence of a profile of EEG abnormalities in the NFL retirees and in those with younger AFE includes features associated with neurodegeneration and the disruption of neuronal transmission between regions. These results support the long-term consequences of RHI and the potential of EEG as a biomarker of persistent changes in brain function.
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Affiliation(s)
- Bo Liang
- BrainScope Company, Chevy Chase, Maryland, USA
| | - Michael L. Alosco
- Boston University CTE Center, Boston University, Boston, Massachusetts, USA
- Department of Neurology, Boston University, Boston, Massachusetts, USA
| | - Ruben Armañanzas
- BrainScope Company, Chevy Chase, Maryland, USA
- Institute for Data Science and Artificial Intelligence, Universidad de Navarra, Pamplona, Spain
- Tecnun School of Engineering, Universidad de Navarra, Donostia-San Sebastian, Spain
| | - Brett M. Martin
- Boston University CTE Center, Boston University, Boston, Massachusetts, USA
| | - Yorghos Tripodis
- Boston University CTE Center, Boston University, Boston, Massachusetts, USA
- Department of Biostatistics, Boston University, Boston, Massachusetts, USA
| | - Robert A. Stern
- Boston University CTE Center, Boston University, Boston, Massachusetts, USA
- Department of Neurology, Boston University, Boston, Massachusetts, USA
- Departments of Neurosurgery and Anatomy & Neurobiology, Boston University, Boston, Massachusetts, USA
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18
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Toman E, Hodgson S, Riley M, Welbury R, Di Pietro V, Belli A. Concussion in the UK: a contemporary narrative review. Trauma Surg Acute Care Open 2022; 7:e000929. [PMID: 36274785 PMCID: PMC9582316 DOI: 10.1136/tsaco-2022-000929] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 09/03/2022] [Indexed: 11/18/2022] Open
Abstract
Concussion has been receiving an increasing amount of media exposure following several high-profile professional sports controversies and multimillion-dollar lawsuits. The potential life-changing sequalae of concussion and the rare, but devasting, second impact syndrome have also gained much attention. Despite this, our knowledge of the pathological processes involved is limited and often extrapolated from research into more severe brain injuries. As there is no objective diagnostic test for concussion. Relying on history and examination only, the diagnosis of concussion has become the rate-limiting step in widening research into the disease. Clinical study protocols therefore frequently exclude the most vulnerable groups of patients such as those with existing cognitive impairment, concurrent intoxication, mental health issues or learning difficulties. This up-to-date narrative review aims to summarize our current concussion knowledge and provides an insight into promising avenues for future research.
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Affiliation(s)
- Emma Toman
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK,Department of Neurosurgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Sam Hodgson
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Max Riley
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Richard Welbury
- School of Dentistry, University of Central Lancashire, Preston, UK
| | - Valentina Di Pietro
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK,NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Antonio Belli
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK,Department of Neurosurgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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19
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Hidden Truth in Cerebral Concussion—Traumatic Axonal Injury: A Narrative Mini-Review. Healthcare (Basel) 2022; 10:healthcare10050931. [PMID: 35628068 PMCID: PMC9141295 DOI: 10.3390/healthcare10050931] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 05/12/2022] [Accepted: 05/17/2022] [Indexed: 01/25/2023] Open
Abstract
This study reviewed traumatic axonal injury (TAI) in patients with concussion. Concussion refers to transient changes in the neurological function of the brain resulting from head trauma that should not involve any organic brain injury. On the other hand, TAI has been reported in autopsy studies of the human brain and histopathological studies of animal brains following concussion before the development of diffusion tensor imaging (DTI). The diagnosis of TAI in live patients with concussion is limited because of the low resolution of conventional brain magnetic resonance imaging. Since the first study by Arfanakis et al. in 2002, several hundred studies have reported TAI in patients with concussion using DTI. Furthermore, dozens of studies have demonstrated TAI using diffusion tensor tractography for various neural tracts in individual patients with concussion. Hence, DTI provides valuable data for the diagnosis of TAI in patients with concussion. Nevertheless, the confirmation of TAI in live patients with concussion can be limited because a histopathological study via a brain biopsy is required to confirm TAI. Accordingly, further studies for a diagnostic approach to TAI using DTI without a histopathological test in individual patients with concussion will be necessary in the clinical field.
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20
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Detection of Chronic Blast-Related Mild Traumatic Brain Injury with Diffusion Tensor Imaging and Support Vector Machines. Diagnostics (Basel) 2022; 12:diagnostics12040987. [PMID: 35454035 PMCID: PMC9030428 DOI: 10.3390/diagnostics12040987] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 01/13/2023] Open
Abstract
Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions.
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21
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Gumus M, Mack ML, Green R, Khodadadi M, Wennberg R, Crawley A, Colella B, Tarazi A, Mikulis DJ, Tator CH, Tartaglia MC. Brain Connectivity Changes in Post-Concussion Syndrome as the Neural Substrate of a Heterogeneous Syndrome. Brain Connect 2022; 12:711-724. [PMID: 35018791 DOI: 10.1089/brain.2021.0127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Post-concussion syndrome (PCS) or persistent symptoms of concussion refers to a constellation of symptoms that persist for weeks and months after a concussion. To better capture the heterogeneity of the symptoms of patients with post-concussion syndrome, we aimed to separate patients into clinical subtypes based on brain connectivity changes. METHODS Subject-specific structural and functional connectomes were created based on Diffusion Weighted and Resting State Functional Magnetic Resonance Imaging, respectively. Following an informed dimensionality reduction, a gaussian mixture model was used on patient specific structural and functional connectivity matrices to find potential patient clusters. For validation, the resulting patient subtypes were compared in terms of cognitive, neuropsychiatric, and post-concussive symptom differences. RESULTS Multimodal analyses of brain connectivity were predictive of behavioural outcomes. Our modelling revealed 2 patient subtypes; mild and severe. The severe group showed significantly higher levels of depression, anxiety, aggression, and a greater number of symptoms than the mild patient subgroup. CONCLUSION This study suggests that structural and functional connectivity changes together can help us better understand the symptom severity and neuropsychiatric profiles of patients with post-concussion syndrome. This work allows us to move towards precision medicine in concussions and provides a novel machine learning approach that can be applicable to other heterogeneous conditions.
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Affiliation(s)
- Melisa Gumus
- University of Toronto, 7938, 60 Leonard Avenue, Krembil Discovery Tower, Toronto, Toronto, Ontario, Canada, M5S 1A1;
| | | | - Robin Green
- University of Toronto, 7938, Toronto, Ontario, Canada;
| | | | | | | | - Brenda Colella
- University Health Network, 7989, Toronto, Ontario, Canada;
| | - Apameh Tarazi
- University Health Network, 7989, Toronto, Ontario, Canada;
| | - David J Mikulis
- Toronto Western Hospital, 26625, Joint Department of Medical Imaging, 399 Bathurst St., Toronto, Ontario, Canada, m5t2s8;
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22
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Vaughn KA, DeMaster D, Kook JH, Vannucci M, Ewing-Cobbs L. Effective connectivity in the default mode network after paediatric traumatic brain injury. Eur J Neurosci 2022; 55:318-336. [PMID: 34841600 PMCID: PMC9198945 DOI: 10.1111/ejn.15546] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 11/17/2021] [Accepted: 11/20/2021] [Indexed: 01/03/2023]
Abstract
Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7 weeks after injury; post-concussion and anxiety symptoms were assessed 7 months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting-state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post-concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal-parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post-concussion symptoms and anxiety.
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Affiliation(s)
- Kelly A. Vaughn
- University of Texas Health Science Center at Houston,,Corresponding Author
| | - Dana DeMaster
- University of Texas Health Science Center at Houston
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23
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Kim E, Yoo RE, Seong MY, Oh BM. A systematic review and data synthesis of longitudinal changes in white matter integrity after mild traumatic brain injury assessed by diffusion tensor imaging in adults. Eur J Radiol 2021; 147:110117. [PMID: 34973540 DOI: 10.1016/j.ejrad.2021.110117] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 10/28/2021] [Accepted: 12/20/2021] [Indexed: 01/16/2023]
Abstract
PURPOSE This study aimed to review diffusion tensor imaging studies of mild traumatic brain injury (mTBI) in adults with longitudinal acquisition of data and investigate the variability of findings in association with related factors, such as the time post-injury. METHODS Eligible studies from PubMed and EMBASE were searched to identify relevant studies for review. Of the 540 studies, 23 observational studies without intervention and with the following characteristics were included: original research in which adults with mTBI were examined, diffusion tensor imaging was acquired at least twice, white matter integrity was investigated by estimating diffusion metrics, and mode of injury was not restricted to sport- or blast-related mTBI. RESULTS Baseline scans were acquired within 3 weeks post-injury, followed by longitudinal scans within 3 months and at 12 months post-injury. During the acute/subacute period, mixed results (increase, decrease, or no significant change) of fractional anisotropy (FA) were observed compared to those in controls. Some studies reported increased FA during the acute/subacute period compared to controls, followed by normalization of FA. Decreased FA was also reported during the acute/subacute period, which lasted long into the chronic phase. In the acute phase, the mean diffusivity (MD) was greater than that in the controls. Compared to the early phase of injury, MD was reduced in the follow-up phase in most studies in the mTBI group. Insignificant differences in FA and MD have been reported in several studies. Such variability limits the clinical usefulness of diffusion tensor metrics. CONCLUSIONS There was a high variability in reported changes in white matter integrity. Decreased FA not only in acute/subacute but also in long-term period after injury may indicate long-term neurodegenerative processes after mTBI. Nevertheless, longitudinal changes in MD towards normalization suggest possible recovery. Long-term cohort studies with research initiatives should be considered to elucidate brain changes after mTBI.
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Affiliation(s)
- Eunkyung Kim
- Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Roh-Eul Yoo
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Min Yong Seong
- Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Byung-Mo Oh
- Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; National Traffic Injury Rehabilitation Hospital, Yangpyeong, Republic of Korea.
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24
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Gumus M, Santos A, Tartaglia MC. Diffusion and functional MRI findings and their relationship to behaviour in postconcussion syndrome: a scoping review. J Neurol Neurosurg Psychiatry 2021; 92:1259-1270. [PMID: 34635568 DOI: 10.1136/jnnp-2021-326604] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 09/22/2021] [Indexed: 11/04/2022]
Abstract
Postconcussion syndrome (PCS) is a term attributed to the constellation of symptoms that fail to recover after a concussion. PCS is associated with a variety of symptoms such as headaches, concentration deficits, fatigue, depression and anxiety that have an enormous impact on patients' lives. There is currently no diagnostic biomarker for PCS. There have been attempts at identifying structural and functional brain changes in patients with PCS, using diffusion tensor imaging (DTI) and functional MRI (fMRI), respectively, and relate them to specific PCS symptoms. In this scoping review, we appraised, synthesised and summarised all empirical studies that (1) investigated structural or functional brain changes in PCS using DTI or fMRI, respectively, and (2) assessed behavioural alterations in patients with PCS. We performed a literature search in MEDLINE (Ovid), Embase (Ovid) and PsycINFO (Ovid) for primary research articles published up to February 2020. We identified 8306 articles and included 45 articles that investigated the relationship between DTI and fMRI parameters and behavioural changes in patients with PCS: 20 diffusion, 20 fMRI studies and 5 papers with both modalities. Most frequently studied structures were the corpus callosum, superior longitudinal fasciculus in diffusion and the dorsolateral prefrontal cortex and default mode network in the fMRI literature. Although some white matter and fMRI changes were correlated with cognitive or neuropsychiatric symptoms, there were no consistent, converging findings on the relationship between neuroimaging abnormalities and behavioural changes which could be largely due to the complex and heterogeneous presentation of PCS. Furthermore, the heterogeneity of symptoms in PCS may preclude discovery of one biomarker for all patients. Further research should take advantage of multimodal neuroimaging to better understand the brain-behaviour relationship, with a focus on individual differences rather than on group comparisons.
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Affiliation(s)
- Melisa Gumus
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
| | - Alexandra Santos
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
| | - Maria Carmela Tartaglia
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
- Canadian Concussion Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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25
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Stenberg J, Eikenes L, Moen KG, Vik A, Håberg AK, Skandsen T. Acute Diffusion Tensor and Kurtosis Imaging and Outcome following Mild Traumatic Brain Injury. J Neurotrauma 2021; 38:2560-2571. [PMID: 33858218 PMCID: PMC8403189 DOI: 10.1089/neu.2021.0074] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
In this prospective cohort study, we investigated associations between acute diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) metrics and persistent post-concussion symptoms (PPCS) 3 months after mild traumatic brain injury (mTBI). Adult patients with mTBI (n = 176) and community controls (n = 78) underwent 3 Tesla magnetic resonance imaging (MRI) within 72 h post-injury, estimation of cognitive reserve at 2 weeks, and PPCS assessment at 3 months. Eight DTI and DKI metrics were examined with Tract-Based Spatial Statistics. Analyses were performed in the total sample in uncomplicated mTBI only (i.e., without lesions on clinical MRI), and with cognitive reserve both controlled for and not. Patients with PPCS (n = 35) had lower fractional anisotropy (in 2.7% of all voxels) and kurtosis fractional anisotropy (in 6.9% of all voxels), and higher radial diffusivity (in 0.3% of all voxels), than patients without PPCS (n = 141). In uncomplicated mTBI, only fractional anisotropy was significantly lower in patients with PPCS. Compared with controls, patients with PPCS had widespread deviations in all diffusion metrics. When including cognitive reserve as a covariate, no significant differences in diffusion metrics between patients with and without PPCS were present, but patients with PPCS still had significantly higher mean, radial, and axial diffusivity than controls. In conclusion, patients who developed PPCS had poorer white matter microstructural integrity acutely after the injury, compared with patients who recovered and healthy controls. Differences became less pronounced when cognitive reserve was controlled for, suggesting that pre-existing individual differences in axonal integrity accounted for some of the observed differences.
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Affiliation(s)
- Jonas Stenberg
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Neurosurgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Live Eikenes
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Kent Gøran Moen
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Radiology, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger, Norway
| | - Anne Vik
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Neurosurgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Asta K. Håberg
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Radiology and Nuclear Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Toril Skandsen
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Physical Medicine and Rehabilitation, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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26
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Shinoda J, Yano H, Nakayama N. Altered biphasic serotonin discharge hypothesis in mild traumatic brain injury. Concussion 2021; 6:CNC94. [PMID: 34408908 PMCID: PMC8369523 DOI: 10.2217/cnc-2021-0001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/21/2021] [Indexed: 11/24/2022] Open
Affiliation(s)
- Jun Shinoda
- Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Kizawa Memorial Hospital, Minokamo, Japan,Department of Clinical Brain Sciences, Gifu University Graduate School of Medicine, Minokamo, Japan,Author for correspondence: Tel.: +81 574 24 2233;
| | - Hirohito Yano
- Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Kizawa Memorial Hospital, Minokamo, Japan,Department of Clinical Brain Sciences, Gifu University Graduate School of Medicine, Minokamo, Japan
| | - Noriyuki Nakayama
- Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan
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27
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Johnson B, Walter AE, Wilkes JR, Papa L, Slobounov SM. Changes in White Matter of the Cervical Spinal Cord after a Single Season of Collegiate Football. Neurotrauma Rep 2021; 2:84-93. [PMID: 34223548 PMCID: PMC8240824 DOI: 10.1089/neur.2020.0035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The involvement of the central nervous system (CNS), specifically the white matter tracts in the cervical spinal cord, was examined with diffusion tensor imaging (DTI) following exposure to repetitive head acceleration events (HAEs) after a single season of collegiate football. Fifteen National Collegiate Athletic Association (NCAA) Division 1 football players underwent DTI of the cervical spinal cord (vertebral level C1–4) at pre-season (before any contact practices began) and post-season (within 1 week of the last regular season game) intervals. Helmet accelerometer data were also collected in parallel throughout the season. From pre-season to post-season, a significant decrease (p < 0.05) of axial diffusivity was seen within the right spino-olivary tract. In addition, a significant decrease (p < 0.05) in global white matter fractional anisotropy (FA) along with increases (p < 0.05) in global white matter mean diffusivity (MD) and radial diffusivity (RD) were found. These changes in FA from pre-season to post-season were significantly moderated by previous concussion history (p < 0.05) and number of HAEs over 80 g (p < 0.05). Despite the absence of sports-related concussion (SRC), we present measurable changes in the white matter integrity of the cervical spinal cord suggesting injury from repetitive HAEs, or SRC, may include the entirety of the CNS, not just the brain.
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Affiliation(s)
- Brian Johnson
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Alexa E Walter
- Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - James R Wilkes
- Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Linda Papa
- Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida, USA.,Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
| | - Semyon M Slobounov
- Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania, USA
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28
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Psycho-affective health, cognition, and neurophysiological functioning following sports-related concussion in symptomatic and asymptomatic athletes, and control athletes. Sci Rep 2021; 11:13838. [PMID: 34226626 PMCID: PMC8257649 DOI: 10.1038/s41598-021-93218-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 05/31/2021] [Indexed: 11/08/2022] Open
Abstract
Little is known about the neuropsychiatric and neurophysiological differences that characterize abnormal recovery following a concussion. The present study aimed to investigate the psycho-affective, cognitive, and neurophysiological profiles of symptomatic, slow-to-recover, concussed athletes, asymptomatic concussed athletes, and control athletes. Seventy-eight athletes (26 symptomatic, 26 asymptomatic, 26 control) completed the Beck Depression Inventory-II, Profile of Mood States, and 2-Back task. Additionally, event-related brain potentials were recorded during an experimental three-stimulus visual Oddball paradigm. Compared to asymptomatic and control groups, the symptomatic group reported greater depression symptoms and negatively altered mood states. Symptomatic athletes also exhibited poorer cognitive performance on the 2-Back task, indicated by more errors and slower reaction time. ERP analyses indicated prolonged P3b latency for both symptomatic and asymptomatic groups, but symptomatic athletes also exhibited reduced P3b amplitude compared to both asymptomatic and control groups. For the asymptomatic group, correlations were observed between time since last concussion and functioning, but no relations were observed within the symptomatic group for any measure. The current findings provide valuable information regarding the psycho-affective, cognitive, and neurophysiological profiles of athletes with and without persistent symptoms following a concussion and highlight the need to assess and treat symptomatic, slow-to-recover athletes from a multidimensional and integrative perspective.
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29
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Lima Santos JP, Kontos AP, Mailliard S, Eagle SR, Holland CL, Suss SJ, Abdul-Waalee H, Stiffler RS, Bitzer HB, Blaney NA, Colorito AT, Santucci CG, Brown A, Kim T, Iyengar S, Skeba A, Diler RS, Ladouceur CD, Phillips ML, Brent D, Collins MW, Versace A. White Matter Abnormalities Associated With Prolonged Recovery in Adolescents Following Concussion. Front Neurol 2021; 12:681467. [PMID: 34248824 PMCID: PMC8264142 DOI: 10.3389/fneur.2021.681467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/27/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Concussion symptoms in adolescents typically resolve within 4 weeks. However, 20 - 30% of adolescents experience a prolonged recovery. Abnormalities in tracts implicated in visuospatial attention and emotional regulation (i.e., inferior longitudinal fasciculus, ILF; inferior fronto-occipital fasciculus, IFOF; uncinate fasciculus; UF) have been consistently reported in concussion; yet, to date, there are no objective markers of prolonged recovery in adolescents. Here, we evaluated the utility of diffusion MRI in outcome prediction. Forty-two adolescents (12.1 - 17.9 years; female: 44.0%) underwent a diffusion Magnetic Resonance Imaging (dMRI) protocol within the first 10 days of concussion. Based on days of injury until medical clearance, adolescents were then categorized into SHORT (<28 days; N = 21) or LONG (>28 days; N = 21) recovery time. Fractional anisotropy (FA) in the ILF, IFOF, UF, and/or concussion symptoms were used as predictors of recovery time (SHORT, LONG). Forty-two age- and sex-matched healthy controls served as reference. Higher FA in the ILF (left: adjusted odds ratio; AOR = 0.36, 95% CI = 0.15 - 0.91, P = 0.030; right: AOR = 0.28, 95% CI = 0.10 - 0.83, P = 0.021), IFOF (left: AOR = 0.21, 95% CI = 0.07 - 0.66, P = 0.008; right: AOR = 0.30, 95% CI = 0.11 - 0.83, P = 0.020), and UF (left: AOR = 0.26, 95% CI = 0.09 - 0.74, P = 0.011; right: AOR = 0.28, 95% CI = 0.10 - 0.73, P = 0.010) was associated with SHORT recovery. In additional analyses, while adolescents with SHORT recovery did not differ from HC, those with LONG recovery showed lower FA in the ILF and IFOF (P < 0.014). Notably, inclusion of dMRI findings increased the sensitivity and specificity (AUC = 0.93) of a prediction model including clinical variables only (AUC = 0.75). Our findings indicate that higher FA in long associative tracts (especially ILF) might inform a more objective and accurate prognosis for recovery time in adolescents following concussion.
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Affiliation(s)
- João Paulo Lima Santos
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Anthony P Kontos
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Sarrah Mailliard
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Shawn R Eagle
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Cynthia L Holland
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Stephen J Suss
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Halimah Abdul-Waalee
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Richelle S Stiffler
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Hannah B Bitzer
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Nicholas A Blaney
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Adam T Colorito
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Christopher G Santucci
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Allison Brown
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Tae Kim
- Department of Radiology, Magnetic Resonance Research Center, University of Pittsburgh, Pittsburgh, PA, United States
| | - Satish Iyengar
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Alexander Skeba
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Rasim S Diler
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Cecile D Ladouceur
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Mary L Phillips
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - David Brent
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States
| | - Michael W Collins
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center (UPMC) Sports Concussion Program-University of Pittsburgh, Pittsburgh, PA, United States
| | - Amelia Versace
- Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, Pittsburgh, PA, United States.,Department of Radiology, Magnetic Resonance Research Center, University of Pittsburgh, Pittsburgh, PA, United States
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Gonzalez AC, Kim M, Keser Z, Ibrahim L, Singh SK, Ahmad MJ, Hasan O, Kamali A, Hasan KM, Schulz PE. Diffusion Tensor Imaging Correlates of Concussion Related Cognitive Impairment. Front Neurol 2021; 12:639179. [PMID: 34108926 PMCID: PMC8180854 DOI: 10.3389/fneur.2021.639179] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 04/20/2021] [Indexed: 11/13/2022] Open
Abstract
Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA). Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load. Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = -0.62, p = 0.00001), middle temporal gyrus MD (r = -0.54, p = 0.0001), angular gyrus MD (r = -0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002). Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.
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Affiliation(s)
- Angelica C. Gonzalez
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Minseon Kim
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Zafer Keser
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Lamya Ibrahim
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Sonia K. Singh
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Mohammed J. Ahmad
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Omar Hasan
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Arash Kamali
- Department of Diagnostic and Interventional Radiology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Khader M. Hasan
- Department of Diagnostic and Interventional Radiology, University of Texas McGovern Medical School, Houston, TX, United States
| | - Paul E. Schulz
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States
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Elevated and Slowed EEG Oscillations in Patients with Post-Concussive Syndrome and Chronic Pain Following a Motor Vehicle Collision. Brain Sci 2021; 11:brainsci11050537. [PMID: 33923286 PMCID: PMC8145977 DOI: 10.3390/brainsci11050537] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 04/16/2021] [Accepted: 04/21/2021] [Indexed: 11/17/2022] Open
Abstract
(1) Background: Mild traumatic brain injury produces significant changes in neurotransmission including brain oscillations. We investigated potential quantitative electroencephalography biomarkers in 57 patients with post-concussive syndrome and chronic pain following motor vehicle collision, and 54 healthy nearly age- and sex-matched controls. (2) Methods: Electroencephalography processing was completed in MATLAB, statistical modeling in SPSS, and machine learning modeling in Rapid Miner. Group differences were calculated using current-source density estimation, yielding whole-brain topographical distributions of absolute power, relative power and phase-locking functional connectivity. Groups were compared using independent sample Mann–Whitney U tests. Effect sizes and Pearson correlations were also computed. Machine learning analysis leveraged a post hoc supervised learning support vector non-probabilistic binary linear kernel classification to generate predictive models from the derived EEG signatures. (3) Results: Patients displayed significantly elevated and slowed power compared to controls: delta (p = 0.000000, r = 0.6) and theta power (p < 0.0001, r = 0.4), and relative delta power (p < 0.00001) and decreased relative alpha power (p < 0.001). Absolute delta and theta power together yielded the strongest machine learning classification accuracy (87.6%). Changes in absolute power were moderately correlated with duration and persistence of symptoms in the slow wave frequency spectrum (<15 Hz). (4) Conclusions: Distributed increases in slow wave oscillatory power are concurrent with post-concussive syndrome and chronic pain.
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Gerhalter T, Chen AM, Dehkharghani S, Peralta R, Adlparvar F, Babb JS, Bushnik T, Silver JM, Im BS, Wall SP, Brown R, Baete SH, Kirov II, Madelin G. Global decrease in brain sodium concentration after mild traumatic brain injury. Brain Commun 2021; 3:fcab051. [PMID: 33928248 PMCID: PMC8066885 DOI: 10.1093/braincomms/fcab051] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/27/2021] [Accepted: 02/22/2021] [Indexed: 11/28/2022] Open
Abstract
The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.
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Affiliation(s)
- Teresa Gerhalter
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Anna M Chen
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Seena Dehkharghani
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
- Department of Neurology, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Rosemary Peralta
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Fatemeh Adlparvar
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - James S Babb
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Tamara Bushnik
- Department of Rehabilitation Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Jonathan M Silver
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Brian S Im
- Department of Rehabilitation Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Stephen P Wall
- Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Ryan Brown
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
- Department of Radiology, Center for Advanced Imaging Innovation and Research, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Steven H Baete
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
- Department of Radiology, Center for Advanced Imaging Innovation and Research, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Ivan I Kirov
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
- Department of Neurology, New York University Grossman School of Medicine, New York, NY 10016, USA
- Department of Radiology, Center for Advanced Imaging Innovation and Research, New York University Grossman School of Medicine, New York, NY 10016, USA
| | - Guillaume Madelin
- Department of Radiology, Center for Biomedical Imaging, New York University Grossman School of Medicine, New York, NY 10016, USA
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Chmielewski TL, Tatman J, Suzuki S, Horodyski M, Reisman DS, Bauer RM, Clugston JR, Herman DC. Impaired motor control after sport-related concussion could increase risk for musculoskeletal injury: Implications for clinical management and rehabilitation. JOURNAL OF SPORT AND HEALTH SCIENCE 2021; 10:154-161. [PMID: 33188963 PMCID: PMC7987572 DOI: 10.1016/j.jshs.2020.11.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/27/2020] [Accepted: 09/18/2020] [Indexed: 05/29/2023]
Abstract
This review presents a conceptual framework and supporting evidence that links impaired motor control after sport-related concussion (SRC) to increased risk for musculoskeletal injury. Multiple studies have found that athletes who are post-SRC have higher risk for musculoskeletal injury compared to their counterparts. A small body of research suggests that impairments in motor control are associated with musculoskeletal injury risk. Motor control involves the perception and processing of sensory information and subsequent coordination of motor output within the central nervous system to perform a motor task. Motor control is inclusive of motor planning and motor learning. If sensory information is not accurately perceived or there is interference with sensory information processing and cognition, motor function will be altered, and an athlete may become vulnerable to injury during sport participation. Athletes with SRC show neuroanatomic and neurophysiological changes relevant to motor control even after meeting return to sport criteria, including a normal neurological examination, resolution of symptoms, and return to baseline function on traditional concussion testing. In conjunction, altered motor function is demonstrated after SRC in muscle activation and force production, movement patterns, balance/postural stability, and motor task performance, especially performance of a motor task paired with a cognitive task (i.e., dual-task condition). The clinical implications of this conceptual framework include a need to intentionally address motor control impairments after SRC to mitigate musculoskeletal injury risk and to monitor motor control as the athlete progresses through the return to sport continuum.
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Affiliation(s)
| | | | - Shuhei Suzuki
- TRIA Orthopedic Center, Bloomington, MN 55431, USA; ATP Tour Inc., Ponte Vedra Beach, FL 32082, USA
| | - MaryBeth Horodyski
- Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL 32607, USA
| | - Darcy S Reisman
- Department of Physical Therapy, University of Delaware, Newark, DE 19716, USA
| | - Russell M Bauer
- Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32611, USA
| | - James R Clugston
- Department of Community Health & Family Medicine, University of Florida, Gainesville, FL 32603, USA
| | - Daniel C Herman
- Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL 32607, USA
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Abstract
Optimizing transcranial magnetic stimulation (TMS) treatments in traumatic brain injury (TBI) and co-occurring conditions may benefit from neuroimaging-based customization. PARTICIPANTS Our total sample (N = 97) included 58 individuals with TBI (49 mild, 8 moderate, and 1 severe in a state of disordered consciousness), of which 24 had co-occurring conditions (depression in 14 and alcohol use disorder in 10). Of those without TBI, 6 individuals had alcohol use disorder and 33 were healthy controls. Of our total sample, 54 were veterans and 43 were civilians. DESIGN Proof-of-concept study incorporating data from 5 analyses/studies that used multimodal approaches to integrate neuroimaging with TMS. MAIN MEASURES Multimodal neuroimaging methods including structural magnetic resonance imaging (MRI), MRI-guided TMS navigation, functional MRI, diffusion MRI, and TMS-induced electric fields. Outcomes included symptom scales, neuropsychological tests, and physiological measures. RESULTS It is feasible to use multimodal neuroimaging data to customize TMS targets and understand brain-based changes in targeted networks among people with TBI. CONCLUSIONS TBI is an anatomically heterogeneous disorder. Preliminary evidence from the 5 studies suggests that using multimodal neuroimaging approaches to customize TMS treatment is feasible. To test whether this will lead to increased clinical efficacy, studies that integrate neuroimaging and TMS targeting data with outcomes are needed.
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35
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Pham L, Wright DK, O'Brien WT, Bain J, Huang C, Sun M, Casillas-Espinosa PM, Shah AD, Schittenhelm RB, Sobey CG, Brady RD, O'Brien TJ, Mychasiuk R, Shultz SR, McDonald SJ. Behavioral, axonal, and proteomic alterations following repeated mild traumatic brain injury: Novel insights using a clinically relevant rat model. Neurobiol Dis 2020; 148:105151. [PMID: 33127468 DOI: 10.1016/j.nbd.2020.105151] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 10/07/2020] [Accepted: 10/23/2020] [Indexed: 12/14/2022] Open
Abstract
A history of mild traumatic brain injury (mTBI) is linked to a number of chronic neurological conditions, however there is still much unknown about the underlying mechanisms. To provide new insights, this study used a clinically relevant model of repeated mTBI in rats to characterize the acute and chronic neuropathological and neurobehavioral consequences of these injuries. Rats were given four sham-injuries or four mTBIs and allocated to 7-day or 3.5-months post-injury recovery groups. Behavioral analysis assessed sensorimotor function, locomotion, anxiety, and spatial memory. Neuropathological analysis included serum quantification of neurofilament light (NfL), mass spectrometry of the hippocampal proteome, and ex vivo magnetic resonance imaging (MRI). Repeated mTBI rats had evidence of acute cognitive deficits and prolonged sensorimotor impairments. Serum NfL was elevated at 7 days post injury, with levels correlating with sensorimotor deficits; however, no NfL differences were observed at 3.5 months. Several hippocampal proteins were altered by repeated mTBI, including those associated with energy metabolism, neuroinflammation, and impaired neurogenic capacity. Diffusion MRI analysis at 3.5 months found widespread reductions in white matter integrity. Taken together, these findings provide novel insights into the nature and progression of repeated mTBI neuropathology that may underlie lingering or chronic neurobehavioral deficits.
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Affiliation(s)
- Louise Pham
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC 3086, Australia
| | - David K Wright
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - William T O'Brien
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Jesse Bain
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Cheng Huang
- Monash Proteomics & Metabolomics Facility, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia
| | - Mujun Sun
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Pablo M Casillas-Espinosa
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia; Department of Medicine, The University of Melbourne, Melbourne, VIC 3052, Australia
| | - Anup D Shah
- Monash Proteomics & Metabolomics Facility, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; Monash Bioinformatics Platform, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia
| | - Ralf B Schittenhelm
- Monash Proteomics & Metabolomics Facility, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia
| | - Christopher G Sobey
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC 3086, Australia
| | - Rhys D Brady
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia; Department of Medicine, The University of Melbourne, Melbourne, VIC 3052, Australia
| | - Terence J O'Brien
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, The Alfred Hospital, Melbourne, VIC 3004, Australia; Department of Medicine, The University of Melbourne, Melbourne, VIC 3052, Australia
| | - Richelle Mychasiuk
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Sandy R Shultz
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, The Alfred Hospital, Melbourne, VIC 3004, Australia; Department of Medicine, The University of Melbourne, Melbourne, VIC 3052, Australia
| | - Stuart J McDonald
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC 3086, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
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Meyer J, Bartolomei C, Sauer A, Sajatovic M, Bailey CM. The relationship between fluid biomarkers and clinical outcomes in sports-related concussions: a systematic review. Brain Inj 2020; 34:1435-1445. [PMID: 32962430 DOI: 10.1080/02699052.2020.1802780] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVES The literature on fluid biomarkers for concussion has primarily focused on comparing athletes with and without a diagnosis of concussion and on examining the relationship between fluid biomarkers and exposure to head trauma. This systematic literature review aims to examine the strength of evidence for fluid biomarkers to be associated with clinically relevant outcomes in sports-related concussion. METHODS A systematic literature review was conducted using EmBASE, PubMed, and CINAHL. English-language articles that included athletes participating in organized sports and reported the relationship between at least one fluid biomarker and at least one clinical outcome measure, or provided data that could be used to analyze this relationship, were included. RESULTS Studies of the relationship between fluid biomarkers and clinical outcomes of concussion have yielded small or variable effects. There were significant inconsistencies in methodology including duration of time post-injury of biomarker collection, use of control groups, the number of time points post-injury that biomarkers were collected, and what clinical outcomes were utilized. CONCLUSION There is currently insufficient evidence to support a relationship between any of the included fluid biomarkers and clinical outcome measures of concussion. Future research including clinical outcome measures and using standardized study design and methodology is necessary.
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Affiliation(s)
- Jessica Meyer
- Department of Neurology, University Hospitals Cleveland Medical Center , Cleveland, OH, USA
| | | | - Adam Sauer
- Case Western Reserve University School of Medicine , Cleveland, OH, USA
| | - Martha Sajatovic
- Department of Neurology, University Hospitals Cleveland Medical Center , Cleveland, OH, USA.,Department of Psychiatry, Case Western Reserve University School of Medicine , Cleveland, OH, USA
| | - Christopher M Bailey
- Department of Neurology, University Hospitals Cleveland Medical Center , Cleveland, OH, USA.,Department of Neurology, Case Western Reserve University School of Medicine , Cleveland, OH, USA
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Abstract
OBJECTIVE The long-term effects of pediatric concussion on white matter microstructure are poorly understood. This study investigated long-term changes in white matter diffusion properties of the corpus callosum in youth several years after concussion. METHODS Participants were 8-19 years old with a history of concussion (n = 36) or orthopedic injury (OI) (n = 21). Mean time since injury for the sample was 2.6 years (SD = 1.6). Participants underwent diffusion magnetic resonance imaging, completed cognitive testing, and rated their post-concussion symptoms. Measures of diffusivity (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from white matter tracts in the genu, body, and splenium regions of the corpus callosum. The genu and splenium tracts were further subdivided into 21 equally spaced regions along the tract and diffusion values were extracted from each of these smaller regions. RESULTS White matter tracts in the genu, body, and splenium did not differ in diffusivity properties between youth with a history of concussion and those with a history of OI. No significant group differences were found in subdivisions of the genu and splenium after correcting for multiple comparisons. Diffusion metrics did not significantly correlate with symptom reports or cognitive performance. CONCLUSIONS These findings suggest that at approximately 2.5 years post-injury, youth with prior concussion do not have differences in their corpus callosum microstructure compared to youth with OI. Although these results are promising from the perspective of long-term recovery, further research utilizing longitudinal study designs is needed to confirm the long-term effects of pediatric concussion on white matter microstructure.
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Hurtubise JM, Gorbet DJ, Hynes LM, Macpherson AK, Sergio LE. White Matter Integrity and Its Relationship to Cognitive-Motor Integration in Females with and without Post-Concussion Syndrome. J Neurotrauma 2020; 37:1528-1536. [PMID: 31928154 DOI: 10.1089/neu.2019.6765] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Fifteen percent of individuals who sustain a concussion go on to develop post-concussion syndrome (PCS). These persistent symptoms are believed to be attributed to damage to white matter tracts and impaired neurotransmission. Specifically, declines in white matter integrity after concussion have been found along the long-coursing axons underlying the frontoparietal network. This network is essential for the performance of visuomotor transformation tasks requiring cognitive-motor integration (CMI). We have previously observed deficits in performance on CMI-based tasks in those who have a history of concussion, but were asymptomatic. The aim of this study was to investigate performance on a CMI task, as well as white matter integrity differences along frontoparietal-cerebellar white matter tracts, in those with PCS compared to healthy controls. We hypothesized an association between the behavioral and brain structural measures. Twenty-six female participants (13 with PCS for ≥6 months and 13 healthy controls) completed four computer-based visuomotor CMI tasks. In addition, diffusion tensor images (DTIs) were acquired. No statistically significant differences were found in CMI performance between groups (p > 0.05). Further, there were no statistically significant differences between groups on any DTI metrics (p > 0.05). However, examination of the data collapsed across participants revealed significant associations between performance on a CMI task and white matter integrity. Further investigation into additional causes of symptoms in those with PCS (including psychological and cervicogenic factors) will strengthen our understanding of this diverse group. Nonetheless, this study demonstrates that white matter integrity is related to levels of performance in tasks that require rule-based movement control.
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Affiliation(s)
- Johanna M Hurtubise
- Centre for Sport and Exercise Education, Camosun College, Victoria, British Columbia, Canada
| | - Diana J Gorbet
- School of Kinesiology and Health Science, York University, Sherman Health Science Research Centre, Toronto, Ontario, Canada.,Centre for Vision Research, York University, Sherman Health Science Research Centre, Toronto, Ontario, Canada
| | - Loriann M Hynes
- School of Kinesiology and Health Science, York University, Sherman Health Science Research Centre, Toronto, Ontario, Canada
| | - Alison K Macpherson
- School of Kinesiology and Health Science, York University, Sherman Health Science Research Centre, Toronto, Ontario, Canada
| | - Lauren E Sergio
- School of Kinesiology and Health Science, York University, Sherman Health Science Research Centre, Toronto, Ontario, Canada.,Centre for Vision Research, York University, Sherman Health Science Research Centre, Toronto, Ontario, Canada
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Panwar J, Hsu CCT, Tator CH, Mikulis D. Magnetic Resonance Imaging Criteria for Post-Concussion Syndrome: A Study of 127 Post-Concussion Syndrome Patients. J Neurotrauma 2020; 37:1190-1196. [DOI: 10.1089/neu.2019.6809] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Affiliation(s)
- Jyoti Panwar
- Department of Radiology, Christian Medical College, Vellore, India
| | - Charlie Chia-Tsong Hsu
- Department of Medical Imaging, Gold Coast University Hospital, Brisbane, Southport, Australia
| | - Charles H. Tator
- Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, Toronto, Ontario, Canada
| | - David Mikulis
- Division of Neuroradiology, Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
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40
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Taghdiri F, Multani N, Ozzoude M, Tarazi A, Khodadadi M, Wennberg R, Mikulis D, Green R, Colella B, Davis K, Blennow K, Zetterberg H, Tator C, Tartaglia M. Neurofilament‐light in former athletes: a potential biomarker of neurodegeneration and progression. Eur J Neurol 2020; 27:1170-1177. [DOI: 10.1111/ene.14251] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 04/02/2020] [Indexed: 01/16/2023]
Affiliation(s)
- F. Taghdiri
- Tanz Centre for Research in Neurodegenerative Diseases University of Toronto OntarioTorontoCanada
| | - N. Multani
- Tanz Centre for Research in Neurodegenerative Diseases University of Toronto OntarioTorontoCanada
| | - M. Ozzoude
- Tanz Centre for Research in Neurodegenerative Diseases University of Toronto OntarioTorontoCanada
| | - A. Tarazi
- Division of Neurology Krembil Neuroscience Centre Toronto OntarioCanada
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
| | - M. Khodadadi
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
| | - R. Wennberg
- Division of Neurology Krembil Neuroscience Centre Toronto OntarioCanada
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Institute of Medical Science University of Toronto Toronto OntarioCanada
| | - D. Mikulis
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Institute of Medical Science University of Toronto Toronto OntarioCanada
- Division of Neuroradiology Joint Department of Medical Imaging University Health Network Toronto OntarioCanada
| | - R. Green
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Department of Rehabilitation Sciences University of Toronto Toronto OntarioCanada
| | - B. Colella
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Department of Rehabilitation Sciences University of Toronto Toronto OntarioCanada
| | - K.D. Davis
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Institute of Medical Science University of Toronto Toronto OntarioCanada
- Department of Surgery University of Toronto Toronto OntarioCanada
- Division of Brain, Imaging and Behaviour‐systems Neuroscience Krembil Brain Institute University Health Network Toronto Ontario Canada
| | - K. Blennow
- Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at the University of Gothenburg MölndalSweden
- Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden
| | - H. Zetterberg
- Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at the University of Gothenburg MölndalSweden
- Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden
- Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square LondonUK
- UK Dementia Research Institute at UCL University College London London UK
| | - C. Tator
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Division of Neurosurgery Toronto Western Hospital Krembil Brain Institute University Health Network Toronto Canada
| | - M.C. Tartaglia
- Tanz Centre for Research in Neurodegenerative Diseases University of Toronto OntarioTorontoCanada
- Division of Neurology Krembil Neuroscience Centre Toronto OntarioCanada
- Canadian Concussion Centre Toronto Western Hospital Krembil Brain Institute University Health Network TorontoCanada
- Institute of Medical Science University of Toronto Toronto OntarioCanada
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41
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Post A, Hashim E, Hoshizaki TB, Gilchrist MD, Cusimano MD. A preliminary examination of the relationship between biomechanical measures and structural changes in the brain. TRAUMA-ENGLAND 2020. [DOI: 10.1177/1460408620916578] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Introduction Currently, biomechanics has not been able to effectively predict when a mild traumatic brain injury may occur as a result of head impact. To improve prediction of brain trauma and the development of protective innovations, it is important to create an understanding of the relationship between the biomechanics of the head impact event and the structural damage incurred by the brain as a result of that event. The purpose of this research was to examine the relationship between diffusion tensor imaging measures and biomechanical characteristics of a head impact. Methods Diffusion tensor imaging was conducted on concussed subjects to identify regions of white matter structural differences. The injury event was reconstructed using physical and finite element methods to identify the biomechanical parameters of the impact as well as strain to the regions of the brain. Results A significant relationship was found between shear strain, rotational acceleration, and impact velocity on increases in radial diffusivity and mean diffusivity in the fornix. Linear acceleration was also found to have a weaker but significant relationship with a decrease in radial diffusivity in the cingulum hippocampus. Conclusion These results demonstrate that impacts resulting in high shear strains may affect radial diffusivity and mean diffusivity measures, and that impact mechanics likely have an important role in what regions may present differences in diffusion tensor imaging measures.
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Affiliation(s)
- Andrew Post
- St. Michael’s Hospital, University of Toronto, Toronto, Canada
- Human Kinetics, University of Ottawa, Ottawa, Canada
- School of Mechanical & Materials Engineering, University College Dublin, Dublin, Ireland
| | - Eyesha Hashim
- St. Michael’s Hospital, University of Toronto, Toronto, Canada
| | | | - Michael D Gilchrist
- School of Mechanical & Materials Engineering, University College Dublin, Dublin, Ireland
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Silverberg ND, Iaccarino MA, Panenka WJ, Iverson GL, McCulloch KL, Dams-O’Connor K, Reed N, McCrea M, Cogan AM, Park Graf MJ, Kajankova M, McKinney G, Weyer Jamora C. Management of Concussion and Mild Traumatic Brain Injury: A Synthesis of Practice Guidelines. Arch Phys Med Rehabil 2020; 101:382-393. [DOI: 10.1016/j.apmr.2019.10.179] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 09/13/2019] [Accepted: 10/09/2019] [Indexed: 12/14/2022]
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Jang SH, Kim OL, Kim SH, Lee HD. Differences in corpus callosum injury between cerebral concussion and diffuse axonal injury. Medicine (Baltimore) 2019; 98:e17467. [PMID: 31593106 PMCID: PMC6799815 DOI: 10.1097/md.0000000000017467] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND We investigated differences in corpus callosum (CC) injuries between patients with concussion and those with diffuse axonal injury (DAI) by using diffusion tensor tractography (DTT). METHODS Twenty-nine patients with concussion, 21 patients with DAI, and 25 control subjects were recruited. We reconstructed the whole CC and 5 regions of the CC after applying Hofer classification (I, II, III, IV, and V). The whole CC and each region of the CC were analyzed to measure DTT parameters (fractional anisotropy [FA], apparent diffusion coefficient [ADC], and fiber number [FN]). RESULTS In the whole CC, significant differences were observed in all DTT parameters between the concussion and control groups and the DAI and control groups (P < .05). Among the 5 regions of the CC, significant differences were observed in FA and ADC between the concussion and control groups and the DAI and control groups (P < .05). Significant differences in FN were observed in CC regions I and II (connected with the prefrontal lobe and secondary motor area) between the concussion and control groups, in CC regions I, II, III, and IV (connected with the frontoparietal lobes) between the DAI and control groups, and in CC regions III, IV (connected with the motor-sensory cortex) between the concussion and DAI groups (P < .05). CONCLUSION It was observed that both concussion and DAI patients showed diffuse neural injuries in the whole CC and all 5 regions of the CC. Neural FN results revealed that concussion patients appeared to be specifically injured in the anterior part of the CC connected with the frontal lobe, whereas DAI patients were injured in more diffuse regions connected with whole frontoparietal lobes.
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Affiliation(s)
- Sung Ho Jang
- Department of Physical Medicine and Rehabilitation
| | - Oh Lyong Kim
- Department of Neurosurgery, College of Medicine, Yeungnam University, Republic of Korea
| | - Seong Ho Kim
- Department of Neurosurgery, College of Medicine, Yeungnam University, Republic of Korea
| | - Han Do Lee
- Department of Physical Therapy, College of Rehabilitation Science, Ulsan College University, Ulsan, Korea
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Abstract
BACKGROUND Excessive worry is a defining feature of generalized anxiety disorder and is present in a wide range of other psychiatric conditions. Therefore, individualized predictions of worry propensity could be highly relevant in clinical practice, with respect to the assessment of worry symptom severity at the individual level. METHODS We applied a multivariate machine learning approach to predict dispositional worry based on microstructural integrity of white matter (WM) tracts. RESULTS We demonstrated that the machine learning model was able to decode individual dispositional worry scores from microstructural properties in widely distributed WM tracts (mean absolute error = 10.46, p < 0.001; root mean squared error = 12.82, p < 0.001; prediction R2 = 0.17, p < 0.001). WM tracts that contributed to worry prediction included the posterior limb of internal capsule, anterior corona radiate, and cerebral peduncle, as well as the corticolimbic pathways (e.g. uncinate fasciculus, cingulum, and fornix) already known to be critical for emotion processing and regulation. CONCLUSIONS The current work thus elucidates potential neuromarkers for clinical assessment of worry symptoms across a wide range of psychiatric disorders. In addition, the identification of widely distributed pathways underlying worry propensity serves to better improve the understanding of the neurobiological mechanisms associated with worry.
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Affiliation(s)
- Chunliang Feng
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China
- College of Information Science and Technology, Beijing Normal University, Beijing 100875, China
| | - Zaixu Cui
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA19104, USA
| | - Dazhi Cheng
- Department of Pediatric Neurology, Capital Institute of Pediatrics, Beijing 100020, China
| | - Rui Xu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Ruolei Gu
- CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
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45
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Booker J, Sinha S, Choudhari K, Dawson J, Singh R. Predicting functional recovery after mild traumatic brain injury: the SHEFBIT cohort. Brain Inj 2019; 33:1158-1164. [DOI: 10.1080/02699052.2019.1629626] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- James Booker
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Saurabh Sinha
- Department of Neurosurgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Kishor Choudhari
- Department of Neurosurgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Jeremy Dawson
- Institute of Work Psychology, University of Sheffield Management School, Sheffield, UK
| | - Rajiv Singh
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
- Osborn Neurorehabilitation Unit, Department of Rehabilitation Medicine, Sheffield Teaching Hospitals, Sheffield, UK
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46
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Iverson GL. Network Analysis and Precision Rehabilitation for the Post-concussion Syndrome. Front Neurol 2019; 10:489. [PMID: 31191426 PMCID: PMC6548833 DOI: 10.3389/fneur.2019.00489] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Accepted: 04/23/2019] [Indexed: 01/25/2023] Open
Abstract
Some people experience persistent symptoms following a mild traumatic brain injury (MTBI), and the etiology of those symptoms has been debated for generations. Post-concussion-like symptoms are caused by many factors both before and after MTBI, and this non-specificity is the bedrock of the conundrum regarding the existence of the post-concussion syndrome. A latent model or common cause theory for the syndrome is inconsistent with the prevailing biopsychosocial conceptualization. It is the thesis of this paper that adopting a network perspective for persistent symptoms following MTBI, including the post-concussion syndrome, could lead to new insights and targeted treatment and rehabilitation strategies. The network perspective posits that symptoms co-occur because they are strongly inter-related, activating, amplifying, and mutually reinforcing, not because they arise from a common latent disease entity. This approach requires a conceptual shift away from thinking that symptoms reflect an underlying disease or disorder toward viewing inter-related symptoms as constituting the syndrome or disorder. The symptoms do not arise from an underlying syndrome—the symptoms are the syndrome. A network analysis approach allows us to embrace heterogeneity and comorbidity, and it might lead to the identification of new approaches to sequenced care. The promise of precision rehabilitation requires us to better understand the interconnections among symptoms and problems so that we can produce more individualized and effective treatment and rehabilitation.
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Affiliation(s)
- Grant L Iverson
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States.,Spaulding Research Institute, Spaulding Rehabilitation Hospital, Charlestown, MA, United States.,MassGeneral Hospital for Children Sport Concussion Program, Boston, MA, United States.,Home Base, A Red Sox Foundation and Massachusetts General Hospital Program, Charlestown, MA, United States
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47
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Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS, Moeller K, Dyssegaard A, Thomsen G, Steinmetz J, Forchhammer BH, Knudsen GM, Pinborg LH. Molecular imaging of neuroinflammation in patients after mild traumatic brain injury: a longitudinal 123 I-CLINDE single photon emission computed tomography study. Eur J Neurol 2019; 26:1426-1432. [PMID: 31002206 DOI: 10.1111/ene.13971] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 04/15/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND PURPOSE Neuroinflammation has been proposed as part of the pathogenesis of post-concussion symptoms (PCS), but the inflammatory response of the human brain to mild traumatic brain injury (mTBI) remains unknown. We hypothesized that a neuroinflammatory response is present in mTBI at 1-2 weeks post-injury and persists in patients with PCS. METHODS We scanned 14 patients with mTBI without signs of structural damage at 1-2 weeks and 3-4 months post-injury and 22 healthy controls once using the single photon emission computed tomography tracer 123 I-CLINDE, which visualizes translocator protein (TSPO), a protein upregulated in active immune cells. PCS was defined as three or more persisting symptoms from the Rivermead Post Concussion Symptoms Questionnaire at 3 months post-injury. RESULTS Across brain regions, patients had significantly higher 123 I-CLINDE binding to TSPO than healthy controls, both at 1-2 weeks after the injury in all patients (P = 0.011) and at 3-4 months in the seven patients with PCS (P = 0.006) and in the six patients with good recovery (P = 0.018). When the nine brain regions were tested separately and results were corrected for multiple comparisons, no individual region differed significantly, but all estimated parameters indicated increased 123 I-CLINDE binding to TSPO, ranging from 2% to 19% in all patients at 1-2 weeks, 13% to 27% in patients with PCS at 3-4 months and -9% to 17% in patients with good recovery at 3-4 months. CONCLUSIONS Neuroinflammation was present in mTBI at 1-2 weeks post-injury and persisted at 3-4 months post-injury with a tendency to be most pronounced in patients with PCS.
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Affiliation(s)
- S E Ebert
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - P Jensen
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark
| | - B Ozenne
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - S Armand
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark
| | - C Svarer
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark
| | - D S Stenbaek
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark
| | - K Moeller
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark
| | - A Dyssegaard
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark
| | - G Thomsen
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark
| | - J Steinmetz
- Trauma Center, Rigshospitalet, Copenhagen, Denmark
| | - B H Forchhammer
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - G M Knudsen
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - L H Pinborg
- Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Neurology, Rigshospitalet, Copenhagen, Denmark
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48
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Taghdiri F, Multani N, Tarazi A, Naeimi SA, Khodadadi M, Esopenko C, Green R, Colella B, Wennberg R, Mikulis D, Davis KD, Goswami R, Tator C, Levine B, Tartaglia MC. Elevated cerebrospinal fluid total tau in former professional athletes with multiple concussions. Neurology 2019; 92:e2717-e2726. [PMID: 31068482 DOI: 10.1212/wnl.0000000000007608] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 02/01/2019] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To identify CSF biomarkers that are related to decreased white matter (WM) integrity and poor cognitive performance in former professional athletes with a history of multiple concussions. METHODS Concentrations of phosphorylated tau181, total tau (t-tau), and β-amyloid in the CSF were measured in 3 groups: 22 former professional athletes with multiple concussions (mean ± SD age 55.9 ± 12.2 years), 5 healthy controls (age 57.4 ± 5.2 years), and 12 participants (age 60.0 ± 6.6 years) diagnosed with Alzheimer disease (AD). All participants in the former athletes group underwent diffusion tensor imaging to determine WM tract integrity and completed neuropsychological testing. We divided the former athletes group into those with normal (<300 pg/mL) and high (>300 pg/mL) CSF t-tau. RESULTS CSF t-tau in the former athletes group was significantly higher than in the healthy control group (349.3 ± 182.6 vs 188.8 ± 39.9 pg/mL, p = 0.003) and significantly lower than in the patients with AD (349.3 ± 182.6 vs 857.0 ± 449.3 pg/mL, p = 0.007). Fractional anisotropy values across all the tracts were significantly lower in the high CSF t-tau group compared to the normal CSF t-tau group (p = 0.036). Participants in the high CSF t-tau group scored significantly lower on the Trail Making Test (TMT) Part B compared to the normal CSF t-tau group (t scores 45.6 ± 18.8 vs 62.3 ± 10.1, p = 0.017). CONCLUSION Our findings indicate that former athletes with multiple concussions are at increased risk of elevated levels of CSF t-tau and that high CSF t-tau is associated with reduced WM integrity and worse scores on the TMT Part B.
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Affiliation(s)
- Foad Taghdiri
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Namita Multani
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Apameh Tarazi
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Seyed Ali Naeimi
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Mozghan Khodadadi
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Carrie Esopenko
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Robin Green
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Brenda Colella
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Richard Wennberg
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - David Mikulis
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Karen Deborah Davis
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Ruma Goswami
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Charles Tator
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Brian Levine
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada
| | - Maria Carmela Tartaglia
- From the Tanz Centre for Research in Neurodegenerative Diseases (F.T., N.M., M.C.T.), Department of Rehabilitation Sciences (R. Green, B.C.), Institute of Medical Science (R. Green, R.W., D.M., K.D.D., C.T., B.L., M.C.T.), Department of Surgery (K.D.D.), and Department of Psychology and Neurology (B.L.), University of Toronto; Canadian Concussion Center (F.T., A.T., S.A.N., M.K., R. Green, B.C., R.W., D.M., K.D.D., R. Goswami, C.T., M.C.T.) and Division of Neurosurgery (C.T.), Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network; Division of Neurology (A.T., S.A.N., R.W., M.C.T.) and Division of Neuroradiology (D.M.), Joint Department of Medical Imaging, University Health Network; and Rotman Research Institute at Baycrest (C.E.), Toronto, Ontario, Canada.
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Yin B, Li DD, Huang H, Gu CH, Bai GH, Hu LX, Zhuang JF, Zhang M. Longitudinal Changes in Diffusion Tensor Imaging Following Mild Traumatic Brain Injury and Correlation With Outcome. Front Neural Circuits 2019; 13:28. [PMID: 31133818 PMCID: PMC6514143 DOI: 10.3389/fncir.2019.00028] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 04/01/2019] [Indexed: 11/13/2022] Open
Abstract
The chronic consequences of traumatic brain injury (TBI) may contribute to the increased risk for early cognitive decline and dementia, primarily due to diffusion axonal injury. Previous studies in mild TBI (mTBI) have been controversial in describing the white matter tract integrity changes occurring at acute and subacute post-injury. In this prospective longitudinal study, we aim to investigate the longitudinal changes of white matter (WM) using diffusion tensor imaging (DTI) and their correlations with neuropsychological tests. Thirty-three patients with subacute mTBI and 31 matched healthy controls were studied with an extensive imaging and clinical battery. Neuroimaging was obtained within 7 days post-injury for acute scans and repeated at 1 and 3 months post-injury. Using a region-of-interest-based approach, tract-based spatial statistics was used to conduct voxel-wise analysis on diffusion changes in mTBI and was compared to those of healthy matched controls, scanned during the same time period and rescanned with an interval similar to that of patients. We found decreased fractional anisotropy (FA) values in the left anterior limb of internal capsule (ALIC) and right inferior fronto-occipital fasciculus (IFOF) during the 7 days post-injury, which showed longitudinal evidence of recovery following 1 month post-injury. Increased FA values in these two tracts at 1 month post-injury were positively associated with better performance on cognitive information processing speed at initial assessment. By contrast, there were also some tracts (right anterior corona radiata, forceps major, and body of corpus callosum) exhibiting the continuing loss of integrity sustaining even beyond 3 months, which can predict the persisting post-concussion syndromes. Continuing loss of structural integrity in some tracts may contribute to the persistent post-concussion syndromes in mTBI patients, suggesting certain tracts providing an objective biomarker for tracking the pathological recovery process following mTBI.
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Affiliation(s)
- Bo Yin
- Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Dan-Dong Li
- Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huan Huang
- Department of Radiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Cheng-Hui Gu
- Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Guang-Hui Bai
- Department of Radiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Liu-Xun Hu
- Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jin-Fei Zhuang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ming Zhang
- Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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50
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Booker J, Sinha S, Choudhari K, Dawson J, Singh R. Description of the predictors of persistent post-concussion symptoms and disability after mild traumatic brain injury: the SHEFBIT cohort. Br J Neurosurg 2019; 33:367-375. [DOI: 10.1080/02688697.2019.1598542] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- James Booker
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Saurabh Sinha
- Department of Neurosurgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Kishor Choudhari
- Department of Neurosurgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Jeremy Dawson
- Institute of Work Psychology, University of Sheffield Management School, Sheffield, UK
| | - Rajiv Singh
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
- Osborn Neurorehabilitation Unit, Department of Rehabilitation Medicine, Sheffield Teaching Hospitals, Sheffield, UK
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