@article{MTMT:34238857, title = {The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partners Scientific Board (PPSB)}, url = {https://m2.mtmt.hu/api/publication/34238857}, author = {Albala, Bruce and Appelmans, Eline and Burress, Ramona and De, Santi Susan and Devins, Theresa and Klein, Gregory and Logovinsky, Veronika and Novak, Gerald P. and Ribeiro, Kim and Schmidt, Mark E. and Schwarz, Adam J. and Scott, David and Shcherbinin, Sergey and Siemers, Eric and Travaglia, Alessio and Weber, Christopher J. and White, Leah and Wolf-Rodda, Julie and Vasanthakumar, Aparna}, doi = {10.1002/alz.13483}, journal-iso = {ALZHEIMERS DEMENT}, journal = {ALZHEIMERS & DEMENTIA}, volume = {20}, unique-id = {34238857}, issn = {1552-5260}, abstract = {The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) encompasses members from industry, biotechnology, diagnostic, and non-profit organizations that have until recently been managed by the Foundation for the National Institutes of Health (FNIH) and provided financial and scientific support to ADNI programs. In this article, we review some of the major activities undertaken by the PPSB, focusing on those supporting the most recently completed National Institute on Aging grant, ADNI3, and the impact it has had on streamlining biomarker discovery and validation in Alzheimer's disease. We also provide a perspective on the gaps that may be filled with future PPSB activities as part of ADNI4 and beyond.}, keywords = {ALZHEIMERS-DISEASE; MEMORY; DEMENTIA; Biomarkers; Biomarkers; SCALE; Alzheimer's Disease Neuroimaging Initiative; ANK1; Alzheimer's disease clinical trials; Financial capacity; COGSTATE BRIEF BATTERY}, year = {2024}, eissn = {1552-5279}, pages = {695-708}, orcid-numbers = {Scott, David/0000-0002-8054-7502} } @article{MTMT:34181781, title = {Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?}, url = {https://m2.mtmt.hu/api/publication/34181781}, author = {Freire, M.A.M. and Rocha, G.S. and Bittencourt, L.O. and Falcao, D. and Lima, R.R. and Cavalcanti, J.R.L.P.}, doi = {10.3390/biology12081139}, journal-iso = {BIOLOGY-BASEL}, journal = {BIOLOGY-BASEL}, volume = {12}, unique-id = {34181781}, year = {2023}, eissn = {2079-7737} } @article{MTMT:34511399, title = {Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/34511399}, author = {Harris, Georgia and Stickland, Clarissa A. and Lim, Matthias and Goldberg, Oppenheimer Pola}, doi = {10.3390/cells12222589}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {34511399}, abstract = {Traumatic brain injury (TBI) affects millions of people of all ages around the globe. TBI is notoriously hard to diagnose at the point of care, resulting in incorrect patient management, avoidable death and disability, long-term neurodegenerative complications, and increased costs. It is vital to develop timely, alternative diagnostics for TBI to assist triage and clinical decision-making, complementary to current techniques such as neuroimaging and cognitive assessment. These could deliver rapid, quantitative TBI detection, by obtaining information on biochemical changes from patient's biofluids. If available, this would reduce mis-triage, save healthcare providers costs (both over- and under-triage are expensive) and improve outcomes by guiding early management. Herein, we utilize Raman spectroscopy-based detection to profile a panel of 18 raw (human, animal, and synthetically derived) TBI-indicative biomarkers (N-acetyl-aspartic acid (NAA), Ganglioside, Glutathione (GSH), Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), Cholesterol, D-Serine, Sphingomyelin, Sulfatides, Cardiolipin, Interleukin-6 (IL-6), S100B, Galactocerebroside, Beta-D-(+)-Glucose, Myo-Inositol, Interleukin-18 (IL-18), Neurofilament Light Chain (NFL)) and their aqueous solution. The subsequently derived unique spectral reference library, exploiting four excitation lasers of 514, 633, 785, and 830 nm, will aid the development of rapid, non-destructive, and label-free spectroscopy-based neuro-diagnostic technologies. These biomolecules, released during cellular damage, provide additional means of diagnosing TBI and assessing the severity of injury. The spectroscopic temporal profiles of the studied biofluid neuro-markers are classed according to their acute, sub-acute, and chronic temporal injury phases and we have further generated detailed peak assignment tables for each brain-specific biomolecule within each injury phase. The intensity ratios of significant peaks, yielding the combined unique spectroscopic barcode for each brain-injury marker, are compared to assess variance between lasers, with the smallest variance found for UCHL1 (sigma 2 = 0.000164) and the highest for sulfatide (sigma 2 = 0.158). Overall, this work paves the way for defining and setting the most appropriate diagnostic time window for detection following brain injury. Further rapid and specific detection of these biomarkers, from easily accessible biofluids, would not only enable the triage of TBI, predict outcomes, indicate the progress of recovery, and save healthcare providers costs, but also cement the potential of Raman-based spectroscopy as a powerful tool for neurodiagnostics.}, keywords = {SERUM; CEREBROSPINAL-FLUID; GLUCOSE; diagnosis; traumatic brain injury; S100B; raman spectroscopy; FIBRILLARY ACIDIC PROTEIN; Mild; Neuron-specific enolase; EXTRACELLULAR N-ACETYLASPARTATE; TBI biomarkers; acute, sub-acute and chronic phases}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Goldberg, Oppenheimer Pola/0000-0002-1014-4724} } @article{MTMT:33858664, title = {Review: Emerging Eye-Based Diagnostic Technologies for Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/33858664}, author = {Harris, Georgia and Rickard, Jonathan James Stanley and Butt, Gibran and Kelleher, Liam and Blanch, Richard James and Cooper, Jonathan and Oppenheimer, Pola Goldberg}, doi = {10.1109/RBME.2022.3161352}, journal-iso = {IEEE REV BIOMED ENG}, journal = {IEEE REVIEWS IN BIOMEDICAL ENGINEERING}, volume = {16}, unique-id = {33858664}, issn = {1937-3333}, abstract = {The study of ocular manifestations of neurodegenerative disorders, Oculomics, is a growing field of investigation for early diagnostics, enabling structural and chemical biomarkers to be monitored overtime to predict prognosis. Traumatic brain injury (TBI) triggers a cascade of events harmful to the brain, which can lead to neurodegeneration. TBI, termed the "silent epidemic" is becoming a leading cause of death and disability worldwide. There is currently no effective diagnostic tool for TBI, and yet, early-intervention is known to considerably shorten hospital stays, improve outcomes, fasten neurological recovery and lower mortality rates, highlighting the unmet need for techniques capable of rapid and accurate point-of-care diagnostics, implemented in the earliest stages. This review focuses on the latest advances in the main neuropathophysiological responses and the achievements and shortfalls of TBI diagnostic methods. Validated and emerging TBI-indicative biomarkers are outlined and linked to ocular neuro-disorders. Methods detecting structural and chemical ocular responses to TBI are categorised along with prospective chemical and physical sensing techniques. Particular attention is drawn to the potential of Raman spectroscopy as a non-invasive sensing of neurological molecular signatures in the ocular projections of the brain, laying the platform for the first tangible path towards alternative point-of-care diagnostic technologies for TBI}, keywords = {Biomarkers; Magnetic Resonance Imaging; MONITORING; Brain Injuries; computed tomography; neurology; neuroimaging; Hospitals; biosensors; Biomedical engineering; optic nerve; Ophthalmology; Molecular imaging; Retina; Raman scattering; OPTICAL SENSORS; Medical Devices; Biomedical optical imaging; Point of care; Biophotonics; Traumatic brain injury (TBI)}, year = {2023}, eissn = {1941-1189}, pages = {530-559}, orcid-numbers = {Harris, Georgia/0000-0001-8826-7057; Kelleher, Liam/0000-0001-6392-8875; Cooper, Jonathan/0000-0002-2358-1050} } @article{MTMT:34238858, title = {A proteomic and phosphoproteomic landscape of spinal cord injury}, url = {https://m2.mtmt.hu/api/publication/34238858}, author = {Li, Zhigang and Quan, Bingxuan and Li, Xiuyan and Xiong, Wei and Peng, Zhibin and Liu, Jingsong and Wang, Yansong}, doi = {10.1016/j.neulet.2023.137449}, journal-iso = {NEUROSCI LETT}, journal = {NEUROSCIENCE LETTERS}, volume = {814}, unique-id = {34238858}, issn = {0304-3940}, abstract = {Spinal cord injury (SCI) is a devastating trauma of the central nervous system, with high levels of morbidity, disability, and mortality. To explore the underlying mechanism of SCI, we analyzed the proteome and phosphoproteome of rats at one week after SCI. We identified 465 up-regulated and 129 down-regulated differentially expressed proteins (DEPs), as well as 184 up-regulated and 40 down-regulated differentially expressed phosphoproteins (DEPPs). Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these proteins from the perspectives of cell component, biological process, and molecular function. We also found a lot of enriched functional pathways such as GABAergic synapse pathway, ErbB signaling pathway, tight junction, adherens junction. The integrated analysis of proteomics and phosphoproteomics yielded 22 differently expressed co-identified proteins of DEPs and DEPPs, which revealed strongly correlative patterns. These findings may help clarify the potential mechanisms of trauma and repair in SCI and may guide the development of novel treatments.}, keywords = {CELL; proteomics; phosphoproteomics; spinal cord injury; PROTEIN-PHOSPHORYLATION}, year = {2023}, eissn = {1872-7972} } @article{MTMT:34430418, title = {Maximizing the Clinical Value of Blood-Based Biomarkers for Mild Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/34430418}, author = {Rauchman, Steven H. and Pinkhasov, Aaron and Gulkarov, Shelly and Placantonakis, Dimitris G. and De, Leon Joshua and Reiss, Allison B.}, doi = {10.3390/diagnostics13213330}, journal-iso = {DIAGNOSTICS}, journal = {DIAGNOSTICS}, volume = {13}, unique-id = {34430418}, issn = {2075-4418}, abstract = {Mild traumatic brain injury (TBI) and concussion can have serious consequences that develop over time with unpredictable levels of recovery. Millions of concussions occur yearly, and a substantial number result in lingering symptoms, loss of productivity, and lower quality of life. The diagnosis may not be made for multiple reasons, including due to patient hesitancy to undergo neuroimaging and inability of imaging to detect minimal damage. Biomarkers could fill this gap, but the time needed to send blood to a laboratory for analysis made this impractical until point-of-care measurement became available. A handheld blood test is now on the market for diagnosis of concussion based on the specific blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl terminal hydrolase L1 (UCH-L1). This paper discusses rapid blood biomarker assessment for mild TBI and its implications in improving prediction of TBI course, avoiding repeated head trauma, and its potential role in assessing new therapeutic options. Although we focus on the Abbott i-STAT TBI plasma test because it is the first to be FDA-cleared, our discussion applies to any comparable test systems that may become available in the future. The difficulties in changing emergency department protocols to include new technology are addressed.}, keywords = {PROTEIN; CLASSIFICATION; PERFORMANCE; MORTALITY; PREDICTION; diagnosis; GFAP; EPIDEMIOLOGY; Mild traumatic brain injury; MRI; biomarker; Diffuse axonal injury; concussion; concussion}, year = {2023}, eissn = {2075-4418} } @article{MTMT:33051550, title = {Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study}, url = {https://m2.mtmt.hu/api/publication/33051550}, author = {Helmrich, Isabel R A Retel and Czeiter, Endre and Amrein, Krisztina and Büki, András and Lingsma, Hester F and Menon, David K and Mondello, Stefania and Steyerberg, Ewout W and von Steinbüchel, Nicole and Wang, Kevin K W and Wilson, Lindsay and Xu, Haiyan and Yang, Zhihui and van Klaveren, David and Maas, Andrew I R}, doi = {10.1016/S1474-4422(22)00218-6}, journal-iso = {LANCET NEUROL}, journal = {LANCET NEUROLOGY}, volume = {21}, unique-id = {33051550}, issn = {1474-4422}, abstract = {Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome.We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models.Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.}, year = {2022}, eissn = {1474-4465}, pages = {792-802}, orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:33047483, title = {Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review}, url = {https://m2.mtmt.hu/api/publication/33047483}, author = {Kocheril, Philip A. and Moore, Shepard C. and Lenz, Kiersten D. and Mukundan, Harshini and Lilley, Laura M.}, doi = {10.1177/11772719221105145}, journal-iso = {BIOMARKER INSIGHTS}, journal = {BIOMARKER INSIGHTS}, volume = {17}, unique-id = {33047483}, issn = {1177-2719}, abstract = {Traumatic brain injury (TBI) is not a single disease state but describes an array of conditions associated with insult or injury to the brain. While some individuals with TBI recover within a few days or months, others present with persistent symptoms that can cause disability, neuropsychological trauma, and even death. Understanding, diagnosing. and treating TBI is extremely complex for many reasons, including the variable biomechanics of head impact. differences in severity and location of injury, and individual patient characteristics. Because of these confounding factors, the development of reliable diagnostics and targeted treatments for brain injury remains elusive. We argue that the development of effective diagnostic and therapeutic strategies for TBI requires a deep understanding of human neurophysiology at the molecular level and that the framework of multiomics may provide some effective solutions for the diagnosis and treatment of this challenging condition. To this end, we present here a comprehensive review of TBI biomarker candidates from across the multiomic disciplines and compare them with known signatures associated with other neuropsychological conditions, including Alzheimer's disease and Parkinson's disease. We believe that this integrated view will facilitate a deeper understanding of the pathophysiology of TBI and its potential links to other neurological diseases.}, keywords = {CEREBROSPINAL-FLUID; ALPHA-LIPOIC ACID; TOP-DOWN; SINGLE NUCLEOTIDE POLYMORPHISMS; traumatic brain injury; proteomics; metabolomics; biomarker; POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY; post-concussion symptoms; multiomics; Amyloid-beta plaques; NEPRILYSIN POLYMORPHISM}, year = {2022}, orcid-numbers = {Kocheril, Philip A./0000-0002-1265-5931; Lenz, Kiersten D./0000-0002-7832-7586} } @article{MTMT:33460358, title = {Methods to capture proteomic and metabolomic signatures from cerebrospinal fluid and serum of healthy individuals}, url = {https://m2.mtmt.hu/api/publication/33460358}, author = {Lilley, Laura M. and Sanche, Steven and Moore, Shepard C. and Salemi, Michelle R. and Vu, Dung and Iyer, Srinivas and Hengartner, Nicolas W. and Mukundan, Harshini}, doi = {10.1038/s41598-022-16598-1}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {12}, unique-id = {33460358}, issn = {2045-2322}, abstract = {Discovery of reliable signatures for the empirical diagnosis of neurological diseases-both infectious and non-infectious-remains unrealized. One of the primary challenges encountered in such studies is the lack of a comprehensive database representative of a signature background that exists in healthy individuals, and against which an aberrant event can be assessed. For neurological insults and injuries, it is important to understand the normal profile in the neuronal (cerebrospinal fluid) and systemic fluids (e.g., blood). Here, we present the first comparative multi-omic human database of signatures derived from a population of 30 individuals (15 males, 15 females, 23-74 years) of serum and cerebrospinal fluid. In addition to empirical signatures, we also assigned common pathways between serum and CSF. Together, our findings provide a cohort against which aberrant signature profiles in individuals with neurological injuries/disease can be assessed-providing a pathway for comprehensive diagnostics and therapeutics discovery.}, year = {2022}, eissn = {2045-2322} } @article{MTMT:32993758, title = {Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness}, url = {https://m2.mtmt.hu/api/publication/32993758}, author = {Mainali, Shraddha and Aiyagari, Venkatesh and Alexander, Sheila and Bodien, Yelena and Boerwinkle, Varina and Boly, Melanie and Brown, Emery and Brown, Jeremy and Claassen, Jan and Edlow, Brian L. and Fink, Erika L. and Fins, Joseph J. and Foreman, Brandon and Frontera, Jennifer and Geocadin, Romergryko G. and Giacino, Joseph and Gilmore, Emily J. and Gosseries, Olivia and Hammond, Flora and Helbok, Raimund and Hemphill, J. Claude and Hirsch, Karen and Kim, Keri and Laureys, Steven and Lewis, Ariane and Ling, Geoffrey and Livesay, Sarah L. and McCredie, Victoria and McNett, Molly and Menon, David and Molteni, Erika and Olson, DaiWai and O'Phelan, Kristine and Park, Soojin and Polizzotto, Len and Provencio, Jose Javier and Puybasset, Louis and Rao, Chethan P. Venkatasubba and Robertson, Courtney and Rohaut, Benjamin and Rubin, Michael and Sharshar, Tarek and Shutter, Lori and Silva, Gisele Sampaio and Smith, Wade and Stevens, Robert D. and Thibaut, Aurore and Vespa, Paul and Wagner, Amy K. and Ziai, Wendy C. and Zink, Elizabeth and Suarez, Jose I}, doi = {10.1007/s12028-022-01505-3}, journal-iso = {NEUROCRIT CARE}, journal = {NEUROCRITICAL CARE}, volume = {37}, unique-id = {32993758}, issn = {1541-6933}, abstract = {This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.}, keywords = {Coma; Disorders of Consciousness; Proceedings; Curing Coma Campaign; National Institute of Health}, year = {2022}, eissn = {1556-0961}, pages = {326-350}, orcid-numbers = {Mainali, Shraddha/0000-0002-9495-3843; Hirsch, Karen/0000-0002-5474-3243; Molteni, Erika/0000-0001-7773-8140} } @article{MTMT:33460359, title = {Connectomic assessment of injury burden and longitudinal structural network alterations in moderate-to-severe traumatic brain injury}, url = {https://m2.mtmt.hu/api/publication/33460359}, author = {Osmanlioglu, Yusuf and Parker, Drew and Alappatt, Jacob A. and Gugger, James J. and Diaz-Arrastia, Ramon R. and Whyte, John and Kim, Junghoon J. and Verma, Ragini}, doi = {10.1002/hbm.25894}, journal-iso = {HUM BRAIN MAPP}, journal = {HUMAN BRAIN MAPPING}, volume = {43}, unique-id = {33460359}, issn = {1065-9471}, abstract = {Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation. Heterogeneity is another characteristic of TBI as severity and cognitive sequelae of the disease have a wide variation across patients, posing a big challenge for treatment. Thus, measures assessing network-wide structural connectivity disruptions in TBI are necessary to quantify injury burden of individuals, which would help in achieving personalized treatment, patient monitoring, and rehabilitation planning. Despite TBI being a disconnectivity syndrome, connectomic assessment of structural disconnectivity has been relatively limited. In this study, we propose a novel connectomic measure that we call network normality score (NNS) to capture the integrity of structural connectivity in TBI patients by leveraging two major characteristics of the disease: diffuseness of axonal injury and heterogeneity of the disease. Over a longitudinal cohort of moderate-to-severe TBI patients, we demonstrate that structural network topology of patients is more heterogeneous and significantly different than that of healthy controls at 3 months postinjury, where dissimilarity further increases up to 12 months. We also show that NNS captures injury burden as quantified by posttraumatic amnesia and that alterations in the structural brain network is not related to cognitive recovery. Finally, we compare NNS to major graph theory measures used in TBI literature and demonstrate the superiority of NNS in characterizing the disease.}, keywords = {traumatic brain injury; DIFFUSION MRI; connectomes; injury burden; connectivity disruption}, year = {2022}, eissn = {1097-0193}, pages = {3944-3957}, orcid-numbers = {Osmanlioglu, Yusuf/0000-0002-9997-9479} } @article{MTMT:33110370, title = {Highlights mild traumatic brain injury 2021}, url = {https://m2.mtmt.hu/api/publication/33110370}, author = {Van, Der Naalt J. and Jacobs, B.}, doi = {10.1097/ACO.0000000000001177}, journal-iso = {CURR OPIN ANESTHESIO}, journal = {CURRENT OPINION IN ANAESTHESIOLOGY}, volume = {35}, unique-id = {33110370}, issn = {0952-7907}, abstract = {PurposeMild traumatic brain injury (TBI) is one of the most common causes of morbidity worldwide. Patients at risk of unfavourable outcome may benefit from additional attention and help but identification of these patients necessitates the development of diagnostic methods to assess indices of brain injury at an early stage. The aim of this overview is to highlight studies that reflect the growing scientific attention to the early diagnosis and prognostication of mild TBI.Recent findingsThe value of serum biomarkers for the diagnosis of TBI severity has been acknowledged in recent studies. The diagnostic and prognostic utility of several biomarkers of brain injury, such as glial fibrillary acidic protein, and of inflammation, such as interleukin (IL)-6 and IL-10, holds promise for application in daily clinical practice in a point-of-care platform. Besides head CT imaging, early advanced MRI brain imaging has been reported as a tool for assessment of injury severity and prognostication. The introduction of direct oral anticoagulants (DOACs) has raised new challenges for the treatment of intracranial traumatic haemorrhage at the Emergency Department.SummaryPromising findings of new diagnostic markers of brain injury severity highlight the potential prognostic value of serum biomarkers and early MRI imaging. The accurate assessment of patients at risk of incomplete recovery after mTBI will enhance more timely and individualized treatment. © 2022 Lippincott Williams and Wilkins. All rights reserved.}, keywords = {Prognosis; Biomarkers; Mild traumatic brain injury; MRI; Imaging; Haemorrhage}, year = {2022}, eissn = {1473-6500}, pages = {577-582} } @article{MTMT:33460357, title = {Concussion Prone Scenarios: A Multi-Dimensional Exploration in Impact Directions, Brain Morphology, and Network Architectures Using Computational Models}, url = {https://m2.mtmt.hu/api/publication/33460357}, author = {Wu, Taotao and Rifkin, Jared A. and Rayfield, Adam C. and Anderson, Erin D. and Panzer, Matthew B. and Meaney, David F.}, doi = {10.1007/s10439-022-03085-x}, journal-iso = {ANN BIOMED ENG}, journal = {ANNALS OF BIOMEDICAL ENGINEERING}, volume = {50}, unique-id = {33460357}, issn = {0090-6964}, abstract = {While individual susceptibility to traumatic brain injury (TBI) has been speculated, past work does not provide an analysis considering how physical features of an individual's brain (e.g., brain size, shape), impact direction, and brain network features can holistically contribute to the risk of suffering a TBI from an impact. This work investigated each of these features simultaneously using computational modeling and analyses of simulated functional connectivity. Unlike the past studies that assess the severity of TBI based on the quantification of brain tissue damage (e.g., principal strain), we approached the brain as a complex network in which neuronal oscillations orchestrate to produce normal brain function (estimated by functional connectivity) and, to this end, both the anatomical damage location and its topological characteristics within the brain network contribute to the severity of brain function disruption and injury. To represent the variations in the population, we analyzed a publicly available database of brain imaging data and selected five distinct network architectures, seven different brain sizes, and three uniaxial head rotational conditions to study the consequences of 74 virtual impact scenarios. Results show impact direction produces the most significant change in connections across brain areas (structural connectome) and the functional coupling of activity across these brain areas (functional connectivity). Axial rotations were more injurious than those with sagittal and coronal rotations when the head kinematics were the same for each condition. When the impact direction was held constant, brain network architecture showed a significantly different vulnerability across axial and sagittal, but not coronal rotations. As expected, brain size significantly affected the expected change in structural and functional connectivity after impact. Together, these results provided groupings of predicted vulnerability to impact-a subgroup of male brain architectures exposed to axial impacts were most vulnerable, while a subgroup of female brain architectures was the most tolerant to the sagittal impacts studied. These findings lay essential groundwork for subject-specific analyses of concussion and provide invaluable guidance for designing personalized protection equipment.}, keywords = {functional connectivity; Finite element model; Kuramoto model; Subject-specific analysis}, year = {2022}, eissn = {1573-9686}, pages = {1423-1436} } @article{MTMT:32998924, title = {COVID-19 and Traumatic Brain Injury (TBI); What We Can Learn From the Viral Pandemic to Better Understand the Biology of TBI, Improve Diagnostics and Develop Evidence-Based Treatments}, url = {https://m2.mtmt.hu/api/publication/32998924}, author = {Agoston, Denes V.}, doi = {10.3389/fneur.2021.752937}, journal-iso = {FRONT NEUR}, journal = {FRONTIERS IN NEUROLOGY}, volume = {12}, unique-id = {32998924}, issn = {1664-2295}, keywords = {Applications; DISEASES; TBI; LESSONS; Definitions; COVID-19; pandemics epidemics}, year = {2021}, eissn = {1664-2295} } @article{MTMT:32195759, title = {Moderators of gene-outcome associations following traumatic brain injury}, url = {https://m2.mtmt.hu/api/publication/32195759}, author = {Carmichael, J. and Hicks, A.J. and Spitz, G. and Gould, K.R. and Ponsford, J.}, doi = {10.1016/j.neubiorev.2021.08.015}, journal-iso = {NEUROSCI BIOBEHAV R}, journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS}, volume = {130}, unique-id = {32195759}, issn = {0149-7634}, year = {2021}, eissn = {1873-7528}, pages = {107-124} } @article{MTMT:32193801, title = {Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study}, url = {https://m2.mtmt.hu/api/publication/32193801}, author = {Gradisek, Primoz and Carrara, Greta and Antiga, Luca and Bottazzi, Barbara and Chieregato, Arturo and Csomós, Ákos and Fainardi, Enrico and Filekovic, Suada and Fleming, Joanne and Hadjisavvas, Andreas and Kaps, Rafael and Kyprianou, Theodoros and Latini, Roberto and Lazar, Isaac and Masson, Serge and Mikaszewska-Sokolewicz, Malgorzata and Novelli, Deborah and Paci, Giulia and Xirouchaki, Nektaria and Zanier, Elisa and Nattino, Giovanni and Bertolini, Guido}, doi = {10.1089/neu.2021.0066}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {38}, unique-id = {32193801}, issn = {0897-7151}, abstract = {Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.}, keywords = {PROTEIN; Cluster Analysis; Glasgow Outcome Scale; Clinical Neurology; Critical Care Medicine; circulating biomarkers; C-TERMINAL HYDROLASE-L1}, year = {2021}, eissn = {1557-9042}, pages = {2667-2676}, orcid-numbers = {Kyprianou, Theodoros/0000-0001-8272-7630} } @article{MTMT:31328719, title = {Blood biomarkers on admission in acute traumatic brain injury : Relations to severity, CT findings and care path in the CENTER-TBI study}, url = {https://m2.mtmt.hu/api/publication/31328719}, author = {Czeiter, Endre and Amrein, Krisztina and Gravesteijn, Benjamin Y and Lecky, Fiona and Menon, David K and Mondello, Stefania and Newcombe, Virginia F J and Richter, Sophie and Steyerberg, Ewout W and Vyvere, Thijs Vande and Verheyden, Jan and Xu, Haiyan and Yang, Zhihui and Maas, Andrew I R and Wang, Kevin K W and Büki, András}, doi = {10.1016/j.ebiom.2020.102785}, journal-iso = {EBIOMEDICINE}, journal = {EBIOMEDICINE}, volume = {56}, unique-id = {31328719}, issn = {2352-3964}, abstract = {Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals.All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone.Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required.CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).}, keywords = {SERUM; Biomarkers; GFAP; diagnostic; traumatic brain injury; Computerized tomography; injury severity; clinical decision rule}, year = {2020}, eissn = {2352-3964}, orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:32519800, title = {Novel approaches to prediction in severe brain injury}, url = {https://m2.mtmt.hu/api/publication/32519800}, author = {Fidali, Brian C. and Stevens, Robert D. and Claassen, Jan}, doi = {10.1097/WCO.0000000000000875}, journal-iso = {CURR OPIN NEUROL}, journal = {CURRENT OPINION IN NEUROLOGY}, volume = {33}, unique-id = {32519800}, issn = {1350-7540}, abstract = {Purpose of review Recovery after severe brain injury is variable and challenging to accurately predict at the individual patient level. This review highlights new developments in clinical prognostication with a special focus on the prediction of consciousness and increasing reliance on methods from data science. Recent findings Recent research has leveraged serum biomarkers, quantitative electroencephalography, MRI, and physiological time-series to build models for recovery prediction. The analysis of high-resolution data and the integration of features from different modalities can be approached with efficient computational techniques. Advances in neurophysiology and neuroimaging, in combination with computational methods, represent a novel paradigm for prediction of consciousness and functional recovery after severe brain injury. Research is needed to produce reliable, patient-level predictions that could meaningfully impact clinical decision making.}, keywords = {Electroencephalography; traumatic brain injury; Consciousness; Coma; Anoxic brain injury}, year = {2020}, eissn = {1473-6551}, pages = {669-675} }