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1. Distribution and volume analysis of early hemorrhagic contusions by MRI after traumatic brain injury: a preliminary report of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx)

Author

La Rocca, Marianna, Barisano, Giuseppe, Bennett, Alexis, Garner, Rachael, Engel, Jerome, Gilmore, Emily J, McArthur, David L, Rosenthal, Eric, Stanis, James, Vespa, Paul, Willyerd, Frederick, Zimmermann, Lara L, Toga, Arthur W, and Duncan, Dominique

Subjects
Psychology, Traumatic Brain Injury (TBI), Physical Injury - Accidents and Adverse Effects, Brain Disorders, Neurosciences, Traumatic Head and Spine Injury, Neurodegenerative, Epilepsy, Biomedical Imaging, Neurological, Brain Injuries, Traumatic, Computational Biology, Contusions, Humans, Magnetic Resonance Imaging, Traumatic brain injury, Lesion segmentation, Posttraumatic late seizures, Lesion volume analysis, EpiBioS4Rx Study Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology, Biomedical and clinical sciences, Health sciences
Abstract

Traumatic brain injury (TBI) can produce heterogeneous injury patterns including a variety of hemorrhagic and non-hemorrhagic lesions. The impact of lesion size, location, and interaction between total number and location of contusions may influence the occurrence of seizures after TBI. We report our methodologic approach to this question in this preliminary report of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx). We describe lesion identification and segmentation of hemorrhagic contusions by early posttraumatic magnetic resonance imaging (MRI). We describe the preliminary methods of manual lesion segmentation in an initial cohort of 32 TBI patients from the EpiBioS4Rx cohort and the preliminary association of hemorrhagic contusion and edema location and volume to seizure incidence.

Published
2021

2. The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol

Author

Vespa, Paul M, Shrestha, Vikesh, Abend, Nicholas, Agoston, Denes, Au, Alicia, Bell, Michael J, Bleck, Thomas P, Blanco, Manuel Buitrago, Claassen, Jan, Diaz-Arrastia, Ramon, Duncan, Dominique, Ellingson, Ben, Foreman, Brandon, Gilmore, Emily J, Hirsch, Lawrence, Hunn, Martin, Kamnaksh, Alaa, McArthur, David, Morokoff, Andrew, O'Brien, Terrence, O'Phelan, Kristine, Robertson, Courtney L, Rosenthal, Eric, Staba, Richard, Toga, Arthur, Willyerd, Frederick A, Zimmermann, Lara, Yam, Elisa, Martinez, Susana, Real, Courtney, and Engel, Jerome

Subjects
Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Traumatic Head and Spine Injury, Precision Medicine, Traumatic Brain Injury (TBI), Epilepsy, Physical Injury - Accidents and Adverse Effects, Clinical Research, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Good Health and Well Being, Biomarkers, Brain, Brain Injuries, Traumatic, Computational Biology, Epilepsy, Post-Traumatic, Humans, Longitudinal Studies, Observational Studies as Topic, Prospective Studies, Clinical Sciences, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.

Published
2019

3. Abstract 317: Brain MRI And Spectroscopy Biomarkers Predict Outcome After Pediatric Cardiac Arrest In POCCA

Author

Fink, Ericka L, Kochanek, Patrick M, Bluml, Stefan, Wisnowski, Jessica, Narayanan, Srikala, subramanian, subramanian, Beers, Sue, Berger, Rachel, Bayir, Hulya, Wang, Chunyan, Pineda, Jose, Topjian, Alexis A, maddux, aline, Willyerd, Frederick, Hunt, Elizabeth A, Chung, Melissa G, Newth, Christopher, Smith, Lincoln, Doughty, Lesley, Diddle, J. Wesley, Piantino, Juan, Walson, Karen H, Balakrishnan, Binod, friess, stuart, Siems, Ashley, Press, Craig, Patregnani, Jason, Meyer, Michael T, Haller, Tamara, Treble-Barna, Amery, Clark, Robert, Fabio, Anthony, and Panigrahy, Ashok

Published
2022
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4. Abstract 265: Social Determinants Of Health Impact Phenotype-based Outcome Prediction After Pediatric Arrest

Author

Fink, Ericka L, Kochanek, Patrick M, Panigrahy, Ashok, Beers, Sue, Berger, Rachel, BAYIR, HULYA, Wang, Chunyan, Pineda, Jose, Topjian, Alexis A, maddux, aline, Willyerd, Frederick, Hunt, Elizabeth A, Chung, Melissa G, Newth, Christopher, Smith, Lincoln, Doughty, Lesley, Diddle, J Wesley, Piantino, Juan, Walson, Karen H, Balakrishnan, Binod, friess, stuart, Siems, Ashley, Press, Craig, Patregnani, Jason, Meyer, Michael T, Haller, Tamara, Treble-Barna, Amery, Clark, Robert, and Fabio, Anthony

Published
2022
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5. Association of Growth Differentiation Factor‐15 With Event Cause and Cardiovascular Failure After Pediatric Cardiac Arrest in a Multi‐Institutional Trial

Author

Herrmann, Jeremy R., primary, Jackson, Travis C., additional, Fabio, Anthony, additional, Clark, Robert S. B., additional, Berger, Rachel P., additional, Janesko‐Feldman, Keri L., additional, Kochanek, Patrick M., additional, Fink, Ericka L., additional, Bayır, Hülya, additional, Panigrahy, Ashok, additional, Maloney, David, additional, Beers, Sue R., additional, Haller, Tamara L., additional, Treble‐Barna, Amery, additional, Pineda, Jose, additional, Newth, Christopher, additional, Topjian, Alexis A., additional, Press, Craig A., additional, Maddux, Aline B., additional, Willyerd, Frederick, additional, Hunt, Elizabeth A., additional, Siems, Ashley, additional, Chung, Melissa G., additional, Smith, Lincoln, additional, Diddle, J. Wesley, additional, Patregnani, Jason, additional, Piantino, Juan, additional, Balakrishnan, Binod, additional, Meyer, Michael T., additional, and Friess, Stuart, additional

Published
2023
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6. Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study

Author

Tubi, Meral A., Lutkenhoff, Evan, Blanco, Manuel Buitrago, McArthur, David, Villablanca, Pablo, Ellingson, Benjamin, Diaz-Arrastia, Ramon, Van Ness, Paul, Real, Courtney, Shrestha, Vikesh, Engel, Jerome, Vespa, Paul M., Agoston, Denes, Au, Alicia, Bell, Michael J., Bleck, Tom, Branch, Craig, Buitrago Blanco, Manuel, Bullock, Ross, Burrows, Brian T., Claassen, Jan, Clarke, Robert, Cloyd, James, Coles, Lisa, Crawford, Karen, Duncan, Dominique, Foreman, Brandon, Galanopoulou, Aristea, Gilmore, Emily, Olli, Grohn, Harris, Neil, Hartings, Jed, Lawrence, Hirsch, Hunn, Martin, Jette, Nathalie, Johnston, Leigh, Jones, Nigel, Kanner, Andres, Monti, Martin, Morokoff, Andrew, Moshe, Solomon, Mowrey, Wenzhu, O’Brien, Terence, O’Phelan, Kristine, Pitkanen, Asla, Raman, Rema, Robertson, Courtney, Rosenthal, Eric, Shultz, Sandy, Snutch, Terrance, Staba, Richard, Toga, Arthur, Van Horn, Jack, Vespa, Paul, Willyerd, Frederick, and Zimmermann, Lara

Subjects
0301 basic medicine, Male, Traumatic, Pediatrics, Brain atrophy, Neurodegenerative, Epileptogenesis, Severity of Illness Index, Epilepsy, 0302 clinical medicine, Brain Injuries, Traumatic, 2.1 Biological and endogenous factors, Longitudinal Studies, Prospective Studies, Post-traumatic epilepsy, Aetiology, Coma, Prospective cohort study, Status epilepticus, screening and diagnosis, Head injury, Temporal Lobe, Detection, Neurology, Neurological, Female, medicine.symptom, Adult, medicine.medical_specialty, Physical Injury - Accidents and Adverse Effects, Traumatic brain injury, Clinical Sciences, Traumatic Brain Injury (TBI), Article, Temporal lobe, lcsh:RC321-571, 03 medical and health sciences, Brain trauma, Clinical Research, Seizures, medicine, Humans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Traumatic Head and Spine Injury, Neurology & Neurosurgery, business.industry, Prevention, Neurosciences, Epilepsy, Post-Traumatic, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, 030104 developmental biology, Brain Injuries, Post-Traumatic, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE. METHODS: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury. RESULTS: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029). CONCLUSION: Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

Published
2019

7. Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest.

Author

Fink, Ericka L., Kochanek, Patrick M., Beers, Sue R., Clark, Robert R. S. B., Berger, Rachel P., Bayir, Hülya, Topjian, Alexis A., Newth, Christopher, Press, Craig, Maddux, Aline B., Willyerd, Frederick, Hunt, Elizabeth A., Siems, Ashley, Chung, Melissa G., Smith, Lincoln, Doughty, Leslie, Diddle, J. Wesley, Patregnani, Jason, Piantino, Juan, and Walson, Karen Hallermeier

Published
2023
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8. Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest.

Author

Fink, Ericka L., Kochanek, Patrick M., Panigrahy, Ashok, Beers, Sue R., Berger, Rachel P., Bayir, Hülya, Pineda, Jose, Newth, Christopher, Topjian, Alexis A., Press, Craig A., Maddux, Aline B., Willyerd, Frederick, Hunt, Elizabeth A., Siems, Ashley, Chung, Melissa G., Smith, Lincoln, Wenger, Jesse, Doughty, Lesley, Diddle, J. Wesley, and Patregnani, Jason

Published
2022
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9. Abstract 11617: Personalizing Outcomes After Child Cardiac Arrest (POCCA): A Preliminary Biomarker Report

Author

Fink, Ericka L, Kochanek, Patrick M, Panigrahy, Ashok, Beers, Sue R, Berger, Rachel P, BAYIR, HULYA, Wang, Chunyan, Pineda, Jose, Topjian, Alexis A, maddux, aline, Willyerd, Frederick, Hunt, Elizabeth A, Chung, Melissa G, Newth, Christopher, Smith, Lincoln, Doughty, Leslie, Diddle, J Wesley, Piantino, Juan, Walson, Karen H, Balakrishnan, Binod, Friess, Stuart, Siems, Ashley, Clark, Robert M, and Fabio, Anthony

Abstract

Blood-based brain injury biomarkers show promise to prognosticate outcome for children resuscitated from cardiac arrest. The objective of this multicenter, observational study was to validate promising biomarkers to accurately prognosticate outcome at 1 year. Early brain injury biomarkers will be associated with outcome at one year for children with cardiac arrest. Fourteen centers in the US enrolled children aged < 18 years with in- or out-of-hospital cardiac arrest and pediatric intensive care unit admission if pre-cardiac arrest Pediatric Cerebral Performance Category score was 1-3. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1), neurofilament light (NfL), and Tau protein concentrations were measured in samples drawn post-arrest day 1 using Quanterix Simoa 4-Plex assay. The primary outcome was unfavorable outcome at one year (Vineland Adaptive Behavioral Scale < 70). Of 164 children enrolled, 120 children had evaluable data (n=50 with unfavorable outcome). Children were median (interquartile range) 1 (0-8.5) years of age, 41% female, and 60% had asphyxia etiology. Of children with unfavorable outcome, 93% had unwitnessed arrests and 43 died. While all 4 day 1 biomarkers were increased in children with unfavorable vs. favorable outcome at 1-year post-arrest, NfL had the best univariate area under the receiver operator curve to predict 1 year outcome at 0.731. In a multivariate logistic regression, NfL concentration trended toward significance on day 1 and was associated with unfavorable outcome at 1-year on days 2 and 3 (day 1: Odds Ratio [95% Confidence Interval] 1.004 [1.000-1.008], p=.062; day 2: 1.005 [1.002-1.008], p=.003, and day 3: 1.002 [1.001-1.004], p=.003, respectively). UCHL1 was associated with outcome on days 2: 1.005 [1.002-1.009], p=.003 and 3: 1.001 [1.000-1.002], p=.019) and Tau trended toward association with outcome on days 2: 1.003 [1.000-1.005], p=.08) and 3: 1.001 [1.000-1.002], p=.077. Brain injury biomarkers predict unfavorable outcome post-pediatric cardiac arrest. Accuracy of biomarkers alone and together with other prognostication tools should be evaluated to predict long term child centered outcomes post-cardiac arrest.

Published
2021
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