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Samuel S. Shin, C. Edward Dixon, David O. Okonkwo, and R. Mark Richardson

T here are multiple therapy modalities for attenuating neurological disabilities in traumatic brain injury (TBI) patients, including occupational, physical, and cognitive rehabilitation, but there is a critical need for more effective therapies, especially pharmacological or surgical treatments. The pathophysiology of TBI is complex and includes inflammation, oxidative stress, apoptosis, excitotoxicity, and mitochondrial dysfunction. After almost a century of translational science, there has yet to be a successful Phase III clinical trial investigating a

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Ross C. Puffer, Luz M. Cumba Garcia, Benjamin T. Himes, Mi-Yeon Jung, Frederic B. Meyer, David O. Okonkwo, and Ian F. Parney

distinct cellular pathways and have distinct cargo. EVs have generated significant interest in neurooncology; tumor-derived EVs shape the microenvironment by downregulating the immune response and upregulating angiogenic factors, among other complex actions. 3–6 Severe traumatic brain injury (TBI) affects more than 200,000 individuals annually in the US and is a leading cause of mortality in men under 35 years of age. 7 Mild TBI is underreported but may be as much as 10 times more common than severe TBI, and is increasingly recognized as a contributor to

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Kristen E. Jones, Ava M. Puccio, Kathy J. Harshman, Bonnie Falcione, Neal Benedict, Brian T. Jankowitz, Martina Stippler, Michael Fischer, Erin K. Sauber-Schatz, Anthony Fabio, Joseph M. Darby, and David O. Okonkwo

patient from each group was lost to follow-up at 6 months. Discussion The present study indicates that levetiracetam monotherapy in the first 7 days following severe TBI is associated with an increased seizure tendency and increased epileptiform activity on electroencephalograms compared with phenytoin. The rates of seizure activity were equivalent in patients treated with levetiracetam and those treated with phenytoin. The implications of increased seizure tendency and epileptiform activity require further study. Traumatic brain injury occurs in approximately 1

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Jay Jagannathan, David O. Okonkwo, Hian Kwang Yeoh, Aaron S. Dumont, Dwight Saulle, Julie Haizlip, Jeffrey T. Barth, John A. Jane Sr., and John A. Jane Jr.

NA , Chesnut RM , du Coudray HE , Goldstein B , : Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 6. Threshold for treatment of intracranial hypertension . Pediatr Crit Care Med 4 : 3 Suppl S25 – S27 , 2003 3 Anderson V , Catroppa C , Morse S , Haritou F , Rosenfeld J : Functional plasticity or vulnerability after early brain injury? . Pediatrics 116 : 1374 – 1382 , 2005 4 Artru F , Jourdan C , Convert J , Terrier A , Deleuze R

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Pawel G. Ochalski, David O. Okonkwo, Michael J. Bell, and P. David Adelson

Alzheimer's disease revisited . Brain Res Bull 45 : 341 – 379 , 1998 15 Mysiw WJ , Bogner JA , Corrigan JD , Fugate LP , Clinchot DM , Kadyan V : The impact of acute care medications on rehabilitation outcome after traumatic brain injury . Brain Inj 20 : 905 – 911 , 2006 16 Palmer AM , Marion DW , Botscheller ML , Bowen DM , DeKosky ST : Increased transmitter amino acid concentration in human ventricular CSF after brain trauma . Neuroreport 6 : 153 – 156 , 1994 17 Salonen M , Kanto J , Iisalo E , Himberg JJ

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Oren Sagher and Hemant A. Parmar

Shin et al. 2 describe their findings in a patient with traumatic brain injury (TBI) using high-definition fiber tracking (HDFT), attempting to show the capabilities of this new technique in assessing white matter injuries that are not apparent in standard anatomical imaging. Standard diffusion tensor imaging (DTI) has long held this promise, but the results have been somewhat disappointing and inconsistent due to the lack of good resolution at the voxel level and due to the presence of crossing fibers within the given voxel. The presence of different

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Samuel S. Shin, Timothy Verstynen, Sudhir Pathak, Kevin Jarbo, Allison J. Hricik, Megan Maserati, Sue R. Beers, Ava M. Puccio, Fernando E. Boada, David O. Okonkwo, and Walter Schneider

developmental CNS anomalies . Radiographics 25 : 53 – 68 , 2005 7 Liu AY , Maldjian JA , Bagley LJ , Sinson GP , Grossman RI : Traumatic brain injury: diffusion-weighted MR imaging findings . AJNR Am J Neuroradiol 20 : 1636 – 1641 , 1999 8 Mac Donald CL , Dikranian K , Song SK , Bayly PV , Holtzman DM , Brody DL : Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury . Exp Neurol 205 : 116 – 131 , 2007 9 Mac Donald CL , Johnson AM , Cooper D , Nelson EC

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Ross C. Puffer, John K. Yue, Matthew Mesley, Julia B. Billigen, Jane Sharpless, Anita L. Fetzick, Ava Puccio, Ramon Diaz-Arrastia, and David O. Okonkwo

F ollowing traumatic brain injury (TBI), midline shift of the brain at the level of the septum pellucidum is often caused by unilateral, space-occupying lesions and is associated with increased intracranial pressure and worsened morbidity and mortality. 1 , 2 , 4 , 6 , 13 , 16 , 20 , 21 , 27 , 33 The degree of shift is associated with abnormal neurological examination results due to progressive dysfunction of the diencephalon subsequent to mass effect. 5 , 9 , 27 In TBI, midline shift can be the result of heterogeneous morphologies consisting of hemorrhage

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David O. Okonkwo

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Jay Jagannathan, David O. Okonkwo, Aaron S. Dumont, Hazem Ahmed, Abbas Bahari, Daniel M. Prevedello, John A. Jane Sr., and John A. Jane Jr.

, du Coudray HE , Goldstein B , : Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 19 The role of antiseizure prophylaxis following severe pediatric traumatic brain injury . Pediatr Crit Care Med 4 : 3 Suppl S72 – S75 , 2003 2 Alberico AM , Ward JD , Choi SC , Marmarou A , Young HF : Outcome after severe head injury. Relationship to mass lesions, diffuse injury, and ICP course in pediatric and adult patients . J Neurosurg 67 : 648 – 656 , 1987 3 Baker SP