•GFAP Out-Performs S100β in Detecting Traumatic Intracranial Lesions on Computed Tomography in Trauma Patients with Mild Traumatic Brain Injury and Those with Extracranial Lesions
Journal of Neurotrauma
Posted online on September 12, 2014.
(doi:10.1089/neu.2013.3245)
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Linda Papa,1 Salvatore Silvestri,1 Gretchen M. Brophy,2 Philip Giordano,1 Jay L. Falk,1 Carolina F. Braga,1 Ciara N. Tan1 Neema J. Ameli1 Jason A. Demery,3 Neha K. Dixit,3 Matthew E. Mendes,4 Ronald L. Hayes,5 Kevin K. W. Wang,6 and Claudia S. Robertson7
1Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida.
2Department of Pharmacotherapy and Outcomes Science and Department or Neurosurgery, Virginia Commonwealth University, Richmond, Virginia.
3Department of Psychology, North Florida's Veteran's Health System, Gainesville, Florida.
4University of Central Florida, Orlando, Florida.
5Center of Innovative Research, Banyan Biomarkers Inc., Alachua, Florida.
6Department of Psychiatry, University of Florida, Gainesville, Florida.
7Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
Address correspondence to:
Linda Papa, MDCM, MSc
Director of Academic Clinical Research and Attending Emergency Physician
Department of Emergency Medicine
Orlando Regional Medical Center
86 W. Underwood (S-200)
Orlando, Florida, 32806
E-mail: lpstat@aol.com
ABSTRACT
Both glial fibrillary acidic protein (GFAP) and S100β are found in glial cells and are released into serum following a traumatic brain injury (TBI), however, the clinical utility of S100β as a biomarker has been questioned because of its release from bone. This study examined the ability of GFAP and S100β to detect intracranial lesions on computed tomography (CT) in trauma patients and also assessed biomarker performance in patients with fractures and extracranial injuries on head CT. This prospective cohort study enrolled a convenience sample of adult trauma patients at a Level I trauma center with and without mild or moderate traumatic brain injury (MMTBI). Serum samples were obtained within 4 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 397 general trauma patients enrolled: 209 (53%) had a MMTBI and 188 (47%) had trauma without MMTBI. Of the 262 patients with a head CT, 20 (8%) had intracranial lesions. There were 137 (35%) trauma patients who sustained extracranial fractures below the head to the torso and extremities. Levels of S100β were significantly higher in patients with fractures, compared with those without fractures (p<0.001) whether MMTBI was present or not. However, GFAP levels were not significantly affected by the presence of fractures (p>0.05). The area under the receiver operating characteristics curve (AUC) for predicting intracranial lesions on CT for GFAP was 0.84 (0.73–0.95) and for S100β was 0.78 (0.67–0.89). However, in the presence of extracranial fractures, the AUC for GFAP increased to 0.93 (0.86–1.00) and for S100β decreased to 0.75 (0.61–0.88). In a general trauma population, GFAP out-performed S100β in detecting intracranial CT lesions, particularly in the setting of extracranial fractures.
•Bilateral Contusion-Compression Model of Incomplete Traumatic Cervical Spinal Cord Injury
Journal of Neurotrauma
Posted online on September 12, 2014.
(doi:10.1089/neu.2014.3388)
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Nicole Forgione,1 Spyridon K. Karadimas,1,2 Warren D. Foltz,3,4 Kajana Satkunendrarajah,1 Alyssa Lip,2 and Michael G. Fehlings1,2,5,6
1Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Center,University Health Network, Toronto, Ontario, Canada.
2Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
3Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, Canada.
4STTARR Innovation Center, University Health Network, Toronto, Ontario, Canada.
5Neuroscience Program, University of Toronto, Toronto, Ontario, Canada.
6Department of Surgery, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
Address correspondence to:
Michael G. Fehlings, MD, PhD
Toronto Western Hospital
University Health Network
Krembil Discovery Tower
Toronto Western Hospital
60 Leonard Street
7KD430
Toronto, Ontario,
Canada M5T 2S8
E-mail: Michael.fehlings@uhn.ca
ABSTRACT
Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosin staining in combination with quantitative stereology, we determined that 18-g injury results in loss of gray matter (GM), white matter (WM), as well as in cavity formation. Magnetization transfer and T2-weighted magnetic resonance imaging were used to analyze lesion dynamics in vivo. This analysis demonstrated that both techniques are able to differentiate between the injury epicenter, subpial rim, and WM distal to the injury. Neurobehavioral assessment of locomotor function using Basso, Beattie, and Bresnahan (BBB) scoring and CatWalk revealed limited recovery from clip-compression injury at C6. Testing of forelimb function using grip strength demonstrated significant forelimb dysfunction, similar to the loss of upper-limb motor function observed in human cSCI. Sensory-evoked potentials recorded from the forelimb and Hoffman reflex recorded from the hindlimb confirmed the fore- and hindlimb deficits observed in our neurobehavioral analysis. Here, we have characterized a clip-compression model of incomplete cSCI that closely models this condition in humans. This work directly addresses the current lack of clinically relevant models of cSCI and will thus contribute to improved success in the translation of putative therapies into the clinic.
•Imaging “Brain Strain” in Youth Athletes with Mild Traumatic Brain Injury during Dual-Task Performance
Journal of Neurotrauma
Posted online on September 11, 2014.
(doi:10.1089/neu.2014.3326)
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Katia J. Sinopoli,1 Jen-Kai Chen,2 Greg Wells,3,4 Philippe Fait, PhD, ATC,5,6 Alain Ptito,2 Tim Taha,3 andMichelle Keightley7,8
1Department of Psychology, Division of Neurology, the Hospital for Sick Children, Toronto, Ontario, Canada.
2McGill University Health Centre and Montreal Neurological Institute, Montreal, Quebec, Canada.
3Department of Kinesiology and Physical Education, University of Toronto, Ontario, Canada.
4Department of Physiology and Experimental Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada.
5Department of Physical Activity Science, University of Quebec at Trois-Rivières, Canada.
6Research Group on Neuromusculoskeletal Dysfunctions, University of Quebec at Trois-Rivières, Canada.
7Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, Toronto, Ontario, Canada.
8Department of Occupational Science and Occupational Therapy and Graduate Department of Rehabilitation Science and Psychology, University of Toronto, Ontario, Canada.
Address correspondence to:
Michelle Keightley, PhD, CPsych
150 Kilgour Road
Toronto, Ontario,
Canada M4G 1R8
E-mail: michelle.keightley@utoronto.ca
ABSTRACT
Mild traumatic brain injury (mTBI) is a common cause of injury in youth athletes. Much of what is known about the sequelae of mTBI is yielded from the adult literature, and it appears that it is mainly those with persistent post-injury symptoms who have ongoing cognitive and neural abnormalities. However, most studies have employed single-task paradigms, which may not be challenging enough to uncover subtle deficits. We sought to examine the neural correlates of dual-task performance in male athletes aged 9-15 years using a functional neuroimaging protocol. Participants included 13 youths with a history of mTBI three to six months prior to testing and 14 typically-developing controls. All participants completed a working memory task in isolation (single-task) and while completing a concurrent motor task (dual-task); neural activity during performance was then compared between groups. Although working memory performance was similar during the single-task condition, increased working memory load resulted in an altered pattern of neural activation in key working memory areas (i.e., dorsolateral prefrontal and parietal cortices) in youth with mTBI relative to controls. During the dual-task condition, accuracy was similar between groups but injured youth performed slower than typically-developing controls, suggesting a speed-accuracy tradeoff in the mTBI group only. The injured youths also exhibited abnormal recruitment of brain structures involved in both working memory and dual-tasking. These data show that the dual-task paradigm can uncover functional impairments in youth with mTBI who are not highly symptomatic and who do not exhibit neuropsychological dysfunction. Moreover, neural recruitment abnormalities were noted in both task conditions, which we argue suggests mTBI-related disruptions in achieving efficient cognitive control and allocation of processing resources.
•Response to Diaz-Arrastia et al., “Pharmacotherapy of Traumatic Brain Injury: State of the Science and the Road Forward”
Journal of Neurotrauma
Posted online on September 11, 2014.
(doi:10.1089/neu.2014.3342)
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J. Humberto Tapia Pérez,1 Martin Sánchez Aguilar,2 and Thomas Schneider1
1Department of Neurosurgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
2Clinical Epidemiology and Public health, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
Address correspondence to:
J. Humberto Tapia Pérez, MD
Departent of Neurosurgery
Otto-von-Guericke University Magdeburg
Magdeburg
Germany
E-mail: lehwand@hotmail.com
jorge.tapia@med.ovgu.de
•The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity
Journal of Neurotrauma
Posted online on September 11, 2014.
(doi:10.1089/neu.2014.3343)
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Victoria P.A. Johnstone,1 Sandy R. Shultz,2 Edwin B. Yan,1 Terence J. O'Brien,2 and Ramesh Rajan1
1Department of Physiology, Monash University, Clayton, Victoria, Australia.
2Department of Medicine, The Royal Melbourne Hospital, The Melbourne Brain Centre, The University of Melbourne, Parkville, Victoria, Australia.
Address correspondence to:
Ramesh Rajan, PhD
Department of Physiology
Monash University
Wellington Road
Melbourne, Victoria 3800
Australia
E-mail: ramesh.rajan@monash.edu
ABSTRACT
The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes.
•Post-Traumatic Multimodal Brain Monitoring: Response to Hypertonic Saline
Journal of Neurotrauma
Posted online on September 11, 2014.
(doi:10.1089/neu.2014.3376)
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Celeste Dias,1 Maria João Silva,2 Eduarda Pereira,1 Sofia Silva,1 António Cerejo,3 Peter Smielewski,4Ana Paula Rocha,2 A. Rita Gaio,2 José-Artur Paiva,1 and Marek Czosnyka4
1Department of Intensive Care, University Hospital Sao Joao, Porto, Portugal.
2Department of Mathematics, University of Porto, Porto, Portugal.
3Department of Neurosurgery, University Hospital Sao Joao, Porto, Portugal.
4Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, United Kingdom.
Address correspondence to:
Celeste Dias, MD
Neurocritical Care Unit, Intensive Care Department
University Hospital Sao Joao, Porto, Portugal
Neurocritical Care Unit, Hospital Sao Joao
Alameda Hernani Monteiro, piso 8
4200-319 Porto,
Portugal
E-mail: mceleste.dias@gmail.com
ABSTRACT
Emerging evidence suggests that hypertonic saline (HTS) is efficient in decreasing intracranial pressure (ICP). However there is no consensus about its interaction with brain hemodynamics and oxygenation. In this study, we investigated brain response to HTS bolus with multimodal monitoring after severe traumatic brain injury (TBI). We included 18 consecutive TBI patients during 10 days after neurocritical care unit admission. Continuous brain monitoring applied included ICP, tissue oxygenation (PtO2) and cerebral blood flow (CBF). Cerebral perfusion pressure (CPP), cerebrovascular resistance (CVR), and reactivity indices related to pressure (PRx) and flow (CBFx) were calculated. ICM+software was used to collect and analyze monitoring data. Eleven of 18 (61%) patients developed 99 episodes of intracranial hypertension (IHT) greater than 20 mm Hg that were managed with 20% HTS bolus. Analysis over time was performed with linear mixed-effects regression modelling. After HTS bolus, ICP and CPP improved over time (p<0.001) following a quadratic model. From baseline to 120 min, ICP had a mean decrease of 6.2 mm Hg and CPP a mean increase of 3.1 mmHg. Mean increase in CBF was 7.8 mL/min/100 g (p<0.001) and mean decrease in CVR reached 0.4 mm Hg*min*100 g/mL (p=0.01). Both changes preceded pressures improvement. PtO2 exhibited a marginal increase and no significant models for time behaviour could be fitted. PRx and CBFx were best described by a linear decreasing model showing autoregulation recover after HTS (p=0.01 and p=0.04 respectively). During evaluation, CO2 remained constant and sodium level did not exhibit significant variation. In conclusion, management of IHT with 20% HTS significantly improves cerebral hemodynamics and cerebrovascular reactivity with recovery of CBF appearing before rise in CPP and decrease in ICP. In spite of cerebral hemodynamic improvement, no significant changes in brain oxygenation were identified.
•Modulating Inflammatory Cell Responses to Spinal Cord Injury: All in Good Time
Journal of Neurotrauma
Posted online on September 8, 2014.
(doi:10.1089/neu.2014.3429)
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Amy L. Bowes and Ping K. Yip, PhD
Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry,Queen Mary University of London, London, United Kingdom.
Address correspondence to
Amy L. Bowes and Ping K. Yip, PhD
Centre for Neuroscience and Trauma
Blizard Institute
4 Newark Street
London E1 2AT
United Kingdom
E-mails: amy.louise.bowes@hotmail.co.uk
and
p.yip@qmul.ac.uk
ABSTRACT
Spinal cord injury can have a range of debilitating effects, permanently impacting a patient's quality of life. Initially thought to be an immune privileged site, the spinal cord is able to mount a timely and well organized inflammatory response to injury. Intricate immune cell interactions are triggered, typically consisting of a staggered multiphasic immune cell response, which can become deregulated if left unchecked. Although several immunomodulatory compounds have yielded success in experimental rodent spinal cord injury models, their translation to human clinical studies needs further consideration. Because temporal differences between rodent and human inflammatory responses to spinal cord injury do exist, drug delivery timing will be a crucial component in recovery from spinal cord injury. Given too early, immunomodulatory therapies may impede beneficial inflammatory reactions to the injured spinal cord or even miss the opportunity to dampen delayed harmful autoimmune processes. Therefore, this review aims to summarize the temporal inflammatory response to spinal cord injury, as well as detailing specific immune cell functions. By clearly defining the chronological order of inflammatory events after trauma, immunomodulatory drug delivery timing can be better optimized. Further, we compare spinal cord injury-induced inflammatory responses in rodent and human studies, enabling clinicians to consider these differences when initiating clinical trials. Improved understanding of the cellular immune response after spinal cord injury would enhance the efficacy of immunomodulatory agents, enabling combined therapies to be considered.
•An Acute Growth Factor Treatment that Preserves Function after Spinal Cord Contusion Injury
Journal of Neurotrauma
Posted online on September 4, 2014.
(doi:10.1089/neu.2013.3294)
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