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Bondi, Corina O.; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Osier, Nicole D.; Carlson, Shaun W.; Dixon, C. Edward; Giza, Christopher C.; Kline, Anthony E.
BONDI, C.O., B.D. Semple, L.J. Noble-Haeusslein, N.D. Osier, S.W. Carlson, C.E. Dixon, C.C. Giza and A.E. Kline. Found in translation: understanding the biology and behavior of experimental traumatic brain injury. NEUROSCI BIOBEHAV REV. The aim of this review is to discuss in greater detail the topics covered in the recent symposium entitled “Traumatic brain injury: laboratory and clinical perspectives,” presented at the 2014 International Behavioral Neuroscience Society annual meeting. Herein we review contemporary laboratory models of traumatic brain injury (TBI) including common assays for sensorimotor and cognitive behavior. New modalities to evaluate social behavior after injury to the developing brain, as well as the attentional set-shifting test (AST) as a measure of executive function in TBI, will be highlighted. Environmental enrichment (EE) will be discussed as a preclinical model of neurorehabilitation, and finally, an evidence-based approach to sports-related concussion will be considered. The review consists predominantly of published data, but some discussion of ongoing or future directions is provided. PMID:25496906
Traumatic brain injury (TBI) happens when a bump, blow, jolt, or other head injury causes damage to the brain. Every year, millions of people in the U.S. suffer brain injuries. More than half are bad enough that ...
Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A
Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI.
Full Text Available Blood-brain barrier (BBB disruption is common following traumatic brain injury (TBI. Dynamic contrast enhanced (DCE MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field and magnetization (M0 distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI, and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI.
Mark W. Wojnarowicz
Full Text Available Animal models of concussion, traumatic brain injury (TBI, and chronic traumatic encephalopathy (CTE are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs” from injury consequences (“outputs” may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and
Wojnarowicz, Mark W; Fisher, Andrew M; Minaeva, Olga; Goldstein, Lee E
Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context ("inputs") from injury consequences ("outputs") may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate clinical
Wojnarowicz, Mark W.; Fisher, Andrew M.; Minaeva, Olga; Goldstein, Lee E.
Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs”) from injury consequences (“outputs”) may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate
Phillips, Michael; Regele, Jonathan D.
Unfortunately, Improvised Explosive Devices (IEDs) are encountered commonly by both civilians and military soldiers throughout the world. Over a decade of medical history suggests that traumatic brain injury (TBI) may result from exposure to the blast waves created by these explosions, even if the person does not experience any immediate injury or lose consciousness. Medical researchers study the exposure of mice and rats to blast waves created in specially designed shock tubes to understand the effect on brain tissue. A newly developed table-top shock tube with a short driver section has been developed for mice experiments to reduce the time necessary to administer the blast radiation and increase the amount of statistical information available. In this study, numerical simulations of this shock tube are performed to assess how the blast wave takes its shape. The pressure profiles obtained from the numerical results are compared with the pressure histories from the experimental pressure transducers. The results show differences in behavior from what was expected, but the blast wave may still be an effective means of studying TBI.
Moro, Nobuhiro; Ghavim, Sima S; Harris, Neil G; Hovda, David A; Sutton, Richard L
Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000mg/kg, i.p.) or ethyl pyruvate (EP; 40mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40mg/kg of EP being as effective as 1000mg/kg of SP, and multiple treatments within 6h of injury did not improve upon outcomes seen following a single treatment. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Abstract Background Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q10 (CoQ10, a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ10 in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ10 administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out. Results In the biochemical tests, tissue malondialdehyde (MDA levels were significantly higher in the traumatic brain-injury group compared to the sham group (p 10 after trauma was shown to be protective because it significantly lowered the increased MDA levels (p 10 group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ10 and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (p Conclusion Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ10 use in rats with traumatic brain injury.
Immonen, Riikka J; Kharatishvili, Irina; Gröhn, Heidi; Pitkänen, Asla; Gröhn, Olli H J
In traumatic brain injury (TBI) the initial impact causes both immediate damage and also launches a cascade of slowly progressive secondary damage. The chronic outcome disabilities vary greatly and can occur several years later. The aim of this study was to find predictive factors for the long-term outcome using multiparametric, non-invasive magnetic resonance imaging (MRI) methodology and a clinically relevant rat model of fluid percussion induced TBI. Our results demonstrated that the multiparametric quantitative MRI (T(2), T(1rho), trace of the diffusion tensor D(av), the extent of hyperintense lesion and intracerebral hemorrhage) acquired during acute and sub acute phases 3 h, 3 days, 9 days and 23 days post-injury has potential to predict the functional and histopathological outcome 6 to 12 months later. The acute D(av) changes in the ipsilateral hippocampus correlated with the chronic spatial learning and memory impairment evaluated using the Morris water maze (phelp to predict the long-term outcome after experimental TBI.
Ganpule, S; Alai, A; Plougonven, E; Chandra, N
Blast waves generated by improvised explosive devices can cause mild, moderate to severe traumatic brain injury in soldiers and civilians. To understand the interactions of blast waves on the head and brain and to identify the mechanisms of injury, compression-driven air shock tubes are extensively used in laboratory settings to simulate the field conditions. The overall goal of this effort is to understand the mechanics of blast wave-head interactions as the blast wave traverses the head/brain continuum. Toward this goal, surrogate head model is subjected to well-controlled blast wave profile in the shock tube environment, and the results are analyzed using combined experimental and numerical approaches. The validated numerical models are then used to investigate the spatiotemporal distribution of stresses and pressure in the human skull and brain. By detailing the results from a series of careful experiments and numerical simulations, this paper demonstrates that: (1) Geometry of the head governs the flow dynamics around the head which in turn determines the net mechanical load on the head. (2) Biomechanical loading of the brain is governed by direct wave transmission, structural deformations, and wave reflections from tissue-material interfaces. (3) Deformation and stress analysis of the skull and brain show that skull flexure and tissue cavitation are possible mechanisms of blast-induced traumatic brain injury.
Kota, Daniel J; Prabhakara, Karthik S; Toledano-Furman, Naama; Bhattarai, Deepa; Chen, Qingzheng; DiCarlo, Bryan; Smith, Philippa; Triolo, Fabio; Wenzel, Pamela L; Cox, Charles S; Olson, Scott D
Traumatic brain injury (TBI) is soon predicted to become the third leading cause of death and disability worldwide. After the primary injury, a complex set of secondary injuries develops hours and days later with prolonged neuroinflammation playing a key role. TBI and other inflammatory conditions are currently being treated in preclinical and clinical trials by a number of cellular therapies. Mesenchymal stem cells (MSC) are of great interest due to their widespread usage, safety, and relative ease to isolate and culture. However, there has been a wide range in efficacy reported using MSC clinically and in preclinical models, likely due to differences in cell preparations and a significant amount of donor variability. In this study, we seek to find a correlation between in vitro activity and in vivo efficacy. We designed assays to explore the responsiveness of MSC to immunological cues to address the immunomodulatory properties of MSC, one of their primary modes of therapeutic activity in TBI. Our results showed intrinsic differences in the immunomodulatory capacity of MSC preparations from different bone marrow and amniotic fluid donors. This difference mirrored the therapeutic capacity of the MSC in an experimental model of TBI, an effect confirmed using siRNA knockdown of COX2 followed by overexpressing COX2. Among the immunomodulatory factors assessed, the therapeutic benefit correlated with the secretion of prostaglandin E2 (PGE2 ) by MSC prior to treatment, suggesting that measurement of PGE2 could be a very useful potency marker to create an index of predicted efficacy for preparations of MSC to treat TBI. Stem Cells 2017;35:1416-1430. © 2017 AlphaMed Press.
Calikoglu, Cagatay; Aytekin, Hikmet; Akgül, Osman; Akgül, Mehmet Hüseyin; Gezen, Ahmet Ferruh; Akyuz, Feyzullah; Cakir, Murteza
Background In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats. Material/Methods This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma treated with pregabalin. The biopsy samples taken from the study animals were histopathologically examined for the presence of edema, inflammation, and neuronal damage. Results All animals in the trauma group had edema, inflammation, and neuronal damage. Four subjects in the control group, 6 in the pregabalin group, and 4 in the trauma + pregabalin group had edema; inflammation was present in 1 subject in the control group, 3 subjects in the pregabalin group, and 3 subjects in the trauma + pregabalin group; neuronal damage existed in 1 subject in the control group, 1 subject in the pregabalin group, and 6 subjects in the trauma + pregabalin group. The trauma group had significantly higher edema and neuronal damage scores than the other groups. Similarly, inflammation was significantly more prevalent in the trauma group than the control and trauma + pregabalin groups. Conclusions The results of the present study indicated anti-edema, anti-inflammatory, and neuroprotective effects of pregabalin in an experimental head trauma model in rats. Pregabalin may thus be beneficial in humans with acute TBI by relieving concomitant edema and inflammation. PMID:25785578
Calikoglu, Cagatay; Aytekin, Hikmet; Akg?l, Osman; Akg?l, Mehmet H?seyin; Gezen, Ahmet Ferruh; Akyuz, Feyzullah; Cakir, Murteza
Background In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats. Material/Methods This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma tr...
Özay, Rafet; Türkoğlu, Mehmet Erhan; Gürer, Bora; Dolgun, Habibullah; Evirgen, Oya; Ergüder, Berrin İmge; Hayırlı, Nazlı; Gürses, Levent; Şekerci, Zeki
The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is a well-known entity. Consequently, the aim of the present study was to evaluate the role of omeprazole (OM) on rat model of TBI. A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, OM, and methylprednisolone (MP). The trauma, OM, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with saline, OM, or MP, respectively. All the animals were sacrificed at 24 hours after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, nitric oxide) and caspase-3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. Levels of MDA and activity of caspase-3 were significantly reduced in the OM and MP groups compared with the trauma group. Glutathione peroxidase and superoxide dismutase levels were increased both in the OM and MP groups compared with the trauma group. The pathology scores were statistically lower in the OM and MP groups than the trauma group. The results of the present study showed that OM was as effective as MP in protecting brain from oxidative stress, and apoptosis in the early phase of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.
Santos, Alejandro; Gonçalves, Pedro; Araújo, João R; Martel, Fátima
Traumatic injuries are the leading cause of mortality in individuals aged 1-44 years, and brain injury significantly contributes to the outcome in nearly one half of all deaths from trauma. At the intestinal level, traumatic brain injury (TBI) induces profound effects, including gastrointestinal mucosa ischaemia and motility dysfunction. However, nothing is known concerning the effect of TBI on the intestinal absorption of glucose. Hence, the aim of this study was to investigate the effect of TBI on the intestinal absorption of glucose by investigating the effect of TBI on the jejunal mucosal-to-serosal apparent permeability (AP-to-BL P(app)) to two glucose model substrates, (3)H-2-deoxy-D-glucose ((3)H-DG) and (3)H-3-O-methyl-D-glucose ((3)H-OMG), and to (14)C-sorbitol. Additionally, we tested if gadopentetate dimeglumine administration could prevent any of the changes observed after TBI. Traumatic brain injury induced an increase in the AP-to-BL P(app) to (3)H-DG. After a 100-min. perfusion of the jejunum, the AP-to-BL P(app) to (3)H-DG in TBI rats was almost 70% higher than in the control rats. There was no change, however, in the AP-to-BL P(app) to neither (3)H-OMG nor (14)C-sorbitol. Interestingly enough, gadopentetate dimeglumine was able to prevent the increase in the AP-to-BL P(app) to (3)H-DG observed after TBI. Given the differences in transport characteristics between (3)H-DG and (3)H-OMG, our results point to the possibility of the Na(+)-independent glucose transporter 2 (GLUT2) being activated by TBI (as the P(app) to (3)H-DG, a GLUT2 substrate, was increased) and the Na(+)-dependent glucose co-transporter (SGLT1) being inhibited by TBI (as the P(app) to (3)H-OMG, a GLUT2 and SGLT1 substrate, remained unchanged). Moreover, gadopentetate dimeglumine prevented these changes associated with TBI.
Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M
PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro...
Casili, Giovanna; Campolo, Michela; Paterniti, Irene; Lanza, Marika; Filippone, Alessia; Cuzzocrea, Salvatore; Esposito, Emanuela
TBI is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in preclinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI). Mice were orally administered with DMF at the doses of 1, 10 and 30 mg/Kg, 1h and 4h after CCI. We performed histological, molecular, and immunohistochemistry analysis on the traumatic penumbral areas of the brain 24 hours after CCI. DMF treatment notably reduced histological damage and behavioral impairments, reducing neurodegeneration as evidenced by assessments of neuronal loss, Fluoro-jade C and TUNEL staining; also, treatment with DMF blocked apoptosis process increasing B-cell lymphoma 2 (Bcl-2) expression in injured cortex. Furthermore, DMF treatment up-regulated antioxidant Kelch-like ECH-associated protein 1/ Nuclear factor erythroid 2- related factor (Keap-1/Nrf-2) pathway, inducing activation of manganese superoxide dismutase (Mn-SOD) and heme-oxygenase-1 (HO-1) and reducing 4-hydroxy-2-nonenal (4-HNE) staining. Also, regulating NF-κB pathway, DMF treatment decreased the severity of inflammation through a modulation of neuronal nitrite oxide synthase (nNOS), interleukin 1 (Il-1β), tumor necrosis factor (TNF-α), cyclooxygenase 2 (COX-2) and myeloperoxidase (MPO) activity, reducing ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Our results support the thesis that DMF may be an effective neuroprotectant after brain trauma and warrants further study.
Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R
Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.
Young, Jennica M; Hoane, Michael R
After sustaining a traumatic brain injury (TBI), a person's ability to make daily decisions can be affected. Simple tasks such as, deciding what to wear are no longer effortless choices, but are instead difficult decisions. This study explored the use of a discrimination task with a magnesium treatment in order to examine how decision-making skills are affected after TBI and if the treatment helped to attenuate cognitive and motor impairments. Thirty-one male rats were separated into MAG/TBI, VEH/TBI, or VEH/Sham groups. Pre-TBI, rats were trained to dig in the sand for a reinforcer. After establishment of consistent digging behavior rats received a bilateral frontal cortex injury. Rats received either an i.p. injection of 2 mmol/kg magnesium chloride or control at 4, 24, 72 hours post-surgery. Dig task testing began 7 days post-injury, lasting for 4 weeks. The discriminations included two scent pairings; basil (baited) versus coffee then the reversal and then cocoa (baited) versus cumin then the reversal. The results indicated that the magnesium treatment was successful at attenuating cognitive and motor deficits after TBI. The results also indicated that the dig task is a sufficient operant conditioning task in the assessment of frontal functioning after TBI. Copyright © 2018. Published by Elsevier Inc.
Moro, Nobuhiro; Ghavim, Sima S; Hovda, David A; Sutton, Richard L
Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n=6; CCI-Veh, n=7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n=7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (pglucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
de la Tremblaye, Patricia B; O'Neil, Darik A; LaPorte, Megan J; Cheng, Jeffrey P; Beitchman, Joshua A; Thomas, Theresa Currier; Bondi, Corina O; Kline, Anthony E
The aim of this review is to discuss the research presented in a symposium entitled "Current progress in characterizing therapeutic strategies and challenges in experimental CNS injury" which was presented at the 2016 International Behavioral Neuroscience Society annual meeting. Herein we discuss diffuse and focal traumatic brain injury (TBI) and ensuing chronic behavioral deficits as well as potential rehabilitative approaches. We also discuss the effects of stress on executive function after TBI as well as the response of the endocrine system and regulatory feedback mechanisms. The role of the endocannabinoids after CNS injury is also discussed. Finally, we conclude with a discussion of antipsychotic and antiepileptic drugs, which are provided to control TBI-induced agitation and seizures, respectively. The review consists predominantly of published data. Copyright © 2017 Elsevier Ltd. All rights reserved.
Blennow, Kaj; Brody, David L; Kochanek, Patrick M; Levin, Harvey; McKee, Ann; Ribbers, Gerard M; Yaffe, Kristine; Zetterberg, Henrik
Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury - the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators.
Department of Veterans Affairs — As the number of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Traumatic Brain Injury (TBI) patients has grown, so has the need to track and monitor...
Baumann, Christian R
Post-traumatic sleep-wake disturbances are frequent and often chronic complications after traumatic brain injury. The most prevalent sleep-wake disturbances are insomnia, excessive daytime sleepiness, and pleiosomnia, (i.e., increased sleep need). These disturbances are probably of multifactorial origin, but direct traumatic damage to key brain structures in sleep-wake regulation is likely to contribute. Diagnosis and treatment consist of standard approaches, but because of misperception of sleep-wake behavior in trauma patients, subjective testing alone may not always suffice. Copyright © 2016 Elsevier Inc. All rights reserved.
Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a nov...... studies taking important experimental factors such as timing of treatment, dosage, and anesthesia into consideration....
Ernst, William J.; Gallo, Adrienne B.; Sellers, Amanda L.; Mulrine, Jessica; MacNamara, Luciana; Abrahamson, Allison; Kneavel, Meredith
The purpose of this study is to determine knowledge of traumatic brain injury among educators. Few studies have examined knowledge of traumatic brain injury in this population and fewer still have included a substantial proportion of general education teachers. Examining knowledge of traumatic brain injury in educators is important as the vast…
Klose, Marianne; Feldt-Rasmussen, Ulla
While hypopituitarism after traumatic brain injury (TBI) was previously considered rare, it is now thought to be a major cause of treatable morbidity among TBI survivors. Consequently, recommendations for assessment of pituitary function and replacement in TBI were recently introduced. Given...
Firas H Kobeissy
Full Text Available Traumatic brain injury (TBI represents a critical health problem of which diagnosis, management and treatment remain challenging. TBI is a contributing factor in approximately 1/3 of all injury-related deaths in the United States. The Centers for Disease Control and Prevention (CDC estimate that 1.7 million TBI people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system (CNS injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day and for the first time, subacute (7 days, post-injury time frame using the established CAX-PAGE LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entities, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day and subacute (7 days periods post TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7-days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is amongst the first to assess temporal neuroproteome
Nícollas Nunes Rabelo
Full Text Available ABSTRACT The neonatal period is a highly vulnerable time for an infant. The high neonatal morbidity and mortality rates attest to the fragility of life during this period. The incidence of birth trauma is 0.8%, varying from 0.2-2 per 1,000 births. The aim of this study is to describe brain traumas, and their mechanism, anatomy considerations, and physiopathology of the newborn traumatic brain injury. Methods A literature review using the PubMed data base, MEDLINE, EMBASE, Science Direct, The Cochrane Database, Google Scholar, and clinical trials. Selected papers from 1922 to 2016 were studied. We selected 109 papers, through key-words, with inclusion and exclusion criteria. Discussion This paper discusses the risk factors for birth trauma, the anatomy of the occipito-anterior and vertex presentation, and traumatic brain lesions. Conclusion Birth-related traumatic brain injury may cause serious complications in newborn infants. Its successful management includes special training, teamwork, and an individual approach.
Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) often coexist because brain injuries are often sustained in traumatic experiences. This review outlines the significant overlap between PTSD and TBI by commencing with a critical outline of the overlapping symptoms and problems of differential diagnosis. The impact of TBI on PTSD is then described, with increasing evidence suggesting that mild TBI can increase risk for PTSD. Several explanations are offered for this enhanc...
Full Text Available Traumatic brain injury (TBI is often associated with cognitive impairments. The psychological sequelae of cognitive deficits and emotional problems contribute significantly to the disability in the patient and to the distress of the family. The study aimed to develop a cognitive retraining programme to enhance cognitive functioning in TBI. 25 years old male presenting with history of left temporal hemorrhagic contusion with cerebral edema underwent 2 months of a cognitive retaining programme, addressing executive functions impairment. A single case experimental design with pre- and post-assessment was adopted to evaluate changes in the patient in response to the intervention. Improvements were found in cognitive functioning, and in symptom reduction and behaviour. The 2 months hospital based cognitive retraining programme was found to be efficacious in ameliorating symptoms and improving cognitive, social and occupational functioning post traumatic brain injury.
van der Horn, Harm J.; Liemburg, Edith J.; Scheenen, Myrthe E.; de Koning, Myrthe E.; Marsman, Jan-Bernard C.; Spikman, Jacoba M.; van der Naalt, Joukje
ObjectivesTo assess the role of brain networks in emotion regulation and post-traumatic complaints in the sub-acute phase after non-complicated mild traumatic brain injury (mTBI). Experimental designFifty-four patients with mTBI (34 with and 20 without complaints) and 20 healthy controls
Hay, Jennifer; Johnson, Victoria E; Smith, Douglas H; Stewart, William
Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article.
Full Text Available Temperature variations after traumatic brain injury are common and devastating. This has been shown most clearly with hypothermia, but the complications associated with hyperthermia in the setting of traumatic brain injury can be just as problematic. We present the case of a soldier with traumatic brain injury exposed to environmental temperatures of 115-120° F with a core temperature of over 108° F. The complications of his conditions are discussed as well as potential treatments for the deadly combination of traumatic brain injury and environmental hyperthermia.
Anghinah, Renato; Freire, Fabio Rios; Coelho, Fernanda; Lacerda, Juliana Rhein; Schmidt, Magali Taino; Calado, Vanessa Tomé Gonçalves; Ianof, Jéssica Natuline; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Basile, Luis Fernando Hindi; Paiva, Wellingson Silva; Amorim, Robson Luis
Annually, 700,000 people are hospitalized with brain injury acquired after traumatic brain injury (TBI) in Brazil. We aim to review the basic concepts related to TBI, and the most common Behavioral and Psychological Symptoms of Dementia (BPSD) findings in moderate and severe TBI survivors. We also discussed our strategies used to manage such patients in the post-acute period. Fifteen TBI outpatients followed at the Center for Cognitive Rehabilitation Post-TBI of the Clinicas Hospital of the University of São Paulo were submitted to a neurological, neuropsychological, speech and occupational therapy evaluation, including the Mini-Mental State Examination. Rehabilitation strategies will then be developed, together with the interdisciplinary team, for each patient individually. Where necessary, the pharmacological approach will be adopted. Our study will discuss options of pharmacologic treatment choices for cognitive, behavioral, or affective disorders following TBI, providing relevant information related to a structured cognitive rehabilitation service and certainly will offer an alternative for patients and families afflicted by TBI. Traumatic brain injury can cause a variety of potentially disabling psychiatric symptoms and syndromes. Combined behavioral and pharmacological strategies, in the treatment of a set of highly challenging behavioral problems, appears to be essential for good patient recovery.
Full Text Available ABSTRACT Annually, 700,000 people are hospitalized with brain injury acquired after traumatic brain injury (TBI in Brazil. Objective: We aim to review the basic concepts related to TBI, and the most common Behavioral and Psychological Symptoms of Dementia (BPSD findings in moderate and severe TBI survivors. We also discussed our strategies used to manage such patients in the post-acute period. Methods: Fifteen TBI outpatients followed at the Center for Cognitive Rehabilitation Post-TBI of the Clinicas Hospital of the University of São Paulo were submitted to a neurological, neuropsychological, speech and occupational therapy evaluation, including the Mini-Mental State Examination. Rehabilitation strategies will then be developed, together with the interdisciplinary team, for each patient individually. Where necessary, the pharmacological approach will be adopted. Results: Our study will discuss options of pharmacologic treatment choices for cognitive, behavioral, or affective disorders following TBI, providing relevant information related to a structured cognitive rehabilitation service and certainly will offer an alternative for patients and families afflicted by TBI. Conclusion: Traumatic brain injury can cause a variety of potentially disabling psychiatric symptoms and syndromes. Combined behavioral and pharmacological strategies, in the treatment of a set of highly challenging behavioral problems, appears to be essential for good patient recovery.
Tsai, Ming-Che; Chang, Ching-Ping; Peng, Syue-Wei; Jhuang, Kai-Sheng; Fang, Yi-Hsien; Lin, Mao-Tsun; Tsao, Thomas Chang-Yao
Traumatic brain injury (TBI) causes increased release of several mediators from injured and dead cells and elicits microglial activation. Activated microglia change their morphology, migrate to injury sites, and release tumor necrosis factor-alpha (TNF-α) and others. In this study we used a controlled fluid percussion injury model of TBI in the rat to determine whether early (4 h post-injury) or late (4 days post-injury) treatment with MLC 601, a Traditional Chinese Medicine, would affect microglial activation and improve recovery. MLC 601 was chosen for this study because its herbal component MLC 901 was beneficial in treating TBI in rats. Herein, rats with induced TBI were treated with MLC 601 (0.2-0.8 mg/kg) 1 h (early treatment) or 4 day post-injury (late treatment) and then injected once daily for consecutive 2 days. Acute neurological and motor deficits were assessed in all rats the day before and 4 days after early MLC 601 treatment. An immunofluorescence microscopy method was used to count the numbers of the cells colocalized with neuron- and apoptosis-specific markers, and the cells colocalized with microglia- and TNF-α-specific markers, in the contused brain regions 4 days post-injury. An immunohistochemistry method was used to evaluate both the number and the morphological transformation of microglia in the injured areas. It was found that early treatment with MLC 601 had better effects in reducing TBI-induced cerebral contusion than did the late therapy with MLC 601. Cerebral contusion caused by TBI was associated with neurological motor deficits, brain apoptosis, and activated microglia (e.g., microgliosis, amoeboid microglia, and microglial overexpression of TNF-α), which all were significantly attenuated by MLC 601 therapy. Our data suggest that MLC 601 is a promising agent for treatment of TBI in rats.
Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François
Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue
Lam, Tina I; Bingham, Deborah; Chang, Ting Ju; Lee, Chih Cheng; Shi, Jian; Wang, Dongmin; Massa, Stephen; Swanson, Raymond A; Liu, Jialing
Effective recovery from functional impairments caused by traumatic brain injury (TBI) requires appropriate rehabilitation therapy. Multiple pathways are involved in secondary injury and recovery suggesting a role for multimodal approaches. Here, we examined the efficacy of the anti-inflammatory agent minocycline and botulinum toxin (botox)-induced limb constraint with structured physical therapy, delivered alone or in combination, after a severe TBI produced by a controlled cortical impact in rats. Minocycline was administered at 25 mg/kg daily for 2 weeks beginning 1 day after TBI or sham surgery. For constraint/physical therapy, botox-type A was injected into the nonaffected forearm muscle 1 day after injury and 2 weeks of physical therapy commenced at 5 days after injury. Functional evaluations were conducted 8 weeks after injury. Minocycline, either as a monotherapy or as combination treatment with botox/physical therapy significantly reduced impairments of spatial learning and memory in the water maze test, whereas botox/physical therapy reduced forelimb motor asymmetry and improved manual dexterity in the cylinder and vermicelli handling tests, A synergistic effect between the 2 treatments was observed when rats performed tasks requiring dexterity. Inflammation was attenuated in the peri-contusion cortex and hippocampus in all TBI groups receiving mono or combination therapies, though there was no significant difference in lesion size among groups. These data provide a rationale for incorporating anti-inflammatory treatment during rehabilitation therapy.
Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh
Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling pathway.
Full Text Available Traumatic brain injury (TBI induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt signaling pathway.Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC, and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro.Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling
Kochanek, Patrick M; Dixon, C Edward; Shellington, David K; Shin, Samuel S; Bayır, Hülya; Jackson, Edwin K; Kagan, Valerian E; Yan, Hong Q; Swauger, Peter V; Parks, Steven A; Ritzel, David V; Bauman, Richard; Clark, Robert S B; Garman, Robert H; Bandak, Faris; Ling, Geoffrey; Jenkins, Larry W
Abstract Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report on blast-induced mild TBI (mTBI) characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head-only exposure to 35 psi in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemical/molecular strategies. Injury produced ∼25% mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2 or 24 h, and brain was sampled in the hippocampus and prefrontal cortex. Hippocampal samples were used to assess gene array (RatRef-12 Expression BeadChip; Illumina, Inc., San Diego, CA) and oxidative stress (OS; ascorbate, glutathione, low-molecular-weight thiols [LMWT], protein thiols, and 4-hydroxynonenal [HNE]). Cortical samples were used to assess neuroinflammation (cytokines, chemokines, and growth factors; Luminex Corporation, Austin, TX) and purines (adenosine triphosphate [ATP], adenosine diphosphate, adenosine, inosine, 2'-AMP [adenosine monophosphate], and 5'-AMP). Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24 h (glial fibrillary acidic protein, vimentin, and complement component 1) with expression patterns bioinformatically consistent with those noted in Alzheimer's disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24 h; by 24 h, HNE was increased. At 2 h, multiple cytokines and chemokines (interleukin [IL]-1α, IL-6, IL-10, and macrophage inflammatory protein 1 alpha [MIP-1α]) were increased; by 24 h, only MIP-1α remained elevated. ATP was not depleted, and adenosine correlated with 2'-cyclic AMP (cAMP), and not 5'-cAMP. Our data reveal (1) gene-array alterations similar to disorders of
Yang, Bo; Wang, Zhe; Sheng, Chenxia; Wang, Yang; Zhou, Jing; Xiong, Xin-gui; Peng, Weijun
Recently, a number of studies conducted and published in China have suggested that traditional Chinese medicine compound recipe (TCMCR) may be beneficial in the treatment of experimental traumatic brain injury (TBI). In this study, we conducted a systematic review and meta-analysis of the efficacy of TCMCR in TBI model with weight drop method to provide robust evidence on the effects of TCMCR and to determine whether TCMCR can be recommended for routine treatment or considered as a standard treatment for TBI. We identified eligible studies by searching five electronic databases on April 1, 2014, and pooled the data using the random-effects model. Results were reported in terms of standardized mean difference (SMD). We also calculated statistical heterogeneity, evaluated the studies' methodological quality and investigated the presence of publication bias. Totally, 187 relevant publications were searched from databases, 25 of which met our inclusion criteria. The overall methodological quality of the most studies was poor, and there was evidence of statistical heterogeneity among studies along with small-study effects. Meta-analysis showed statistically significant effects indicating that TCMCR has a beneficial effect on TBI. Despite the limitations, we concluded that TCMCR may reduce brain water content, improve BBB permeability, and decrease TNF-α/NO expression after experimental TBI in terms of overall efficacy. However, our review also indicates that more well-designed and well-reported animal studies are needed.
Hay, Jennifer; Johnson, Victoria E.; Smith, Douglas H.; Stewart, William
Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of non-boxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article. PMID:26772317
Chesire, David J.; Buckley, Valerie A.; Canto, Angela I.
The incidence of brain injuries, as well as their impact on individuals who sustain them, has received growing attention from American media in recent years. This attention is likely the result of high profile individuals suffering brain injuries. Greater public awareness of traumatic brain injuries (TBIs) has also been promoted by sources such as…
Full Text Available Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI, and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1 has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI.
Full Text Available Marcelo Schwarzbold1, Alexandre Diaz1, Evandro Tostes Martins2, Armanda Rufino1, Lúcia Nazareth Amante1,3, Maria Emília Thais1, João Quevedo4, Alexandre Hohl1, Marcelo Neves Linhares1,5,6, Roger Walz1,61Núcleo de Pesquisas em Neurologia Clínica e Experimental (NUPNEC, Departamento de Clínica Médica, Hospital Universitário, UFSC, Florianópolis, SC, Brazil; 2Unidade de Terapia Intensiva, Hospital Governador Celso Ramos, Florianópolis, SC, Brazil; 3Departamento de Enfermagem, UFSC, Florianópolis, SC, Brazil; 4Laboratório de Neurociências, UNESC, Criciúma, SC, Brazil; 5Departamento de Cirurgia, Hospital Universitário, UFSC, Florianópolis, SC, Brazil; 6Centro de Cirurgia de Epilepsia de Santa Catarina (CEPESC, Hospital Governador Celso Ramos, Florianópolis, SC, BrazilAbstract: Psychiatric disorders after traumatic brain injury (TBI are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed.Keywords: psychiatric disorders, traumatic brain injury, neuropsychiatry, diagnostic, epidemiology, pathophysiology
Full Text Available Mari Viola-Saltzman, Camelia Musleh Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA Abstract: Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. Keywords: traumatic brain injury, insomnia, hypersomnia, sleep apnea, periodic limb movement disorder, fatigue
Patet, Camille; Suys, Tamarah; Carteron, Laurent; Oddo, Mauro
Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome.
12(6): p. 564-574. 71. Lee, M.-C., J.W. Melvin , and K. Ueno, Finite element analysis of traumatic subdural hematoma. 1987, SAE Technical Paper. 72...130. Moss , W.C., M.J. King, and E.G. Blackman, Skull Flexure from Blast Waves: A Mechanism for Brain Injury with Implications for Helmet Design
Zheng Gang Zhang
Full Text Available Stroke and traumatic brain injury (TBI damage white and grey matter. Loss of oligodendrocytes and their myelin, impairs axonal function. Remyelination involves oligodendrogenesis during which new myelinating oligodendrocytes are generated by differentiated oligodendrocyte progenitor cells (OPCs. This article briefly reviews the processes of oligodendrogenesis in adult rodent brains, and promising experimental therapies targeting the neurovascular unit that reduce oligodendrocyte damage and amplify endogenous oligodendrogenesis after stroke and TBI.
Mollayeva, Tatyana; Kendzerska, Tetyana; Mollayeva, Shirin
. CONCLUSIONS: The review will summarize the current knowledge in the field with the aim of increasing understanding and guiding future research on the associations between fatigue and clinically important factors, as well as the consequences of fatigue in traumatic brain injury. PROSPERO registry number: CRD......BACKGROUND: Despite strong indications that fatigue is the most common and debilitating symptom after traumatic brain injury, little is known about its frequency, natural history, or relation to other factors. The current protocol outlines a strategy for a systematic review that will identify......, assess, and critically appraise studies that assessed predictors for fatigue and the consequences of fatigue on at least two separate time points following traumatic brain injury. METHODS/DESIGN: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CINAHL, and PsycINFO will be systematically...
Parmenion P. Tsitsopoulos
Full Text Available Traumatic brain injury (TBI survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP. Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ peptides, a hallmark finding in Alzheimer’s disease (AD. At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF using cerebral microdialysis and/or cerebrospinal fluid (CSF following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long
Golan, Jeff Dror; Marcoux, Judith; Golan, Eyal; Schapiro, Robert; Johnston, Karen M; Maleki, Mahammed; Khetarpal, Suneel; Jacques, Line
We sought to evaluate the effect alcohol intoxication may have had in nonsurgically treated patients with severe traumatic brain injury. The Montreal General Hospital Traumatic Brain Injury Registry was used to identify all adult patients with a Glasgow Coma Scale score toxic blood alcohol levels (BAL > or =21.7 mmol/L), 24 were alcohol negative (BAL Coma Scale score < or =8. Intoxicated patients had a mean delay of 151 minutes more in the insertion time of an intracranial pressure monitoring device, compared with alcohol-negative patients. Alcohol was a confounding factor in the treatment of some of our patients.
Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury
Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne
gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 microm gold particles near the lesion. Placebo......Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic......-treated mice subjected to cryo-lesion served as controls. The effects of gold-treatment were investigated by examining gold-induced growth factor expression (VEGF and FGF) in the first two weeks after the insult, and the extent of the neurostimulatory effect of gold was explored by comparing cell proliferation...
Philips, M F; Mattiasson, G; Wieloch, T; Björklund, A; Johansson, B B; Tomasevic, G; Martínez-Serrano, A; Lenzlinger, P M; Sinson, G; Grady, M S; McIntosh, T K
Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.
Kamnaksh, Alaa; Kovesdi, Erzsebet; Kwon, Sook-Kyung; Wingo, Daniel; Ahmed, Farid; Grunberg, Neil E; Long, Joseph; Agoston, Denes V
The overlapping pathologies and functional outcomes of blast-induced TBI (bTBI) and stress-related neurobehavioral disorders like post-traumatic stress disorder (PTSD) are significant military health issues. Soldiers are exposed to multiple stressors with or without suffering bTBI, making diagnosis and treatment as well as experimental modeling of bTBI a challenge. In this study we compared anxiety levels of Naïve rats to ones that were exposed to each of the following conditions daily for 4 consecutive days: C I: transportation alone; C II: transportation and anesthesia; C III: transportation, anesthesia, and blast sounds; Injured: all three variables plus mild blast overpressure. Following behavioral testing we analyzed sera and select brain regions for protein markers and cellular changes. C I, C II, and C III animals exhibited increased anxiety, but serum corticosterone levels were only significantly elevated in C III and Injured rats. C III and Injured animals also had elevated interferon-γ (IFN-γ) and interleukin-6 (IL-6) levels in the amygdala (AD) and ventral hippocampus (VHC). Glial fibrillary acidic protein (GFAP) levels were only significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured animals; they showed an apparent increase in ionized calcium-binding adapter molecule (Iba1) and GFAP immunoreactivity, as well as increased numbers of TUNEL-positive cells in the VHC. Our findings demonstrate that experimental conditions, particularly the exposure to blast acoustics, can increase anxiety and trigger specific behavioral and molecular changes without injury. These findings should be taken into consideration when designing bTBI studies, to better understand the role of stressors in the development of post-traumatic symptoms, and to establish a differential diagnosis for PTSD and bTBI.
Background: Traumatic brain injury is an important aspect of paediatric trauma because of its contribution to mortality ant post trauma seqeulae. Management of traumatic brain injury remains a challenge to surgeons, especially in developing countries. This study aims to determine the pattern of traumatic brain injury among ...
persons, and leaves 99,000 persons permanently disabled . The total cost for treatment and rehabilitation of patients with brain injuries is...registry based or retrospective or include only secondary insults that occur in the intensive care unit ( ICU ) setting. Most prior investigations have...in the surgical and neurosurgical ICU diagnosed with a traumatic brain injury requiring a diagnostic procedure were eligible for the study. The study
Cross, Donna J.; Garwin, Gregory G.; Cline, Marcella M.; Richards, Todd L.; Yarnykh, Vasily; Mourad, Pierre D.; Ho, Rodney J.Y.; Minoshima, Satoshi
Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Ca...
Carpenter, KLH; Young, AMH; Hutchinson, PJ
Purpose of review: Here, we review the present state-of-the-art of microdialysis for monitoring patients with severe traumatic brain injury, highlighting the newest developments. Microdialysis has evolved in neurocritical care to become an established bedside monitoring modality that can reveal unique information on brain chemistry. Recent findings: A major advance is recent consensus guidelines for microdialysis use and interpretation. Other advances include insight obtained from microdi...
Dec 23, 2011 ... Objective: Traumatic brain injury (TBI) is a public health problem and is associated with many complications. However little is known about the psychiatric sequelae of TBI in Nigeria. This study described the pattern and determinants of psychiatric sequelae among subjects with TBI. Materials and Methods: ...
Sánchez-Catasús, Carlos A; Vállez Garcia, David; Le Riverend Morales, Eloísa; Galvizu Sánchez, Reinaldo; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; de Vries, Erik FJ; van Waarde, Aren; Leenders, Klaus L
This chapter provides an up-to-date review of nuclear medicine neuroimaging in traumatic brain injury (TBI). 18F-FDG PET will remain a valuable tool in researching complex mechanisms associated with early metabolic dysfunction in TBI. Although evidence-based imaging studies are needed, 18F-FDG PET
Fowler, Marc; McCabe, Paul C.
Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in the United States for individuals below the age of 45. Current estimates from the Center for Disease Control (CDC) indicate that at least 1.4 million Americans sustain a TBI annually. TBI affects 475,000 children under age 14 each year in the United States alone.…
Marini, Andrea; Galetto, Valentina; Zampieri, Elisa; Vorano, Lorenza; Zettin, Marina; Carlomagno, Sergio
Persons with traumatic brain injury (TBI) often show impaired linguistic and/or narrative abilities. The present study aimed to document the features of narrative discourse impairment in a group of adults with TBI. 14 severe TBI non-aphasic speakers (GCS less than 8) in the phase of neurological stability and 14 neurologically intact participants…
Jenkins, Peter O; Mehta, Mitul A; Sharp, David J
Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
Carpenter, Keri L H; Young, Adam M H; Hutchinson, Peter J
Here, we review the present state-of-the-art of microdialysis for monitoring patients with severe traumatic brain injury, highlighting the newest developments. Microdialysis has evolved in neurocritical care to become an established bedside monitoring modality that can reveal unique information on brain chemistry. A major advance is recent consensus guidelines for microdialysis use and interpretation. Other advances include insight obtained from microdialysis into the complex, interlinked traumatic brain injury disorders of electrophysiological changes, white matter injury, inflammation and metabolism. Microdialysis has matured into being a standard clinical monitoring modality that takes its place alongside intracranial pressure and brain tissue oxygen tension measurement in specialist neurocritical care centres, as well as being a research tool able to shed light on brain metabolism, inflammation, therapeutic approaches, blood-brain barrier transit and drug effects on downstream targets. Recent consensus on microdialysis monitoring is paving the way for improved neurocritical care protocols. Furthermore, there is scope for future improvements both in terms of the catheters and microdialysate analyser technology, which may further enhance its applicability.
Salzar, Robert S; Treichler, Derrick; Wardlaw, Andrew; Weiss, Greg; Goeller, Jacques
The potential of blast-induced traumatic brain injury from the mechanism of localized cavitation of the cerebrospinal fluid (CSF) is investigated. While the mechanism and criteria for non-impact blast-induced traumatic brain injury is still unknown, this study demonstrates that local cavitation in the CSF layer of the cranial volume could contribute to these injuries. The cranial contents of three post-mortem human subject (PMHS) heads were replaced with both a normal saline solution and a ballistic gel mixture with a simulated CSF layer. Each were instrumented with multiple pressure transducers and placed inside identical shock tubes at two different research facilities. Sensor data indicates that cavitation may have occurred in the PMHS models at pressure levels below those for a 50% risk of blast lung injury. This study points to skull flexion, the result of the shock wave on the front of the skull leading to a negative pressure in the contrecoup, as a possible mechanism that contributes to the onset of cavitation. Based on observation of intracranial pressure transducer data from the PMHS model, cavitation onset is thought to occur from approximately a 140 kPa head-on incident blast.
Viola-Saltzman, Mari; Watson, Nathaniel F.
Sleep disturbance is common following traumatic brain injury (TBI), affecting 30–70% of individuals, many occurring after mild injuries. Insomnia, fatigue and sleepiness are the most frequent post-TBI sleep complaints with narcolepsy (with or without cataplexy), sleep apnea (obstructive and/or central), periodic limb movement disorder, and parasomnias occurring less commonly. In addition, depression, anxiety and pain are common TBI co-morbidities with substantial influence on sleep quality. T...
Hartings, Jed A; Vidgeon, Steven; Strong, Anthony J
OBJECT: Mass lesions from traumatic brain injury (TBI) often require surgical evacuation as a life-saving measure and to improve outcomes, but optimal timing and surgical technique, including decompressive craniectomy, have not been fully defined. The authors compared neurosurgical approaches...... enrolled in the Co-Operative Studies on Brain Injury Depolarizations (COSBID) at King's College Hospital (KCH, n = 27) and Virginia Commonwealth University (VCU, n = 24) from July 2004 to March 2010. Subdural electrode strips were placed at the time of surgery for subsequent electrocorticographic...
Full Text Available Traumatic brain injury (TBI occurs when a sudden trauma causes brain damage. Depending on the severity, outcome can be anything from complete recovery to permanent disability or death. Emergency medical services play a dominant role in provision of primary care at the site of injury. Since little can be done to reverse the initial brain damage due to trauma, attempts to prevent further brain damage and stabilize the patient before he can be brought to a specialized trauma care centre play a pivotal role in the final outcome. Recognition and early treatment of hypoten-sion, hypoxemia, and hypoglycemia, objective neurological assessment based on GCS and pupils, and safe transport to an optimal care centre are the key elements of prehospital care of a TBI patient.
Silachev, D N; Plotnikov, E Yu; Babenko, V A; Danilina, T I; Zorov, L D; Pevzner, I B; Zorov, D B; Sukhikh, G T
We compared the efficiency of delivery of multipotent mesenchymal stem cells into the brain after their intravenous and intra-arterial injection. Analysis of the therapeutic effects of cells after experimental traumatic brain injury revealed improvement of the neurological status and motor functions of the damaged hemisphere, the effect being more pronounced after intraarterial injection of cells. Intra-arterial administration was followed by rapid infiltration of the cells into the brain tissue and their number considerably surpassed that after intravenous infusion. Targeted delivery of multipotent mesenchymal stromal cells into the brain after their injection into the carotid arteries substantially potentiated their neuroprotective effects in traumatic brain injury.
Full Text Available Traumatic brain injury (TBI initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4- and nuclear factor kappa B (NF-κB-related signaling pathways in mice following TBI.Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg(-1 or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg(-1 wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2.Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.
... does not include children with brain injuries that are congenital or degenerative or caused by birth... 45 Public Welfare 4 2010-10-01 2010-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A...
Vázquez-Solís, María G; Villa-Manzano, Alberto I; Sánchez-Mosco, Dalia I; Vargas-Lares, José de Jesús; Plascencia-Fernández, Irma
traumatic brain injury is a main cause of hospital admission and death in children. Our objective was to identify prognostic factors of pediatric traumatic brain injury. this was a dynamic cohort study of traumatic brain injury with 6 months follow-up. The exposition was: mild or moderate/severe traumatic brain injury, searching for prognosis (morbidity-mortality and decreased Glasgow scale). Relative risk and logistic regression was estimated for prognostic factors. we evaluated 440 patients with mild traumatic brain injury and 98 with moderate/severe traumatic brain injury. Morbidity for mild traumatic brain injury was 1 %; for moderate/severe traumatic brain injury, 5 %. There were no deaths. Prognostic factors for moderate/severe traumatic brain injury were associated injuries (RR = 133), fractures (RR = 60), street accidents (RR = 17), night time accidents (RR = 2.3) and weekend accidents (RR = 2). Decreased Glasgow scale was found in 9 %, having as prognostic factors: visible injuries (RR = 3), grown-up supervision (RR = 2.5) and time of progress (RR = 1.6). there should be a prognosis established based on kinetic energy of the injury and not only with Glasgow Scale.
Severe cases of traumatic brain injury (TBI) require neurocritical care, the goal being to stabilize hemodynamics and systemic oxygenation to prevent secondary brain injury. It is reported that approximately 45 % of dysoxygenation episodes during critical care have both extracranial and intracranial causes, such as intracranial hypertension and brain edema. For this reason, neurocritical care is incomplete if it only focuses on prevention of increased intracranial pressure (ICP) or decreased cerebral perfusion pressure (CPP). Arterial hypotension is a major risk factor for secondary brain injury, but hypertension with a loss of autoregulation response or excess hyperventilation to reduce ICP can also result in a critical condition in the brain and is associated with a poor outcome after TBI. Moreover, brain injury itself stimulates systemic inflammation, leading to increased permeability of the blood-brain barrier, exacerbated by secondary brain injury and resulting in increased ICP. Indeed, systemic inflammatory response syndrome after TBI reflects the extent of tissue damage at onset and predicts further tissue disruption, producing a worsening clinical condition and ultimately a poor outcome. Elevation of blood catecholamine levels after severe brain damage has been reported to contribute to the regulation of the cytokine network, but this phenomenon is a systemic protective response against systemic insults. Catecholamines are directly involved in the regulation of cytokines, and elevated levels appear to influence the immune system during stress. Medical complications are the leading cause of late morbidity and mortality in many types of brain damage. Neurocritical care after severe TBI has therefore been refined to focus not only on secondary brain injury but also on systemic organ damage after excitation of sympathetic nerves following a stress reaction.
Finnie, J W
Traumatic brain injury constitutes a significant proportion of cases requiring forensic examination, and it encompasses (1) blunt, nonmissile head injury, especially involving motor vehicle accidents, and (2) penetrating, missile injury produced by a range of high- and lower-velocity projectiles. This review examines the complex pathophysiology and biomechanics of both types of neurotrauma and assesses the macroscopic and histologic features of component lesions, which may be used to determine the cause and manner of death resulting from an intentional assault or accident. Estimation of the survival time postinjury by pathologic examination is also important where malicious head injury is suspected, in an attempt to ascertain a time at which the traumatic event might have been committed, thereby evaluating the authenticity of statements made by the alleged perpetrator. © The Author(s) 2015.
Erin D. Bigler
Full Text Available Depending on severity, traumatic brain injury (TBI induces immediate neuropathological effects that in the mildest form may be transient but as severity increases results in neural damage and degeneration. The first phase of neural degeneration is explainable by the primary acute and secondary neuropathological effects initiated by the injury; however, neuroimaging studies demonstrate a prolonged period of pathological changes that progressively occur even during the chronic phase. This review examines how neuroimaging may be used in TBI to understand (1 the dynamic changes that occur in brain development relevant to understanding the effects of TBI and how these relate to developmental stage when the brain is injured, (2 how TBI interferes with age-typical brain development and the effects of aging thereafter, and (3 how TBI results in greater frontotemporolimbic damage, results in cerebral atrophy, and is more disruptive to white matter neural connectivity. Neuroimaging quantification in TBI demonstrates degenerative effects from brain injury over time. An adverse synergistic influence of TBI with aging may predispose the brain injured individual for the development of neuropsychiatric and neurodegenerative disorders long after surviving the brain injury.
Full Text Available ABSTRACT Traumatic brain injury (TBI represents a significant public health problem in modern societies. It is primarily a consequence of traffic-related accidents and falls. Other recently recognized causes include sports injuries and indirect forces such as shock waves from battlefield explosions. TBI is an important cause of death and lifelong disability and represents the most well-established environmental risk factor for dementia. With the growing recognition that even mild head injury can lead to neurocognitive deficits, imaging of brain injury has assumed greater importance. However, there is no single imaging modality capable of characterizing TBI. Current advances, particularly in MR imaging, enable visualization and quantification of structural and functional brain changes not hitherto possible. In this review, we summarize data linking TBI with dementia, emphasizing the imaging techniques currently available in clinical practice along with some advances in medical knowledge.
Ramalho, Joana; Castillo, Mauricio
Traumatic brain injury (TBI) represents a significant public health problem in modern societies. It is primarily a consequence of traffic-related accidents and falls. Other recently recognized causes include sports injuries and indirect forces such as shock waves from battlefield explosions. TBI is an important cause of death and lifelong disability and represents the most well-established environmental risk factor for dementia. With the growing recognition that even mild head injury can lead to neurocognitive deficits, imaging of brain injury has assumed greater importance. However, there is no single imaging modality capable of characterizing TBI. Current advances, particularly in MR imaging, enable visualization and quantification of structural and functional brain changes not hitherto possible. In this review, we summarize data linking TBI with dementia, emphasizing the imaging techniques currently available in clinical practice along with some advances in medical knowledge.
Brownell, Hiram; Lundgren, Kristine; Cayer-Meade, Carol; Milione, Janet; Katz, Douglas I; Kearns, Kevin
To improve oral interpretation of metaphors by patients with traumatic brain injury (TBI). Both single subject experimental design and group analysis. Patients' homes. Eight adult patients with moderate to severe traumatic brain injury sustained 3 to 20 years before testing. The Metaphor Training Program consisted typically of 10 baseline sessions, 3 to 9 1-hour sessions of structured intervention, and 10 posttraining baseline sessions. Training used extensive practice with simple graphic displays to illustrate semantic associations. Quality of orally produced metaphor interpretation and accuracy of line orientation judgments served as dependent measures obtained during baseline, training, posttraining, and at a 3- to 4-month follow-up. Untrained line orientation judgments provided a control measure. Group data showed significant improvement in metaphor interpretation but not in line orientation. Six of 8 patients individually demonstrated significant improvement in metaphor interpretation. Gains persisted for 3 of the 6 patients at the 3- to 4-month follow-up. The Metaphor Training Program can improve cognitive-communication performance for individuals with moderate to severe traumatic brain injury. Results support the potential for treating patients' residual cognitive-linguistic deficits.
Chauhan, Neelima B
Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.
Ling, Geoffrey S. F.; Hawley, Jason; Grimes, Jamie; Macedonia, Christian; Hancock, James; Jaffee, Michael; Dombroski, Todd; Ecklund, James M.
Traumatic brain injury (TBI) is common and especially with military service. In Iraq and Afghanistan, explosive blast related TBI has become prominent and is mainly from improvised explosive devices (IED). Civilian standard of care clinical practice guidelines (CPG) were appropriate has been applied to the combat setting. When such CPGs do not exist or are not applicable, new practice standards for the military are created, as for TBI. Thus, CPGs for prehospital care of combat TBI CPG  and mild TBI/concussion  were introduced as was a DoD system-wide clinical care program, the first large scale system wide effort to address all severities of TBI in a comprehensive organized way. As TBI remains incompletely understood, substantial research is underway. For the DoD, leading this effort are The Defense and Veterans Brain Injury Center, National Intrepid Center of Excellence and the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. This program is a beginning, a work in progress ready to leverage advances made scientifically and always with the intent of providing the best care to its military beneficiaries.
Kim, Dae Jung; Kim, Hyun Sook; Jeong, Min Sun; Kim, Deok Ryeong; Cho, Young Kwon; Choi, Yun Sun [Eulji Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of)
Only a few studies have been reported on the MR contrast enhancement and the apparent diffusion coefficient (ADC) findings of the post-traumatic lesion of the brain. We report a case of the venous ischemia in the left frontal lobe observed in the MRI obtained one day after the incidence of trauma. Considering the presented slight increase in the ADC, the vasogenic edema was thought to be the major mechanism of the venous ischemia and excitotoxic injury. In spite of a slight increase in the ADC, the hyperintensity in the diffusion weighted imaging and contrast-enhanced areas eventually changed into hemorrhagic lesions.
Odgaard, Lene; Poulsen, Ingrid; Kammersgaard, Lars Peter
PURPOSE: To identify all hospitalized patients surviving severe traumatic brain injury (TBI) in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS: Patients surviving severe TBI were identified from...... severe TBI were admitted to HS-rehabilitation. Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark...
Full Text Available Almost half of the people suffering traumatic brain injury (TBI may later be diagnosed with psychiatric disorders. The literature (PubMed, IndMed of past 30 years on psychiatric disturbances associated with TBI is reviewed. The authors highlight the close link between head injury and psychiatry and provide an overview of the epidemiology, risk-factors, and mechanisms of psychiatric sequelae including, cognitive deficits, substance abuse, psychoses, mood disorders, suicide, anxiety disorders, dissociative disorders, post-concussion syndrome, and personality changes following head injury. The various psychiatric sequelae are briefly discussed.
Vella, Michael A; Crandall, Marie L; Patel, Mayur B
Traumatic brain injury (TBI) is a leading cause of death and disability in patients with trauma. Management strategies must focus on preventing secondary injury by avoiding hypotension and hypoxia and maintaining appropriate cerebral perfusion pressure (CPP), which is a surrogate for cerebral blood flow. CPP can be maintained by increasing mean arterial pressure, decreasing intracranial pressure, or both. The goal should be euvolemia and avoidance of hypotension. Other factors that deserve important consideration in the acute management of patients with TBI are venous thromboembolism, stress ulcer, and seizure prophylaxis, as well as nutritional and metabolic optimization. Published by Elsevier Inc.
Nygren-de Boussard, Catharina; Holm, Lena W; Cancelliere, Carol
OBJECTIVE: To synthesize the best available evidence regarding the impact of nonsurgical interventions on persistent symptoms after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) with terms including "rehabilitation." Inclusion criteria were...... original, peer-reviewed research published in English and other languages. References were also identified from the bibliographies of eligible articles. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30...
During the nineteenth century, physicians either discovered or invented a variety of clinical autobiography called "traumatic memory." Freud produced two versions of this memory, the final version in the 1920s. A revolutionary nosology (DSM-III), adopted in 1980, promised to extirpate Freud and the concept of neurosis from American psychiatry. However, it made a tacit exception for Freud's concept of traumatic neurosis, renaming it "postraumatic stress disorder." The following decades have been a period of intense clinical and scientific interest in this disorder. An influential research program has investigated traumatic neurosis and its brain through variations in cortisol excretion. I describe the history of this program, and examine its distinctive knowledge product. its running narrative of its achievements. The narrative's structure is analyzed and found to resemble a crossword puzzle constructed from heterogenous kinds of inference, recalling The Interpretation of Dreams. My conclusion is that, far from extirpating Freud's neurosis, biological research has secured a place for it in today's post-Freudian psychiatry.
Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685
Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk
OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... an uptake area of 2.4 million in Denmark were included at admission to a regional brain injury unit (BIU), on average 19 days after injury. Patients in the retrospective study used for comparison were randomly chosen from the national hospital register. RESULTS AND CONCLUSIONS: Out of 117 patients...... post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge...
Robert A. Scranton
Full Text Available Pituitary dysfunction following traumatic brain injury (TBI is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.
Clayton, E; Kinley-Cooper, S K; Weber, R A; Adkins, D L
There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. This article is part of a Special Issue entitled SI:Brain injury and recovery. Copyright © 2016. Published by Elsevier B.V.
Jared F Benge
Full Text Available Moderate to severe traumatic brain injury (TBI is one of the leading causes of acquired epilepsy. Prophylaxis for seizures is the standard of care for individuals with moderate to severe injuries at risk for developing seizures, though relatively limited comparative data is available to guide clinicians in their choice of agents. There have however been experimental studies which demonstrate potential neuroprotective qualities of levetiracetam after TBI, and in turn there is hope that eventually such agents may improve neurobehavioral outcomes post-TBI. This mini-review summarizes the available studies and suggests areas for future studies.
Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E
Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident.
Full Text Available Background/Aims: Neural stem cells (NSCs hold considerable potential as a therapeutic tool for repair of the damaged nervous system. In the current study, we examined whether transplanted N-acetyl aspartyl-glutamate synthetase (NAAGS-activated NSCs (NAAGS/NSCs further improve neurological recovery following traumatic brain injury (TBI in Sprague-Dawley rats. Methods: Animals received TBI and stereotactic injection of NSCs, NAAGS/NSCs or phosphate buffered saline without cells (control into the injured cortex. NAAGS protein expression was detected through western blot analysis. Dialysate NAAG levels were analyzed with radioimmunoassay. Cell apoptosis was detected via TUNEL staining. The expression levels of specific pro-inflammatory cytokines were detected with enzyme-linked immunosorbent assay. Results: Groups with transplanted NSCs and NAAGS/NSCs displayed significant recovery of the motor behavior, compared to the control group. At 14 and 21 days post-transplantation, the motor behavior in NAAGS/NSC group was significantly improved than that in NSC group (pConclusion: Our results collectively demonstrate that NAAGS/NSCs provide a more powerful autoplastic therapy for the injured nervous system.
Full Text Available Introduction & objective: Despite of young and adolescence intent to the boxing sport, because of dominant aggression and direct blows contact to head, face and central nervous system, it is continuously criticize by different groups. The groups of sporting and physician conventions are distinguished boxing with physical and neuropsychological disorders and some groups believe that side effects of this sport are not more than other sports. For this base the aim of this study was to determine the chronic traumatic brain injury in a group amateur boxers.Materials & Methods: In a case-control study, three groups of sport men were considered, each group contained 20 randomly selected cases. The first group were amateur boxers with 4 years minimal activity(directly has been presented to the head blows, second group were amateur soccer players with 4 years minimal activity(has been presented to the not very severe head blows, third group were non athlete subjects .The groups were matched in weight, height, age and education .To understand brain disorder interview by medicine method has been used, then Wiskancin, Bonardele, Bender geshtalt, Kim karad visual memory, Benton and wechler memory (Alef type tests has been performed and EEG has got in the same hour and condition.Results: The homogeneity of between group variances was gained by the statistical method. Also between structural–visual abilities neuropsychological aspect in groups, significant difference has been gained (p= 0.000. In Kim karad visual memory test at the mild and long term visual memory deficit, significant differences between three groups was observed (P= 0.000, P=0.009 that least score has been belonged to the boxers. Also in boxers 6 abnormal EEGs is observed.Conclusion: It can be said that of four years amateur boxing can affect on boxers visual and memory perception and their spatial orientation. Additionally our study have showed that amateur boxing has a significant
May, Geoffrey; Benson, Randall; Balon, Richard; Boutros, Nash
Neurofeedback is a form of biofeedback whereby a patient can learn to control measurements of brain activity such as those recorded by an electroencephalogram. It has been explored as a treatment for sequelae of traumatic brain injury, although the use of neurofeedback remains outside the realm of routine clinical practice. Google Scholar™ was used to find 22 examples of primary research. Measures of symptom improvement, neuropsychological testing, and changes in subjects' quantitative electroencephalogram were included in the analysis. A single reviewer classified each study according to a rubric devised by 2 societies dedicated to neurofeedback research. All studies demonstrated positive findings, in that neurofeedback led to improvement in measures of impairment, whether subjective, objective, or both. However, placebo-controlled studies were lacking, some reports omitted important details, and study designs differed to the point where effect size could not be calculated quantitatively. Neurofeedback is a promising treatment that warrants double-blind, placebo-controlled studies to determine its potential role in the treatment of traumatic brain injury. Clinicians can advise that some patients report improvement in a wide range of neuropsychiatric symptoms after undergoing neurofeedback, although the treatment remains experimental, with no standard methodology.
Hart, Tessa; Kozlowski, Allan; Whyte, John
functional levels received more treatment and more treatment was associated with slower recovery, presumably because treatment was allocated according to need. Thus, effects of treatment on outcome could not be disentangled from effects of case mix factors. CONCLUSIONS: FIM gain during inpatient recovery......OBJECTIVE: To examine person, injury, and treatment characteristics associated with recovery trajectories of people with severe traumatic brain injury (TBI) during inpatient rehabilitation. DESIGN: Observational prospective longitudinal study. SETTING: Two specialized inpatient TBI rehabilitation...... recovery was best modeled with linear, cubic, and quadratic components: relatively steep recovery was followed by deceleration of improvement, which attenuated prior to discharge. Slower recovery was associated with older age, longer coma, and interruptions to rehabilitation. Patients admitted at lower...
A sample of 476 male sexual offenders, seen at a university psychiatric hospital for forensic assessment, was examined for the incidence of traumatic head injuries. A total of 49.3% had sustained head injuries that led to unconsciousness and of these 22.5% sustained significant neurological insults. A major causative factor was motor vehicle accidents, but lifestyle variables including alcohol and drug abuse and history of violence also contributed. The brain-injured group was convicted for a wide range of sexual offenses and was comparable to the non-injured group in this respect, but tended more often to offend against adults than against children and to show somewhat more exhibiting and polymorphous sexual behavior. In spite of the serious legal implications for these men and the additional distress to their families, psychologists, psychiatrists, and the professional literature have been relatively silent on the subject which calls for more attention to sexual behavior as part of assessments and treatment planning.
Fortin, Audrey; Lefebvre, Mathilde Beaulieu; Ptito, Maurice
PRIMARY OBJECTIVE: Olfactory functions are not systematically evaluated following traumatic brain injury (TBI). This study aimed at comparing two smell tests that are used in a clinical setting. RESEARCH DESIGN: The University of Pennsylvania Smell Identification Test (UPSIT) and the Alberta Smell...... Test were compared in terms of assessment time, cost and diagnosis. Parameters associated with olfactory loss such as injury severity, type of cerebral lesion and depressive data were considered. Forty-nine TBI patients admitted to an outpatient rehabilitation programme took part in this experiment....... RESULTS: The scores of the two smell tests were significantly correlated. Both tests indicated that patients with frontal lesion performed significantly worse than patients with other types of lesion. Mood and injury severity were not associated with olfactory impairment when age was taken into account...
Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.
Full Text Available Traumatic brain injury is one of the major causes of morbidity and mortality in children. The anatomical features, physiological response to injury, neuronal development, and low myelination in children cause different clinical features compared to the adult traumatic brain injury. Our aim is to study the incidence, predisposing factors, clinical presentations, and outcome in pediatric head injuries. The patients included in this retrospective study are under the age of 14 years admitted in the Neurosurgery Department of King George Hospital, Visakhapatnam, which is a tertiary care centre. The study period is two years’ duration from 1.1.2013 to 31.12.2014. Data collected on the basis of history, physical examination, base line investigations, and the plain CT scan is all cases. The pediatric patients were 226 in total 1643 case of head injury cases. There were 64.6% (n=146 males and 35.4% (n=80 females. The age ranged from 12 days to 14 years. Fall from height was the commonest cause of head injury found in 48.6% (n=110 cases, road traffic accidents (RTA in 34.5% (n=78 and other causes 16.8% (n=38; 49 (21.68% patients had associated injuries. At 55.75% (n=126 cases mild head injury with GCS 13-15 was present and severe head injury with GCS less than 8 in 29 (12.8% patients. The 188 patients are treated conservatively, 38 patients underwent different neurosurgical procedures in which 5 patients died. CONCLUSION: Head injury in pediatric age group carries high risk of morbidity and mortality. Good outcome achieved by early diagnosis and referral from primary care centers to tertiary care centers.
Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury.
Sandra A Acosta
Full Text Available Traumatic brain injury (TBI is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of
Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.
Chen, Xiangrong; Wu, Shukai; Chen, Chunnuan; Xie, Baoyuan; Fang, Zhongning; Hu, Weipeng; Chen, Junyan; Fu, Huangde; He, Hefan
Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological
Konigs, M.; de Kieviet, J.F.; Oosterlaan, J.
Context: Worldwide, millions of patients with traumatic brain injury (TBI) suffer from persistent and disabling intelligence impairment. Post-traumatic amnesia (PTA) duration is a promising predictor of intelligence following TBI. Objectives: To determine (1) the impact of TBI on intelligence
Sinski, Jennifer Blevins
Postsecondary institutions currently face the largest influx of veteran students since World War II. As the number of veteran students who may experience learning problems caused by Post-Traumatic Stress Disorder and/or Traumatic Brain Injury continues to rise, the need for instructional strategies that address their needs increases. Educators may…
haemorrhage, and 6 with subarach- noid hemorrhage from ruptured aneurysm . There were 4 cases of cerebral contusions and a single case of traumatic...B. Goldstein, 2003: Significance of Intracranial Pressure Pulse Morphology in Pediatric Traumatic Brain Injury. IEEE, 2491-2494. Anile, C., H. D
Freire-Aragón, María Dolores; Rodríguez-Rodríguez, Ana; Egea-Guerrero, Juan José
There has been concern for many years regarding the identification of patients with mild traumatic brain injury (TBI) at high risk of developing an intracranial lesion (IL) that would require neurosurgical intervention. The small percentage of patients with these characteristics and the exceptional mortality associated with mild TBI with IL have led to the high use of resources such as computerised tomography (CT) being reconsidered. The various protocols developed for the management of mild TBI are based on the identification of risk factors for IL, which ultimately allows more selective indication or discarding both the CT application and the hospital stay for neurological monitoring. Finally, progress in the study of brain injury biomarkers with prognostic utility in different clinical categories of TBI has recently been incorporated by several clinical practice guidelines, which has allowed, together with clinical assessment, a more accurate prognostic approach for these patients to be established. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Full Text Available Huiling Huang,1 Lin Chen,2,3 Hongyun Huang4–61Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin Neurosurgical Institute, Tianjin, People's Republic of China; 2Medical Center, Tsinghua University, Beijing, People's Republic of China; 3Tsinghua University Yuquan Hospital, Beijing, People's Republic of China; 4General Hospital of Chinese people's Armed Police Forces, 5Beijing Rehabilitation Hospital of Capital Medical University, Beijing, People's Republic of China; 6Beijing Hongtianji Neuroscience Academy, Beijing, People's Republic of ChinaAbstract: Traumatic brain injury (TBI is a leading cause of death and disability from trauma to the central nervous system. Besides the surgical interventions and symptomatic management, the conventional therapies for TBI and its sequelae are still limited. Recently emerging evidence suggests that some neurorestorative treatments appear to have a potential therapeutic role for TBI and improving the patient's quality of life. The current clinical neurorestorative strategies available in TBI include pharmacological treatments (recombinant human interleukin-1 receptor antagonist, amantadine, lithium, and valproate, the neuromodulation treatments (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and low-level laser therapy, cell transplantation (bone marrow stromal cells and umbilical cord stromal cells, and combined neurorehabilitation. In this review, we summarize the recent clinical neurorestorative progress in the management of neurodegeneration as well as cognitive and motor deficits after TBI; indeed further clinical trials are required to provide more robust evidence.Keywords: brain trauma, neurorestorative treatment, cell transplantation, clinical study
Full Text Available The aim of this review is to discuss the basic forms of neuropsychological rehabilitation for patients with traumatic brain injury (TBI. More broadly, we discussed cognitive rehabilitation therapy (CRT which constitutes a fundamental component in therapeutic interaction at many centres worldwide. Equally presented is a comprehensive model of rehabilitation, the fundamental component of which is CRT. It should be noted that the principles of this approach first arose in Poland in the 1970s, in other words, several decades before their appearance in other programmemes. Taken into consideration are four factors conditioning the effectiveness of such a process: comprehensiveness, earlier interaction, universality and its individualized character. A comprehensive programmeme of rehabilitation covers: cognitive rehabilitation, individual and group rehabilitation with the application of a therapeutic environment, specialist vocational rehabilitation, as well as family psychotherapy. These training programmemes are conducted within the scope of the ‘Academy of Life,’ which provides support for the patients in their efforts and shows them the means by which they can overcome existing difficulties. Equally emphasized is the close cooperation of the whole team of specialists, as well as the active participation of the family as an essential condition for the effectiveness of rehabilitation and, in effect, a return of the patient to a relatively normal life. Also presented are newly developing neurothechnologies and the neuromarkers of brain injuries. This enables a correct diagnosis to be made and, as a result, the selection of appropriate methods for neuropsychological rehabilitation, including neurotherapy.
Rickels, E; von Wild, K; Wenzlaff, P
The relationship between severe, moderate and mild traumatic brain injury (TBI) as well as the course of treatment and quality management, were studied in a 1-year prospective study in regions of Hannover and Münster Germany. A total of 6,783 patients were documented at the initial examination (58.4% male, 28.1% children <16 years old) and 63.5% participated in the follow-up survey 1 year after the accident. Of these TBI patients 5,220 (73%) were admitted to hospital for clinical treatment but only 258 (<4%) received inpatient rehabilitation. The incidence of TBI was 332/100,000 inhabitants and according to the Glasgow Coma Scale (GCS) brain injury was mild in 90.9%, severe in 5.2% and moderate in 3.9%. The main cause of injury was a fall (52.5%) followed by a traffic accident (26.3%). In-hospital mortality was 1%. Only 56% of TBI patients were neurological examined and 63% were examined in hospital within the first hour after the accident. An immediate x-ray of the skull with a doubtful evidential value was made in 82%. Of the participants 35.9% were still receiving medical treatment 1 year after the accident although the majority only suffered mild TBI. An overabundance of severe socioeconomic consequences, e.g. loss of job, accommodation, family, were also found following only mild TBI.
Freire, Fabio Rios; Coelho, Fernanda; Lacerda, Juliana Rhein; da Silva, Marcio Fernando; Gonçalves, Vanessa Tome; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Basile, Luis Fernando Hindi; Oliveira, Arthur Maynart Pereira; Paiva, Wellingson Silva; Kanda, Paulo Afonso Medeiros; Anghinah, Renato
Annually, some 500,000 people are hospitalized with brain lesions acquired after traumatic brain injury (TBI) in Brazil. Between 75,000 and 100,000 individuals die within hours of the event and 70,000 to 90,000 evolve to irreversible loss of some neurological function. The principal causes of TBI include motor vehicle accidents (50%), falls (21%), assaults and robberies (12%) and accidents during leisure activities (10%). Within this context, cognitive rehabilitation, a clinical area encompassing interdisciplinary action aimed at recovery as well as compensation of cognitive functions altered as a result of cerebral injury, is extremely important for these individuals. Therefore, the aim of this study was to review the basic concepts related to TBI, including mechanisms of injury, severity levels of TBI, the most common findings in moderate and severe TBI survivors, and the most frequent cognitive impairments following TBI, and also to discuss the strategies used to handle patients post-TBI. The study results yielded relevant information on a structured cognitive rehabilitation service, representing an alternative for patients and families afflicted by TBI, enabling the generation of multiple research protocols.
Ryan, Nicholas P.; Catroppa, Cathy; Godfrey, Celia; Noble-Haeusslein, Linda J.; Shultz, Sandy R.; O'Brien, Terence J.; Anderson, Vicki; Semple, Bridgette D.
Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the emergence, development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. PMID:26949224
Krämer, Tobias; Grob, Theresa; Menzel, Lutz; Hirnet, Tobias; Griemert, Eva; Radyushkin, Konstantin; Thal, Serge C; Methner, Axel; Schaefer, Michael K E
Dimethyl fumarate (DMF) is an immunomodulatory compound to treat multiple sclerosis and psoriasis with neuroprotective potential. Its mechanism of action involves activation of the antioxidant pathway regulator Nuclear factor erythroid 2-related factor 2 thereby increasing synthesis of the cellular antioxidant glutathione (GSH). The objective of this study was to investigate whether post-traumatic DMF treatment is beneficial after experimental traumatic brain injury (TBI). Adult C57Bl/6 mice were subjected to controlled cortical impact followed by oral administration of DMF (80 mg/kg body weight) or vehicle at 3, 24, 48, and 72 h after the inflicted TBI. At 4 days after lesion (dal), DMF-treated mice displayed less neurological deficits than vehicle-treated mice and reduced histopathological brain damage. At the same time, the TBI-evoked depletion of brain GSH was prevented by DMF treatment. However, nuclear factor erythroid 2-related factor 2 target gene mRNA expression involved in antioxidant and detoxifying pathways was increased in both treatment groups at 4 dal. Blood brain barrier leakage, as assessed by immunoglobulin G extravasation, inflammatory marker mRNA expression, and CD45 + leukocyte infiltration into the perilesional brain tissue was induced by TBI but not significantly altered by DMF treatment. Collectively, our data demonstrate that post-traumatic DMF treatment improves neurological outcome and reduces brain tissue loss in a clinically relevant model of TBI. Our findings suggest that DMF treatment confers neuroprotection after TBI via preservation of brain GSH levels rather than by modulating neuroinflammation. © 2017 International Society for Neurochemistry.
Sande, Allison; West, Chad
To review current information regarding the pathophysiology associated with traumatic brain injury (TBI), and to outline appropriate patient assessment, diagnostic, and therapeutic options. TBI in veterinary patients can occur subsequent to trauma induced by motor vehicle accidents, falls, and crush injuries. Primary brain injury occurs at the time of initial impact as a result of direct mechanical damage. Secondary brain injury occurs in the minutes to days following the trauma as a result of systemic extracranial events and intracranial changes. The initial diagnosis is often made based on history and physical examination. Assessment should focus on the cardiovascular and respiratory systems followed by a complete neurologic examination. Advanced imaging may be indicated in a patient that fails to respond to appropriate medical therapy. Primary brain injury is beyond the control of the veterinarian. Therefore, treatment should focus on minimizing the incidence or impact of secondary brain injury. Because of a lack of prospective or retrospective clinical data, treatment recommendations for veterinary TBI patients are primarily based on human and experimental studies and personal experience. Therapeutic guidelines have been developed that center on maintaining adequate cerebral perfusion. Severe head trauma is associated with high mortality in humans and animals. However, dogs and cats have a remarkable ability to compensate for loss of cerebral tissue. It is therefore important not to reach hasty prognostic conclusions based on initial appearance. Many pets go on to have a functional outcome and recover from injury.
U.S. Department of Health & Human Services — The Federal Interagency Traumatic Brain Injury Research (FITBIR) informatics system is an extensible, scalable informatics platform for TBI relevant imaging,...
Blennow, Kaj; Hardy, John; Zetterberg, Henrik
... both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE...
Hartings, Jed A; Bullock, M Ross; Okonkwo, David O
Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50-60% of patients after traumatic brain injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable...
McKee, Ann C.; Robinson, Meghan E.
Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and
Munk, Bo; Jensen, Steen Lund; Olsen, Bo Sanderhoff
The aim of this study was to evaluate changes in stability of the wrist after experimental traumatic triangular fibrocartilage complex lesions.......The aim of this study was to evaluate changes in stability of the wrist after experimental traumatic triangular fibrocartilage complex lesions....
The Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial aims to determine whether the administration of erythropoietin to patients with moderate or severe traumatic brain injury improves patient-centred outcomes.
Gardner, Raquel C.; Yaffe, Kristine
Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion. More severe traumatic brain injury (TBI) is a well-established risk factor for a variety of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Recently, large epidemiological studies have additionally identified MTBI as a risk factor for dementia. The role of MTBI in risk of PD or ALS is less well established. Repet...
To assess the safety of various products, equipment, and vehicles during traumatic events injury risk curves have been developed correlate measurable parameters with risk of injury. The first risk curves to predict head injuries focused on severe head injuries such as skull fractures. These curves were generated by impacting cadaver heads. To understand the biomechanics of mild traumatic brain injuries, cadaver heads have also been used to monitor pressure and strain in the brain during impac...
currently valid 0MB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 12. REPORT TYPE 30-0 6-201 6... hypotension independently increases morbidity and mortality after traumatic brain injury. The goal of all treatments is avoid hypotension and maintain cerebral...perfusion pressure management in· patients with severe traumatic brain injury: preliminary results of a randomized controlled trial. J Trauma Acute Care
Eva Esther Tejerina Alvarez
Increased intracranial pressure is associated with mortality and with unfavorable functional outcomes is patients with severe traumatic brain injury. The main clinical practice guidelines recommend using a number of staggered therapeutic measures. However, although these measures seem to be efficient in reducing intracranial pressure, this effect is not often translated into clinical improvement. This review describes the essential principles of the management of patients with severe traumatic brain injury in intensive care units.
Faden, Alan I; Wu, Junfang; Stoica, Bogdan A; Loane, David J
Traumatic brain injury (TBI) has been linked to dementia and chronic neurodegeneration. Described initially in boxers and currently recognized across high contact sports, the association between repeated concussion (mild TBI) and progressive neuropsychiatric abnormalities has recently received widespread attention, and has been termed chronic traumatic encephalopathy. Less well appreciated are cognitive changes associated with neurodegeneration in the brain after isolated spinal cord injury. Also under-recognized is the role of sustained neuroinflammation after brain or spinal cord trauma, even though this relationship has been known since the 1950s and is supported by more recent preclinical and clinical studies. These pathological mechanisms, manifested by extensive microglial and astroglial activation and appropriately termed chronic traumatic brain inflammation or chronic traumatic inflammatory encephalopathy, may be among the most important causes of post-traumatic neurodegeneration in terms of prevalence. Importantly, emerging experimental work demonstrates that persistent neuroinflammation can cause progressive neurodegeneration that may be treatable even weeks after traumatic injury. © 2015 The British Pharmacological Society.
Ghayoumi, Zahra; Yadegari, Fariba; Mahmoodi-Bakhtiari, Behrooz; Fakharian, Esmaeil; Rahgozar, Mehdi; Rasouli, Maryam
Considering the cognitive and linguistic complexity of discourse production, it is expected that individuals with traumatic brain injury (TBI) should face difficulties in this task. Therefore, clinical examination of discourse has become a useful tool for studying and assessment of communication skills of people suffering from TBI. Among different genres of discourse, persuasive discourse is considered as a more cognitively demanding task. However, little is known about persuasive discourse in individuals suffering from TBI. The purpose of this study was to evaluate the performance of adults with TBI on a task of spoken persuasive discourse to determine the impaired linguistic measures. Thirteen TBI nonaphasic Persian speaking individuals, ranged between 19 to 40 years (Mean = 25.64 years; SD = 6.10) and 59 healthy adults matched by age, were asked to perform the persuasive discourse task. The task included asking the participants to express their opinion on a topic, and after the analysis of the produced discourse, the two groups were compared on the basis of their language productivity, sentential complexity, maze ratio and cohesion ratio. The TBI group produced discourses with less productivity, sentential complexity, cohesion ratio and more maze ratio compared the control group. As it is important to consider acquired communication disorders particularly discourse impairment of brain injured patients along with their other clinical impairments and regarding the fact that persuasive discourse is crucial in academic and social situations, the persuasive discourse task presented in this study could be a useful tool for speech therapists, intending to evaluate communication disorders in patients with TBI.
An 8 yr old spayed female Yorkshire terrier was referred for evaluation of progressive neurological signs after a routine dental prophylaxis with tooth extractions. The patient was circling to the left and blind in the right eye with right hemiparesis. Neurolocalization was to the left forebrain. MRI revealed a linear tract extending from the caudal oropharynx, through the left retrobulbar space and frontal lobe, into the left parietal lobe. A small skull fracture was identified in the frontal bone through which the linear tract passed. Those findings were consistent with iatrogenic trauma from slippage of a dental elevator during extraction of tooth 210. The dog was treated empirically with clindamycin. The patient regained most of its normal neurological function within the first 4 mo after the initial injury. Although still not normal, the dog has a good quality of life. Traumatic brain injury is a rarely reported complication of extraction. Care must be taken while performing dental cleaning and tooth extraction, especially of the maxillary premolar and molar teeth to avoid iatrogenic damage to surrounding structures.
Armstrong, Richard A
Traumatic brain injury (TBI) and its associated concussion are major causes of disability and death. All ages can be affected but children, young adults and the elderly are particularly susceptible. A decline in mortality has resulted in many more individuals living with a disability caused by TBI including those affecting vision. This review describes: (1) the major clinical and pathological features of TBI; (2) the visual signs and symptoms associated with the disorder; and (3) discusses the assessment of quality of life and visual rehabilitation of the patient. Defects in primary vision such as visual acuity and visual fields, eye movement including vergence, saccadic and smooth pursuit movements, and in more complex aspects of vision involving visual perception, motion vision ('akinopsia'), and visuo-spatial function have all been reported in TBI. Eye movement dysfunction may be an early sign of TBI. Hence, TBI can result in a variety of visual problems, many patients exhibiting multiple visual defects in combination with a decline in overall health. Patients with chronic dysfunction following TBI may require occupational, vestibular, cognitive and other forms of physical therapy. Such patients may also benefit from visual rehabilitation, including reading-related oculomotor training and the prescribing of spectacles with a variety of tints and prism combinations. © 2018 Optometry Australia.
Mauritz, Walter; Brazinova, Alexandra; Majdan, Marek; Leitgeb, Johannes
Traumatic brain injury (TBI) is an important cause of preventable deaths. The goal of this study was to provide data on epidemiology of TBI in Austria. Data on all hospital discharges, outpatients, and extra- as well as in-hospital deaths due to TBI were collected from various sources for the years 2009-2011. Population data (number of male/female people per age-group, population of Austrian cities, towns, and villages) for 2009-2011 were collected from the national statistical office. Incidence, case fatality rate(s) (CFR), and mortality rate(s) (MR) were calculated for the whole population and for age groups. Incidence (303/100,000/year), CFR (3.6 %), and MR (11/100,000/year) of TBI in Austria are comparable with those from other European countries. We found a high rate of geriatric TBI. The ratio between male and female cases was 1.4:1 for all cases, and was 2.2:1 for fatal cases. The most common mechanism was falls; traffic accidents accounted for only 7 % of the cases. Males died more frequently from traffic accidents and suicides, and females died more frequently from falls. CFRs and MRs increased with increasing age. CFRs were higher in patients from less populated areas, and MRs were lower in cases who lived closer to hospitals that admitted TBI. The high rate of geriatric TBI warrants better prevention of falls in this age group.
Rasmussen, Mikkel Mylius; Clemmensen, Dorte; Jensen, Steffen Skov
Patients with mild traumatic brain injury (MTBI) do not undergo consistent follow-up in Denmark and the risk factors for long-term symptoms are not fully known. The purpose of this study was to look into symptom frequency, sick-leave frequency and to try to identify risk factors for long-term symptoms following MTBI. Patients were recruited from the emergency room at Viborg Hospital. Initial data were registered and telephone interviews were conducted one month and one year after trauma. 60% were asymptomatic within the first month; an additional 11% became asymptomatic within the next year, leaving 29% with residual symptoms one year after trauma. 70% reported a sick leave period one month and 2% > one year. The average trauma-to-emergency room contact reached 158 min (median 65 min). Gender, age, blood pressure (BP), pulse, Glasgow coma score (GCS), admission to hospital, unconsciousness, amnesia, alcohol intake, time or type of trauma were not associated with long term symptoms. Even patients with minor head trauma have a relatively high risk of long-term symptoms regardless of gender, age, BP, pulse, GCS, admission to hospital, unconsciousness, amnesia, alcohol intake, time or type of trauma. Nevertheless, the risk of long-term sick leave is relatively small.
Bales, James W.; Kline, Anthony E.; Wagner, Amy K.; Dixon, C. Edward
In addition to the initial mechanical damage, traumatic brain injury (TBI) induces a series of secondary insults, such as, but not limited to, excitotoxicity, metabolic disruption, and oxidative stress. Neuroprotective strategies after TBI have traditionally focused on cellular preservation as the measurable endpoint although multiple lines of evidence indicate that even with significant neuronal sparing deficits remain at both the cellular and behavioral level. As such, the development of therapies that can effectively confer both neuronal sparing and post-injury functional benefit is critical to providing the best treatment options for clinical TBI. Targeting dopaminergic signaling pathways is a novel approach in TBI that provides benefits to both neuronal survival and functional outcomes. Dopamine, like glutamate, can cause oxidative stress and significant cellular dysfunction when either depleted or over-expressed, and also plays an important role in central nervous system inflammation. The purpose of this review is to discuss dopamine in acute TBI and the role that dopaminergic therapies have as neuroprotective strategies. PMID:22308176
Goldberg, Yael; Danckert, James
Traumatic brain injury (TBI) often presents with co-morbid depression and elevated levels of boredom. We explored the relationship between boredom and depression in a group of mild (n = 38), moderate-to-severe TBI patients (n = 14) and healthy controls (n = 88), who completed the Beck Depression Inventory and Boredom Proneness Scales as part of a larger study. Results showed that the relationship between boredom and depression was strongest in moderate-to-severe TBI patients. We explored two boredom proneness factors that index an individual's need for external or internal stimulation. Results indicated that the need for external stimulation was the critical driver in the relation between boredom and depression. Once again, this relationship was strongest in the moderate-to-severe TBI group. These results suggest that one common factor underlying boredom and depression is the need for stimulation from the external environment and, presumably, a failure to satisfy that need-a disconnection felt most strongly in moderate-to-severe TBI.
Full Text Available Traumatic brain injury (TBI often presents with co-morbid depression and elevated levels of boredom. We explored the relationship between boredom and depression in a group of mild (n = 38, moderate-to-severe TBI patients (n = 14 and healthy controls (n = 88, who completed the Beck Depression Inventory and Boredom Proneness Scales as part of a larger study. Results showed that the relationship between boredom and depression was strongest in moderate-to-severe TBI patients. We explored two boredom proneness factors that index an individual’s need for external or internal stimulation. Results indicated that the need for external stimulation was the critical driver in the relation between boredom and depression. Once again, this relationship was strongest in the moderate-to-severe TBI group. These results suggest that one common factor underlying boredom and depression is the need for stimulation from the external environment and, presumably, a failure to satisfy that need—a disconnection felt most strongly in moderate-to-severe TBI.
Esterov, Dmitry; Greenwald, Brian D.
A mild traumatic brain injury (mTBI) is a complex pathophysiologic process that has a systemic effect on the body aside from solely an impairment in cognitive function. Dysfunction of the autonomic nervous system (ANS) has been found to induce abnormalities in organ systems throughout the body, and may contribute to cardiovascular dysregulation and increased mortality. Autonomic dysfunction, also known as dysautonomia, has been studied in moderate and severe TBI, and has emerged as a major contributing factor in the symptomatology in mTBI as well. Analysis of the ANS has been studied through changes in heart rate variability (HRV), pupillary dynamics, eye pressure, and arterial pulse wave in those with mild TBI. Graded exercise testing has been studied as both a method of diagnosis and as a means of recovery in those with mild TBI, especially in those with persistent symptoms. Given the studies showing persistence of autonomic dysfunction after symptomatic resolution of concussions, further research is needed to establish return to play protocols PMID:28800081
Rajandram, Rama Krsna; Syed Omar, Syed Nabil; Rashdi, Muhd Fazly Nizam; Abdul Jabar, Mohd Nazimi
Maxillofacial injuries comprising hard tissue as well as soft tissue injuries can be associated with traumatic brain injuries due to the impact of forces transmitted through the head and neck. To date, the role of maxillofacial injury on brain injury has not been properly documented with some saying it has a protective function on the brain while others opposing this idea. This cross-sectional retrospective study evaluated all patients with maxillofacial injuries. The aim of the study was to analyze the occurrence and relationship of maxillofacial injuries with traumatic brain injuries. We retrospectively studied the hospital charts of all trauma patients seen at the accident and emergency department of UKM Medical Centre from November 2010 until November 2011. A detail analysis was then carried out on all patients who satisfied the inclusion and exclusion criteria. A total of 11294 patients were classified as trauma patients in which 176 patients had facial fractures and 292 did not have facial fractures. Middle face fractures was the most common pattern of facial fracture seen. Traumatic brain injury was present in 36.7% of maxillofacial cases. A significant association was found between facial fractures and traumatic brain injury (P maxillofacial injuries with or without facial fractures are at risk of acute or delayed traumatic brain injury. All patients should always have proper radiological investigations together with a proper observation and follow-up schedule. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Rose Dawn Bharath
Full Text Available Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI. 25 subjects with mild head injury were longitudinally evaluated within 36 hours, 3 and 6 months using resting state functional connectivity (RSFC. Region of interest (ROI based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p<0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within three months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Initial imaging within 36 hours of injury revealed hyper connectivity predominantly involving the salience network and default mode network, which reduced at 3 months when lingual, inferior frontal and fronto-parietal networks revealed hyper connectivity. At six months all the evaluated networks revealed hyper connectivity and became comparable to the healthy controls. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3-6 months after injury. Hyper connectivity of several networks supported normal recovery in the first six months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.
Hendricks, H.T.; Geurts, A.C.H.; Ginneken, B.C. van; Heeren, A.J.; Vos, P.E.
OBJECTIVE: To assess brain injury severity, autonomic dysregulation and systemic infection as risk factors for the occurrence of heterotopic ossification in patients with severe traumatic brain injury. DESIGN: Historic cohort study. SETTING: Radboud University Medical Centre. SUBJECTS: All
Baker-Sparr, Christina; Hart, Tessa; Bergquist, Thomas; Bogner, Jennifer; Dreer, Laura; Juengst, Shannon; Mellick, David; OʼNeil-Pirozzi, Therese M; Sander, Angelle M; Whiteneck, Gale G
To characterize Internet and social media use among adults with moderate to severe traumatic brain injury (TBI) and to compare demographic and socioeconomic factors associated with Internet use between those with and without TBI. Ten Traumatic Brain Injury Model Systems centers. Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems National Database and eligible for follow-up from April 1, 2014, to March 31, 2015. Prospective cross-sectional observational cohort study. Internet usage survey. The proportion of Internet users with TBI was high (74%) but significantly lower than those in the general population (84%). Smartphones were the most prevalent means of Internet access for persons with TBI. The majority of Internet users with TBI had a profile account on a social networking site (79%), with more than half of the sample reporting multiplatform use of 2 or more social networking sites. Despite the prevalence of Internet use among persons with TBI, technological disparities remain in comparison with the general population. The extent of social media use among persons with TBI demonstrates the potential of these platforms for social engagement and other purposes. However, further research examining the quality of online activities and identifying potential risk factors of problematic use is recommended.
Shetty, Teena; Raince, Avtar; Manning, Erin; Tsiouris, Apostolos John
The diagnosis of chronic traumatic encephalopathy (CTE) can only be made pathologically, and there is no concordance of defined clinical criteria for premorbid diagnosis. The absence of established criteria and the insufficient imaging findings to detect this disease in a living athlete are of growing concern. The article is a review of the current literature on CTE. Databases searched include Medline, PubMed, JAMA evidence, and evidence-based medicine guidelines Cochrane Library, Hospital for Special Surgery, and Cornell Library databases. Clinical review. Level 4. Chronic traumatic encephalopathy cannot be diagnosed on imaging. Examples of imaging findings in common types of head trauma are discussed. Further study is necessary to correlate the clinical and imaging findings of repetitive head injuries with the pathologic diagnosis of CTE. © 2015 The Author(s).
adrenal insufficiency, hypopituitarism, hypothyroidism , growth- hormone deficiency and posterior pituitary dysfunction [53, 54, 56-60]. Growth...central hypothyroidism which can result in fatigue, apathy, decreased strength and cognitive dysfunction, symptoms commonly observed in PTSD [54...Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer’s disease beta- secretase (BACE-1). J
Full Text Available Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocognition with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, respectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most significant positive correlations were found between mismatch negativity in the fronto-central region and measures of functional outcomes. The most significant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positively associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental findings suggest that mismatch negativity might efficiently reflect functional outcomes in patients after traumatic brain injury.
Ledig, Christian; Heckemann, Rolf A; Hammers, Alexander; Lopez, Juan Carlos; Newcombe, Virginia F J; Makropoulos, Antonios; Lötjönen, Jyrki; Menon, David K; Rueckert, Daniel
We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to
D.C. Engel (Doortje Caroline)
textabstractTraumatic brain injury (TBI) is defined as a microscopic or macroscopic injury to the brain caused by external physical forces. Road traffic accidents, falls, sports injuries (i.e. boxing), recreational accidents (i.e. parachute jumping), the use of firearms, assault, child abuse,
Worldwide, the most frequent cause of death and disability appears to be acquired brain injury.. Traumatic brain injury (TBI) is a devastating condition that affects more than 10 million people a year worldwide. In the United States (US), Faul et al. estimate that TBIs affect 1.7 million people annually. According to the.
Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James
White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…
Gurley, James M; Hujsak, Bryan D; Kelly, Jennifer L
Vertigo, dizziness, and imbalance are a symptom complex that is commonly found following concussion. Early metabolic changes following concussion may lead to worsening of the injury and symptoms in individuals not properly managed from the outset. When symptoms do not recover spontaneously, skilled vestibular rehabilitation can be an effective modality in an attempt to normalize the individual's vestibular responses. The purpose of this review is to appraise the current and accepted methods available to the skilled clinician in quantifying and treating vestibular dysfunction following concussion. Incidence and prognostic indicators will be reviewed along with common barriers to recovery. Vestibular Rehabilitation following concussion utilizes similar tools and techniques employed when treating those solely with peripheral pathology. The clinician must not only have a solid understanding of when and why certain exercises are required, but also be willing to accept that less exercise may be indicated in this population. As injury to the system following mild traumatic brain injury can include both peripheral and central structures, the duration of therapy and the time to recovery may be prolonged. Co-morbidities including cognitive and behavioral issues, visual-perceptual dysfunction, metabolic dysfunction, and autonomic dysfunction may hamper the effectiveness of the traditional Vestibular Rehabilitation approach. As successful treatment does not occur in a vacuum, working closely with other disciplines well versed in treating these co-morbid issues will help the individual to obtain optimal recovery. Vestibular Rehabilitation is an effective modality for managing dizziness, vertigo, and imbalance following concussion. Careful consideration of the acuity of the injury, along with effective management of co-morbid conditions will optimize the result.
Walker, Kendall R; Tesco, Giuseppina
Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.
Walker, Kendall R.; Tesco, Giuseppina
Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533
Kendall Rae Walker
Full Text Available Traumatic brain injury (TBI results in significant disability due to cognitive deficits particularly in attention, learning and memory and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer’s disease (AD, Parkinson’s disease (PD, Amyotrophic Lateral Sclerosis (ALS and most recently chronic traumatic encephalopathy (CTE is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.
Nelson, David V; Esty, Mary Lee
Previous report suggested the beneficial effects of an adaptation of the Flexyx Neurotherapy System (FNS) for the amelioration of mixed traumatic brain injury/post-traumatic stress symptoms in veterans of the Afghanistan and Iraq wars. As a novel variant of electroencephalograph biofeedback, FNS falls within the bioenergy domain of complementary and alternative medicine. Rather than learning voluntary control over the production/inhibition of brain wave patterns, FNS involves offsetting stimulation of brain wave activity by means of an external energy source, specifically, the conduction of electromagnetic energy stimulation via the connecting electroencephalograph cables. Essentially, these procedures subliminally induce strategic distortion of ongoing brain wave activity to presumably facilitate resetting of more adaptive patterns of activity. Reported herein are two cases of Vietnam veterans with mixed traumatic brain injury/post-traumatic stress symptoms, each treated with FNS for 25 sessions. Comparisons of pre- and post-treatment questionnaire assessments revealed notable decreases for all symptoms, suggesting improvements across the broad domains of cognition, pain, sleep, fatigue, and mood/emotion, including post-traumatic stress symptoms, as well as for overall activity levels. Findings suggest FNS treatment may be of potential benefit for the partial amelioration of symptoms, even in some individuals for whom symptoms have been present for decades. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.
Faden, Alan I; Loane, David J
It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).
Westerhof-Evers, Herma J.; Visser-Keizer, Annemarie C.; Fasotti, Luciano; Schönherr, Marleen C.; Vink, Martie; van der Naalt, Joukje; Spikman, Jacoba M.
OBJECTIVE: To evaluate the effects of a multifaceted Treatment for Social cognition and Emotion regulation (T-ScEmo) in patients with a traumatic brain injury. PARTICIPANTS: Sixty-one patients with moderate to severe traumatic brain injury randomly assigned to an experimental T-ScEmo intervention or
Kreutzer, Jeffrey S; Marwitz, Jennifer H; Sima, Adam P; Bergquist, Thomas F; Johnson-Greene, Douglas; Felix, Elizabeth R; Whiteneck, Gale G; Dreer, Laura E
To examine resilience at 3 months after traumatic brain injury (TBI). Cross-sectional analysis of an ongoing observational cohort. Five inpatient rehabilitation centers, with 3-month follow-up conducted primarily by telephone. Persons with TBI (N=160) enrolled in the resilience module of the TBI Model System study with 3-month follow-up completed. Not applicable. Connor-Davidson Resilience Scale. Resilience scores were lower than those of the general population. A multivariable regression model, adjusting for other predictors, showed that higher education, absence of preinjury substance abuse, and less anxiety at follow-up were significantly related to greater resilience. Analysis suggests that lack of resilience may be an issue for some individuals after moderate to severe TBI. Identifying persons most likely at risk for low resilience may be useful in planning clinical interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Clausen, T; Bullock, R
The goal of this article is to give an overview about the established current treatment concepts of traumatic brain injury, as well as an outlook on possible future developments in pharmacological neuroprotection. Modern medical treatment modalities of traumatic brain injury (TBI), including the preclinical management of severely head-injured patients, are reviewed. Since an increased intracranial pressure represents the most common complication of severe traumatic brain injury, frequently associated with the development of secondary brain damage, special emphasis was given to an updated treatment algorithm for this important condition. New insight into the pathophysiology of severe traumatic brain injury, especially the realization that brain damage develops sequentially, initiated several new treatment approaches aiming at the interruption of pathophysiological mechanisms leading to secondary brain injury. A high number of pharmacological substances have been tested for their ability to ameliorate secondary damage after TBI, or are currently under clinical trial. Although no drug has achieved this goal so far, the most promising of these therapeutical approaches, glutamate receptor antagonists, calcium channel antagonists, free radical scavengers, and cyclosporin A will be discussed in this review. Although a "magical bullet" for the treatment of traumatic brain injury has not been developed yet, several of the currently investigated neuroprotective strategies seem to be encouraging. A promising future approach might be to evaluate treatment strategies that combine several pharmacological agents, and possibly other treatment modalities, such as mild hypothermia, "tailored" according to the special pathology of patient subgroups, or even to every single patient in order to achieve an improvement in outcome after TBI.
Oddo, Mauro; Levine, Joshua M; Kumar, Monisha; Iglesias, Katia; Frangos, Suzanne; Maloney-Wilensky, Eileen; Le Roux, Peter D
To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome. This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11; >11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2) 11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p < 0.001). Anemia with simultaneous PbtO(2) < 20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score. In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.
Albrecht, Jennifer S; Liu, Xinggang; Baumgarten, Mona; Langenberg, Patricia; Rattinger, Gail B; Smith, Gordon S; Gambert, Steven R; Gottlieb, Stephen S; Zuckerman, Ilene H
The increased risk of hemorrhage associated with anticoagulant therapy following traumatic brain injury creates a serious dilemma for medical management of older patients: Should anticoagulant therapy be resumed after traumatic brain injury, and if so, when? To estimate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption following traumatic brain injury. Retrospective analysis of administrative claims data for Medicare beneficiaries aged at least 65 years hospitalized for traumatic brain injury during 2006 through 2009 who received warfarin in the month prior to injury (n = 10,782). Warfarin use in each 30-day period following discharge after hospitalization for traumatic brain injury. The primary outcomes were hemorrhagic and thrombotic events following discharge after hospitalization for traumatic brain injury. Hemorrhagic events were defined on inpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification codes and included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction. A composite of hemorrhagic or ischemic stroke was a secondary outcome. Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0
Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.
Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics
Alberto García- Molina
Full Text Available There are many misconceptions about traumatic brain injuries, their recovery and outcome; misconceptions that have their origin in a lack of information influenced by the image that the media show of the brain damage. Development. Based on clinical experience, the authors of this essay sets out his personal view on some of the most frequent misconceptions in the field of neuropsychological rehabilitation of traumatic brain injury: 1 All deficits are evident; 2 The recovery depends mainly on the involvement of the patient: more effort, more rapid recovery; 3 Two years after traumatic brain injury there is no possibility of improvement and recovery; and 4 The “miracle” of recovery will occur when is found the appropriate professional or treatment. These and other beliefs may influence directly or indirectly on the recovery process and the expectations placed on it by the families and patients. Conclusions. Provide accurate, clear and honest information, at the right time, helps patients and their families to better understand the deficits, the course of recovery and to adapt to the new reality resulting from a traumatic brain injury.
Diana G Hernadez-Ontiveros
Full Text Available Traumatic brain injury (TBI has become the signature wound of wars in Afghanistan and Iraq. Injury may result from a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. A cascade of secondary cell death events ensues after the initial injury. In particular, multiple inflammatory responses accompany TBI. A series of inflammatory cytokines and chemokines spreads to normal brain areas juxtaposed to the core impacted tissue. Among the repertoire of immune cells involved, microglia is a key player in propagating inflammation to tissues neighboring the core site of injury. Neuroprotective drug trials in TBI have failed, likely due to their sole focus on abrogating neuronal cell death and ignoring the microglia response despite these inflammatory cells’ detrimental effects on the brain. Another relevant point to consider is the veracity of results of animal experiments due to deficiencies in experimental design, such as incomplete or inadequate method description, data misinterpretation and reporting may introduce bias and give false-positive results. Thus, scientific publications should follow strict guidelines that include randomization, blinding, sample-size estimation and accurate handling of all data (Landis et al., 2012. A prolonged state of inflammation after brain injury may linger for years and predispose patients to develop other neurological disorders, such as Alzheimer’s disease. TBI patients display progressive and long-lasting impairments in their physical, cognitive, behavioral, and social performance. Here, we discuss inflammatory mechanisms that accompany TBI in an effort to increase our understanding of the dynamic pathological condition as the disease evolves over time and begin to translate these findings for defining new and existing inflammation-based biomarkers and treatments for TBI.
O'Connell, Karen M; Littleton-Kearney, Marguerite T
Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.
Marwitz, Jennifer H; Sima, Adam P; Kreutzer, Jeffrey S; Dreer, Laura E; Bergquist, Thomas F; Zafonte, Ross; Johnson-Greene, Douglas; Felix, Elizabeth R
To evaluate (1) the trajectory of resilience during the first year after a moderate-severe traumatic brain injury (TBI); (2) factors associated with resilience at 3, 6, and 12 months postinjury; and (3) changing relationships over time between resilience and other factors. Longitudinal analysis of an observational cohort. Five inpatient rehabilitation centers. Patients with TBI (N=195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3-, 6-, and 12-month follow-up. Not applicable. Connor-Davidson Resilience Scale. Initially, resilience levels appeared to be stable during the first year postinjury. Individual growth curve models were used to examine resilience over time in relation to demographic, psychosocial, and injury characteristics. After adjusting for these characteristics, resilience actually declined over time. Higher levels of resilience were related to nonminority status, absence of preinjury substance abuse, lower anxiety and disability level, and greater life satisfaction. Resilience is a construct that is relevant to understanding brain injury outcomes and has potential value in planning clinical interventions. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang
Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644
Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk
in the prospective study, six died, and 92 (1.27 per 100,000 population per year) survived after a post-traumatic amnesia (PTA) period of at least 28 days. All 19 patients with PTA 7-27 days and 48% of survivors with PTA at least 4 weeks were discharged directly home. The incidence of patients vegetative at 1 month...
May 29, 2012 ... had a residual left hemiparesis of grade 4/5. He is awaiting formal neuropsychological assessment. Discussion. Surgical decompression is an acceptable modality of treatment for traumatic malignant intracranial hypertension with or without associated haematoma. The benefit of this form of surgery in terms ...
brain slices were treated after injury with either a nootropic agent (aniracetam, cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...pharmacological approach. 15. SUBJECT TERMS traumatic brain injury, cell necrosis, neuroprotection, nootropics , epilepsy, long-term potentiation...render their use problematic in an effective brain tourniquet system. We chose to focus our investigations on the nootropic (cognition enhancing) drugs
Alharfi, Ibrahim M; Stewart, Tanya Charyk; Foster, Jennifer; Morrison, Gavin C; Fraser, Douglas D
To determine the occurrence rate of central diabetes insipidus in pediatric patients with severe traumatic brain injury and to describe the clinical, injury, biochemical, imaging, and intervention variables associated with mortality. Retrospective chart and imaging review. Children's Hospital, level 1 trauma center. Severely injured (Injury Severity Score ≥ 12) pediatric trauma patients (>1 month and diabetes insipidus between January 2000 and December 2011. Of 818 severely injured trauma patients, 180 had severe traumatic brain injury with an overall mortality rate of 27.2%. Thirty-two of the severe traumatic brain injury patients developed acute central diabetes insipidus that responded to desamino-8-D-arginine vasopressin and/or vasopressin infusion, providing an occurrence rate of 18%. At the time of central diabetes insipidus diagnosis, median urine output and serum sodium were 6.8 ml/kg/hr (interquartile range = 5-11) and 154 mmol/L (interquartile range = 149-159), respectively. The mortality rate of central diabetes insipidus patients was 87.5%, with 71.4% declared brain dead after central diabetes insipidus diagnosis. Early central diabetes insipidus onset, within the first 2 days of severe traumatic brain injury, was strongly associated with mortality (p diabetes insipidus were more likely to have intracranial pressure monitoring (p = 0.03), have thiopental administered to induce coma (p = 0.04) and have received a decompressive craniectomy for elevated intracranial pressure (p = 0.04). The incidence of central diabetes insipidus in pediatric patients with severe traumatic brain injury is 18%. Mortality was associated with early central diabetes insipidus onset and cerebral edema on head computed tomography. Central diabetes insipidus nonsurvivors were less likely to have received intracranial pressure monitoring, thiopental coma and decompressive craniectomy.
Vanderploeg, 2009). Belanger et al believe that in the OEF/OIF population, even poor performance on neuropsychological 26 tests may be more associated...and may increase the risk for Alzheimer‟s disease and Parkinson ‟s disease as the person ages (Traumatic Brain Injury: Hope Through Research, 2002
Jin, Guang; Duggan, Michael; Imam, Ayesha
We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [...... [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS....
injuries. Convincing evidence has emerged that TBI patients with moderate or severe injuries will have their hospital stay reduced by approximately 30% and the re-acquisition of personal independence increased by the provision of a formal specialised inpatient rehabilitation programme. (3). •. Severe traumatic brain injury ...
Objective. To investigate the incidence and type of misconceptions about traumatic brain injuries (TBIs) harboured by university students. Method. A convenience sample of 705 university students were recruited and data were collected using an electronic survey. The link to the survey was sent via e-mail to all registered ...
Background: Management of brain injury can pose enormous challenges to the health team. There are many studies aimed at discovering or developing pharmacotherapeutic agents targeted at improving outcome of head-injured patients. This paper reviews the role of oxidative stress in neuronal loss following traumatic ...
Objective. Secondary insults of hypotension and hypoxia significantly impact on outcome in patients with traumatic brain injury (TBI). More than 4 hours' delay in evacuation of intracranial haematomas has been demonstrated to have an additional impact on outcome. The objective of this study was to document the ...
Sollid, S.; Sundstrom, T.; Kock-Jensen, C.
. Evidence-based guidelines already exist that focus on all steps in the process. In the present article members of the Scandinavian Neurotrauma Committee present recommendations on prehospital management of traumatic brain injury adapted to the infrastructure of the Nordic region Udgivelsesdato: 2008/6/26...
Davies, Susan C.
Traumatic brain injuries (TBIs), including concussions, can result in a constellation of physical, cognitive, emotional, and behavioral symptoms that affect students' well-being and performance at school. Despite these effects, school personnel remain underprepared identify, educate, and assist this population of students. This article describes a…
Stulemeijer, M.; Werf, S.P. van der; Bleijenberg, G.; Biert, J.; Brauer, J.; Vos, P.E.
BACKGROUND: Fatigue is one of the most frequently reported symptoms after Mild Traumatic Brain Injury (MTBI). To date, systematic and comparative studies on fatigue after MTBI are scarce, and knowledge on causal mechanisms is lacking. OBJECTIVES: To determine the severity of fatigue six months after
Traumatic Brain Injury (TBI) is a common health problem which is one of the main causes of chronic disability and it is associated with hormonal and metabolic disorders. This work was carried out to investigate the relationship between some stress hormones (i.e. prolactin and cortisol) and plasma glucose level in TBI.
Background: Traumatic brain injury is a major public health problem in Nigeria, as it could be associated with long term and life long deficits. Unlike other parts of the world, in our country, motorcycles are possibly the main cause of this injury. Unfortunately, we do not have a national epidemiological data base yet. This study ...
Background: Trauma is an eminently preventable disease. However, prevention programs divert resources away from other priorities. Costing trauma related diseases helps policy makers to make decisions on re-source allocation. We used data from a prospective digital trauma registry to cost Traumatic Brain Injury (TBI) at ...
This study explores the experiences of four adolescents, each living with a parent who has sustained a traumatic brain injury, against the theoretical backdrop of existential-phenomenological psychology. In-depth interviews were conducted and analysed within the context of the existential phenomenology, in an attempt to ...
Objective. Secondary insults of hypotension and hypoxia significantly impact on outcome in patients with traumatic brain injury (TBI). More than 4 hours' delay in evacuation of intracranial haematomas has been demonstrated to have an additional impact on outcome. The objective of this study was to document the ...
Background: Severe traumatic brain injury (TBI) is a major challenge to the patient, the relatives, the care givers, and the society in general. The primary and secondary injuries, and the high metabolism are formidable stages of the injury, each capable of taking the life of the patient. The objectives were to determine the ...
2 School of Child and Adolescent Health, Division of Neurosurgery, Department of Surgery, Red Cross War Memorial Children's Hospital,. Cape Town, South Africa. Corresponding author: L E Schrieff (email@example.com). Background. Paediatric traumatic brain injury (PTBI) is a major public health problem. However ...
Stevens, Alice M.
This resource guide of annotated references on traumatic brain injury (TBI) was created to help educators locate information from such disciplines as neurology, neuropsychology, rehabilitation, and pediatric medicine. Twenty-four resources published from 1990 to 1994 are listed, with annotations. The resources include research reports/reviews,…
Chelse, Ana B.; Epstein, Leon G.
Investigators from New York Presbyterian Morgan Stanley Children’s Hospital examined whether having an isolated headache following minor blunt head trauma was suggestive of traumatic brain injury (TBI) among a large cohort of children 2-18 years of age.
Keightley, Michelle L; Côté, Pierre; Rumney, Peter
OBJECTIVE: To synthesize the best available evidence regarding psychosocial consequences of mild traumatic brain injury (MTBI) in children. DATA SOURCES: MEDLINE, Embase, CINAHL, PsycINFO, and SPORTDiscus were searched (2001-2012). Inclusion criteria included published peer-reviewed reports...
Aldrich, Erin M.; Obrzut, John E.
Traumatic brain injury (TBI) in children and adolescents can significantly affect their lives and educational needs. Deficits are often exhibited in areas such as attention, concentration, memory, executive function, emotional regulation, and behavioral functioning, but specific outcomes are not particular to any one child or adolescent with a…
Traumatic Brain Injury (TBI) is a common health problem which is one of the main causes of chronic disability and it is associated with hormonal and metabolic disorders. This work was carried out to investigate the relationship between some stress hormones (i.e. prolactin and cortisol) and plasma glucose level in TBI ...
Byom, Lindsey; Turkstra, Lyn S.
Background: Social communication problems are common in adults with traumatic brain injury (TBI), particularly problems in spoken discourse. Social communication problems are thought to reflect underlying cognitive impairments. Aims: To measure the contribution of two cognitive processes, executive functioning (EF) and theory of mind (ToM), to the…
... of traumatic brain injury (TBI) in children and adolescents and to compare it with previous audits from our local environment and from other developing world centres. All TBI patients admitted to hospital were included in this study. We reviewed the age, gender, outcomes, radiological findings and treatment of the patients.
TBIs relate to the use of seatbelts, the effects of unconsciousness, what individuals with TBIs are ... Objective. To investigate the incidence and type of misconceptions about traumatic brain injuries (TBIs) harboured by university students. Method. .... students from the psychology honours class to determine which. Table 1.
Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia
Michael A. Kiraly
Full Text Available Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI and mild traumatic brain injury (MTBI. Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.
Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita
Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific
Al-Sarraj, Safa; Laxton, Ross; Swift, Ben; Kolar, Alexander J; Chapman, Rob C; Fegan-Earl, Ashley W; Cary, Nat R B
Traumatic (crush) asphyxia is a rare condition caused by severe compression of the chest and trunk leading to often extreme so-called asphyxial signs, including cyanosis in head and neck regions, multiple petechiae, and subconjunctival haemorrhage as well as neurological manifestations. To investigate the neuropathology and brain weight in traumatic asphyxia caused by different accidents such as industrial accidents and road traffic collision. Post mortem records of 20 cases of traumatic asphyxia (TA) resulting from different causes of which four brains are available for comprehensive neuropathological examination. The expected brain weights for given body height and associated 95% confidence range were calculated according to the following formula: baseline brain weight (BBW) + body height x rate (g/cm). The 95% confidence range was calculated by adding and subtracting the standard error (SE) x 1.96 (7-8). There was a trend for higher brain weight in the TA cohort but it was not significant (1494 g vs 1404 g, p = 0.1). The upper limits of the brain weight of 95% confidence was 1680 g vs 1660 g, p = 0.9. The neuropathological examination of four available brains from the TA cohort showed severe congestion of blood vessels, perivascular haemorrhages and occasional βAPP deposits consistent with early axonal disruption. Brain examination is informative as part of investigation of TA. Developing ischaemic changes and an increase in brain weight are the most likely indicators of a prolonged period of patient's survival. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Jordan, Barry D
Acute and chronic sports-related traumatic brain injuries (TBIs) are a substantial public health concern. Various types of acute TBI can occur in sport, but detection and management of cerebral concussion is of greatest importance as mismanagement of this syndrome can lead to persistent or chronic postconcussion syndrome (CPCS) or diffuse cerebral swelling. Chronic TBI encompasses a spectrum of disorders that are associated with long-term consequences of brain injury, including chronic traumatic encephalopathy (CTE), dementia pugilistica, post-traumatic parkinsonism, post-traumatic dementia and CPCS. CTE is the prototype of chronic TBI, but can only be definitively diagnosed at autopsy as no reliable biomarkers of this disorder are available. Whether CTE shares neuropathological features with CPCS is unknown. Evidence suggests that participation in contact-collision sports may increase the risk of neurodegenerative disorders such as Alzheimer disease, but the data are conflicting. In this Review, the spectrum of acute and chronic sport-related TBI is discussed, highlighting how examination of athletes involved in high-impact sports has advanced our understanding of pathology of brain injury and enabled improvements in detection and diagnosis of sport-related TBI.
Ghajari, Mazdak; Hellyer, Peter J; Sharp, David J
Traumatic brain injury can lead to the neurodegenerative disease chronic traumatic encephalopathy. This condition has a clear neuropathological definition but the relationship between the initial head impact and the pattern of progressive brain pathology is poorly understood. We test the hypothesis that mechanical strain and strain rate are greatest in sulci, where neuropathology is prominently seen in chronic traumatic encephalopathy, and whether human neuroimaging observations converge with computational predictions. Three distinct types of injury were simulated. Chronic traumatic encephalopathy can occur after sporting injuries, so we studied a helmet-to-helmet impact in an American football game. In addition, we investigated an occipital head impact due to a fall from ground level and a helmeted head impact in a road traffic accident involving a motorcycle and a car. A high fidelity 3D computational model of brain injury biomechanics was developed and the contours of strain and strain rate at the grey matter-white matter boundary were mapped. Diffusion tensor imaging abnormalities in a cohort of 97 traumatic brain injury patients were also mapped at the grey matter-white matter boundary. Fifty-one healthy subjects served as controls. The computational models predicted large strain most prominent at the depths of sulci. The volume fraction of sulcal regions exceeding brain injury thresholds were significantly larger than that of gyral regions. Strain and strain rates were highest for the road traffic accident and sporting injury. Strain was greater in the sulci for all injury types, but strain rate was greater only in the road traffic and sporting injuries. Diffusion tensor imaging showed converging imaging abnormalities within sulcal regions with a significant decrease in fractional anisotropy in the patient group compared to controls within the sulci. Our results show that brain tissue deformation induced by head impact loading is greatest in sulcal locations
Bae, Dong-Hyeon; Choi, Kyu-Sun; Yi, Hyeong-Joong; Chun, Hyoung-Joon; Ko, Yong; Bak, Koang Hum
Objective Post-traumatic cerebral infarction (PTCI) is one of the most severe secondary insults after traumatic brain injury (TBI), and is known to be associated with poor outcome and high mortality rate. We assessed the practical incidence and risk factors for the development of PTCI. Methods We conducted retrospective study on 986 consecutive patients with TBI from the period May 2005 to November 2012 at our institution. The definition of PTCI was made on non-enhanced CT scan based on a wel...
Full Text Available Wellingson Silva Paiva, Douglas Alexandre França Bezerra, Robson Luis Oliveira Amorim, Eberval Gadelha Figueiredo, Wagner Malago Tavares, Almir Ferreira De Andrade, Manoel Jacobsen TeixeiraIntensive Care Unit, Division of Neurosurgery, Hospital Das Clinicas, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Sodium disorders are the most common and most poorly understood electrolyte disorders in neurological patients. The aim of this study was to determine the incidence of sodium disorders and its association with different traumatic brain injuries. This prospective study was conducted in 80 patients diagnosed with moderate and severe traumatic brain injuries. All patients underwent cerebral computed tomography. Incidence of sodium disorders, presence of injuries in the first computed tomography after traumatic brain injury, and level of consciousness were analyzed. Patients that presented other potential causes of sodium disorders and systemic trauma were excluded from the study. The incidence of sodium disturbances was 45%: 20 patients presented hypernatremia and 16 hyponatremia. Refers to all patients with sodium disturbances 53% were detected in the first sample. We recorded at least one measurement <125 mEq/L in 50% of the patients with hyponatremia. A greater incidence of sodium disorders was found in patients with subdural, intracerebral hematoma and with diffuse axonal injury. The incidence of sodium disorders among the patients with diffuse lesions was greater than in the group of patients with brain contusion (P = 0.022. The incidence of sodium disorders is higher in patients with diffuse traumatic brain injuries. No association was found between focal lesions and proportion of sodium disorders.Keywords: brain trauma, hypernatremia, hyponatremia
Buzan, Randall D; Kupfer, Jeff; Eastridge, Dixie; Lema-Hincapie, Andres
Patients and their families struggle with accepting changes in personality after traumatic brain injury (TBI). A neuroanatomic understanding may assist with this process. We briefly review the history of the Western conceptualization of the Self, and discuss how neuroscience and changes in personality wrought by brain injuries modify and enrich our understanding of our selves and our patients. The sense of self, while conflated with the concept of a "soul" in Western thinking, is more rationally considered a construct derived from neurophysiologic structures. The self or personality therefore often changes when the brain changes. A neuroanatomic perspective can help patients, families, and clinicians accept and cope with the sequellae of TBI.
Ho Jeong Kim
Full Text Available Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.
NOTES 14. ABSTRACT Background: Studies suggest an increased risk of Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE) after traumatic...traumatic encephalopathy (CTE) as a result of traumatic brain injury (TBI) sustained during military service. Greater understanding of the chronic ...brain injury (TBI). Greater understanding of the chronic effects of TBI may lead to new therapies. This proposal will add a TBI cohort, tau PET
Department of Veterans Affairs — This Service provides access to Tramatic Brain injury patient data consult notes. The service also provides one write service method writeNote. The Service supports...
... disorder associated with a variety of symptoms, including cognition and communication problems, motor disorders, problems with impulse ... nerve cells in the brain causing strange sensations, emotions, and behavior, or sometimes convulsions, muscle spasms, and ...
Full Text Available Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently under research. CTE can be diagnosed only by post mortem neuropathological examination of the brain. Great efforts are being made to better understand the clinical signs and symptoms of CTE, obtained in most cases retrospectively from families of affected persons.Patients with CTE are described as having behavioral, mood, cognitive and motor impairments, occurring after a long latency from the traumatic events. Recent pathogenetic studies have provided new insights to CTE mechanisms, offering important clues in understanding neurodegenerative process and relations between physical factors and pathologic protein deposition. Further research is needed to better identify the genetic and environmental risk factors for CTE, as well as rehabilitation and treatment strategies.
F.K. Korley (Frederick K.); R. Diaz-Arrastia (Ramon); A.H.B. Wu (Alan H. B.); J.K. Yue (John); G. Manley (Geoffrey); H.I. Sair (Haris I.); J.E. van Eyk (Jennifer); A.D. Everett (Allen D.); D. Okonkwo (David); A.B. Valadka (Alex); W.A. Gordon (Wayne A.); A.I.R. Maas (Andrew I.R.); P. Mukherjee (Pratik); E.L. Yuh (Esther); H.F. Lingsma (Hester); A.M. Puccio (Ava); D.M. Schnyer (David)
textabstractBrain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency
Shumskaya, E.; Andriessen, T.; Norris, David Gordon; Vos, P.E.
Objectives: To evaluate the whole-brain resting-state networks in a homogeneous group of patients with acute mild traumatic brain injury (MTBI) and to identify alterations in functional connectivity induced by MTBI. Methods: Thirty-five patients with acute MTBI and 35 healthy control subjects,
Full Text Available Background: Trauma is the most common cause of morbidity and mortality in industrialized countries and also in Iran. Anatomical imaging (AI CT and MRI is helpful in the diagnosis of acute traumatic complications however it is not efficient in the diagnosis of disabling injury syndrome. In contrast, brain perfusion SPECT (Single Photon Emission Computed Tomography can be more useful for evaluation of microvascular structure. This study was designed to compare these two diagnostic methods. Methods: A total of 50 patients who had been suffering from traumatic brain injury for more than 1 year, and were followed as mild traumatic brain injury group according to “the Brain Injury Interdisciplinary Special Interest Group of the Ameri can Congress of Rehabilitation Medicine” criteria, were examined by brain perfusion SPECT and AI. The common anatomical classification of the lobes of brain was used. Results: The male to female ratio was 3:2. The mean age was 32.32±11.8 years and mean post-traumatic time was 1.48±0.65 years. The most common symptoms were headache (60%, agusia (36% and anosmia (32%. Among 400 examined brain lobes in this study, brain perfusion SPECT revealed remarkable abnormality in 76 lobes (19%, but AI determined abnormalities in 38 lobes (9.5% therefore, SPECT was twice sensitive than AI in mild traumatic brain injury (P<0.001. The correlation between SPECT and AI findings was 84%. SPECT was more sensitive than AI in demonstrating brain abnormalities in frontal lobe it was more obvious in the male group however, there was no significant difference between more and less than 30 years old groups. Conclusion: According to the findings of this study, we recommend using brain perfusion SPECT for all patients with chronic complications of head trauma, particularly those who have signs and symptoms of hypofrontalism, even though with some abnormalities in AI.
Tyler, Christopher W; Likova, Lora T; Mineff, Kristyo N; Elsaid, Anas M; Nicholas, Spero C
Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters. Disparity vergence eye movements were measured for a population of 123 normally sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI) in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions. The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters. The results support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI.
Blennow, Kaj; Hardy, John; Zetterberg, Henrik
The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and neural mechanisms associated with TBI, drawing on findings from sports-induced TBI in athletes, in whom acute TBI damages axons and elicits both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE). We also consider how the neuropathology and neurobiology of CTE in many ways resembles other neurodegenerative illnesses such as Alzheimer's disease, particularly with respect to mismetabolism and aggregation of tau, β-amyloid, and TDP-43. Finally, we explore how translational research in animal models of acceleration/deceleration types of injury relevant for concussion together with clinical studies employing imaging and biochemical markers may further elucidate the neurobiology of TBI and CTE. Copyright © 2012 Elsevier Inc. All rights reserved.
Finnie, J W
The neuropathological alterations in sheep associated with head wounds inflicted by a .22 calibre rifle are reported. Brain damage was manifest as a permanent haemorrhagic wound cavity produced by crushing and laceration of tissue during missile penetration, secondary tracks due to bone and bullet fragments, widely distributed stretch injuries to blood vessels, nerve fibres and neurons as a consequence of the radial forces of the temporary cavity which develops as a bullet penetrates tissue, marked subarachnoid and intraventricular haemorrhage, and distortion and displacement of the brain.
Klose, M; Juul, A; Struck, J
To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations.......To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations....
GCS Glasgow Coma Scale GUI graphic user interface HMMWV Highly Mobile Multipurpose Wheeled Vehicle HSI Human Systems Integration ICU Intensive Care...It was originally designed to assess a patient’s level of consciousness in an Intensive Care Unit ( ICU ) setting though it is now widely used by...mild traumatic brain injury,” Journal of Rehabilitation Medicine, vol. 43, pp. 113–125, 2004.  National Institute of Justice, “Ballistic
GERRARD-MORRIS, AIMEE; Taylor, H. Gerry; Yeates, Keith Owen; Walz, Nicolay Chertkoff; Stancin, Terry; Minich, Nori; Wade, Shari L.
The primary aims of this study were to examine post-injury cognitive development in young children with traumatic brain injury (TBI) and to investigate the role of the proximal family environment in predicting cognitive outcomes. Age at injury was 3–6 years, and TBI was classified as severe (n = 23), moderate (n = 21), and complicated mild (n = 43). A comparison group of children who sustained orthopedic injuries (OI, n = 117) was also recruited. Child cognitive assessments were administered ...
Full Text Available This study explores the experiences of four adolescents, each living with a parent who has sustained a traumatic brain injury, against the theoretical backdrop of existential-phenomenological psychology. Opsomming Hierdie navorsing verken die belewenisse van vier adolessente wat saam met ‘n ouer wat ‘n traumatiese breinbesering opgedoen het, leef. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.
Aitken, Mary E; McCarthy, Melissa L; Slomine, Beth S; Ding, Ru; Durbin, Dennis R; Jaffe, Kenneth M; Paidas, Charles N; Dorsch, Andrea M; Christensen, James R; Mackenzie, Ellen J
Traumatic brain injury has a substantial impact on caregivers. This study describes the burden experienced by caregivers of children with traumatic brain injury and examines the relationship between child functioning and family burden during the first year after injury. Children aged 5 to 15 years hospitalized for traumatic brain injury at 4 participating trauma centers were eligible. Caregivers completed baseline and 3- and 12-month telephone interviews measuring the child's health-related quality of life using the Pediatric Quality of Life Inventory. The emotional impact scale of the Child Health Questionnaire was used to identify caregivers with substantial distress, including general worry or interference with family routine. Caregiver perceptions of whether health care needs were met or unmet and days missed from work were also measured. A total of 330 subjects enrolled; follow-up was conducted with 312 at 3 months and 288 at 12 months. Most subjects were white (68%) and male (69%). Abnormal Pediatric Quality of Life Inventory subscores were related to substantial caregiver burden (either general worry or interference in routine). These abnormalities were reported by >75% of patients at 3 months and persisted to 1 year in some patients. Parental perception of unmet health care needs was strongly related to family burden outcomes, with up to 69% of this subset of parents reporting substantial worry, and nearly one quarter reporting interference with daily routine/concentration 1 year after injury. Child dysfunction predicted parental burden at 3 and 12 months. Burden was greater when health care need was unmet. Abnormalities on the Pediatric Quality of Life Inventory predicted the amount of work missed by parents, especially in the presence of unmet needs. Caregivers are more likely to report family burden problems when child functioning is poorer and health care needs are unmet. Improved identification and provision of services is a potentially modifiable
Kirac Unal; Karaca Umay; Tombak; Gundogdu; Erdem Sultanoglu; Aytul Cakci
Introduction Guillain-Barre syndrome (GBS) is an immune-mediated acute inflammatory disorder of the peripheral nervous system. Infectious agents were usually accused of playing a role in the etiology of GBS. Guillain-Barre syndrome has rarely been reported following subdural and subarachnoid hemorrhage after head trauma. Case Presentation We report on a 63-year-old male patient presenting GBS following Traumatic Brain Injury (TBI)...
Seoane, Fernando; Atefi, S. Reza
Electrical Bioimpedance (EBI) is a well spread technology used in clinical practice across the world. Advancements in Textile material technology with conductive textile fabrics and textile-electronics integration have allowed exploring potential applications for Wearable Measurement Sensors and Systems exploiting. The sensing principle of electrical bioimpedance is based on the intrinsic passive dielectric properties of biological tissue. Using a pair of electrodes, tissue is electrically stimulated and the electrical response can be sensed with another pair of surface electrodes. EBI spectroscopy application for cerebral monitoring of neurological conditions such as stroke and perinatal asphyxia in newborns have been justified using animal studies and computational simulations. Such studies have shown proof of principle that neurological pathologies indeed modify the dielectric composition of the brain that is detectable via EBI. Similar to stroke, Traumatic Brain Injury (TBI) also affects the dielectric properties of brain tissue that can be detected via EBI measurements. Considering the portable and noninvasive characteristics of EBI it is potentially useful for prehospital triage of TBI patients where. In the battlefield blast induced Traumatic Brain Injuries are very common. Brain damage must be assessed promptly to have a chance to prevent severe damage or eventually death. The relatively low-complexity of the sensing hardware required for EBI sensing and the already proven compatibility with textile electrodes suggest the EBI technology is indeed a candidate for developing a handheld device equipped with a sensorized textile cap to produce an examination in minutes for enabling medically-guided prompt intervention.
currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 24 Jun 2015 2. REPORT TYPE Journal...transport, intracranial pressure, monitoring, hypoxia, hypotension 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF...of productivity8 Previous studies suggest that secondary insults such as hypoxia and hypotension may worsen a brain injury.9-’ 9 Recent recognition
Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin
Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence...... treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves....... to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma...
Full Text Available Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF, a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI. Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI (n = 109 and non-head injured controls (n = 38 for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT at three different time periods: pre-injury on induction into the military, Phase II (10-15 years post-injury, and Phase III (30-35 years post-injury. Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery.
Rafiq, Mirza Faisal Ahmed; Ahmed, Noor; Khan, Adil Aziz
Electrolyte derangements are common sequel of traumatic brain injury. Use of intravenous fluids, diuretics, syndrome of inappropriate ADH secretion and cerebral salt washing are some of the factors responsible for this. Proper in time detection followed by appropriate treatment not only improves neurological status but also decrease morbidity and mortality. This study was conducted to know serum derangements of different electrolytes in patients with traumatic brain injury. This cross-sectional study was conducted in Pakistan Institute of Medical Sciences. Islamabad, Pakistan from Feb 2009 to Feb 2010. All adult patients with traumatic brain injury who presented to Neurosurgical department with severe head injury (GCS < 8) and who need monitoring in high dependency unit, were included in this study. Initially twice daily serum electrolyte monitoring for one week then once daily for remaining period of hospital stay was carried out. All samples were sent to Pathology department of Pakistan Institute of Medical Sciences, Islamabad. Patients who need corrective measures for imbalance had repetition of sampling after giving appropriate therapy. Statistical analysis was performed on SPSS-16. Total 215 patients presented with severe head injury that were managed in high dependency unit. Out of which 127 (59.1%) were male and 88 (40.9%) were females. Most of them were adults between 21-40) years of age (21.4%; 24.7%). Sodium was the main electrolyte that underwent change & out of which hyper-natremia was major abnormality that occurred in 140 (65.1%) of patients. This is followed by hypo-kalemia that occurred in 79 (36.7%) of patients. Serum calcium & magnesium levels show little derangements. Electrolyte imbalance following traumatic head injury is an important cause to look for in patient monitoring. Sodium is the chief electrolytes of concern. Serum potassium and calcium levels also under goes notable changes.
I describe an approach to art therapy treatment for survivors of traumatic brain injury developed at a rehabilitation facility for adults that serves inpatient, outpatient, and long-term residential clients. This approach is based on a review of the literature on traumatic brain injury, comprehensive neurorehabilitation, brain plasticity, and art…
Pervez, Mubashir; Kitagawa, Ryan S; Chang, Tiffany R
Traumatic brain injury (TBI) disrupts the normal function of the brain. This condition can adversely affect a person's quality of life with cognitive, behavioral, emotional, and physical symptoms that limit interpersonal, social, and occupational functioning. Although many systems exist, the simplest classification includes mild, moderate, and severe TBI depending on the nature of injury and the impact on the patient's clinical status. Patients with TBI require prompt evaluation and multidisciplinary management. Aside from the type and severity of the TBI, recovery is influenced by individual patient characteristics, social and environmental factors, and access to medical and rehabilitation services. Copyright © 2017 Elsevier Inc. All rights reserved.
AWARD NUMBER: W81XWH-16-2-0046 TITLE: The Epidemiology of Epilepsy and Traumatic Brain Injury: Severity, Mechanism, and Outcomes PRINCIPAL...COVERED 30 Sep 2016 – 29 SEP 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Epidemiology of Epilepsy and Traumatic Brain Injury: Severity...previous research has found that Post-9/11 Veterans with any kind of traumatic brain injury (TBI) were more likely to develop epilepsy than those without
Acute, transient hemorrhagic hypotension does not aggravate structural damage or neurologic motor deficits but delays the long-term cognitive recovery following mild to moderate traumatic brain injury
Schütz, Christian; Stover, John F.; Thompson, Hilaire J.; Hoover, Rachel C.; Morales, Diego M.; Schouten, Joost W.; McMillan, Asenia; Soltesz, Kristie; Motta, Melissa; Spangler, Zachery; Neugebauer, Edmund; McIntosh, Tracy K.
Objectives Posttraumatic hypotension is believed to increase morbidity and mortality in traumatically brain-injured patients. Using a clinically relevant model of combined traumatic brain injury with superimposed hemorrhagic hypotension in rats, the present study evaluated whether a reduction in mean arterial blood pressure aggravates regional brain edema formation, regional cell death, and neurologic motor/cognitive deficits associated with traumatic brain injury. Design Experimental prospective, randomized study in rodents. Setting Experimental laboratory at a university hospital. Subjects One hundred nineteen male Sprague-Dawley rats weighing 350-385 g. Interventions Experimental traumatic brain injury of mild to moderate severity was induced using the lateral fluid percussion brain injury model in anesthetized rats (n = 89). Following traumatic brain injury, in surviving animals one group of animals was subjected to pressure-controlled hemorrhagic hypotension, maintaining the mean arterial blood pressure at 50-60 mm Hg for 30 mins (n = 47). The animals were subsequently either resuscitated with lactated Ringer’s solution (three times shed blood volume, n = 18) or left uncompensated (n = 29). Other groups of animals included those with isolated traumatic brain injury (n = 34), those with isolated hemorrhagic hypotension (n = 8), and sham-injured control animals receiving anesthesia and surgery alone (n = 22). Measurements and Main Results The withdrawal of 6-7 mL of arterial blood significantly reduced mean arterial blood pressure by 50% without decreasing arterial oxygen saturation or Pao2. Brain injury induced significant cerebral edema (p hypotension. Brain injury-induced neurologic deficits persisted up to 20 wks after injury and were also not aggravated by the hemorrhagic hypotension. Cognitive dysfunction persisted for up to 16 wks postinjury. The superimposition of hemorrhagic hypotension significantly delayed the time course of cognitive recovery
following both sport -related and experimental blast TBI7. Taken together, these data suggest a model linking trauma, WM injury, and chronic...Mice model of blast traumatic brain injury injury: An imaging, behavior and pathological assessment. 2014 Summer Biomechanics , Bioengineering, and
Full Text Available Objective. To investigate the incidence and type of misconceptions about traumatic brain injuries (TBIs harboured by university students. Method. A convenience sample of 705 university students were recruited and data were collected using an electronic survey. The link to the survey was sent via e-mail to all registered students at Stellenbosch University. The participants had to complete the Common Misconceptions about Traumatic Brain Injury (CM-TBI questionnaire. Results. The findings of this study suggest that the students subscribe to misconceptions from each of the 7 categories of misconceptions about TBIs. The mean percentages of misconceptions about TBIs were calculated and the amnesia (mean 49.7% and unconsciousness (mean 46.1% categories were identified as the categories about which the respondents had the most misconceptions, while the mean percentages of misconceptions were lower for the categories of recovery (mean 27.6%, rehabilitation (mean 26.56%, prevention (mean 20.8%, brain injury sequelae (mean 18.7% and brain damage (mean 8.4%. Conclusion. Generally, these findings appear to be in keeping with previous literature, which suggests that misconceptions about TBIs are common among the general population. This study’s identification of these misconceptions could help create awareness, provide a focus for information provision, and contribute to the development of educational intervention programmes tailored for the South African context.
Full Text Available Traumatic brain injury (TBI leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.
Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.
Zuckerman, Amitai; Ram, Omri; Ifergane, Gal; Matar, Michael A; Sagi, Ram; Ostfeld, Ishay; Hoffman, Jay R; Kaplan, Zeev; Sadot, Oren; Cohen, Hagit
The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.
Full Text Available The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect
Frassanito, Paolo; Tamburrini, Gianpiero; Massimi, Luca; Peraio, Simone; Caldarelli, Massimo; Di Rocco, Concezio
Cranial repair after traumatic brain injury in children is still burdened by unsolved problems and controversial issues, mainly due to the high rate of resorption of autologous bone as well as the absence of valid alternative material to replace the autologous bone. Indeed, inert biomaterials are associated to satisfactory results in the short period but bear the continuous risk of complications related to the lack of osteointegration capacity. Biomimetic materials claiming osteoconductive properties that could balance their mechanical limits seem to allow good cranial bone reconstruction. However, these results should be confirmed in the long term and in larger series. Further complicating factors that may affect cranial reconstruction after head injury should be identified in the possible associated alterations of CSF dynamics and in difficulties to manage the traumatic skin lesion and the surgical wound, which also might impact on the cranioplasty outcome. All the abovementioned considerations should be taken into account when dealing with the cranial reconstruction after decompressive craniectomy in children.
Teasdale, T W; Engberg, A W
OBJECTIVES: To determine the rates of suicide among patients who have had a traumatic brain injury. METHODS: From a Danish population register of admissions to hospital covering the years 1979-93 patients were selected who had had either a concussion (n=126 114), a cranial fracture (n=7560......), or a cerebral contusion or traumatic intracranial haemorrhage (n=11 766). All cases of deaths by the end of the study period were identified. RESULTS: In the three diagnostic groups there had been 750 (0.59%), 46 (0.61%), and 99 (0.84%) cases of suicide respectively. Standardised mortality ratios, stratified...... by sex and age, showed that the incidence of suicide among the three diagnostic groups was increased relative to the general population (3.0, 2.7, and 4.1 respectively). In all diagnosis groups the ratios were higher for females than for males, and lower for patients injured before the age of 21 or after...
Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M
Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Full Text Available Previous research has shown an association between emotions, particularly social emotions, and moral judgments. Some studies suggested an association between blunted emotion and the utilitarian moral judgments observed in patients with prefrontal lesions. In order to investigate how prefrontal brain damage affects moral judgment, we asked a sample of 29 TBI patients (12 females and 17 males and 41 healthy participants (16 females and 25 males to judge 22 hypothetical dilemmas split into three different categories (non-moral, impersonal and personal moral. The TBI group presented a higher proportion of affirmative (utilitarian responses for personal moral dilemmas when compared to controls, suggesting an atypical pattern of utilitarian judgements. We also found a negative association between the performance on recognition of social emotions and the proportion of affirmative responses on personal moral dilemmas. These results suggested that the preference for utilitarian responses in this type of dilemmas is accompanied by difficulties in social emotion recognition. Overall, our findings suggest that deontological moral judgments are associated with normal social emotion processing and that frontal lobe plays an important role in both emotion and moral judgment.
Full Text Available A review of the top-cited articles in a scientific discipline can identify areas of research that are well established and those in need of further development, and may, as a result, inform and direct future research efforts. Our objective was to identify and characterize the top-cited articles in traumatic brain injury (TBI. We used publically available software to identify the 50 TBI articles with the most lifetime citations, and the 50 TBI articles with the highest annual citation rates. A total of 73 articles were included in this review, with 27 of the 50 papers with the highest annual citation rates common to the cohort of 50 articles with the most lifetime citations. All papers were categorized by their primary topic or focus, namely: predictor of outcome, pathology/natural history, treatment, guidelines and consensus statements, epidemiology, assessment measures, or experimental model of TBI. The mean year of publication of the articles with the most lifetime citations and highest annual citation rates was, respectively, 1990 ± 14.9 years and 2003 ± 6.7 years. The 50 articles with the most lifetime citations typically studied predictors of outcome (34.0%, 17/50 and were specific to severe TBI (38.0%, 19/50. In contrast, the most common subject of papers with the highest annual citation rates was treatment of brain injury (22.0%, 11/50, and these papers most frequently investigated mild TBI (36.0%, 18/50. These findings suggest an intensified focus on mild TBI, which is perhaps a response to the dedicated attention these injuries are currently receiving in the context of sports and war, and because of their increasing incidence in developing nations. Our findings also indicate increased focus on treatment of TBI, possibly due to the limited efficacy of current interventions for TBI. This review provides a cross-sectional summary of some of the most influential articles in TBI, and a bibliometric examination of the current status of TBI
Combs, Hannah L; Berry, David T R; Pape, Theresa; Babcock-Parziale, Judith; Smith, Bridget; Schleenbaker, Randal; Shandera-Ochsner, Anne; Harp, Jordan P; High, Walter M
United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment.
Full Text Available Background and Aims: Literature from medical and health sciences indicated that sensory stimulation had a positive effect on traumatic brain injury patients. The present study was aimed to find out the effectiveness of a specific sensory stimulation (4 modalities in comparison with another sensory stimulation (5 modalities on recovery in comatose patients following severe traumatic brain injury. Methods: The study design was experimental, repeated measured with three groups. Two sensory stimulation models were compared with one control group. Forty-five participants with traumatic brain injury were recruited from surgical wards at Maharaj Nakhon Sri Thammarat Hospital, Thailand. The participants were randomly assigned to three groups, each group of 15 participants. Outcomes of the program were recovery determined by the Coma Recovery Scale-Revised (CRS-R. Inter rater agreement of the CRS-R was 0.85. Descriptive statistics, Fisher’s exact test, repeated measure analysis of variance, and post hoc comparison were used for data analysis. Results: All the patients were equally comparable regarding their baseline characteristics, and basic recovery determined by CRS-R. Recovery scores of the three groups were improved. However, those who received the sensory stimulation program (4 modalities had significantly higher CRS-R scores (P<0.001 after 5 days when compared to the two other groups. Conclusion: The sensory stimulation therapy had positive effects on traumatic brain injury patients. Application of the program required few stimuli materials which could be stored at the patient’s bedside making them accessible to care providers. However, monitoring physiologic parameters should be done before, during and after the stimulation.
Ling, Geoffrey S. F.; Grimes, Jamie; Ecklund, James M.
Traumatic brain injury (TBI) and Post Traumatic Stress Disorder (PTSD) are common conditions. In Iraq and Afghanistan, explosive blast related TBI became prominent among US service members but the vast majority of TBI was still due to typical causes such as falls and sporting events. PTS has long been a focus of the US military mental health providers. Combat Stress Teams have been integral to forward deployed units since the beginning of the Global War on Terror. Military medical management of disease and injury follows standard of care clinical practice guidelines (CPG) established by civilian counterparts. However, when civilian CPGs do not exist or are not applicable to the military environment, new practice standards are created. Such is the case for mild TBI. In 2009, the VA-DoD CPG for management of mild TBI/concussion was published and a system-wide clinical care program for mild TBI/concussion was introduced. This was the first large scale effort on an entire medical care system to address all severities of TBI in a comprehensive organized way. In 2010, the VA-DoD CPG for management of PTSD was published. Nevertheless, both TBI and PTS are still incompletely understood. Investment in terms of money and effort has been committed by the DoD to their study. The Defense and Veterans Brain Injury Center, National Intrepid Center of Excellence and the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury are prominent examples of this effort. These are just beginnings, a work in progress ready to leverage advances made scientifically and always striving to provide the very best care to its military beneficiaries.
Kulbe, Jacqueline R; Hall, Edward D
In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, American football, Australian football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.
Workewych, Adriana M; Ciuffetelli Muzzi, Madeline; Jing, Rowan; Zhang, Stanley; Topolovec-Vranic, Jane; Cusimano, Michael D
Sport-related traumatic brain injuries are a significant public health burden, with hundreds of thousands sustained annually in North America. While sports offer numerous physical and social health benefits, traumatic brain injuries such as concussion can seriously impact a player's life, athletic career, and sport enjoyment. The culture in many sports encourages winning at all costs, placing athletes at risk for traumatic brain injuries. As social media has become a central part of everyday life, the content of users' messages often reflects the prevailing culture related to a particular event or health issue. We hypothesized that Twitter data might be useful for understanding public perceptions and misperceptions of sport-related traumatic brain injuries. We performed a content and sentiment analysis of 7483 Twitter® tweets related to traumatic brain injuries in sports collected during June and July 2013. We identified five major themes. Users tweeted about personal traumatic brain injuries experiences, reported traumatic brain injuries in professional athletes, shared research about sport-related concussions, and discussed policy and safety in injury prevention, such as helmet use. We identified mixed perceptions of and sentiment toward traumatic brain injuries in sports: both an understanding that brain injuries are serious and disregard for activities that might reduce the public burden of traumatic brain injuries were prevalent in our Twitter analysis. While the scientific and medical community considers a concussion a form of traumatic brain injuries, our study demonstrates a misunderstanding of this fact among the public. In our current digital age, social media can provide useful insight into the culture around a health issue, facilitating implementation of prevention and treatment strategies.
Yang, W-J; Chen, W; Chen, L; Guo, Y-J; Zeng, J-S; Li, G-Y; Tong, W-S
Traumatic brain injury (TBI) results in significant morbidity and mortality throughout the world. In TBI patients suffering cognitive, emotional, and behavioral deficits, the leading cause derives from the physical injury to the central nervous system (CNS) that impairs brain function. Here, we applied a targeted approach to understand the potential mechanisms of neuron damage after TBI. Tau protein phosphorylation was compared in the brain tissues collected from patients underwent brain surgery based on the assessment of brain injury extent by Glasgow Coma Scale (GCS). The results indicated that the levels of phosphorylated tau were significantly higher in the severe and extremely severe TBI groups, compared to the moderate group of patients. Phosphorylated, but not the total tau protein was uniquely correlated with the GCS score (R2 =.7849, P<.01) in 142 TBI patients. Consistently, the activities of key players associated with tau hyperphosphorylation GSK-3β and PP2A showed parallel correlations with the severity of TBI as well. These data suggest that the enhanced tau protein phosphorylation occurs upon severe neuron injures and may contribute to the pathological structural changes of CNS leading to brain damage of TBI. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Östberg, Anna; Virta, Jere; Rinne, Juha O
subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN:: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity...
van der Horn, Harm J.; Liemburg, Edith J.; Scheenen, Myrthe E.; de Koning, Myrthe E.; Spikman, Jacoba M.; van der Naalt, Joukje
Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions
Keightley, Michelle L.; Yule, Ashley; Garland, Kimberley; Reed, Nicholas; McAuliffe, Jim; Garton, Janice; Green, Stephanie; Taha, Tim
Sports-related concussion or mild-traumatic brain injury (mTBI) is common in children who participate in organised sports. We describe two case studies involving 14-year-old girls who each sustained a mTBI during ice hockey competition. Neurocognitive functioning post-injury is compared to baseline pre-injury assessment on the same measures. Results from Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Conners' Continuous Performance Test II (CPT-II) and the Attention Netw...
McIntosh, G C
Mild traumatic brain injury (TBI) encompasses the postconcussion syndrome characterized by symptoms that include a variety of physical symptoms as well as cognitive and behavioral impairments. The focus of this discussion is on the medical management of posttraumatic headaches, posttraumatic seizures, dizziness, auditory impairments, anosmia, tremor, paraspinal pain, and visual symptoms. Adjustment disorders with disturbances of affect and emotion lability also may accompany mild TBI. All of these conditions may be approached with medications or a variety of therapy techniques or both. The approach to concussion in sports-related injuries is also reviewed.
of imaging may provide a means for monitor- ing longitudinal changes in iron content in dementia, multiple sclerosis , traumatic brain injury, and...criteria: Patients aged 18 or older with an initial Glasgow Coma Scale (GCS) score of 3 13-15 in ED with any period of loss of consciousness less than 30...n=18), 61% 8 were men and 39% women, and the average patient age was 34.83±14.30 years. There 9 was no age difference between patient and controls
Lannsjö, Marianne; Raininko, Raili; Bustamante, Mariana; von Seth, Charlotta; Borg, Jörgen
To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination. A prospective follow-up study. Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15. The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE). At follow-up, 7 patients (37%) reported ≥ 3 symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.
Kiernan, Patrick T; Montenigro, Philip H; Solomon, Todd M; McKee, Ann C
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of hyperphosphorylated tau in neurons and astrocytes. The tau abnormalities begin focally and perivascularly at the depths of the cerebral sulci, spread to the superficial layers of the adjacent cortex, and eventually become widespread throughout the medial temporal lobes, diencephalon, and brainstem. Abnormalities in 43 kDa TAR DNA-binding protein are also found in most cases of CTE. To date, CTE can only be diagnosed by postmortem neuropathological examination, although there are many ongoing research studies examining imaging techniques and biomarkers that might prove to have diagnostic utility. Currently, the incidence and prevalence of CTE are unknown, although great strides are being made to better understand the clinical symptoms and signs of CTE. Further research is critically needed to better identify the genetic and environmental risk factors for CTE as well as potential rehabilitation and therapeutic strategies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Kampen, P.J. van; Martina, J.D.; Vos, P.E.; Hoedemaekers, C.W.E.; Hendricks, H.T.
BACKGROUND: Heterotopic ossification (HO) is a frequent complication after traumatic brain injury (TBI). The current preliminary study is intended to provide additional data on the potential roles that brain injury severity, concomitant orthopaedic trauma, and specific intensive care complicating
Losoi, Heidi; Silverberg, Noah D; Wäljas, Minna; Turunen, Senni; Rosti-Otajärvi, Eija; Helminen, Mika; Luoto, Teemu Miikka Artturi; Julkunen, Juhani; Öhman, Juha; Iverson, Grant L
Resilient individuals manifest adaptive behavior and are better able to recover from adversity. The association between resilience and outcome from mild traumatic brain injury (mTBI) is examined, and the reliability and validity of the Resilience Scale and its short form in mTBI research is evaluated. Patients with mTBI (n=74) and orthopedic controls (n=39) completed the Resilience Scale at one, six, and 12 months after injury. Additionally, self-reported post-concussion symptoms, fatigue, insomnia, pain, post-traumatic stress, and depression, as well as quality of life, were evaluated. The internal consistency of the Resilience Scale and the short form ranged from 0.91 to 0.93 for the mTBI group and from 0.86 to 0.95 for controls. The test-retest reliability ranged from 0.70 to 0.82. Patients with mTBI and moderate-to-high resilience reported significantly fewer post-concussion symptoms, less fatigue, insomnia, traumatic stress, and depressive symptoms, and better quality of life, than the patients with low resilience. No association between resilience and time to return to work was found. Resilience was associated with self-reported outcome from mTBI, and based on this preliminary study, can be reliably evaluated with Resilience Scale and its short form in those with mTBIs.
Orhan, Nurcan; Ugur Yilmaz, Canan; Ekizoglu, Oguzhan; Ahishali, Bulent; Kucuk, Mutlu; Arican, Nadir; Elmas, Imdat; Gürses, Candan; Kaya, Mehmet
This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. The gene expression levels for occludin, glucose transporter (Glut)-1, aquaporin4 (AQP4) and nuclear factor-kappaB (NF-κB) were performed, and Glut-1 and NF-κB activities were analyzed. BHB treatment decreased GSH and MDA levels in intact animals and in those exposed to TBI (P<0.05). Glut-1 protein levels decreased in sham, BHB and TBI plus BHB groups (P<0.05). NF-κB protein levels increased in animals treated with BHB and/or exposed to TBI (P<0.05). The expression levels of occludin and AQP4 did not significantly change among experimental groups. Glut-1 expression levels increased in BHB treated and untreated animals exposed to TBI (P<0.05). While NF-κB expression levels increased in animals in TBI (P<0.01), a decrease was noticed in these animals upon BHB treatment (P<0.01). In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals. Copyright © 2015 Elsevier B.V. All rights reserved.
AWARD NUMBER: W81XWH-12-2-0109 TITLE: Telephone -Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury...2015 - 29 Sep 2016 4. TITLE AND SUBTITLE Telephone -Delivered Cognitive Behavioral Therapy for Chronic Pain 5a. CONTRACT NUMBER Following Traumatic...evaluate the efficacy of a telephone -delivered cognitive behavioral treatment (T-CBT) in Veterans with a history of traumatic brain injury (TBI) for the
Bilgin, Sevil; Guclu-Gunduz, Arzu; Oruckaptan, Hakan; Kose, Nezire; Celik, Bülent
Fifty-one patients with mild (n = 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score. Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury.
National Information Center for Children and Youth with Disabilities, Washington, DC.
This fact sheet, written in both English and Spanish, offers general information about traumatic brain injury. Information includes a definition, incidence, individual characteristics, and educational implications. The signs of traumatic brain injury are listed and include physical disabilities, difficulties with thinking, and social, behavioral,…
Bilgin, Sevil; Guclu-Gunduz, Arzu; Oruckaptan, Hakan; Kose, Nezire; Celik, Bülent
Fifty-one patients with mild (n = 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score. Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury. PMID:25624828
de Koning, M.E.; Gareb, Barzi; El Moumni, M.; Scheenen, M. E.; van der Horn, H. J.; Timmerman, M. E.; Spikman, J. M.; van der Naalt, J.
Objective: To identify the frequency, nature and profile of complaints for trauma patients with and without mild traumatic brain injury (mTBI), and to assess their relation to anxiety and depression. Methods: A prospective cohort study in a level-one trauma centre was conducted. Mild traumatic brain
Giacino, Joseph T; Whyte, John; Bagiella, Emilia
Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.......Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery....
TBI (“Multidrug treatment of traumatic brain injury”, PT073028) from the Fiscal Year 2007 CDMRP program for Psychological Health/Traumatic Brain...ncbi.nlm.nih.gov/pubmed/20166806). Inman, C.F., et al., 2005. Validation of computer-assisted, pixel-based analysis of multiple- colour immunofluorescence
Bouzat, Pierre; Marques-Vidal, Pedro; Zerlauth, Jean-Baptiste; Sala, Nathalie; Suys, Tamarah; Schoettker, Patrick; Bloch, Jocelyne; Daniel, Roy T; Levivier, Marc; Meuli, Reto; Oddo, Mauro
To examine the accuracy of brain multimodal monitoring-consisting of intracranial pressure, brain tissue PO2, and cerebral microdialysis--in detecting cerebral hypoperfusion in patients with severe traumatic brain injury. Prospective single-center study. Patients with severe traumatic brain injury. Medico-surgical ICU, university hospital. Intracranial pressure, brain tissue PO2, and cerebral microdialysis monitoring (right frontal lobe, apparently normal tissue) combined with cerebral blood flow measurements using perfusion CT. Cerebral blood flow was measured using perfusion CT in tissue area around intracranial monitoring (regional cerebral blood flow) and in bilateral supra-ventricular brain areas (global cerebral blood flow) and was matched to cerebral physiologic variables. The accuracy of intracranial monitoring to predict cerebral hypoperfusion (defined as an oligemic regional cerebral blood flow < 35 mL/100 g/min) was examined using area under the receiver-operating characteristic curves. Thirty perfusion CT scans (median, 27 hr [interquartile range, 20-45] after traumatic brain injury) were performed on 27 patients (age, 39 yr [24-54 yr]; Glasgow Coma Scale, 7 [6-8]; 24/27 [89%] with diffuse injury). Regional cerebral blood flow correlated significantly with global cerebral blood flow (Pearson r = 0.70, p < 0.01). Compared with normal regional cerebral blood flow (n = 16), low regional cerebral blood flow (n = 14) measurements had a higher proportion of samples with intracranial pressure more than 20 mm Hg (13% vs 30%), brain tissue PO2 less than 20 mm Hg (9% vs 20%), cerebral microdialysis glucose less than 1 mmol/L (22% vs 57%), and lactate/pyruvate ratio more than 40 (4% vs 14%; all p < 0.05). Compared with intracranial pressure monitoring alone (area under the receiver-operating characteristic curve, 0.74 [95% CI, 0.61-0.87]), monitoring intracranial pressure + brain tissue PO2 (area under the receiver-operating characteristic curve, 0.84 [0
Full Text Available Traumatic brain injury (TBI represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox, ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS, have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI.
Kozlov, Andrey V; Bahrami, Soheyl; Redl, Heinz; Szabo, Csaba
Changes in nitric oxide (NO) levels have been often associated with various forms of trauma, including secondary damage after traumatic brain injury (TBI). Several studies demonstrate the upregulation of NO synthase (NOS) enzymes, and concomitant increases in brain NO levels, which contribute to the TBI-associated glutamate cytotoxicity, including the pathogenesis of mitochondrial dysfunction. TBI is also associated with elevated NO levels in remote organs, indicating that TBI can induce systemic changes in NO regulation, which can be either beneficial or detrimental. Here we review the possible mechanisms responsible for changes in NO metabolism during TBI. Better understanding of the changes in NO homeostasis in TBI will be necessary to design rational therapeutic approaches for TBI. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju. Copyright © 2017 Elsevier B.V. All rights reserved.
Bird, Julie; Parente, Rick
Individuals who have had a traumatic brain injury (TBI) often have difficulty processing nonverbal communication (Ekman, 1976) The published research in this area has focused on a TBI patient's ability to recognize facial expression, vocal intonation, and postural expression (Croker, 2005; Hopkins, Dywan & Segalowitz, 2002). This study compared the non-verbal processing skills of brain-injured patients versus non-injured controls in all three domains. The stimuli were photographs of facial and postural expressions and audio recordings of intonational expressions. The results indicated that persons with TBI have particular difficulty recognizing non-verbal communication resulting from vocal intonations. The TBI patients had difficulty processing tonality, therefore, it is reasonable to suggest that clinicians, friends, and family members should emphasize the explicit verbal content of spoken language when speaking to a person with TBI.
Van Horn, John Darrell; Bhattrai, Avnish; Irimia, Andrei
The impact of traumatic brain injury (TBI) involves a combination of complex biochemical processes beginning with the initial insult and lasting for days, months and even years post-trauma. These changes range from neuronal integrity losses to neurotransmitter imbalance and metabolite dysregulation, leading to the release of pro- or anti-apoptotic factors which mediate cell survival or death. Such dynamic processes affecting the brain's neurochemistry can be monitored using a variety of neuroimaging techniques, whose combined use can be particularly useful for understanding patient-specific clinical trajectories. Here, we describe how TBI changes the metabolism of essential neurochemical compounds, summarize how neuroimaging approaches facilitate the study of such alterations, and highlight promising ways in which neuroimaging can be used to investigate post-TBI changes in neurometabolism. Copyright © 2016. Published by Elsevier Ltd.
Pietrzak, Eva; Pullman, Stephen; McGuire, Annabel
This article reviews the available literature about the use of novel methods of rehabilitation using virtual reality interventions for people living with posttraumatic brain injuries. The MEDLINE, EMBASE, SCOPUS, and Cochrane Library databases were searched using the terms "virtual reality" OR "video games" AND "traumatic brain injury." Included studies investigated therapeutic use of virtual reality in adults with a brain trauma resulting from acquired closed head injury, reported outcomes that included measures of motor or cognitive functionality, and were published in a peer-reviewed journal written in English. Eighteen articles fulfilled inclusion criteria. Eight were case studies, five studies had a quasi-experimental design with a pre-post comparison, and five were pilot randomized control trials or comparative studies. The virtual reality systems used were commercial or custom designed for the study and ranged from expensive, fully immersive systems to cheap online games or videogames. In before-after comparisons, improvements in balance were seen in four case studies and two small randomized control trials. Between-group comparisons in these randomized control trials showed no difference between virtual reality and traditional therapy. Post-training improvements were also seen for upper extremity functions (five small studies) and for various cognitive function measures (four case studies and one pilot randomized control trial). Attitudes of participants toward virtual reality interventions was more positive than for traditional therapy (three studies). The evidence that the use of virtual reality in rehabilitation of traumatic brain injury improves motor and cognitive functionality is currently very limited. However, this approach has the potential to provide alternative, possibly more affordable and available rehabilitation therapy for traumatic brain injury in settings where access to therapy is limited by geographical or financial constraints.
Schwedt, Todd J; Chong, Catherine D; Peplinski, Jacob; Ross, Katherine; Berisha, Visar
The majority of individuals with post-traumatic headache have symptoms that are indistinguishable from migraine. The overlap in symptoms amongst these individuals raises the question as to whether post-traumatic headache has a unique pathophysiology or if head trauma triggers migraine. The objective of this study was to compare brain structure in individuals with persistent post-traumatic headache (i.e. headache lasting at least 3 months following a traumatic brain injury) attributed to mild traumatic brain injury to that of individuals with migraine. Twenty-eight individuals with persistent post-traumatic headache attributed to mild traumatic brain injury and 28 individuals with migraine underwent brain magnetic resonance imaging on a 3 T scanner. Regional volumes, cortical thickness, surface area and curvature measurements were calculated from T1-weighted sequences and compared between subject groups using ANCOVA. MRI data from 28 healthy control subjects were used to interpret the differences in brain structure between migraine and persistent post-traumatic headache. Differences in regional volumes, cortical thickness, surface area and brain curvature were identified when comparing the group of individuals with persistent post-traumatic headache to the group with migraine. Structure was different between groups for regions within the right lateral orbitofrontal lobe, left caudal middle frontal lobe, left superior frontal lobe, left precuneus and right supramarginal gyrus (p comparing the migraine cohort to healthy controls. In conclusion, persistent post-traumatic headache and migraine are associated with differences in brain structure, perhaps suggesting differences in their underlying pathophysiology. Additional studies are needed to further delineate similarities and differences in brain structure and function that are associated with post-traumatic headache and migraine and to determine their specificity for each of the headache types.
Christopher W Tyler
Full Text Available Purpose: Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters.Methods: Disparity vergence eye movements were measured for a population of 123 normally-sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions.Results: The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters.Conclusions: The support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI.
Steven R Flanagan
Full Text Available Steven R Flanagan1, Joshua B Cantor2, Teresa A Ashman21New York University School of Medicine, The Rusk Institute of Rehabilitation, New York, NY, USA; 2Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY, USAAbstract: Traumatic brain injury (TBI is widespread and leads to death and disability in millions of individuals around the world each year. Overall incidence and prevalence of TBI are likely to increase in absolute terms in the future. Tackling the problem of treating TBI successfully will require improvements in the understanding of normal cerebral anatomy, physiology, and function throughout the lifespan, as well as the pathological and recuperative responses that result from trauma. New treatment approaches and combinations will need to be targeted to the heterogeneous needs of TBI populations. This article explores and evaluates the research evidence in areas that will likely lead to a reduction in TBI-related morbidity and improved outcomes. These include emerging assessment instruments and techniques in areas of structural/chemical and functional neuroimaging and neuropsychology, advances in the realms of cell-based therapies and genetics, promising cognitive rehabilitation techniques including cognitive remediation and the use of electronic technologies including assistive devices and virtual reality, and the emerging field of complementary and alternative medicine.Keywords: traumatic brain injury, assessments, treatments
Rushby, Jacqueline A; McDonald, Skye; Fisher, Alana C; Kornfeld, Emma J; De Blasio, Frances M; Parks, Nicklas; Piguet, Olivier
Severe traumatic brain injury (TBI) often leads to deficits in physiological arousal and empathy, which are thought to be linked. This study examined whether injury-related brain volume loss in key limbic system structures is associated with these deficits. Twenty-four adults with TBI and 24 matched Controls underwent MRI scans to establish grey matter volumes in the amygdala, thalamus, and hippocampus. EEG and skin conductance levels were recorded to index basal physiological arousal. Self-report emotional empathy levels were also assessed. The TBI group had reduced brain volumes, topographic alpha differences, and lower emotional empathy compared to Controls. Regional brain volumes were differentially correlated to arousal and self-report empathy. Importantly, lower volume in pertinent brain structures correlated with lower empathy, for participants with and without TBI. Overall we provide new insights into empathic processes after TBI and their relationship to brain volume loss.
Jacqueline A. Rushby
Full Text Available Severe traumatic brain injury (TBI often leads to deficits in physiological arousal and empathy, which are thought to be linked. This study examined whether injury-related brain volume loss in key limbic system structures is associated with these deficits. Twenty-four adults with TBI and 24 matched Controls underwent MRI scans to establish grey matter volumes in the amygdala, thalamus, and hippocampus. EEG and skin conductance levels were recorded to index basal physiological arousal. Self-report emotional empathy levels were also assessed. The TBI group had reduced brain volumes, topographic alpha differences, and lower emotional empathy compared to Controls. Regional brain volumes were differentially correlated to arousal and self-report empathy. Importantly, lower volume in pertinent brain structures correlated with lower empathy, for participants with and without TBI. Overall we provide new insights into empathic processes after TBI and their relationship to brain volume loss.
Maxwell, William L.
There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter. PMID:24961533
Maxwell, William L
There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1-2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.
William L. Maxwell
Full Text Available There is increasing evidence in the experimental and clinical traumatic brain injury (TBI literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.
Full Text Available Traumatic brain injury (TBI is a serious public health problem in the United States. Survivors of TBI are often left with significant cognitive, behavioral, and communicative disabilities. So far there is no effective treatment/intervention in the daily clinical practice for TBI patients. The protective effects of hyperbaric oxygen therapy (HBOT have been proved in stroke; however, its efficiency in TBI remains controversial. In this review, we will summarize the results of HBOT in experimental and clinical TBI, elaborate the mechanisms, and bring out our current understanding and opinions for future studies.
S. A. Valiulina
Full Text Available Background: Currently, analyzing the economic losses caused by health problems in population is of particular importance since it stipulates calculations of the volumes invested in healthcare systems in order to improve population’s health. Objective: The aim of our study was to find out economic losses caused by traumatic brain injury (TBI in children. Methods: The given work has utilized governmental statistical reports for Russia, for federal regions as well as for individual subjects. Direct medical expenses (medical services and indirect expenses (losses due to a temporary disability of parents having a sick child were calculated both in general and per patient. Results: Among all the direct medical costs of treatment of children with TBI inpatient care costs account for 85%. In the Central and Volga Federal District accounted for half of nationwide spending in general, brain injury and to provide certain kinds of healthcare. The structure of Russian costs as a result of the incidence of TBI children Moscow accounts for 20%. In Moscow, the cost of treating cases of traumatic brain injury in children is 3.2 times higher than the average for Russia. The resulting calculations of the value of health care costs attributable to a case of child head injury, behind the cost of treatment of the case of a child with head trauma, calculated according to the standards of Russia and the territories. This difference in the whole RF is 23%. Conclusion: The obtained findings have shown that in 2010 in Russia the magnitude of losses caused by TBI incidence in children amounted to 3 billion roubles or 0.008% of the gross product 1.2 billion roubles of which were direct expenses. However, this figure is considerably lower of the real amount; it becomes evident after the analysis of direct medical expenses per one case of pediatric TBI. Our calculations have shown that in Russia and in its regions the amount of expenses per one TBI patient is a quarter less
Wu, Qiuhe; Huang, Ying-Ying; Dhital, Saphala; Sharma, Sulbha K.; Chen, Aaron C.-H.; Whalen, Michael J.; Hamblin, Michael R.
Low level laser (or light) therapy (LLLT) has been clinically applied for many indications in medicine that require the following processes: protection from cell and tissue death, stimulation of healing and repair of injuries, and reduction of pain, swelling and inflammation. One area that is attracting growing interest is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may have beneficial effects in the acute treatment of brain damage injury by increasing respiration in the mitochondria, causing activation of transcription factors, reducing key inflammatory mediators, and inhibiting apoptosis. We tested LLLT in a mouse model of TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with 660-nm, 810-nm or 980-nm laser (36 J/cm2) four hours post-injury and were followed up by neurological performance testing for 4 weeks. Mice with moderate to severe TBI treated with 660- nm and 810-nm laser had a significant improvement in neurological score over the course of the follow-up and histological examination of the brains at sacrifice revealed less lesion area compared to untreated controls. Further studies are underway.
Ogburn described the "culture lag" between technology and attitudes, as people take time to assimilate new technologies, and new facts, into their worldviews. Traumatic brain injury is now a common diagnosis, thanks to neurosurgical expertise. Where thirty years ago mortality from head injuries was high, today mortality rates have improved dramatically; yet even while neurosurgeons spare thousands of people each year, our society struggles to develop appropriate rehabilitation protocols. To date, we are in the lag phase, between diagnosis and treatment. This paper discusses that lag, including reasons for the lack of an effective rehabilitation protocol (the paucity of funds for research, the nature of brain injuries per se), the reluctance of insurers to cover brain injury rehabilitation (the lengthy time involved in rehabilitation, the blurring between rehabilitation and long term care, the nature of experience-rated contracting to businesses for health care insurance, the burgeoning of proprietary brain injury rehabilitation centers), and the prospects for closing the gap in the near future. The paper concludes that preventive measures (seat belt laws, motorcycle helmet laws, laws for helmets in contact sports) allow policy-makers to confront the growing societal problem of the mounting census of head-injured, by avoiding that census and focusing instead on the prevention, or diminution, of future head injuries.
Full Text Available Traumatic brain injury (TBI is a common cause of morbidity and mortality worldwide. There has been a constant search for therapeutic modalities in an attempt to reduce this burden, but till date, none of them have proved to have a significant clinical impact. The interest in whole-body hypothermia as a treatment modality for severe TBI arose from enthusiastic experiences with the patients having anoxic brain damage after cardiac arrest. However, despite numerous randomised controlled trials (RCTs and systematic reviews, its role in improving the outcomes after TBI are still far from being certain to warrant its clinical usage. The concept that hypothermia may be beneficial in improving the outcomes after TBI evolved with the discovery that the final neuronal injury pattern after an ischemic event could be lessened by cooling the brain. Several subsequent animal studies and clinical trials have now been conducted, which have led the Brain Trauma Foundation to issue a Level III recommendation for the use of primary therapeutic hypothermia in the management of TBI. Induced hypothermia should logically be useful in improving the mortality and neurologic outcome after severe TBI. However, the beneficial, effect of hypothermia only exists in high-quality trials, and presently, there is no Level I or Level II evidence. The relative scarcity of high-quality data in this setting entails well-designed large multicentric RCT′s to prove any association if it exists.
The goal of this supplemental issue is to address major knowledge, research, and clinical practice gaps regarding the limited focus on brain injury in girls and women as well as limited analysis of the effect of sex and gender in research on acquired brain injury. Integrating sex and gender in research is recognized as leading to better science and, ultimately, to better clinical practice. A sex and gender analytical approach to rehabilitation research is crucial to understanding traumatic brain injury and improving quality of life outcomes for survivors. Put another way, the lack of focus on sex and gender reduces the rigor of research design, the generalizability of study findings, and the effectiveness of clinical implementation and knowledge dissemination practices. The articles in this supplement examine sex and gender using a variety of methodological approaches and research contexts. Recommendations for future research on acquired brain injury that consciously incorporates sex and gender are made throughout this issue. This supplement is a product of the Girls and Women with ABI Task Force of the American Congress of Rehabilitation Medicine. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Full Text Available Andrei Irimia, John Darrell Van Horn USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Abstract: Functional deficits due to traumatic brain injury (TBI can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. Keywords: cognitive decline, personality change, magnetic resonance imaging, diffusion tensor imaging
Yeates, Keith Owen; Gerhardt, Cynthia A; Bigler, Erin D; Abildskov, Tracy; Dennis, Maureen; Rubin, Kenneth H; Stancin, Terry; Taylor, H Gerry; Vannatta, Kathryn
This study examined peer relationships in children with traumatic brain injury (TBI) relative to children with orthopedic injuries (OI), and explored whether differences in peer relationships correlated with white matter volumes. Classroom procedures were used to elicit peer perceptions of social behavior, acceptance, and friendships for eighty-seven 8- to 13-year-old children, 15 with severe TBI, 40 with complicated mild/moderate TBI, and 32 with OI. Magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) were used to investigate volumetric correlates of peer relationship measures. Children with severe TBI were rated higher in rejection-victimization than children with OI, and were less likely than children with OI to have a mutual friendship in their classroom (47% vs. 88%). Children with TBI without a mutual friend were rated lower than those with a mutual friend on sociability-popularity and prosocial behavior and higher on rejection-victimization, and had lower peer acceptance ratings. Mutual friendship ratings were related to white matter volumes in several posterior brain regions, but not to overall brain atrophy. Severe TBI in children is associated with detrimental peer relationships that are related to focal volumetric reductions in white matter within regions of the brain involved in social information-processing.
Rodríguez, N; Febrer, A; Meléndez, M
Autonomic dysfunction syndrome following traumatic brain injury is a situation involving adrenergic hyperactivity produced by the lack of control over the autonomous nervous system at a central level. The difficulties involved in its therapeutic management make it even more important. We report the cases of a boy and a girl aged 6 and 12 years, respectively, who had suffered a severe traumatic brain injury with important brain damage that included diencephalic and mesencephalic compromise and areas of diffuse axonal injury. From the acute phase onwards, they presented episodes of hypertension, tachycardia, excessive sweating and spasticity in the form of attacks that initially led to a differential diagnosis between sepsis, opiate and/or benzodiazepine withdrawal syndrome and epilepsy. The length of time spent in coma was very long and the attacks went on throughout the awakening phase almost until the moment they were discharged from hospital, despite trying different treatments. In our cases, orally administered baclofen and midazolam seemed to be the most effective. Autonomic dysfunction is difficult to manage. There are no standardised treatments and speculation continues with regard to its true promoter. We might think that the central injury is the cause of the process and that the autonomic dysfunction increases the secondary lesion and contributes to the functional worsening. If we take into account that the survival rate of the children is high despite the severity of the injuries and although the dysautonomia can be self-limiting with time, we believe that its treatment is essential if the ultimate aim is to minimise the sequelae.
Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne
Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.
Tudor, Mario; Jandric, Ivan; Marovic, Anton; Gjurasin, Miroslav; Perovic, Darko; Radic, Bozo; Blagaic, Alenka Boban; Kolenc, Danijela; Brcic, Luka; Zarkovic, Kamelija; Seiwerth, Sven; Sikiric, Predrag
Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported, improved muscle crush injury. After an induced traumatic brain injury (TBI) in mice by a falling weight, BPC 157 regimens (10.0microg, 10.0ng/kgi.p.) demonstrated a marked attenuation of damage with an improved early outcome and a minimal postponed mortality throughout a 24h post-injury period. Ultimately, the traumatic lesions (subarachnoidal and intraventricular haemorrhage, brain laceration, haemorrhagic laceration) were less intense and consecutive brain edema had considerably improved. Given prophylactically (30 min before TBI) the improved conscious/unconscious/death ratio in TBI-mice was after force impulses of 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, and 0.159 Ns. Counteraction (with a reduction of unconsciousness, lower mortality) with both microg- and ng-regimens included the force impulses of 0.068-0.145 Ns. A higher regimen presented effectiveness also against the maximal force impulse (0.159 Ns). Furthermore, BPC 157 application immediately prior to injury was beneficial in mice subjected to force impulses of 0.093 Ns-TBI. For a more severe force impulse (0.130 Ns, 0.145 Ns, or 0159 Ns), the time-relation to improve the conscious/unconscious/death ratio was: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) or 30 min (0.159 Ns-TBI). Copyright 2009 Elsevier B.V. All rights reserved.
Sawyer, T. W.; Josey, T.; Wang, Y.; Villanueva, M.; Ritzel, D. V.; Nelson, P.; Lee, J. J.
The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.
chronic traumatic encephalopathy (CTE), post‐traumatic stress disorder (PTSD), aging Overall Project Summary Task 1: Screen retired military service...in individuals with TBI exists, which has relevance for future treatment. 15. SUBJECT TERMS Traumatic brain injury (TBI), dementia, chronic traumatic... encephalopathy (CTE), post-traumatic stress disorder (PTSD), aging 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES
Alway, Yvette; Gould, Kate Rachel; McKay, Adam; Johnston, Lisa; Ponsford, Jennie
Increasing evidence indicates that post-traumatic stress disorder (PTSD) may develop following traumatic brain injury (TBI), despite most patients having no conscious memory of their accident. This prospective study examined the frequency, timing of onset, symptom profile, and trajectory of PTSD and its psychiatric comorbidities during the first 4 years following moderate-to-severe TBI. Participants were 85 individuals (78.8% male) with moderate or severe TBI recruited following admission to acute rehabilitation between 2005 and 2010. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders (SCID-I), participants were evaluated for pre- and post-injury PTSD soon after injury and reassessed at 6 months, 12 months, 2 years, 3 years, and 4 years post-injury. Over the first 4 years post-injury, 17.6% developed injury-related PTSD, none of whom had PTSD prior to injury. PTSD onset peaked between 6 and 12 months post-injury. The majority of PTSD cases (66.7%) had a delayed-onset, which for a third was preceded by subsyndromal symptoms in the first 6 months post-injury. PTSD frequency increased over the first year post-injury, remained stable during the second year, and gradually declined thereafter. The majority of subjects with PTSD experienced a chronic symptom course and all developed one or more than one comorbid psychiatric disorder, with mood, other anxiety, and substance-use disorders being the most common. Despite event-related amnesia, post-traumatic stress symptoms, including vivid re-experiencing phenomena, may develop following moderate-to-severe TBI. Onset is typically delayed and symptoms may persist for several years post-injury.
Montenigro, Philip H; Bernick, Charles; Cantu, Robert C
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct pattern of hyperphosphorylated tau (p-tau). Thought to be caused by repetitive concussive and subconcussive injuries, CTE is considered largely preventable. The majority of neuropathologically confirmed cases have occurred in professional contact sport athletes (eg, boxing, football). A recent post-mortem case series has magnified concerns for the public's health following its identification in six high school level athletes. CTE is diagnosed with certainty only following a post-mortem autopsy. Efforts to define the etiology and clinical progression during life are ongoing. The goal of this article is to characterize the clinical concepts associated with short- and long-term effects of repetitive traumatic brain injury, with a special emphasis on new clinical diagnostic criteria for CTE. Utilizing these new diagnostic criteria, two cases of neuropathologically confirmed CTE, one in a professional football player and one in a professional boxer, are reported. Differences in cerebellar pathology in CTE confirmed cases in boxing and football are discussed. © 2015 International Society of Neuropathology.
Good, Cameron H.
Glutamate is the primary excitatory neurotransmitter used by the central nervous system (CNS) for synaptic communication, and its extracellular concentration is tightly regulated by glutamate transporters located on nearby astrocytes. Both animal models and human clinical studies have demonstrated elevated glutamate levels immediately following a traumatic brain event, with the duration and severity of the rise corresponding to prognosis. This rise in extracellular glutamate likely results from a combination of excessive neurotransmitter release from damaged neurons and down regulation of uptake mechanisms in local astrocytes. The immediate results of a traumatic event can lead to necrotic tissue in severely injured regions, while prolonged increases in excitatory transmission can cause secondary excitotoxic injury through activation of delayed apoptotic pathways. Initial TBI animal studies utilized a variety of broad glutamate receptor antagonists to successfully combat secondary injury mechanisms, but unfortunately this same strategy has proven inconclusive in subsequent human trials due to deleterious side effects and heterogeneity of injuries. More recent treatment strategies have utilized specific glutamate receptor subunit antagonists in an effort to minimize side effects and have shown promising results. Future challenges will be detecting the concentration and kinetics of the glutamate rise following injury, determining which patient populations could benefit from antagonist treatment based on their extracellular glutamate concentrations and when drugs should be administered to maximize efficacy.
Połczyńska-Fiszer, M; Mazaux, J M
Post-traumatic language and memory impairment, as well as a subsequent recovery in monolinguals have been widely documented in the literature, yet little is known about learning the second language after a severe head trauma followed by coma, as well as the relationship of this process with cognitive recovery, psychological status and quality of life. The present study investigates the relationship of learning the second language (English) in the process of rehabilitation, with quality of life in a Polish female university student who, as a result of a car accident, suffered a major closed-head injury and was comatose for a month. The subject was enrolled in an English learning program nine months after the trauma. The experiment lasted six months and comprised monthly meetings. The patient improved the major components of the second language, including vocabulary. Within the 6 months, the subject was gradually capable of learning additional and more complex lexical items. Learning the second language after traumatic brain injury may positively influence emotional well-being, self-esteem, and, perhaps, recovery of quality of life. A long-term beneficial effect of learning L2 was a consequential improvement of the patient's memory.
Wilson, Lindsay; Stewart, William; Dams-O'Connor, Kristen; Diaz-Arrastia, Ramon; Horton, Lindsay; Menon, David K; Polinder, Suzanne
Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population. Copyright © 2017 Elsevier Ltd. All rights reserved.
Kulbe, Jacqueline R.; Geddes, James W.
Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. Athletes and military personnel are at great risk for repeat injury which can result in second impact syndrome or chronic traumatic encephalopathy. An objective and quantifiable measure, such as a serum biomarker, is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments, and would further elucidate mTBI pathophysiology. The majority of TBI biomarker research focuses on severe TBI with few studies specific to mild injury. Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers. PMID:25981889
Vile, Alexander R; Atkinson, Leigh
This review aims to integrate current literature on the pathogenic mechanisms of Chronic Traumatic Encephalopathy (CTE) to create a multifactorial understanding of the disease. CTE is a progressive neurodegenerative disease, classed as a tauopathy, although it appears the pathogenic mechanisms are more complex than this. It affects those with a history of repetitive mild traumatic brain injury. Currently, there are no treatments for CTE and the disease can only be affirmatively diagnosed in post mortem. Understanding the pathogenesis of the disease will provide an avenue to explore possible treatment and diagnostic modalities. The pathological hallmarks of CTE have been well characterised and have been linked to the pathophysiologic mechanisms in this review. Human studies are limited due to ethical implications of exposing subjects to head trauma. Phosphorylation of tau, microglial activation, TAR DNA-binding protein 43 and diffuse axonal injury have all been implicated in the pathogenesis of CTE. The neuronal loss and axonal dysfunction mediated by these pathognomonic mechanisms lead to the broad psycho-cognitive symptoms seen in CTE. Copyright © 2017 Elsevier Ltd. All rights reserved.
Michael E Hoffer
Full Text Available Mild Traumatic Brain Injury (mTBI is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications.
Bae, Dong-Hyeon; Choi, Kyu-Sun; Yi, Hyeong-Joong; Chun, Hyoung-Joon; Ko, Yong; Bak, Koang Hum
Post-traumatic cerebral infarction (PTCI) is one of the most severe secondary insults after traumatic brain injury (TBI), and is known to be associated with poor outcome and high mortality rate. We assessed the practical incidence and risk factors for the development of PTCI. We conducted retrospective study on 986 consecutive patients with TBI from the period May 2005 to November 2012 at our institution. The definition of PTCI was made on non-enhanced CT scan based on a well-demarcated or fairly discernible region of low attenuation following specific vascular territory with normal initial CT. Clinical and radiological findings that related to patients' outcome were reviewed and statistically compared. PTCI was observed in 21 (2.1%) patients. Of various parameters, age (p=0.037), initial Glasgow coma scale score (paccident and PTCI, patterns of TBI and vascular territory of PTCI were not specific. The mortality rates were significantly higher in patients with PTCI than without PTCI. The development of PTCI is rare after TBI, but it usually results in serious outcome and high mortality. Early recognition for risks and aggressive managements is mandatory to prevent PTCI.
Full Text Available Background: Traumatic brain injury (TBI is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A. The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.
Lecoq, A-L; Chanson, P
Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q
Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n = 8) or normal air (n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI.
Aubert, S; Barat, M; Campan, M; Dehail, P; Joseph, P A; Mazaux, J-M
Discursive abilities of severe brain injured patient are always impaired: loss of flexibility, lack of cohesion and coherence, often more elliptic. We know few about nonverbal competencies during discourse. The objective is to verify nonverbal abilities of these patients by pragmatic analysis. Four men were examined more than 7 years after severe traumatic brain injury. Nonverbal Prutting and Kirchner Pragmatic Protocol (1987) were done allowing to a qualitative and quantitative measurement of paralinguistic behaviour: prosody and quality of speech, facial expression, posture, gaze, gesture. Two conditions were recorded: dual (descriptive discourse) and group (conversational discourse). Associated impairments such as cognitive and dysexecutive functioning were also investigated. Impoverishment (loss of ability) or impaired inadequacity was observed in all patients. Paralinguistic competences of conversational discourse was worse than descriptive one. Facial expression, gaze functioning, referential gesture were more often impaired. Maladjustment could be interpretated in reference with dysexecutive syndrome. In spite of the lack of information about the range of normal pragmatic behaviour, it seems that brain injured patients have shown poor nonverbal abilities during discourse. Rehabilitation training of communication skills would integrate this fact in order to improve interactivity and social relationship.
Full Text Available Traumatic brain injury (TBI is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI.
Carron, Simone Francina
Different forms of Traumatic brain injury (TBI) disrupt brain excitation/inhibition balance. This thesis examined changes in brain inhibition following two different types of brain injury and its consequences on behaviour. A key finding of this thesis is that particular forms of inhibition are altered after trauma confirming that susceptibility of brain inhibitory cells to trauma is brain area specific, injury type and time dependent. These findings have important implicatio...
Keri Linda Carpenter
Full Text Available In traumatic brain injury (TBI patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well recognised, and are associated statistically with unfavourable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolised via glycolysis (Embden-Meyerhof-Parnas pathway to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate’s association with unfavourable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilise lactate by feeding into the tricarboxylic acid (TCA cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilisation of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of 13C-labelled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with 13C NMR analysis, revealed 13C labelling in glutamine consistent with lactate utilisation via the TCA cycle. This suggests that where neurons are too damaged to utilise the lactate produced from glucose by astrocytes, i.e. uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining association between high lactate and poor outcome. An intravenous exogenous lactate supplementation study in TBI patients showed evidence for a beneficial effect judged by surrogate endpoints. Here we review current knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better
Full Text Available Traumatic brain injury (TBI is a major cause of mortality and morbidity worldwide. Despite improvements in acute intensive care, there are currently no specific therapies to ameliorate the effects of TBI. Successful therapeutic strategies for TBI should target multiple pathophysiologic mechanisms that occur at different stages of brain injury. The kallikrein–kinin system is a promising therapeutic target for TBI as it mediates key pathologic events of traumatic brain damage, such as edema formation, inflammation, and thrombosis. Selective and specific kinin receptor antagonists and inhibitors of plasma kallikrein and coagulation factor XII have been developed, and have already shown therapeutic efficacy in animal models of stroke and TBI. However, conflicting preclinical evaluation, as well as limited and inconclusive data from clinical trials in TBI, suggests that caution should be taken before transferring observations made in animals to humans. This review summarizes current evidence on the pathologic significance of the kallikrein–kinin system during TBI in animal models and, where available, the experimental findings are compared with human data.
Jagannathan, Pavan; Jagannathan, Jay
Despite advances in molecular biology and genetics, the precise pathophysiology of traumatic brain injury (TBI) in children is unknown. In this paper the authors review what is currently known about intra- and extracellular responses to pediatric TBI and relate these factors to future investigations. Although hyperemia and vascular congestion have long been thought to be the hallmarks of pediatric TBI, on a cellular level, calcium influx as well as modulation of local neurotransmitters appears to play a major role in its onset. Recent genetic and proteomic research has identified specific neurotrophic factors as well as apoptotic and antiapoptotic genes that appear to control the progression of inflammation and neuronal damage. The search for a therapeutic target will ultimately require a thorough understanding of these factors and their interplay on a proteomic, genomic, and neuromic level.
Keightley, Michelle L; Yule, Ashley; Garland, Kimberley; Reed, Nicholas; McAuliffe, Jim; Garton, Janice; Green, Stephanie; Taha, Tim
Sports-related concussion or mild-traumatic brain injury (mTBI) is common in children who participate in organised sports. We describe two case studies involving 14-year-old girls who each sustained a mTBI during ice hockey competition. Neurocognitive functioning post-injury is compared to baseline pre-injury assessment on the same measures. Results from Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Conners' Continuous Performance Test II (CPT-II) and the Attention Network Test (ANT) revealed decreased performance in attention, memory functioning and reaction time. Furthermore, some measures had not returned to baseline at midseason testing sessions approximately 30–40 days post-injury. The results are discussed with respect to the difference in recovery profiles and the need for thorough and ongoing evaluation following mTBI in the paediatric population, and for girls in particular. PMID:22791784
Kong, Xiao-Dong; Bai, Sheng; Chen, Xin; Wei, Hui-Jie; Jin, Wei-Na; Li, Min-Shu; Yan, Yaping; Shi, Fu-Dong
To investigate the relationship between natural killer (NK) cells and traumatic brain injury (TBI), we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3(-) CD56(+) lymphocytes. Compared to healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. Furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points. That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI.
Hartings, Jed A; Strong, Anthony J; Fabricius, Martin
Here we investigated the incidence of cortical spreading depolarizations (spreading depression and peri-infarct depolarization) after traumatic brain injury (TBI) and their relationship to systemic physiologic values during neurointensive care. Subdural electrode strips were placed on peri......-contusional cortex in 32 patients who underwent surgical treatment for TBI. Prospective electrocorticography was performed during neurointensive care with retrospective analysis of hourly nursing chart data. Recordings were 84 hr (median) per patient and 2,503 hr in total. In 17 patients (53%), 280 spreading...... depolarizations (spreading depressions and peri-infarct depolarizations) were observed. Depolarizations occurred in a bimodal pattern with peak incidence on days 1 and 7. The probability of a depolarization occurring increased significantly as a function of declining mean arterial pressure (MAP; R(2) = 0.78; p...
Krause, Miriam; Byom, Lindsey; Meulenbroek, Peter; Richards, Stephanie; O'Brien, Katy
Traumatic brain injury (TBI) can affect developmental trajectories as well as language, attention, memory, executive functions, and other cognitive skills related to literacy. Literacy demands change through adolescence and into young adulthood, with academic literacy demands increasing and vocational literacy demands being introduced. Speech-language pathology services must evolve with the literacy needs of each client. This article discusses assessment and treatment approaches designed for adolescents with TBI and recommendations for adapting literacy interventions from the learning disabilities literature. Through proper assessment and intervention, speech-language pathologists can have a meaningful impact on the academic and vocational literacy needs of adolescents with TBI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Gauvin-Lepage, Jérôme; Lefebvre, Hélène; Malo, Denise
This study aims to coconstruct the building blocks for an intervention program to support family resilience in conjunction with families with an adolescent suffering from traumatic brain injury and rehabilitation professionals. This is a qualitative and inductive study, supported by a collaborative research approach. Based on the complex intervention design and validation model, the investigator follows a three-stage data collection process: (1) identifying the building blocks of the intervention program in the eyes of families and rehabilitation professionals, (2) prioritizing, and (3) validating the building blocks with the same participants. After analyzing the data, the investigator identifies five encompassing themes as the building blocks of the intervention program. This study offers promising avenues for practitioners and researchers in nursing and other fields with respect to the implementation of concrete strategies to support the resilience process of families facing particularly difficult times in their lives. © 2015 Association of Rehabilitation Nurses.
Dorfman, Jon D; Burns, Joseph D; Green, Deborah M; DeFusco, Christina; Agarwal, Suresh
Intracranial hypertension is a crucial modifiable risk factor for poor outcome after traumatic brain injury (TBI). Limited evidence suggests that decompressive laparotomy may be an effective treatment for refractory ICH in patients who have elevated intra-abdominal pressure. Case report. We present a multi-trauma patient who sustained severe TBI in a motor vehicle collision. Intracranial pressure (ICP) was initially medically managed but became refractory to standard therapies. Emergent decompressive laparotomy performed in the surgical intensive care unit for abdominal compartment syndrome concomitantly improved the patient's ICP. Elevated intra-abdominal pressure can exacerbate intracranial hypertension in patients with TBI. Recognition of this condition and treatment with decompressive laparotomy may be useful in patients with intracranial hypertension refractory to optimal medical therapy.
Ilyas, Chaudhary Muhammad Aqdus; Nasrollahi, Kamal; Moeslund, Thomas B.
In this paper, we investigate the issues associated with facial expression recognition of Traumatic Brain Insured (TBI) patients in a realistic scenario. These patients have restricted or limited muscle movements with reduced facial expressions along with non-cooperative behavior, impaired...... reasoning and inappropriate responses. All these factors make automatic understanding of their expressions more complex. While the existing facial expression recognition systems showed high accuracy by taking data from healthy subjects, their performance is yet to be proved for real TBI patient data...... by considering the aforementioned challenges. To deal with this, we devised scenarios for data collection from the real TBI patients, collected data which is very challenging to process, devised effective way of data preprocessing so that good quality faces can be extracted from the patients facial video...
Amoroso, Timothy; Iverson, Katherine M
Since the Iraq and Afghanistan wars began, an unprecedented number of women have been engaging in combat operations. Likewise, the number of women using Department of Veterans Affairs (VA) services has doubled since 2001. Military service, and deployment to combat in particular, poses certain risks for traumatic brain injury (TBI)-for all service members. However, women may have additional military and nondeployment risk factors such as intimate partner violence (IPV). We briefly review the definition and classification issues related to TBI, as well as common acute and chronic health symptoms after TBI. Specific sex differences in prognosis after TBI, in particular the neurobehavioral symptoms, are also reviewed. We then focus on the emerging literature regarding TBI in women veterans including the etiologies, outcomes, and unique challenges this population faces. The article concludes with suggestions for enhanced screening by VA and non-VA providers alike, as well as directions for future research and clinical inquiry.
Full Text Available Introduction Guillain-Barre syndrome (GBS is an immune-mediated acute inflammatory disorder of the peripheral nervous system. Infectious agents were usually accused of playing a role in the etiology of GBS. Guillain-Barre syndrome has rarely been reported following subdural and subarachnoid hemorrhage after head trauma. Case Presentation We report on a 63-year-old male patient presenting GBS following Traumatic Brain Injury (TBI. Only five other similar cases are described in the literature. Conclusions Sudden onset of GBS symptoms following trauma may erroneously be assessed as secondary complications of the TBI and can lead to unnecessary procedures such as computerized tomography (CT scan and magnetic resonance imaging (MRI for a definitive diagnosis and may be a waste of time.
Full Text Available Endocrine dysfunction is a common effect of traumatic brain injury (TBI. In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.
Fernandez-Ortega, Juan F; Baguley, Ian J; Gates, Thomas A; Garcia-Caballero, Manuel; Quesada-Garcia, Juan G; Prieto-Palomino, Miguel A
Paroxysmal sympathetic hyperactivity (PSH) affects a significant minority of people in the intensive care unit after severe traumatic brain injury. Systematic research has yet to elucidate or quantify the extent of the role of the catecholamines or adrenocortical and thyroid axis hormonal influences in the condition. Data were prospectively collected on 80 consecutive patients, 18 of whom developed clinical signs of PSH (22.5%). Catecholamine and hormonal data were collected sequentially at 4-h intervals or during and between episodes of PSH. Evaluated variables showed 200-300% increases in catecholamines and, to a lesser extent, adrenocortical hormones during paroxysms. The majority of PSH episodes (72%) were noted to be in response to an observable triggering event. These changes were not observed in subjects without PSH. These data go some way to explain why PSH produces adverse consequences in survivors of TBI with the condition.
Shum, D H; Harris, D; O'Gorman, J G
The study aimed to clarify the effects of severe traumatic brain injury (TBI) on visual memory. Three groups of participants (14 late-recovery and 14 early-recovery TBI individuals and 18 controls) were administered the following: The Shum Visual Learning Test (SVLT), a test that measures the ability to remember visual patterns, an electronic maze test, a test that measures the ability to remember spatial positions, and the Rey Auditory Verbal Learning Test (RAVLT), a test of verbal memory and learning. The individuals with TBI (late- and early-recovery) were found to be impaired on the SVLT and the RAVLT but not on the electronic maze. Specifically, on the SVLT, they were found to learn at a slower rate and make more false-positive errors than the controls. The advantages of the SVLT over visual memory tests used in previous studies and the significance of findings of the present study were discussed.
Park, Soohyun; Williams, Reg Arthur; Lee, Donghyun
Agitation is a common behavioral problem after traumatic brain injury (TBI), which threatens the safety of patients and caregivers and disrupts the rehabilitation process. This study aimed to evaluate the effects of a preferred music intervention on the reduction of agitation in TBI patients and to compare the effects of preferred music with those of classical "relaxation" music. A single group, within-subjects, randomized crossover trial design was formed, consisting of 14 agitated patients with cognitive impairment after severe TBI. Patients listened to preferred music and classical "relaxation" music, with a wash-out period in between. Patients listening to the preferred music reported a significantly greater reduction in agitation compared with the effect seen during the classical "relaxation" music intervention (p = .046). These findings provide preliminary evidence that the preferred music intervention may be effective as an environmental therapeutic approach for reducing agitation after TBI. © The Author(s) 2015.
Roy, Durga; Jayaram, Geetha; Vassila, Alex; Keach, Shari; Rao, Vani
There are several challenges in diagnosing and treating mental illness amongst South Asians. Often times, formulating a patient's case presentation cannot adequately be accomplished strictly using a biopsychosocial model. The cultural components play an imperative role in explaining certain psychiatric symptoms and can guide treatment. With the growing population of immigrants coming to the United States, many of which require treatment for mental illness, it is essential that clinicians be cognizant in incorporating cultural perspectives when treating such patients. The authors describe the case of a 24-year old South Asian male who suffered an exacerbation of a depressive syndrome after a traumatic brain injury. Using a biopsychosocial cultural approach, this case highlights how South Asian cultural values can contribute to and incite psychiatric symptoms while simultaneously providing protective drivers for treatment outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.
Yuhasz, James E
This study explored the prevalence of misconceptions of traumatic brain injury (TBI) among a sample of correctional health care professionals. Prior research has identified a high prevalence of TBI among criminal offenders, and misconceptions about TBI exist among laypersons and nonexpert professionals. Participants (N = 155) completed a 25-item survey about the sequelae of TBI. Results were compared with previous studies. This sample performed significantly better than laypersons and commensurable to other nonexpert professionals. Misconceptions were higher on items related to loss of consciousness, memory, and recovery. Gender, prior familiarity to someone with a history of TBI, and prior training in TBI accounted for statistically fewer misconceptions. The findings support the need for continued training and increased awareness about TBI among inmates.
McDonald, Stuart J; Sun, Mujun; Agoston, Denes V; Shultz, Sandy R
Traumatic injuries are physical insults to the body that are prevalent worldwide. Many individuals involved in accidents suffer injuries affecting a number of extremities and organs, otherwise known as multitrauma or polytrauma. Traumatic brain injury is one of the most serious forms of the trauma-induced injuries and is a leading cause of death and long-term disability. Despite over dozens of phase III clinical trials, there are currently no specific treatments known to improve traumatic brain injury outcomes. These failures are in part due to our still poor understanding of the heterogeneous and evolving pathophysiology of traumatic brain injury and how factors such as concomitant extracranial injuries can impact these processes. Here, we review the available clinical and pre-clinical studies that have investigated the possible impact of concomitant injuries on traumatic brain injury pathobiology and outcomes. We then list the pathophysiological processes that may interact and affect outcomes and discuss promising areas for future research. Taken together, many of the clinical multitrauma/polytrauma studies discussed in this review suggest that concomitant peripheral injuries may increase the risk of mortality and functional deficits following traumatic brain injury, particularly when severe extracranial injuries are combined with mild to moderate brain injury. In addition, recent animal studies have provided strong evidence that concomitant injuries may increase both peripheral and central inflammatory responses and that structural and functional deficits associated with traumatic brain injury may be exacerbated in multiply injured animals. The findings of this review suggest that concomitant extracranial injuries are capable of modifying the outcomes and pathobiology of traumatic brain injury, in particular neuroinflammation. Though additional studies are needed to further identify the factors and mechanisms involved in central and peripheral injury
Ma, Zechen; Bayley, Mark T; Perrier, Laure; Dhir, Priya; Dépatie, Lana; Comper, Paul; Ruttan, Lesley; Lay, Christine; Munce, Sarah E P
Adverse childhood experiences are significant risk factors for physical and mental illnesses in adulthood. Traumatic brain injury/concussion is a challenging condition where pre-injury factors may affect recovery. The association between childhood adversity and traumatic brain injury/concussion has not been previously reviewed. The research question addressed is: What is known from the existing literature about the association between adverse childhood experiences and traumatic brain injury/concussion in adults? All original studies of any type published in English since 2007 on adverse childhood experiences and traumatic brain injury/concussion outcomes were included. The literature search was conducted in multiple electronic databases. Arksey and O'Malley and Levac et al.'s scoping review frameworks were used. Two reviewers independently completed screening and data abstraction. The review yielded six observational studies. Included studies were limited to incarcerated or homeless samples, and individuals at high-risk of or with mental illnesses. Across studies, methods for childhood adversity and traumatic brain injury/concussion assessment were heterogeneous. A positive association between adverse childhood experiences and traumatic brain injury occurrence was identified. The review highlights the importance of screening and treatment of adverse childhood experiences. Future research should extend to the general population and implications on injury recovery. Implications for rehabilitation Exposure to adverse childhood experiences is associated with increased risk of traumatic brain injury. Specific types of adverse childhood experiences associated with risk of traumatic brain injury include childhood physical abuse, psychological abuse, household member incarceration, and household member drug abuse. Clinicians and researchers should inquire about adverse childhood experiences in all people with traumatic brain injury as pre-injury health conditions can
Full Text Available 【Abstract】 Objective: To evaluate all the possible therapeutic measures concerning the acute management of traumatic brain injury (TBI mentioned in Cochrane System-atic Reviews published in the Cochrane Database of Sys-tematic Reviews (CDSR. Methods: An exhausted literature search for all pub-lished Cochrane Systematic Reviews discussing therapeu-tic rather than prevention or rehabilitative interventions of TBI was conducted. We retrieved such databases as CDSR and Cochrane Injury Group, excluded the duplications, and eventually obtained 20 results, which stand for critical ap-praisal for as many as 20 different measures for TBI patients. The important data of each systematic review, including total population, intervention, outcome, etc, were collected and presented in a designed table. Besides, we also tried to find out the possible weakness of these clinical trials in-cluded in each review. Results: Analysis of these reviews yielded meanfuling observations: (1 The effectiveness of most ordinary treat-ments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI. (2 A majority of the systematic reviews in-clude a small number of clinical trials and the modest num-bers of patients, largely due to the uncertainty of the effectiveness. (3 The quality of most trials reported in the systematic reviews is more or less questionable. (4 In addition, lots of other complex factors together may lead to the inconclusive results demonstrated in the Cochrane Sys-tematic Reviews. Conclusions: For clinical physicians, to translate these conclusions into practice with caution is essential. Basic medication and nursing care deserve additional attention as well and can be beneficial. For researchers, high quality trials with perfect design and comprehensive consideration of
Mendez, Mario F
There is a long history linking traumatic brain injury (TBI) with the development of dementia. Despite significant reservations, such as recall bias or concluding causality for TBI, a summary of recent research points to several conclusions on the TBI-dementia relationship. 1) Increasing severity of a single moderate-to-severe TBI increases the risk of subsequent Alzheimer's disease (AD), the most common type of dementia. 2) Repetitive, often subconcussive, mild TBIs increases the risk for chronic traumatic encephalopathy (CTE), a degenerative neuropathology. 3) TBI may be a risk factor for other neurodegenerative disorders that can be associated with dementia. 4) TBI appears to lower the age of onset of TBI-related neurocognitive syndromes, potentially adding "TBI cognitive-behavioral features". The literature further indicates several specific risk factors for TBI-associated dementia: 5) any blast or blunt physical force to the head as long as there is violent head displacement; 6) decreased cognitive and/or neuronal reserve and the related variable of older age at TBI; and 7) the presence of apolipoprotein E ɛ4 alleles, a genetic risk factor for AD. Finally, there are neuropathological features relating TBI with neurocognitive syndromes: 8) acute TBI results in amyloid pathology and other neurodegenerative proteinopathies; 9) CTE shares features with neurodegenerative dementias; and 10) TBI results in white matter tract and neural network disruptions. Although further research is needed, these ten findings suggest that dose-dependent effects of violent head displacement in vulnerable brains predispose to dementia; among several potential mechanisms is the propagation of abnormal proteins along damaged white matter networks.
Bieniek, Kevin F; Ross, Owen A; Cormier, Kerry A; Walton, Ronald L; Soto-Ortolaza, Alexandra; Johnston, Amelia E; DeSaro, Pamela; Boylan, Kevin B; Graff-Radford, Neill R; Wszolek, Zbigniew K; Rademakers, Rosa; Boeve, Bradley F; McKee, Ann C; Dickson, Dennis W
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future
Full Text Available Context: Coagulopathy frequently occurs following traumatic brain injury (TBI and usually occurs 6-72 hour post-trauma. The incidence and the probable risk factors for development of coagulopathy and poor outcome following TBI are largely unknown and vary considerably. Aims: To assess the incidence and probable risk factors for development of coagulopathy and to identify the risk factors for poor outcome in terms of median survival time following TBI. Materials and Methods: In this prospective study over two years, patients of isolated moderate and severe traumatic brain injury (GCS≤12 admitted to trauma center had coagulation profile (PT, APTT, thrombin time, fibrinogen and D-dimer, arterial lactate and ABG analysis done on day of admission and on day three. Coagulopathy was defined as prothrombin time (PT or/and activated partial thromboplastin time (APTT more than 1.5 times the normal control. Incidence of in-hospital mortality was assessed in all cases. Statistical Analysis: A stepwise logistic regression analysis was performed to identify risk factors for coagulopathy and mortality in these patients. Results: A total of 208 patients were enrolled in the study. The mean age was 32 ± 12 years and mean GCS was 7.1 ± 2.8. Coagulopathy was present in 46% ( n = 96 of patients. Risk factors for development of coagulopathy were found out to be severity of head injury (OR: 2.81, elevated D-dimer (OR: 3.43, low hemoglobin (OR: 3.13, and effaced cisterns in the CT scan (OR: 2.72. Presence of coagulopathy (OR: 2.97 and severity of head injury (OR: 5.70 strongly predicted poor outcome, and were associated with a decreased median survival time. Conclusions: There is a high incidence of coagulopathy following TBI. The presence of coagulopathy as well as of severity of TBI are strong predictors of in-hospital mortality in these patients.
Agrawal, Rahul; Noble, Emily; Vergnes, Laurent; Ying, Zhe; Reue, Karen; Gomez-Pinilla, Fernando
Fructose consumption has been on the rise for the last two decades and is starting to be recognized as being responsible for metabolic diseases. Metabolic disorders pose a particular threat for brain conditions characterized by energy dysfunction, such as traumatic brain injury. Traumatic brain injury patients experience sudden abnormalities in the control of brain metabolism and cognitive function, which may worsen the prospect of brain plasticity and function. The mechanisms involved are poorly understood. Here we report that fructose consumption disrupts hippocampal energy homeostasis as evidenced by a decline in functional mitochondria bioenergetics (oxygen consumption rate and cytochrome C oxidase activity) and an aggravation of the effects of traumatic brain injury on molecular systems engaged in cell energy homeostasis (sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1alpha) and synaptic plasticity (brain-derived neurotrophic factor, tropomyosin receptor kinase B, cyclic adenosine monophosphate response element binding, synaptophysin signaling). Fructose also worsened the effects of traumatic brain injury on spatial memory, which disruption was associated with a decrease in hippocampal insulin receptor signaling. Additionally, fructose consumption and traumatic brain injury promoted plasma membrane lipid peroxidation, measured by elevated protein and phenotypic expression of 4-hydroxynonenal. These data imply that high fructose consumption exacerbates the pathology of brain trauma by further disrupting energy metabolism and brain plasticity, highlighting the impact of diet on the resilience to neurological disorders. © The Author(s) 2015.
O'Rourke, Conall; Linden, Mark A; Lohan, Maria
The prevalence of traumatic brain injury (TBI) among offender populations is significantly higher than among the general population. Despite this, no study has yet assessed the knowledge of members of the probation service surrounding TBI. Knowledge was assessed among members of the Probation Board for Northern Ireland (PBNI) using a cross-sectional online version of the Common Misconceptions about TBI (CM-TBI) questionnaire. Mean total misconception scores, along with scores on four subdomains (recovery, sequelae, insight, and hidden injury) were calculated. Analysis of variance was used to explore differences in misconceptions based on the collected demographic information. The overall mean percentage of misconceptions for the group was 22.37%. The subdomain with the highest rate of misconceptions (38.21%) was insight into injury which covered misconceptions around offenders' self-awareness of injuries. Those who knew someone with a brain injury scored significantly higher in the CM-TBI total score, F(1,63) = 6.639, p = 0.012, the recovery subdomain, F(1,63) = 10.080, p = 0.002, and the insight subdomain, F(1,63) = 5.834, p = 0.019. Additionally, significant training deficits around TBI were observed among the probation service. This study is the first of its kind to examine the level of understanding around TBI within probation services. The findings reflect potential barriers to identification and rehabilitation of TBI for offenders coming into contact with the criminal justice system. A lack of identification coupled with misconceptions about TBI could lead to inaccurate court reporting with a subsequent impact on sentencing. Implications for Rehabilitation Despite being one of the first points of contact for offenders entering the criminal justice system, members of the probation service reported having no formal training on traumatic brain injury (TBI). The subdomain with the highest rate of misconceptions (insight into injury
Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay
To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Biasca, N; Lovell, M R; Collins, M W; Jordan, B D; Matser, E; Weber, J; Slemmer, J E; Piccininni, P; Maxwell, W; Agosti, R; Wirth, S; Schneider, T O
The minor traumatic brain injury (mTBI) in sports is often looked at as a bagatelle. The treating physician underestimates the severity of the injury suspecting that a mTBI is a nonstructural lesion with an overall excellent prognosis in the majority of the cases. This paper shows that the minor traumatic brain injury may be a structural brain lesion with potentially life-threatening dangers. The therapy should follow exactly defined guidelines, e.g., stepwise protocol of the Concussion in Sports (CIS-) Group. Return to sports activities should happen only when all physical but also cognitive symptoms have subsided. All mTBIs that have been sustained prior to the actual injury have to be recorded properly because repeated mTBIs may cause chronic degenerative brain damage. Neuropsychological testing will aid in the correct diagnosis of a mTBI and is a useful parameter in the course of the injury. In the future biochemical markers may serve as indicators of the severity of the brain injury and may also aid in predicting the outcome after TBI. Today biochemical markers do not serve as a substitute for neuroimaging.
Full Text Available Characterization of cognitive and behavioral complaints is explored in Post-traumatic stress disorder (PTSD and mild traumatic brain injury (MTBI samples according to the severity of PTSD, depression and general anxiety conditions. Self-reported questionnaires on cognitive and behavioral changes are administered to PTSD, MTBI, MTBI/PTSD and control groups. Confounding variables are controlled. All groups report more complaints since the traumatic event. PTSD and MTBI/PTSD groups report more anxiety symptoms, depression and complaints compared to the MTBI group. Relatives of the PTSD group confirm most of the behavioral changes reported. Results suggest the utility of self-reported questionnaires to personalize cognitive and behavioral interventions in PTSD and MTBI to cope with the impacts of the traumatic event.
Full Text Available Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.
if I had a bad headache, I’ll just take a couple of aspirin or something like that to try and make it go away . . . . Sometimes I just have to...The assessment and treatment of individuals with history of traumatic brain injury and post-traumatic stress disorder: A systematic review of the
van der Horn, Harm Jan; Kok, Jelmer G.; de Koning, Myrthe E.; Scheenen, Myrthe E.; Leemans, Alexander; Spikman, Jacoba M.; van der Naalt, Joukje
In this study, structural connectivity after mild traumatic brain injury (mTBI) was examined from a network perspective, with a particular focus on post-traumatic complaints. Fifty-three patients with and without self-reported complaints at 2 weeks after uncomplicated mTBI were included, in addition
Taylor, Douglas D.; Gercel-Taylor, Cicek
We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. PMID:25135964
Turner, Daniel; Schöttle, Daniel; Krueger, Richard; Briken, Peer
Traumatic brain injury (TBI) is one of the leading causes of permanent disability in young adults and is frequently accompanied by changes in sexual behaviors. Satisfying sexuality is an important factor for overall quality of life in people with disabilities. The purpose of this article is to review the studies evaluating the assessment, correlates and management of sexuality following TBI. The Brain Injury Questionnaire of Sexuality is the first validated questionnaire specifically developed for adults with TBI. A considerable amount of individuals with TBI show inappropriate sexual behaviors and sexual dysfunctions. Whereas inappropriate sexual behaviors are related to younger age, less social participation and more severe injuries, sexual dysfunctions show an association with higher fatigue, higher depression scores, less self-esteem and female sex. Healthcare professionals have suggested that because of discomfort at the individual or institutional level, sexual problems are often not sufficiently addressed and have suggested that a specialist should treat sexual problems. Although some important correlates of sexual problems could be identified, methodological differences across studies limit their comparability. Furthermore, there is an absence of evidence-based treatment strategies for addressing sexual problems. Therapeutic efforts should take into account the identified correlates of sexual problems following TBI.
Adhikari, Upendra; Goliaei, Ardeshir; Berkowitz, Max L
Collapse of bubbles, microscopic or nanoscopic, due to their interaction with the impinging pressure wave produces a jet of particles moving in the direction of the wave. If there is a surface nearby, the high-speed jet particles hit it, and as a result damage to the surface is produced. This cavitation effect is well known and intensely studied in case of microscopic sized bubbles. It can be quite damaging to materials, including biological tissues, but it can also be beneficial when controlled, like in case of sonoporation of biological membranes for the purpose of drug delivery. Here we consider recent simulation work performed to study collapse of nanobubbles exposed to shock waves, in order to understand the detailed mechanism of the cavitation induced damage to soft materials, such as biological membranes. We also discuss the connection of the cavitation effect with the traumatic brain injury caused by blasts. Specifically, we consider possible damage to model membranes containing lipid bilayers, bilayers with embedded ion channel proteins like the ones found in neural cells and also protein assemblies found in the tight junction of the blood brain barrier.
Quintana, Albert; Giralt, Mercedes; Molinero, Amalia
Traumatic brain injury is one of the leading causes of incapacity and death among young people. Injury to the brain elicits a potent inflammatory response, comprising recruitment of inflammatory cells, reactive astrogliosis and activation of brain macrophages. Under the influence of presumably se...
Ponsford, Jennie L; Spitz, Gershon; McKenzie, Dean
Duration of post-traumatic amnesia (PTA) has emerged as a strong measure of injury severity after traumatic brain injury (TBI). Despite the growing international adoption of this measure, there remains a lack of consistency in the way in which PTA duration is used to classify severity of injury. This study aimed to establish the classification of PTA that would best predict functional or productivity outcomes. We conducted a cohort study of 1041 persons recruited from inpatient admissions to a TBI rehabilitation center between 1985 and 2013. Participants had a primary diagnosis of TBI, emerged from PTA before discharge from inpatient hospital, and engaged in productive activities before injury. Eight models that classify duration of PTA were evaluated-six that were based on the literature and two that were statistically driven. Models were assessed using area under the receiver operating characteristic curve (AUC) as well as model-based Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) statistics. All categorization models showed longer PTA to be associated with a greater likelihood of being nonproductive at 1 year after TBI. Classification systems with a greater number of categories performed better than two-category systems. The dimensional (continuous) form of PTA resulted in the greatest AUC, and lowest AIC as well as BIC, of the classification systems examined. This finding indicates that the greatest accuracy in prognosis is likely to be achieved using PTA as a continuous variable. This enables the probability of productive outcomes to be estimated with far greater precision than that possible using a classification system. Categorizing PTA to classify severity of injury may be reducing the precision with which clinicians can plan the treatment of patients after TBI.
Brouwer, WH; Withaar, FK; Tant, MLM; van Zomeren, AH
Background: Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task
... evidenced by loss of consciousness or post- traumatic amnesia due to brain trauma or by objective... examination. Both penetrating and non- penetrating wounds that fit this criteria are included, but, primary...
Full Text Available Neuropsychiatric or cognitive disturbances are common complications after traumatic brain injury. They are commonly regarded as irreversible sequelae of organic brain injuries. We report a case of hypopituitarism in a 77-year-old man who presented with long-term neuropsychiatric disturbances, including cognitive impairment, disturbed sleep patterns, personality change, loss of affect, and visual and auditory hallucinations after a traumatic subdural hemorrhage. The treatment response to hormone replacement therapy was nearly complete. Hypopituitarism is rarely considered in patients who sustain traumatic brain injury and the neuropsychiatric manifestations of posttraumatic hypopituitarism have rarely been reported. This case highlights the importance of hypopituitarism as a potential reversible cause of neuropsychiatric disturbances after traumatic brain injury.
Boniface Respicious; Lugazia Edwin Rwebugisa; Ntungi Abel Mussa; Kiloloma Othman
.... However, access to neurosurgical care is poor in low income countries like Tanzania. The aim of this study was to assess the management and outcome of Traumatic brain injury patients at a tertiary level health facility in Tanzania...
J.L. Nielson (Jessica L.); S.R. Cooper (Shelly); J.K. Yue (John); M.D. Sorani (Marco); T. Inoue (Tomoo); E.L. Yuh (Esther); P. Mukherjee (Pratik); T.C. Petrossian (Tanya C.); J. Paquette (Jesse); P.Y. Lum (Pek Y.); G.E. Carlsson (Gunnar E.); M.J. Vassar (Mary); H.F. Lingsma (Hester); W.A. Gordon (Wayne A.); A.B. Valadka (Alex); D. Okonkwo (David); G. Manley (Geoffrey); A.R. Ferguson (Adam)
markdownabstractBackground: Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating
...) Application of TBI, neurobehavioral testing and collection of biofluids and tissues; 2) Optimization of proteomic protocols for the identification of differentially expressed proteins in the plasma of brain-traumatized rats; 3...
Baguley, Ian J; Heriseanu, Roxana E; Gurka, Joseph A
The pharmacological management of dysautonomia, otherwise known as autonomic storms, following acute neurological insults, is problematic and remains poorly researched. This paper presents six subjects with dysautonomia following extremely severe traumatic brain injury where gabapentin controlled...
Young, Adam M. H.; Donnelly, Joseph; Czosnyka, Marek; Jalloh, Ibrahim; Liu, Xiuyun; Aries, Marcel J.; Fernandes, Helen M.; Garnett, Matthew R.; Smielewski, Peter; Hutchinson, Peter J.; Agrawal, Shruti
Introduction Multimodality monitoring is regularly employed in adult traumatic brain injury (TBI) patients where it provides physiologic and therapeutic insight into this heterogeneous condition. Pediatric studies are less frequent. Methods An analysis of data collected prospectively from 12
Shively, Sharon; Scher, Ann I; Perl, Daniel P; Diaz-Arrastia, Ramon
Traumatic brain injury (TBI) is among the earliest illnesses described in human history and remains a major source of morbidity and mortality in the modern era. It is estimated that 2% of the US population lives with long-term disabilities due to a prior TBI, and incidence and prevalence rates are even higher in developing countries. One of the most feared long-term consequences of TBIs is dementia, as multiple epidemiologic studies show that experiencing a TBI in early or midlife is associated with an increased risk of dementia in late life. The best data indicate that moderate and severe TBIs increase risk of dementia between 2- and 4-fold. It is less clear whether mild TBIs such as brief concussions result in increased dementia risk, in part because mild head injuries are often not well documented and retrospective studies have recall bias. However, it has been observed for many years that multiple mild TBIs as experienced by professional boxers are associated with a high risk of chronic traumatic encephalopathy (CTE), a type of dementia with distinctive clinical and pathologic features. The recent recognition that CTE is common in retired professional football and hockey players has rekindled interest in this condition, as has the recognition that military personnel also experience high rates of mild TBIs and may have a similar syndrome. It is presently unknown whether dementia in TBI survivors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a common cause of acquired dementia. Herein, we will review the epidemiologic data linking TBI and dementia, existing clinical and pathologic data, and will identify areas where future research is needed.
Wong, David K; Lurie, Fedor; Wong, Linda L
Patients are living longer with cardiovascular disease managed with antiplatelet drugs. These seniors are asked to be more physically active and are prone to falls or injuries. Few have studied the mortality or morbidity from anticoagulants in patients with traumatic brain injuries (TBI). With the increasing use of clopidogrel in the elderly, studies on the consequences of TBI are warranted. This is a retrospective case-controlled study using a trauma data registry of 3,817 closed head trauma cases (2001-2005). Patients with preinjury use of clopidogrel, aspirin or warfarin, and evidence of traumatic intracranial bleeding were identified (n = 131). These were compared with a frequency-matched control group (n = 178) with similar age, gender, Glasgow Coma Scale, and Injury Severity Scores. Main outcome measure included mortality, hospital or intensive care unit duration, and discharge disposition. Of 131 patients on anticoagulants, patients on clopidogrel (n = 21) were more likely to die (OR = 14.7; 95% CI: 2.3-93.6) and be discharged to an inpatient long-term facility (OR = 3.25; 95%CI: 1.06-9.96). Length of hospital stay and intensive care unit stay were not different from control. Mortality in aspirin patients (n = 90) and warfarin patients (n = 20) did not differ from control. Warfarin patients had increased hospital and ICU stay (10.6 and 5.3 days) when compared with the control (4.7 and 0.9 days, respectively). TBI patients on clopidogrel may have increased long-term disability and fatal consequences when compared with patients who are not on these drugs or on other anticoagulants. Patients on clopidogrel should be advised of safety when engaging in potentially dangerous activities to avoid the consequences of TBI.
Fetta, Joseph; Starkweather, Angela; Gill, Jessica M
Computer-based interventions have been developed to improve cognitive performance after mild traumatic brain injury; however, a thorough evaluation of this body of research has not been addressed in the literature. The aim of this study was to provide a synthesis and critical review of current research studies that have tested the efficacy of computer-based interventions on cognitive performance after mild traumatic brain injury. A critical review was conducted by identifying relevant studies in the electronic databases PubMed/MEDLINE, PsycInfo, and CINAHL from 2011 to the present. Because of the limited number of publications focused exclusively on mild traumatic brain injury, research studies that assessed the impact of computer-based interventions on cognitive outcomes in populations with acquired brain injury were included. Of the 58 studies identified, only 10 publications included participants with mild traumatic brain injury. Overall, the identified studies did not use a standard method for assessing the severity of traumatic brain injury, and many studies included participants with a wide variety of etiologies for acquired brain injury and used multiple measures of cognitive performance, which made comparisons difficult across studies. In addition to small sample sizes, the study samples were heterogeneous in regard to the number of previous traumatic brain injuries, time elapsed since injury, and age and gender distributions. Preinjury comorbidities that may affect cognitive performance, such as depression, anxiety, or learning disabilities, were often not assessed. There is weak evidence that computer-based interventions can improve working memory and cognitive function in individuals after mild traumatic brain injury. Because of the low-quality evidence, seminal questions remain regarding the optimal format, dosage, timing, and duration of computer-based intervention for improving cognitive performance. Future studies should focus on using a strong
Anthonymuthu, Tamil Selvan; Kenny, Elizabeth Megan; Bayır, Hülya
Lipid peroxidation can be broadly defined as the process of inserting a hydroperoxy group into a lipid. Polyunsaturated fatty acids present in the phospholipids are often the targets for peroxidation. Phospholipids are indispensable for normal structure of membranes. The other important function of phospholipids stems from their role as a source of lipid mediators - oxygenated free fatty acids that are derived from lipid peroxidation. In the CNS, excessive accumulation of either oxidized phospholipids or oxygenated free fatty acids may be associated with damage occurring during acute brain injury and subsequent inflammatory responses. There is a growing body of evidence that lipid peroxidation occurs after severe traumatic brain injury in humans and correlates with the injury severity and mortality. Identification of the products and sources of lipid peroxidation and its enzymatic or non-enzymatic nature is essential for the design of mechanism-based therapies. Recent progress in mass spectrometry-based lipidomics/oxidative lipidomics offers remarkable opportunities for quantitative characterization of lipid peroxidation products, providing guidance for targeted development of specific therapeutic modalities. In this review, we critically evaluate previous attempts to use non-specific antioxidants as neuroprotectors and emphasize new approaches based on recent breakthroughs in understanding of enzymatic mechanisms of lipid peroxidation associated with specific death pathways, particularly apoptosis. We also emphasize the role of different phospholipases (calcium-dependent and -independent) in hydrolysis of peroxidized phospholipids and generation of pro- and anti-inflammatory lipid mediators. This article is part of a Special Issue entitled SI:Brain injury and recovery. Copyright © 2016 Elsevier B.V. All rights reserved.
Lee, Jisook; Costantini, Todd W; D'Mello, Ryan; Eliceiri, Brian P; Coimbra, Raul; Bansal, Vishal
Traumatic brain injury (TBI)-induced cerebral inflammation involves several mediators including activation of resident microglia, infiltration of leukocytes, and release of proinflammatory cytokines and chemokines at the site of injury. Invading leukocytes, mainly neutrophil and inflammatory monocytes, contribute to ongoing post-TBI cerebral edema and neuronal injury. Based on the beneficial effect of ghrelin hormone treatment following TBI, we hypothesized that ghrelin may alter the infiltrating inflammatory cell profile. A weight drop model was used to create severe TBI. C57 mice were divided into three groups: sham, no TBI or ghrelin treatment; TBI, TBI only; TBI/ghrelin, animals were treated with ghrelin 20 μg (intraperitoneally) immediately following TBI and again 1 hour later. Seven days after injury, brain sections were immunostained with Iba-1 and CD11b to assess the recruitment and activation of resident microglia and infiltrated leukocytes. Alternatively, brain dissociates were isolated, and flow cytometry was used to gate for microglia (CD11b, CD45 cells), monocytes (CD11b, CD45, F4/80 cells), and neutrophils (CD11b, CD45, F4/80 cells) to measure their recruitment to injury site. TBI resulted in a rapid invasion (16-fold) of inflammatory leukocytes to the site of injury, which persisted for at least 1 week. Ghrelin treatment significantly reduced infiltration of peripheral leukocytes (2.8-fold). In particular, recruitment of CD11bCD45 inflammatory monocytes (2.4-fold) and CD11bCD45F4/80 neutrophils (1.7-fold) was reduced following ghrelin treatment. There were no observed ghrelin-mediated changes in either the number of CD11bCD45 resident microglia or its activation state. Together, our data demonstrate that ghrelin attenuated leukocyte recruitment, which correlates with improved histologic outcome following TBI.
Emily L. Dennis
Full Text Available Traumatic brain injury (TBI is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI cohort, assessed at two time points. Children were first assessed 2–5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8–18 years old and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT, with significant structural disruption of the white matter (WM at 2–5 months post injury. We investigated how this subgroup (TBI-slow, N = 11 differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10 with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory.
Traumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.
Khalili, Hosseinali; Derakhshan, Nima; Malekmohammadi, Zahed; Ghaffarpasand, Fariborz
Mycotic aneurysm of external carotid artery is extremely rare. We herein report a case of external carotid artery (ECA) aneurysm following severe traumatic brain injury. A 24-year-old man with severe traumatic brain injury (TBI) following a car accident was referred to Rajaee Trauma Center Emergency Room affiliated to Shiraz University of Medical Sciences in Shiraz, Iran. He underwent ventriculostomy on arrival for intracerebral pressure (ICP) monitoring and for a second time due to hydroceph...
Moth Wolffbrandt, Mia; Poulsen, Ingrid; Engberg, Aase W
To investigate the occurrence and severity of agitation in patients after severe traumatic brain injury (TBI), to identify predictors of agitation and to study interrater reliability for a translated version of the Agitated Behavior Scale (ABS).......To investigate the occurrence and severity of agitation in patients after severe traumatic brain injury (TBI), to identify predictors of agitation and to study interrater reliability for a translated version of the Agitated Behavior Scale (ABS)....
AWARD NUMBER: W81XWH-16-1-0588 TITLE: Genetic variation underlying traumatic brain injury (TBI) and Late Onset Alzheimer’s Disease (LOAD...14 Sep 2017 4. TITLE AND SUBTITLE Late-Onset Alzheimer’s Disease (LOAD) 5a. CONTRACT NUMBER Genetic variation underlying traumatic brain injury...accelerating individual’s memory decline and possibly accelerating LOAD like neuro-degeneration. In addition, genetic risk factors including non- coding and
Amen, Daniel G; Wu, Joseph C; Taylor, Derek; Willeumier, Kristen
Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.
Rowe, Rachel K; Ellis, Gavin I; Harrison, Jordan L; Bachstetter, Adam D; Corder, Gregory F; Van Eldik, Linda J; Taylor, Bradley K; Marti, Francesc; Lifshitz, Jonathan
Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation. To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1-9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs). We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are identified as a potential target for
Haefeli, Jenny; Ferguson, Adam R; Bingham, Deborah; Orr, Adrienne; Won, Seok Joon; Lam, Tina I; Shi, Jian; Hawley, Sarah; Liu, Jialing; Swanson, Raymond A; Massa, Stephen M
Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint. Data was curated and analyzed in a linked workflow involving non-linear principal component analysis followed by hypothesis testing with a linear mixed model. Results revealed significant benefits of the neurotrophic agent LM11A-31 on learning and memory outcomes after traumatic brain injury. In addition, modulations of LM11A-31 effects by co-administration of minocycline and by the type of physical therapy applied reached statistical significance. These results suggest a combinatorial effect of drug and physical therapy interventions that was not evident by univariate analysis. The study designs and analytic techniques applied here form a structured, unbiased, internally validated workflow that may be applied to other combinatorial studies, both in animals and humans.
Ahl, Rebecka; Sjolin, Gabriel; Mohseni, Shahin
Depressive symptoms occur in approximately half of trauma patients, negatively impacting on functional outcome and quality of life following severe head injury. Pontine noradrenaline has been shown to increase upon trauma and associated β-adrenergic receptor activation appears to consolidate memory formation of traumatic events. Blocking adrenergic activity reduces physiological stress responses during recall of traumatic memories and impairs memory, implying a potential therapeutic role of β-blockers. This study examines the effect of pre-admission β-blockade on post-traumatic depression. All adult trauma patients (≥18 years) with severe, isolated traumatic brain injury (intracranial Abbreviated Injury Scale score (AIS) ≥3 and extracranial AIS depression was defined as the prescription of antidepressants within one year of trauma. Patients with and without pre-admission β-blockers were matched 1:1 by age, gender, Glasgow Coma Scale, Injury Severity Score and head AIS. Analysis was carried out using McNemar's and Student's t-test for categorical and continuous data, respectively. A total of 545 patients met the study criteria. Of these, 15% (n=80) were prescribed β-blockers. After propensity matching, 80 matched pairs were analyzed. 33% (n=26) of non β-blocked patients developed post-traumatic depression, compared to only 18% (n=14) in the β-blocked group (p=0.04). There were no significant differences in ICU (mean days: 5.8 (SD 10.5) vs. 5.6 (SD 7.2), p=0.85) or hospital length of stay (mean days: 21 (SD 21) vs. 21 (SD 20), p=0.94) between cohorts. β-blockade appears to act prophylactically and significantly reduces the risk of post-traumatic depression in patients suffering from isolated severe traumatic brain injuries. Further prospective randomized studies are warranted to validate this finding. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pappu, Suguna; Lerma, Jesus; Khraishi, Tariq
Morphologic features of computed tomography (CT) scans of the brain can be used to estimate intracranial pressure (ICP) via an image-processing algorithm. Clinically, such estimations can be used to prognosticate outcomes and avoid placement of invasive intracranial monitors in certain patients with severe traumatic brain injury. Features on a CT scan that may correlate with measurements of low ICP are sought. A measure is proposed that is a function of the distribution of cerebrospinal fluid (CSF) in and around the brain. In our method, we present an algorithm that semiautomatically segments brain parenchyma from CSF, and apply standard image processing calculations. The ratio of CSF volume to the size of the intracranial vault (ICV) or volume inside the skull, csf(v) /icv(v) is calculated and then plotted against the actual recorded ICP, yielding a relationship between the image features and ICP. We analyzed a total of 45 scans from 20 patients with severe traumatic brain injury (TBI). We showed that a ratio csf(v)/icv(v) > .034 correlates with an ICP < 20 mmHg (P = .0046). For csf(v)/icv(v) ≤ .034, a distinction between low and high ICP cannot be effectively estimated by this univariate measure. This method permits a noninvasive means of identifying patients who are low risk for having elevated ICP; by following Brain Trauma Foundation guidelines strictly such a patient may be subjected to an unnecessary, invasive procedure. This work is a promising pilot study that will need to be analyzed for a larger population. Copyright © 2015 by the American Society of Neuroimaging.
Full Text Available Jutaporn Maneewong,1 Benchalak Maneeton,1 Narong Maneeton,1 Tanat Vaniyapong,2 Patrinee Traisathit,3 Natthanidnan Sricharoen,3 Manit Srisurapanont1 1Department of Psychiatry, 2Department of Surgery, Faculty of Medicine, 3Department of Statistics, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand Background: Delirium in traumatic brain injury (TBI is common, may be predictable, and has a multifaceted symptom complex. This study aimed to examine: 1 the sum score of Glasgow Coma Scale (GCS and if its component scores could predict delirium in TBI patients, and 2 the prominent symptoms and their courses over the first days after TBI. Methods: TBI patients were recruited from neurosurgical ward inpatients. All participants were hospitalized within 24 hours after their TBI. Apart from the sum score of GCS, which was obtained at the emergency department (ED, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for delirium were applied daily. The severity of delirium symptoms was assessed daily using the Delirium Rating Scale – Revised-98 (DRS-R-98. Results: The participants were 54 TBI patients with a mean GCS score of 12.7 (standard deviation [SD] =2.9. A total of 25 patients (46.3% met the diagnosis of delirium and had a mean age of 36.7 years (SD =14.8. Compared with 29 non-delirious patients, 25 delirious patients had a significantly lower mean GCS score (P=0.04, especially a significantly lower verbal component score (P=0.03. Among 18 delirious patients, four symptoms of the DRS-R-98 cognitive domain (orientation, attention, long-term memory, and visuospatial ability were moderate symptoms (score ≥2 at the first day of admission. After follow-up, three cognitive (orientation, attention, and visuospatial ability and two noncognitive symptoms (lability of affect and motor agitation rapidly resolved. Conclusion: Almost half of patients with mild to moderate head injuries may develop
Abou-El-Hassan, Hadi; Dia, Batoul; Choucair, Khalil; Eid, Stephanie A; Najdi, Farah; Baki, Lama; Talih, Farid; Eid, Assaad A; Kobeissy, Firas
Traumatic brain injury is a detrimental medical condition particularly when accompanied by diabetes. There are several comorbidities going along with diabetes including, but not limited to, kidney failure, obesity, coronary artery disease, peripheral vascular disease, hypertension, stroke, neuropathies and amputations. Unlike diabetes type 1, diabetes type 2 is more common in adults who simultaneously suffer from other comorbid conditions making them susceptible to repetitive fall incidents and sustaining head trauma. The resulting brain insult exacerbates current psychiatric disorders such as depression and anxiety, which, in turn, increases the risk of sustaining further brain traumas. The relationship between diabetes, traumatic brain injury and psychiatric health constitutes a triad forming a non-reversible vicious cycle. At the proteomic and psychiatric levels, cellular, molecular and behavioral alterations have been reported with the induction of non-traumatic brain injury in diabetic models such as stroke. However, research into traumatic brain injury has not been systematically investigated. Thus, in cases of diabetic neuropathy complicated with traumatic brain injury, utilizing fine structural and analytical techniques allows the identification of key biological markers that can then be used as innovative diagnostics as well as novel therapeutic targets in an attempt to treat diabetes and its sequelae especially those arising from repetitive mild brain trauma. Copyright © 2017 Elsevier Ltd. All rights reserved.
Simarjot K Dhaliwal
Full Text Available Background: Traumatic brain injury (TBI is a common cause of physical, psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms.Objective: This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS and transcranial Direct Current Stimulation (tDCS have been used to treat symptoms following a traumatic brain injury. A subsequent discussion attempts to determine the value of these methods in light of their potential risks.Methods: The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI.Results: Eight case-studies and four multi-subject reports using rTMS and six multi-subject studies using tDCS were found. Two instances of seizure are discussed. Conclusions: There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild-TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional
Magnoni, Sandra; Mac Donald, Christine L; Esparza, Thomas J; Conte, Valeria; Sorrell, James; Macrì, Mario; Bertani, Giulio; Biffi, Riccardo; Costa, Antonella; Sammons, Brian; Snyder, Abraham Z; Shimony, Joshua S; Triulzi, Fabio; Stocchetti, Nino; Brody, David L
Axonal injury is a major contributor to adverse outcomes following brain trauma. However, the extent of axonal injury cannot currently be assessed reliably in living humans. Here, we used two experimental methods with distinct noise sources and limitations in the same cohort of 15 patients with severe traumatic brain injury to assess axonal injury. One hundred kilodalton cut-off microdialysis catheters were implanted at a median time of 17 h (13-29 h) after injury in normal appearing (on computed tomography scan) frontal white matter in all patients, and samples were collected for at least 72 h. Multiple analytes, such as the metabolic markers glucose, lactate, pyruvate, glutamate and tau and amyloid-β proteins, were measured every 1-2 h in the microdialysis samples. Diffusion tensor magnetic resonance imaging scans at 3 T were performed 2-9 weeks after injury in 11 patients. Stability of diffusion tensor imaging findings was verified by repeat scans 1-3 years later in seven patients. An additional four patients were scanned only at 1-3 years after injury. Imaging abnormalities were assessed based on comparisons with five healthy control subjects for each patient, matched by age and sex (32 controls in total). No safety concerns arose during either microdialysis or scanning. We found that acute microdialysis measurements of the axonal cytoskeletal protein tau in the brain extracellular space correlated well with diffusion tensor magnetic resonance imaging-based measurements of reduced brain white matter integrity in the 1-cm radius white matter-masked region near the microdialysis catheter insertion sites. Specifically, we found a significant inverse correlation between microdialysis measured levels of tau 13-36 h after injury and anisotropy reductions in comparison with healthy controls (Spearman's r = -0.64, P = 0.006). Anisotropy reductions near microdialysis catheter insertion sites were highly correlated with reductions in multiple additional white matter
Gary E Strangman
Full Text Available Cognitive deficits following traumatic brain injury (TBI commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS. Primary outcome measures (HVLT, RBMT were collected at the time of the MRI scan, immediately following therapy, and again at one month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores. We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.
Tan, Liwen; Zhang, Li; Qi, Rongfeng; Lu, Guangming; Li, Lingjiang; Liu, Jun; Li, Weihui
This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.
Araujo, Gabriel C; Antonini, Tanya N; Anderson, Vicki; Vannatta, Kathryn A; Salley, Christina G; Bigler, Erin D; Taylor, H Gerry; Gerhardt, Cynthia; Rubin, Kenneth; Dennis, Maureen; Lo, Warren; Mackay, Mark T; Gordon, Anne; Hajek Koterba, Christine; Gomes, Alison; Greenham, Mardee; Owen Yeates, Keith
This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Participants were children with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke (N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch) subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).
Ponnada A. Narayana
Full Text Available Multi-modal magnetic resonance imaging (MRI that included high resolution structural imaging, diffusion tensor imaging (DTI, magnetization transfer ratio (MTR imaging, and magnetic resonance spectroscopic imaging (MRSI were performed in mild traumatic brain injury (mTBI patients with negative computed tomographic scans and in an orthopedic-injured (OI group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h and at follow-up (~90 days. DTI data was analyzed using tract based spatial statistics (TBSS. Global and regional atrophies were calculated using tensor-based morphometry (TBM. MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI.
Jacky T Yeung
Full Text Available Context: Animal and molecular studies have shown that cocaine exerts a neuroprotective effect against cerebral ischemia. Aims: To determine if the presence of cocaine metabolites on admission following traumatic brain injury (TBI is associated with better outcomes. Settings and Design: Level-1 trauma center, retrospective cohort. Materials and Methods: After obtaining Institutional Review Board (IRB approval, the trauma registry was searched from 2006 to 2009 for all patients aged 15-55 years with blunt head trauma and non-head AIS <3. Exclusion criteria were pre-existing brain pathology and death within 30 min of admission. The primary outcome was in-hospital mortality; secondary outcomes were hospital length of stay (LOS, and Glasgow Outcome Score (GOS. Statistical Analysis: Logistic regression was used to determine the independent effect of cocaine on mortality. Hospital LOS was compared with multiple linear regression. Results: A total of 741 patients met criteria and had drug screens. The screened versus unscreened groups were similar. Cocaine positive patients were predominantly African-American (46% vs. 21%, P < 0.0001, older (40 years vs. 30 years, P < 0.0001, and had ethanol present more often (50.7% vs. 37.8%, P = 0.01. There were no differences in mortality (cocaine-positive 1.4% vs. cocaine-negative 2.7%, P = 0.6 on both univariate and multivariate analysis. Conclusions: Positive cocaine screening was not associated with mortality in TBI. An effect may not have been detected because of the low mortality rate. LOS is affected by many factors unrelated to the injury and may not be a good surrogate for recovery. Similarly, GOS may be too coarse a measure to identify a benefit.
Mailhan, Laurence; Azouvi, Philippe; Dazord, Alice
To assess the relationships between life satisfaction and disability after a severe traumatic brain injury (TBI). Cross-sectional study, including 75 patients 2 years or more after a severe TBI. Life satisfaction was assessed with the Subjective Quality of Life Profile. Impairments, activities and participation were assessed with standardized tests. The satisfaction profile was flat, i.e. the majority of items obtained mean satisfaction scores close to 0, suggesting that participants felt indifferent to these items or in other words that they were neither satisfied nor unsatisfied. Patients were on average slightly dissatisfied with their cognitive functions, physical abilities and self-esteem. A factor analysis revealed three underlying factors. The main finding was that the relationships between life satisfaction and disability were not linear: the lowest satisfaction scores were reported by participants with moderate disability rated by the Glasgow Outcome Scale, while individuals with severe disability did not significantly differ from the good recovery group. Life satisfaction is not linearly related to disability after severe TBI.
Full Text Available The conflicts in Iraq and Afghanistan have placed an increased awareness on traumatic brain injury (TBI. Various publications have estimated the incidence of TBI for our deployed servicemen, however all have been based on extrapolations of data sets or subjective evaluations due to our current method of diagnosing a TBI. Therefore it has been difficult to get an accurate rate and severity of deployment related TBIs, or the incidence of multiple TBIs our service members are experiencing. As such, there is a critical need to develop a rapid objective method to diagnose TBI on the battlefield. Because of the austere environment of the combat theatre the ideal diagnostic platform faces numerous logistical constraints not encountered in civilian trauma centers. Consequently, a simple blood test to diagnosis TBI represents a viable option for the military. This perspective will provide information on some of the current options for TBI biomarkers, detail concerning battlefield constraints and a possible acquisition strategy for the military. The end result is a non-invasive TBI diagnostic platform capable of providing much needed advances in objective triage capabilities and improved clinical management of in-Theatre TBI.
Full Text Available Therapeutic hypothermia (TH is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS and traumatic brain injury (TBI, however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention.Among the various methods for hypothermia induction, intravascular cooling (IVC may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.
Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.
Hobart-Porter, Laura; Wade, Shari; Minich, Nori; Kirkwood, Michael; Stancin, Terry; Taylor, Hudson Gerry
To characterize the effects of caregiver mental health and coping strategies on interactions with an injured adolescent acutely after traumatic brain injury (TBI). Multi-site, cross-sectional study. Outpatient setting of 3 tertiary pediatric hospitals and 2 tertiary general medical centers. Adolescents (N = 125) aged 12-17 years, 1-6 months after being hospitalized with complicated mild to severe TBI. Data were collected as part of a multi-site clinical trial of family problem-solving therapy after TBI. Multiple regression analyses were used to examine the relationship of caregiver and environmental characteristics to the dimensions of effective communication, warmth, and negativity during caregiver-adolescent problem-solving discussions. Adolescent and caregiver interactions, as measured by the Iowa Family Interaction Rating Scales. Caregivers who utilized problem-focused coping strategies were rated as having higher levels of effective communication (P adolescent and fewer children in the home were associated with increased parental warmth during the interaction (P adolescent TBI severity nor caregiver depression significantly influenced caregiver-teen interactions. Problem-focused coping strategies are associated with higher levels of effective communication and lower levels of caregiver negativity during the initial months after adolescent TBI, suggesting that effective caregiver coping may facilitate better caregiver-adolescent interactions after TBI. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
Dennis, Maureen; Simic, Nevena; Agostino, Alba; Taylor, H Gerry; Bigler, Erin D; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen
Social communication involves influencing what other people think and feel about themselves. We use the term conative theory of mind (ToM) to refer to communicative interactions involving one person trying to influence the mental and emotional state of another, paradigmatic examples of which are irony and empathy. This study reports how children with traumatic brain injury (TBI) understand ironic criticism and empathic praise, on a task requiring them to identify speaker belief and intention for direct conative speech acts involving literal truth, and indirect speech acts involving either ironic criticism or empathic praise. Participants were 71 children in the chronic state of a single TBI and 57 age- and gender-matched children with orthopedic injuries (OI). Group differences emerged on indirect speech acts involving conation (i.e., irony and empathy), but not on structurally and linguistically identical direct speech acts, suggesting specific deficits in this aspect of social cognition in school-age children with TBI. Deficits in children with mild-moderate TBI were less widespread and more selective than those of children with more severe injuries. Deficits in understanding the social, conative function of indirect speech acts like irony and empathy have widespread and deep implications for social function in children with TBI.
McCauley, Stephen R; Levin, Harvey S
Prospective memory (PM) performance was investigated in a preliminary study of children and adolescents ages 10-19 in 3 groups: individuals with orthopedic injuries (not involving the head) requiring hospitalization (Ortho, N = 15), mild traumatic brain injury (TBI, N = 17), and severe TBI (N = 15). All participants with TBI were at least 5 years postinjury and participants in the Ortho group were at least 3 years postinjury. The PM task involved reporting words presented in blue during a category decision task in which words were presented in several different colors and participants were to determine which of two categories the word belonged. Participants were asked to make their choices as quickly as possible. After a 10- to 15-min intervening computer task in which all words were presented in black letters, a large proportion of participants with mild or severe TBI failed to indicate any blue words when they appeared. After a reminder to perform the PM task was given to all at the same point in the task, PM performance increased in the Ortho and Mild TBI groups, but remained comparably impaired in the Severe TBI group. Reaction time (RT) data indicated that mean RT was slower with increasing TBI severity. Further, there was a significant cost in RT for performing the PM task during the ongoing category decision task for all groups. The cost in terms of slowed RT increased with greater TBI severity.
Richmond, Erick; Rogol, Alan D
Traumatic brain injury (TBI) is a common cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioral, psychological and social defects. Recent data suggest that pituitary hormone deficiency is not infrequent among TBI survivors; the prevalence of reported hypopituitarism following TBI varies widely among published studies. The most common cause of TBI is motor vehicle accidents, including pedestrian-car and bicycle car encounters, falls, child abuse, violence and sports injuries. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90 %. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Endocrine dysfunction after TBI in children and adolescents is common. Adolescence is a time of growth, freedom and adjustment, consequently TBI is also common in this group. Sports-related TBI is an important public health concern, but many cases are unrecognized and unreported. Sports that are associated with an increased risk of TBI include those involving contact and/or collisions such as boxing, football, soccer, ice hockey, rugby, and the martial arts, as well as high velocity sports such as cycling, motor racing, equestrian sports, skiing and roller skating. The aim of this paper is to summarize the best evidence of TBI as a cause of pituitary deficiency in children and adults.
Peltz, Carrie B; Gardner, Raquel C; Kenney, Kimbra; Diaz-Arrastia, Ramon; Kramer, Joel H; Yaffe, Kristine
While traumatic brain injury (TBI) is common across the life span, the detailed neurobehavioral characteristics of older adults with prior TBI remain unclear. Our goal was to compare the clinical profile of older independently living veterans with and without prior TBI. Two veterans' retirement communities. Seventy-five participants with TBI and 71 without (mean age = 78 years). Cross-sectional. TBI history was determined by the Ohio State University TBI Questionnaire. We assessed psychiatric and medical history via interviews and chart review and conducted measures assessing functional/lifestyle, psychiatric, and cognitive outcomes. Regression analyses (adjusted for demographics, diabetes, prior depression, substance abuse, and site) were performed to compare between TBI and non-TBI participants. Compared with veterans without TBI, those with TBI had greater functional impairment (adjusted P = .05), endorsed more current depressive (adjusted P = .04) and posttraumatic stress disorder symptoms (adjusted P = .01), and had higher rates of prior depression and substance abuse (both adjusted Ps < .01). While composite memory and language scores did not differ between groups, participants with TBI performed worse on tests of executive functioning/processing speed (adjusted P = .01). Our results suggest that TBI may have adverse long-term neurobehavioral consequences and that TBI-exposed adults may require careful screening and follow-up.
Full Text Available Background. Individuals with traumatic brain injury (TBI face many challenges when attempting to return to work (RTW. Vocational evaluation (VE is a systematic process that involves assessment and appraisal of an individual’s current work-related characteristics and abilities. Objective. The aims of this study are to (1 examine demographic and employment characteristics of vocational rehabilitation providers (VRPs, (2 identify the specific evaluation methods that are used in the VE of individuals with TBI, and (3 examine the differences in assessment method practices based upon evaluator assessment preferences. Methods. This exploratory case study used a forty-six-item online survey which was distributed to VRPs. Results. One hundred and nine VRPs accessed the survey. Of these, 74 completed the survey. A majority of respondents were female (79.7%, Caucasian (71.6%, and holding a master’s degree (74.3%, and more than half (56.8% were employed as state vocational rehabilitation counselors (VRCs. In addition, over two-thirds (67.6% were certified rehabilitation counselors (CRCs. Respondents reported using several specific tools and assessments during the VE process. Conclusions. Study findings reveal differences in use of and rationales for specific assessments amongst VRPs. Understanding VRP assessment practices and use of an evidence-based framework for VE following TBI may inform and improve VE practice.
Full Text Available In this study, using two different injury models in two different species, we found that early post-injury treatment with N-Acetyl Cysteine (NAC reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting, to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI. For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30-60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man.
Gaines, Katy D; Soper, Henry V; Berenji, Gholam R
This study investigates neuropsychological deficits in recently deployed veterans with mild traumatic brain injury (mTBI). Veterans discharged from 2007 to 2012 were recruited from Veterans Affairs clinics. Independent groups of participants with mTBI (n = 57) and those without TBI (n = 57) were administered the Beck Depression Inventory-II, Combat Exposure Scale, Word Memory Test, and the Self-Awareness of Deficits Interview. Neuropsychological instruments included the Rey-Osterrieth Complex Figure Test, Letter and Category Fluency, Trail-Making Test-Parts A and B, Christiansen H-abbreviated, Soper Neuropsychology Screen, Wechsler Memory Scale subtests Logical Memory I and II, and the Street Completion Test. The mTBI group performed significantly worse on all of the executive and nonexecutive measurements with the exception of Category Fluency, after controlling for age, depression effort, and combat exposure. Depression and combat exposure were greater for the mTBI group. The mTBI group scored poorer on effort, but only the Multiple Choice subtest was significant. The mTBI group had good awareness of their deficits.
Geary, Elizabeth K; Kraus, Marilyn F; Rubin, Leah H; Pliskin, Neil H; Little, Deborah M
That learning and memory deficits persist many years following mild traumatic brain injury (mTBI) is controversial due to inconsistent objective evidence supporting subjective complaints. Our prior work demonstrated significant reductions in performance on the initial trial of a verbal learning task and overall slower rate of learning in well-motivated mTBI participants relative to demographically matched controls. In our previous work, we speculated that differences in strategy use could explain the differences in rate of learning. The current study serves to test this hypothesis by examining strategy use on the California Verbal Learning Test-Second Edition. Our present findings support the primary hypothesis that mTBI participants under-utilize semantic clustering strategies during list-learning relative to control participants. Despite achieving comparable total learning scores, we posit that the persisting learning and memory difficulties reported by some mTBI patients may be related to reduced usage of efficient internally driven strategies that facilitate learning. Given that strategy training has demonstrated improvements in learning and memory in educational and occupational settings, we offer that these findings have translational value in offering an additional approach in remediation of learning and memory complaints reported by some following mTBI.
Larrabee, Glenn J; Rohling, Martin L
The diagnosis and evaluation of mild traumatic brain injury (mTBI) is reviewed from the perspective of meta-analyses of neuropsychological outcome, showing full recovery from a single, uncomplicated mTBI by 90 days post-trauma. Persons with history of complicated mTBI characterized by day-of-injury computed tomography or magnetic resonance imaging abnormalities, and those who have suffered prior mTBIs may or may not show evidence of complete recovery similar to that experienced by persons suffering a single, uncomplicated mTBI. Persistent post-concussion syndrome (PCS) is considered as a somatoform presentation, influenced by the non-specificity of PCS symptoms which commonly occur in non-TBI samples and co-vary as a function of general life stress, and psychological factors including symptom expectation, depression and anxiety. A model is presented for forensic evaluation of the individual mTBI case, which involves open-ended interview, followed by structured interview, record review, and detailed neuropsychological testing. Differential diagnosis includes consideration of other neurologic and psychiatric disorders, symptom expectation, diagnosis threat, developmental disorders, and malingering. Copyright © 2013 John Wiley & Sons, Ltd.
Losoi, Heidi; Wäljas, Minna; Turunen, Senni; Brander, Antti; Helminen, Mika; Luoto, Teemu M; Rosti-Otajärvi, Eija; Julkunen, Juhani; Öhman, Juha
To examine resilience as a predictor of change in self-reported fatigue after mild traumatic brain injury (MTBI). A consecutive series of 67 patients with MTBI and 34 orthopedic controls. Prospective longitudinal study. Resilience Scale, Beck Depression Inventory-Second Edition, and Pain subscale from Ruff Neurobehavioral Inventory 1 month after injury and Barrow Neurological Institute Fatigue Scale 1 and 6 months after injury. Insomnia, pain, and depressive symptoms were significantly correlated with fatigue, but even when these variables were controlled for, resilience significantly predicted the change in fatigue from 1 to 6 months after MTBI. In patients with MTBI, the correlation between resilience and fatigue strengthened during follow-up. In controls, significant associations between resilience and fatigue were not found. Resilience is a significant predictor of decrease in self-reported fatigue following MTBI. Resilience seems to be a relevant factor to consider in the management of fatigue after MTBI along with the previously established associated factors (insomnia, pain, and depressive symptoms).
S S Dhandapani
Full Text Available Background: Age is a strong prognostic factor following traumatic brain injury (TBI, with discrepancies defining the critical prognostic age threshold. This study was undertaken to determine the impact of various age thresholds on outcome after TBI. Materials and Methods : The ages of patients admitted with TBI were prospectively studied in relation to mode of injury, Glasgow coma score (GCS, CT category and surgical intervention. Mortality was assessed at 1 month, and neurological outcome was assessed at 6 months. Appropriate statistical analyzes (details in article were performed. Results: Of the total 244 patients enrolled, 144 patients had severe, 38 patients had moderate and 62 patients had mild TBI, respectively. Age had significant association with grade of injury, CT category and surgical intervention (P 59 years respectively (P 40 years in all subgroups, based on GCS and surgical intervention (P < 0.05. Conclusions : In patients with TBI, age demonstrates independent association with unfavorable outcome at 6 months, in stepwise manner centered on a threshold of 40 years.
Full Text Available Traumatic brain injuries (TBI are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.
Lakhani, Ali; Townsend, Clare; Bishara, Jason
To identify the types of research focusing on Traumatic Brain Injury (TBI) amongst Indigenous people in order to (i) synthesise their findings and (ii) ascertain where research gaps exist. A systematic review using the PRISMA approach was employed. Eight databases were searched for peer-reviewed literature published at any date. Twenty-six studies met the inclusion criteria and were included in this review. The majority of studies focused on the prevalence or incidence of TBI amongst Indigenous people (n = 15). Twelve of these found Indigenous people had a higher prevalence or incidence of TBI compared to non-Indigenous people. Under-researched areas include (with number of articles identified in brackets): Indigenous level of injury or recovery (n = 2), neuropsychological assessment and TBI (n = 3), Indigenous perspectives of TBI (n = 2), Indigenous intervention for TBI (n = 1), and rehabilitation for TBI (n = 4). Published studies demonstrate that Indigenous people have a higher prevalence or incidence of TBI compared to non-Indigenous people. Limited studies explore culturally appropriate rehabilitation and intervention methods and Indigenous understandings of TBI. It is imperative that future research consider the nature and efficacy of culturally appropriate approaches and their contribution towards better outcomes for Indigenous people with TBI, and their families and communities.
Morais, Dionei F.; Gaia, Felipe F.P. [Hospital de Base de Sao Jose do Rio Preto, SP (Brazil). Servico de Neurocirurgia]. E-mail: firstname.lastname@example.org; Spotti, Antonio R.; Tognola, Waldir A. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Ciencias Neurologicas; Andrade, Almir F. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Neurocirurgia da Emergencia
Purpose: To evaluate the clinical applications of magnetic resonance imaging (MRI) in patients with acute traumatic brain injury (TBI): to identify the type, quantity, severity; and improvement clinical-radiological correlation. Method: Assessment of 55 patients who were imaged using CT and MRI, 34 (61.8%) males and 21 (38.2%) females, with acute (0 to 5 days) and closed TBI. Results: Statistical significant differences (McNemar test): occurred fractures were detected by CT in 29.1% and by MRI in 3.6% of the patients; subdural hematoma by CT in 10.9% and MRI in 36.4 %; diffuse axonal injury (DAI) by CT in 1.8% and MRI in 50.9%; cortical contusions by CT in 9.1% and MRI in 41.8%; subarachnoid hemorrhage by CT in 18.2% and MRI in 41.8%. Conclusion: MRI was superior to the CT in the identification of DAI, subarachnoid hemorrhage, cortical contusions, and acute subdural hematoma; however it was inferior in diagnosing fractures. The detection of DAI was associated with the severity of acute TBI. (author)
Wäljas, Minna; Iverson, Grant L; Lange, Rael T; Liimatainen, Suvi; Hartikainen, Kaisa M; Dastidar, Prasun; Soimakallio, Seppo; Ohman, Juha
To examine factors relating to return to work (RTW) following mild traumatic brain injury (mTBI). One hundred and nine patients (Age: M = 37.4 years, SD = 13.2; 52.3% women) who sustained an mTBI. Inception cohort design with questionnaires and neuropsychological testing completed approximately 3 to 4 weeks postinjury. Emergency Department of Tampere University Hospital, Finland. Self-report (postconcussion symptoms, depression, fatigue, and general health) and neurocognitive measures (attention and memory). The cumulative RTW rates were as follows: 1 week = 46.8%, 2 weeks = 59.6%, 3 weeks = 67.0%, 4 weeks = 70.6%, 2 months = 91.7%, and 1 year = 97.2%. Four variables were significant predictors of the number of days to RTW: age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue ratings (all P work fewer than 30 days after injury (n = 82, 75.2%) versus more than 30 days (n = 27, 24.8%) did not differ on demographic or neuropsychological variables. The vast majority of this cohort returned to work within 2 months. Predictors of slower RTW included age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue.
Vasily A Vakorin
Full Text Available Accurate means to detect mild traumatic brain injury (mTBI using objective and quantitative measures remain elusive. Conventional imaging typically detects no abnormalities despite post-concussive symptoms. In the present study, we recorded resting state magnetoencephalograms (MEG from adults with mTBI and controls. Atlas-guided reconstruction of resting state activity was performed for 90 cortical and subcortical regions, and calculation of inter-regional oscillatory phase synchrony at various frequencies was performed. We demonstrate that mTBI is associated with reduced network connectivity in the delta and gamma frequency range (>30 Hz, together with increased connectivity in the slower alpha band (8-12 Hz. A similar temporal pattern was associated with correlations between network connectivity and the length of time between the injury and the MEG scan. Using such resting state MEG network synchrony we were able to detect mTBI with 88% accuracy. Classification confidence was also correlated with clinical symptom severity scores. These results provide the first evidence that imaging of MEG network connectivity, in combination with machine learning, has the potential to accurately detect and determine the severity of mTBI.
Full Text Available Background. Identifying which patients are most likely to be at risk of chronic pain and other postconcussion symptoms following mild traumatic brain injury (MTBI is a difficult clinical challenge. Objectives. To examine the relationship between pain catastrophizing, defined as the exaggerated negative appraisal of a pain experience, and early MTBI outcome. Methods. This cross-sectional design included 58 patients diagnosed with a MTBI. In addition to medical chart review, postconcussion symptoms were assessed by self-report at 1 month (Time 1 and 8 weeks (Time 2 after MTBI. Pain severity, psychological distress, level of functionality, and pain catastrophizing were measured by self-report at Time 2. Results. The pain catastrophizing subscales of rumination, magnification, and helplessness were significantly correlated with pain severity (r=.31 to .44, number of postconcussion symptoms reported (r=.35 to .45, psychological distress (r=.57 to .67, and level of functionality (r=-.43 to -.29. Pain catastrophizing scores were significantly higher for patients deemed to be at high risk of postconcussion syndrome (6 or more symptoms reported at both Time 1 and Time 2. Conclusions. Higher levels of pain catastrophizing were related to adverse early MTBI outcomes. The early detection of pain catastrophizing may facilitate goal-oriented interventions to prevent or minimize the development of chronic pain and other postconcussion symptoms.
Full Text Available Each year in the United States, approximately 1.5 million people sustain a traumatic brain injury (TBI. Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms—and why some patients experience differing assortments of persistent maladies—are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential.
Muller, François; Simion, Audrey; Reviriego, Elsa; Galera, Cédric; Mazaux, Jean-Michel; Barat, Michel; Joseph, Pierre-Alain
Previous studies have reported a dissociation between social behavioral impairments after severe traumatic brain injury (TBI) and relatively preserved performances in traditional tasks that investigate cognitive abilities. Theory of mind (ToM) refers to the ability to make inferences about other's mental states and use them to understand and predict others' behavior. We tested a group of 15 patients with severe TBI and 15 matched controls on a series of four verbal and non-verbal ToM tasks: the faux pas test, the first-order and second-order false belief task, the character intention task and the Reading the Mind in the Eyes Test. Participants with severe TBI were also compared to controls on non-ToM inference tasks of indirect speech act from the Montreal Evaluation of Communication (M.E.C.) Protocol and empathy (Davis Interpersonal Reactivity Index - I.R.I.) and tests for executive functions. Subjects with TBI performed worse than control subjects on all ToM tasks, except the first-order false belief task. The findings converge with previous evidence for ToM deficit in TBI and dissociation between ToM and executive functions. We show that ToM deficit is probably distinct from other aspects of social cognition like empathy and pragmatic communication skills. Copyright © 2009 Elsevier Srl. All rights reserved.
Marini, Andrea; Zettin, Marina; Galetto, Valentina
Traumatic brain injuries (TBIs) are often associated with communicative deficits. The incoherent and impoverished language observed in non-aphasic individuals with severe TBI has been linked to a problem in the global organization of information at the text level. The present study aimed to analyze the features of narrative discourse impairment in a group of adults with moderate TBI (modTBI). 10 non-aphasic speakers with modTBI and 20 neurologically intact participants were recruited for the experiment. Their cognitive, linguistic and narrative skills were thoroughly assessed. The persons with modTBI exhibited normal phonological, lexical and grammatical skills. However, their narratives were characterized by lower levels of Lexical Informativeness and more errors of both Local and Global Coherence that, at times, made their narratives vague and ambiguous. Significant correlations were found between these narrative difficulties and the production of both perseverative and non-perseverative errors on the WCST. These disturbances confirm previous findings which suggest a deficit at the interface between cognitive and linguistic processing rather than a specific linguistic disturbance in these patients. Copyright © 2014 Elsevier Ltd. All rights reserved.
Scheff, Stephen W; Roberts, Kelly N
We have previously shown that pycnogenol (PYC) increases antioxidants, decreases oxidative stress, suppresses neuroinflammation and enhances synaptic plasticity following traumatic brain injury (TBI). Here, we investigate the effects of PYC on cognitive function following a controlled cortical impact (CCI). Adult Sprague-Dawley rats received a CCI injury followed by an intraperitoneal injection of PYC (50 or 100mg/kg). Seven days post trauma, subjects were evaluated in a Morris water maze (MWM) and evaluated for changes in lesion volume. Some animals were evaluated at 48h for hippocampal Fluoro-jade B (FJB) staining. The highest dose of PYC therapy significantly reduced lesion volume, with no improvement in MWM compared to vehicle controls. PYC failed to reduce the total number of FJB positive neurons in the hippocampus. These results suggest that the reduction of oxidative stress and neuroinflammation are not the key components of the secondary injury that contribute to cognitive deficits following TBI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Wright, W G; Tierney, R T; McDevitt, J
The search for reliable and valid signs and symptoms of mild traumatic brain injury (mTBI), commonly synonymous with concussion, has lead to a growing body of evidence that individuals with long-lasting, unremitting impairments often experience visual and vestibular symptoms, such as dizziness, postural and gait disturbances. Investigate the role of visual-vestibular processing deficits following concussion. A number of clinically accepted vestibular, oculomotor, and balance assessments as well as a novel virtual reality (VR)-based balance assessment device were used to assess adults with post-acute concussion (n = 14) in comparison to a healthy age-matched cohort (n = 58). Significant between-group differences were found with the VR-based balance device (p = 0.001), with dynamic visual motion emerging as the most discriminating balance condition. The symptom reports collected after performing the oculomotor and vestibular tests: rapid alternating horizontal eye saccades, optokinetic stimulation, and gaze stabilization, were all sensitive to health status (p vestibular tasks most closely linked to spatial and self-motion perception had the greatest discriminatory outcomes. The current findings suggest that mesencephalic and parieto-occipital centers and pathways may be involved in concussion.
Duclos, C; Dumont, M; Wiseman-Hakes, C; Arbour, C; Mongrain, V; Gaudreault, P-O; Khoury, S; Lavigne, G; Desautels, A; Gosselin, N
Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Wang, Wang-Xia; Sullivan, Patrick G; Springer, Joe E
Traumatic brain injury (TBI) is a leading cause of long-term impairments in higher cognitive functioning, including deficits in attention and memory. It is well known that some of these persistent deficits are related, in part, to ongoing secondary injury events characterized by pervasive biochemical and pathophysiological stressors, including a rapid and sustained phase of mitochondrial dysfunction. A loss of mitochondrial function impacts a number of important cellular events and we have begun to investigate the novel hypothesis that mitochondria play a critical role in regulating the cellular activity of specific microRNAs in response to cellular demands and stressors. In this special issue report, we summarize briefly the rationale for investigating the crosstalk between mitochondria and microRNA, and provide recent preliminary data suggesting that mitochondria-microRNA interactions are modified in response to TBI-related cellular stressors. We postulate that this interaction is critical for regulating appropriate cellular microRNA responses, which opens up opportunities for therapeutic interventions targeting both mitochondrial function and microRNA activity. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Truelle, J-L; Wild, K Von; Onillon, M; Montreuil, M
Traumatic Brain Injury (TBI) may lead to specific handicap, often hidden, mainly due to cognitive and behavioural sequelae. Social re-entry is a long-term, fluctuant and precarious process. The French experience will be illustrated by 6 initiatives answering to 6 challenges to do with TBI specificities:1. bridging the gap, between initial rehabilitation and community re-entry, via transitional units dealing with assessment, retraining, social/vocational orientation and follow-up. Today, there are 30 such units based on multidisciplinary teams.2. assessing recovery by TBI-specific and validated evaluation tools: EBIS holistic document, BNI Screening of higher cerebral functions, Glasgow outcome extended, and QOLIBRI, a TBI-specific quality of life tool.3. promoting specific re-entry programmes founded on limited medication, ecological neuro-psychological rehabilitation, exchange groups and workshops, violence prevention, continuity of care, environmental structuration, and "resocialisation".4. taking into account the "head injured family"5. facilitating recovery after sports-related concussion6. facing medico-legal consequences and compensation: In that perspective, we developed guidelines for TBI-specific expert appraisal, including mandatory neuro-psychological assessment, family interview and an annual forum gathering lawyers and health professionals.
Sorinola, Abayomi; Buki, Andras; Sandor, Janos; Czeiter, Endre
The aim of this study was to describe the impact of the Traumatic Brain Injury management guideline introduction in Hungary. Hospital discharge records (HDR) including age, gender, codes of interventions applied, ICD codes of diagnosed disorders of patients admitted between 01/01/2004 and 31/12/2010 with diagnosis of intracranial injury (S06 by ICD10) from every inpatient institution in Hungary were collected from the database of National Health Insurance Fund (NHIF). The Case Fatality Rates (CFR) for one week, one month and six months were calculated for the periods before and after the guideline introduction. The change of CFRs was applied as indicators for change of clinical quality elicited by guideline. The centers together at one week, one month and six months had pre-guideline introduction CFRs of 23.4 %, 37.7 % and 47.5 % and post-guideline introduction CFRs of 22.1%, 39.1%, and 50.0% respectively. The secondary institutions together at one week, one month and six months had pre-guideline introduction CFRs of 21.5 %, 34.8 % and 46.3 % and post-guideline introduction CFRs of 21.9%, 37.0%, and 48.9% respectively. None of the CFRs showed significant change. The effectiveness of TBI management guideline adaptation in Hungary is poor. Without supportive financing and external auditing system, guideline introduction alone cannot achieve standard clinical practice and a reduction in CFR.
Lang, Yuhuang; Fu, Fengming; Sun, Dalong; Xi, Chenhui; Chen, Fengyuan
Beta-adrenergic blockade has been hypothesized to have a protective effect on intestinal dysfunction and increased intestinal permeability associated with the epinephrine surge after traumatic brain injury (TBI). Wister rats were subjected to either a weight drop TBI, and intraperitoneally injected or not with labetalol, or a sham procedure (18 rats per group). After 3, 6, or 12h (6 rats per subgroup), intestinal permeability to 4.4 kDa FITC-Dextran and plasma epinephrine levels were measured as was intestinal tight junction protein ZO-1 expression at 12h. Terminal ileum was harvested to measure levels of intestinal tumor necrosis factor (TNF)-α and to evaluate histopathology. In TBI group vs. sham group, intestinal permeability (Plabetalol group, 1) intestinal permeability was significantly lower at 6 and 12h (94.31±7.64 vs. 102.16±6.40 μg/mL; 110.21±7.52 vs. 118.95±7.11 μg/mL, respectively); 2) levels of plasma epinephrine and intestinal TNF-α were significantly lower at 3, 6 and 12h; and 3) intestinal ZO-1 expression was higher at 3, 6 and 12h (p=0.018). Histopathological evaluation showed that labetalol use preserved intestinal architecture throughout. In a rat model of TBI, labetalol reduced TBI-induced sympathetic hyperactivity, and prevented histopathological intestinal injury accompanied by changes in gut permeability and gut TNF-α expression.
Wood, Rodger Ll; Doughty, Caitríona
Individuals who develop maladaptive coping styles after traumatic brain injury (TBI) usually experience difficulty expressing their emotional state, increasing the risk of psychological distress. Difficulties expressing emotion and identifying feelings are features of alexithymia, which is prevalent following TBI. To examine the relations among coping styles, alexithymia, and psychological distress following TBI. Seventy-one patients with TBI drawn from a head injury clinic population and 54 demographically matched healthy controls. Toronto Alexithymia Scale-20, Estonian COPE-D Inventory, Beck Depression Inventory-II, and Beck Anxiety Inventory. The participants with TBI exhibited significantly higher rates of alexithymia and psychological distress and lower levels of task-oriented coping than healthy controls. Levels of avoidance coping and psychological distress were significantly higher in a subgroup of TBI patients with alexithymia than in a non-alexithymic TBI subsample. There were significant relations among alexithymia, avoidance coping, and levels of psychological distress. Regression analysis revealed that difficulty identifying feelings was a significant predictor for psychological distress. Early screening for alexithymia following TBI might identify those most at risk of developing maladaptive coping mechanisms. This could assist in developing early rehabilitation interventions to reduce vulnerability to later psychological distress.
Rodger Ll. Wood
Full Text Available Objective: This article will address how anomalies of executive function after traumatic brain injury (TBI can translate into altered social behavior that has an impact on a person’s capacity to live safely and independently in the community.Method: Review of literature on executive and neurobehavioral function linked to cognitive ageing in neurologically healthy populations and late neurocognitive effects of serious TBI. Information was collated from internet searches involving MEDLINE, PubMed, PyscINFO and Google Scholar as well as the authors’ own catalogs.Conclusions: The conventional distinction between cognitive and emotional-behavioral sequelae of TBI is shown to be superficial in the light of increasing evidence that executive skills are critical for integrating and appraising environmental events in terms of cognitive, emotional and social significance. This is undertaken through multiple fronto-subcortical pathways within which it is possible to identify a predominantly dorsolateral network that subserves executive control of attention and cognition (so-called cold executive processes and orbito-frontal/ventro-medial pathways that underpin the hot executive skills that drive much of behavior in daily life. TBI frequently involves disruption to both sets of executive functions but research is increasingly demonstrating the role of hot executive deficits underpinning a wide range of neurobehavioral disorders that compromise relationships, functional independence and mental capacity in daily life.
Rushby, Jacqueline Ann; McDonald, Skye; Randall, Rebekah; de Sousa, Arielle; Trimmer, Emily; Fisher, Alana
Empathy deficits are widely-documented in individuals after severe traumatic brain injury (TBI). This study examined the relationship between empathy deficits and psychophysiological responsivity in adults with TBI to determine if impaired responsivity is ameliorated through repeated emotional stimulus presentations. Nineteen TBI participants (13 males; 41 years) and 25 control participants (14 males; 31 years) viewed five repetitions of six 2-min film clip segments containing pleasant, unpleasant, and neutral content. Facial muscle responses (zygomaticus and corrugator), tonic heart rate (HR) and skin conductance level (SCL) were recorded. Mean responses for each viewing period were compared to a pre-experiment 2-min resting baseline period. Self-reported emotional empathy was also assessed. TBI participants demonstrated identical EMG response patterns to controls, i.e. an initial large facial response to both pleasant and unpleasant films, followed by habituation over repetitions for pleasant films, and sustained response to unpleasant films. Additionally, an increase in both arousal and HR deceleration to stimulus repetitions was found, which was larger for TBI participants. Compared to controls, TBI participants self-reported lower emotional empathy, and had lower resting arousal, and these measures were positively correlated. Results are consistent with TBI producing impairments in emotional empathy and responsivity. While some normalisation of physiological arousal appeared with repeated stimulus presentations, this came at the cost of greater attentional effort. Copyright © 2013 Elsevier B.V. All rights reserved.
Traumatic brain injury: clinical and pathological parameters in an experimental weightdrop model Lesão cerebral traumática: parâmetros clínicos e patológicos em um modelo experimental de queda de peso
Danilo dos Santos Silva
Full Text Available PURPOSE: To investigate the function of an experimental cranium trauma model in rats. METHODS: The equipment, already described in the literature and under discreet adaptations, is composed by a platform that produces closed head impact controlled by weight drop with pre-defined and known energy. 25 Wistar male rats (Rattus norvegicus albinus were divided into five equal groups that received different quantities of cranial impact energy: G1, G2, G3 and G4 with 0,234J, 0,5J, 0,762J and 1J respectively and G5 (Sham. Under intense analgesia, each group was evaluated clinically in a sequence of intervals and had their encephalon removed for pathologic analysis. RESULTS: Important clinical alterations (convulsions, bradycardia, bradypnea and abnormal postures and focal pathologic (hematomas and hemorrhages kept proportion with the intensity of the impact. No fracture was observed and the group 4 had 80% mortality rate. CONCLUSION: The experimental cranium trauma animal model by weight drop is an alternative of low cost and easy reproduction that allows evaluating clinical and pathological alterations in accordance with studies in experimental surgery aims for new traumatic brain injury approach in rats.OBJETIVO: Investigar o uso de um modelo de trauma craniano experimental em ratos. MÉTODOS: O equipamento, já descrito na literatura e sob discretas adaptações, contitui-se de uma plataforma para produção de lesão craniana fechada controlada por queda de peso com energia pré-definida e conhecida. 25 ratos Wistar machos (Rattus norvegicus albinus foram divididos em cinco grupos iguais que receberam níveis diferentes de energia de impacto craniano: G1, G2, G3 e G4 com 0,234J, 0,5J, 0, 762J e 1J respectivamente e G5 (Sham. Sob intensa analgesia, cada grupo foi avaliado clinicamente em uma seqüência de intervalos e tiveram seus encéfalos removidos para análise patológica. RESULTADOS: Alterações clínicas importantes (convulsões, bradicardia
Full Text Available The fact that therapeutic hypothermia (TH has lowered intracranial pressure and protected brain in severe traumatic brain injury (TBI is well known throughout past sources and experimental data. In this paper, the result of TH in TBI needs to be confirmed. The result of North American Brain Injury Study; Hypothermia (NAVIS-H 1 and 2, Eurotherm3235, Japan trauma society study was reviewed throughout randomized controlled study which performed recently. The prognosis was not confirmed throughout TH in NAVIS-H1; however, there was statistical significance among the group of 45 years or less and below 35 degree in celcius which checked when he or she visited initially. Hence, NAVIS-H2 study was preceded. In patient who had surgically removed hematoma, the effects of TH were proved compared to diffuse brain damage in NAVIS-H2 study. This was found in the result of Japan neurotrauma data bank. Eurotherm study has been doing, which leads to collect many data later on. The TBI of TH makes them better prognosis in patients who had surgically removed hematoma and lowered initial body temperature. Later on, it is considered further study is necessary.
Warren, Matthew W; Kobeissy, Firas H; Liu, Ming Cheng; Hayes, Ronald L; Gold, Mark S; Wang, Kevin K W
Neurotoxicity in rat cortex and hippocampus following acute methamphetamine administration was characterized and compared to changes following traumatic brain injury. Doses of 10, 20, and 40 mg/kg of methamphetamine produced significant increases in calpain- and caspase-cleaved alpha II-spectrin and tau protein fragments, suggesting cell injury or death. Changes in proteolytic products were significantly increased over vehicle controls. Use of fragment specific biomarkers detected prominent calpain-mediated protein fragments in the cortex and hippocampus while caspase-mediated protein fragments were also detected in the hippocampus. Remarkably, proteolytic product increases at the 40 mg/kg dose after 24 h were as high as those observed in experimental traumatic brain injury. Use of calpain and caspase proteolytic inhibitors may be useful in preventing methamphetamine-induced neurotoxicity.
Fagerholm, Erik D; Hellyer, Peter J; Scott, Gregory; Leech, Robert; Sharp, David J
Traumatic brain injury affects brain connectivity by producing traumatic axonal injury. This disrupts the function of large-scale networks that support cognition. The best way to describe this relationship is unclear, but one elegant approach is to view networks as graphs. Brain regions become nodes in the graph, and white matter tracts the connections. The overall effect of an injury can then be estimated by calculating graph metrics of network structure and function. Here we test which graph metrics best predict the presence of traumatic axonal injury, as well as which are most highly associated with cognitive impairment. A comprehensive range of graph metrics was calculated from structural connectivity measures for 52 patients with traumatic brain injury, 21 of whom had microbleed evidence of traumatic axonal injury, and 25 age-matched controls. White matter connections between 165 grey matter brain regions were defined using tractography, and structural connectivity matrices calculated from skeletonized diffusion tensor imaging data. This technique estimates injury at the centre of tract, but is insensitive to damage at tract edges. Graph metrics were calculated from the resulting connectivity matrices and machine-learning techniques used to select the metrics that best predicted the presence of traumatic brain injury. In addition, we used regularization and variable selection via the elastic net to predict patient behaviour on tests of information processing speed, executive function and associative memory. Support vector machines trained with graph metrics of white matter connectivity matrices from the microbleed group were able to identify patients with a history of traumatic brain injury with 93.4% accuracy, a result robust to different ways of sampling the data. Graph metrics were significantly associated with cognitive performance: information processing speed (R(2) = 0.64), executive function (R(2) = 0.56) and associative memory (R(2) = 0.25). These
Sala, Nathalie; Suys, Tamarah; Zerlauth, Jean-Baptiste; Bouzat, Pierre; Messerer, Mahmoud; Bloch, Jocelyne; Levivier, Marc; Magistretti, Pierre J; Meuli, Reto; Oddo, Mauro
Growing evidence suggests that endogenous lactate is an important substrate for neurons. This study aimed to examine cerebral lactate metabolism and its relationship with brain perfusion in patients with severe traumatic brain injury (TBI). A prospective cohort of 24 patients with severe TBI monitored with cerebral microdialysis (CMD) and brain tissue oxygen tension (PbtO2) was studied. Brain lactate metabolism was assessed by quantification of elevated CMD lactate samples (>4 mmol/L); these ...
Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John
Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.
Alricsson M (2012) Physical exercise ameliorates deficits induced by traumatic brain injury. Acta Neurol Scand 125, 293-302.  Qu C, Mahmood A...AWARD NUMBER: W81XWH-12-1-0582 TITLE: Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer’s...COVERED 09/25/2012-09/24/2015 4. TITLE AND SUBTITLE Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for
Guevara, Andrea Brioschi; Demonet, Jean-Francois; Polejaeva, Elena; Knutson, Kristine M; Wassermann, Eric M; Grafman, Jordan; Krueger, Frank
To investigate the association between traumatic brain injury (TBI)-related brain lesions and long-term caregiver burden in relation to dysexecutive syndrome. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. A total of 256 participants: 105 combat veterans with TBI, 23 healthy control combat veterans (HCv), and 128 caregivers. Caregiver burden assessed by the Zarit Burden Interview at 40 years postinjury. Participants with penetrating TBI were compared with HCv on perceived caregiver burden and neuropsychological assessment measures. Data of computed tomographic scans (overlay lesion maps of participants with a penetrating TBI whose caregivers have a significantly high burden) and behavioral statistical analyses were combined to identify brain lesions associated with caregiver burden. Burden was greater in caregivers of veterans with TBI than in caregivers of HCv. Caregivers of participants with lesions affecting cognitive and behavioral indicators of dysexecutive syndrome (ie, left dorsolateral prefrontal cortex and dorsal anterior cingulate cortex) showed greater long-term burden than caregivers of participants with lesions elsewhere in the brain. The TBI-related brain lesions have a lasting effect on long-term caregiver burden due to cognitive and behavioral factors associated with dysexecutive syndrome.
Tazoe, Jun; Yamada, Kei; Akazawa, Kentaro [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City, Kyoto (Japan); Sakai, Koji [Kyoto University, Department of Human Health Science, Graduate School of Medicine, Kyoto (Japan); Mineura, Katsuyoshi [Kyoto Prefectural University of Medicine, Department of Neurosurgery, Graduate School of Medical Science, Kyoto City, Kyoto (Japan)
The aim of this study was to assess the brain core temperature of patients with mild traumatic brain injury (mTBI) using a noninvasive temperature measurement technique based on the diffusion coefficient of the cerebrospinal fluid. This retrospective study used the data collected from April 2008 to June 2011. The patient group comprised 20 patients with a Glasgow Coma Scale score of 14 or 15 who underwent magnetic resonance imaging within 30 days after head trauma. The normal control group comprised 14 subjects who volunteered for a brain checkup (known in Japan as ''brain dock''). We compared lateral ventricular (LV) temperature between patient and control groups. Follow-up studies were performed for four patients. LV temperature measurements were successfully performed for both patients and controls. Mean (±standard deviation) measured LV temperature was 36.9 ± 1.5 C in patients, 38.7 ± 1.8 C in follow-ups, and 37.9 ± 1.2 C in controls, showing a significant difference between patients and controls (P = 0.017). However, no significant difference was evident between patients and follow-ups (P = 0.595) or between follow-ups and controls (P = 0.465). A reduction in brain core temperature was observed in patients with mTBI, possibly due to a global decrease in metabolism. (orig.)
Westfall, Daniel R.; West, John D.; Bailey, Jessica N.; Arnold, Todd W.; Kersey, Patrick A.; Saykin, Andrew J.; McDonald, Brenna C.
Purpose The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. Methods Nineteen adolescents (mean age 14.7 years) who experienced mTBI 3–12 months previously (mean 7.5 months) and 19 matched healthy controls (mean age 14.0 years) completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. Results No between-group differences were found for cognition, behavior, or N-back task performance, though the expected decreased accuracy and increased reaction time as task difficulty increased were apparent. However, the mTBI group showed significantly greater brain activation than controls during the most difficult working memory task condition. Conclusion Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of natural recovery, which could have important clinical implications. PMID:26684070
Rachel Anne Bernier
Full Text Available ObjectiveChanges in functional network connectivity following traumatic brain injury (TBI have received increasing attention in recent neuroimaging literature. This study sought to understand how disrupted systems adapt to injury during resting and goal-directed brain states. Hyperconnectivity has been a common finding, and dedifferentiation (or loss of segregation of networks is one possible explanation for this finding. We hypothesized that individuals with TBI would show dedifferentiation of networks (as noted in other clinical populations and these effects would be associated with cognitive dysfunction.MethodsGraph theory was implemented to examine functional connectivity during periods of task and rest in 19 individuals with moderate/severe TBI and 14 healthy controls (HCs. Using a functional brain atlas derived from 83 functional imaging studies, graph theory was used to examine network dynamics and determine whether dedifferentiation accounts for changes in connectivity. Regions of interest were assigned to one of three groups: task-positive, default mode, or other networks. Relationships between these metrics were then compared with performance on neuropsychological tests.ResultsHyperconnectivity in TBI was most commonly observed as increased within-network connectivity. Network strengths within networks that showed differences between TBI and HCs were correlated with performance on five neuropsychological tests typically sensitive to deficits commonly reported in TBI. Hyperconnectivity within the default mode network (DMN during task was associated with better performance on Digit Span Backward, a measure of working memory [R2(18 = 0.28, p = 0.02]. In other words, increased differentiation of networks during task was associated with better working memory. Hyperconnectivity within the task-positive network during rest was not associated with behavior. Negative correlation weights were not associated with behavior
Objectives. I sought to describe current state-wide youth sports traumatic brain injury (TBI) laws and their relationship to prevailing scientific understandings of youth sports TBIs, and to facilitate further research by creating an open-source data set of current laws. Methods. I used Westlaw and LexisNexis databases to create a 50-state data set of youth sports TBI laws enacted between January 2009 and December 2012. I collected and coded the text and citations of each law and developed a protocol and codebook to facilitate future research. Results. Forty-four states and Washington, DC, passed youth sports TBI laws between 2009 and 2012. No state’s youth sports TBI law focuses on primary prevention. Instead, such laws focus on (1) increasing coaches’ and parents’ ability to identify and respond to TBIs and (2) reducing the immediate risk of multiple TBIs. Conclusions. Existing youth sports TBI laws were not designed to reduce initial TBIs. Evaluation is required to assess their effectiveness in reducing the risk and consequences of multiple TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive youth TBI-reduction solution. PMID:23678903
Harvey, Hosea H
I sought to describe current state-wide youth sports traumatic brain injury (TBI) laws and their relationship to prevailing scientific understandings of youth sports TBIs, and to facilitate further research by creating an open-source data set of current laws. I used Westlaw and LexisNexis databases to create a 50-state data set of youth sports TBI laws enacted between January 2009 and December 2012. I collected and coded the text and citations of each law and developed a protocol and codebook to facilitate future research. Forty-four states and Washington, DC, passed youth sports TBI laws between 2009 and 2012. No state's youth sports TBI law focuses on primary prevention. Instead, such laws focus on (1) increasing coaches' and parents' ability to identify and respond to TBIs and (2) reducing the immediate risk of multiple TBIs. Existing youth sports TBI laws were not designed to reduce initial TBIs. Evaluation is required to assess their effectiveness in reducing the risk and consequences of multiple TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive youth TBI-reduction solution.
Hart, Tessa; Whyte, John; Poulsen, Ingrid
OBJECTIVE: Determine effects of inpatient and outpatient treatment intensity on functional and emotional well-being outcomes at 1 year post severe traumatic brain injury (TBI). DESIGN: Prospective, quasi-experimental study comparing outcomes in a US TBI treatment center with those in a Denmark (DK...... treatments were estimated per discipline using a structured interview administered to patients and/ or caregivers at 12 months. MAIN OUTCOME MEASURES: FIM, Glasgow Outcome Scale- Extended, Disability Rating Scale, Participation Assessment with Recombined Tools-Objective, Perceived Quality of Life, SF-12....... CONCLUSIONS: Contrary to expectation, DK patients who received significantly more rehabilitation services during the year following severe TBI did not differ in outcome from their less intensively treated US counterparts, after adjusting for initial severity. The negative association of functional treatment...
Barrow, Irene M; Hough, Monica; Rastatter, Michael P; Walker, Marianna; Holbert, Donald; Rotondo, Michael F
To compare confrontation-naming in adults with MTBI to a group of normal adults under increased processing load conditions. A randomized block, repeated measures design was used to examine confrontation-naming response latency and accuracy using a computerized experimental program. Twenty-four adults having sustained a MTBI (aged 18-53) and 24 age-matched controls named pictures from three levels of vocabulary as quickly and accurately as possible. All MTBI participants were assessed with the Scales of Cognitive Ability for Traumatic Brain Injury (SCATBI) for later comparison. The results revealed a main effect of group ( p < or = 0.001) for the latency data and a group by vocabulary level interaction ( p = 0.043) for the accuracy data. No significant correlations were found between response latency and accuracy with performance on the SCATBI. Reaction time measures may reveal inefficiencies not tapped by traditional measures.
Full Text Available Abstract Background The majority of research on health outcomes after a traumatic brain injury is focused on male participants. Information examining gender differences in health outcomes post traumatic brain injury is limited. The purpose of this study was to investigate gender differences in symptoms reported after a traumatic brain injury and to examine the degree to which these symptoms are problematic in daily functioning. Methods This is a secondary data analysis of a retrospective cohort study of 306 individuals who sustained a moderate to severe traumatic brain injury 8 to 24 years ago. Data were collected using the Problem Checklist (PCL from the Head Injury Family Interview (HIFI. Using Bonferroni correction, group differences between women and men were explored using Chi-square and Wilcoxon analysis. Results Chi-square analysis by gender revealed that significantly more men reported difficulty setting realistic goals and restlessness whereas significantly more women reported headaches, dizziness and loss of confidence. Wilcoxon analysis by gender revealed that men reported sensitivity to noise and sleep disturbances as significantly more problematic than women, whereas for women, lack of initiative and needing supervision were significantly more problematic in daily functioning. Conclusion This study provides insight into gender differences on outcomes after traumatic brain injury. There are significant differences between problems reported by men compared to women. This insight may facilitate health service planners and clinicians when developing programs for individuals with brain injury.
Skrifvars, Markus B; Bailey, Michael; French, Craig; Presneill, Jeffrey; Nichol, Alistair; Little, Lorraine; Duranteau, Jacques; Huet, Olivier; Haddad, Samir; Arabi, Yaseen; McArthur, Colin; Cooper, D James; Bellomo, Rinaldo
Erythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone. A post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality. Of 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score > 3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007). In this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies. Therapeutic study, level III.
Simonsen, Louise Lau; Sonne-Holm, Stig; Krasheninnikoff, Michael
The incidence of heterotopic ossification (HO) among patients with traumatic brain injury (TBI) varies in the literature from 11 to 73.3%. The aim of this study was to determine the incidence of HO among patients with very severe TBI treated in a new established intensive rehabilitation Brain...
Martinez, Sarah; Davalos, Deana
Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…
Vállez García, David
Traumatic brain injury is the leading cause of brain injury in our society with 235 per 100,000 inhabitants per year in the European Union and about 500 per 100,000 inhabitants per year in the United States. About 80% of all these events are accounted for as mild cases. At the same time,
Background: Traumatic brain injury (TBI) is a nondegenerative, noncongenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness.This study was ...
Niogi, Sumit N.; Mukherjee, Pratik; Ghajar, Jamshid; Johnson, Carl E.; Kolster, Rachel; Lee, Hana; Suh, Minah; Zimmerman, Robert D.; Manley, Geoffrey T.; McCandliss, Bruce D.
Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether…
... mechanical force as evidenced by loss of consciousness or post-traumatic amnesia due to brain trauma or by... examination. Both penetrating and non- penetrating wounds that fit these criteria are included, but primary... of Head Trauma Rehabilitation, 25(2), 72-80. Defense and Veterans Brain Injury Center. (2012). DoD...
Hansen, Trine S; Engberg, Aase W; Larsen, Klaus
OBJECTIVES: To investigate the status of functional oral intake for patients with severe traumatic brain injury (TBI) and time to return to unrestricted dieting; and to investigate whether severity of brain injury is a predictor for unrestricted dieting. DESIGN: Observational retrospective cohort...
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Erdman, Ellen A; Pierce, Samuel R
The purpose of this case report was to describe the use of hippotherapy with a boy who sustained a brain injury. A 13-year-old boy, 6 months after traumatic brain injury received 12 physical therapy sessions, which included hippotherapy. Improvements were noted in balance, strength, gross motor skills, gait speed, functional mobility, and reported participation. Hippotherapy used with a 13-year-old boy after traumatic brain injury may have had a positive effect in the body structure, activity, and participation domains.
Martinez, Bridget; Peplow, Philip V
Traumatic brain injury (TBI) is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as development, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma (miR-425-p, -21, -93, -191 and -499) and cerebro-spinal fluid (CSF) (miR-328, -362-3p, -451, -486a) as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI (e.g., miR-21, miR-23b). MicroRNA profiling was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI (e.g., miR-21) have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups (children, adults, and elderly).
Full Text Available Traumatic brain injury (TBI is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as development, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma (miR-425-p, -21, -93, -191 and -499 and cerebro-spinal fluid (CSF (miR-328, -362-3p, -451, -486a as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI (e.g., miR-21, miR-23b. MicroRNA profiling was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI (e.g., miR-21 have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups (children, adults, and elderly.
Ilie, Gabriela; Cusimano, Michael D; Li, Wenshan
Traumatic brain injury (TBI) survivors often report difficulties with understanding and producing paralinguistic cues, as well as understanding and producing basic communication tasks. However, a large range of communicative deficits in this population cannot be adequately explained by linguistic impairment. The review examines prosodic processing performance post-TBI, its relationship with injury severity, brain injury localization, recovery and co-occurring psychiatric or mental health issues post-TBI METHODS: A systematic review using several databases including MEDLINE, EMBASE, Cochrane, LLBA (Linguistics and Language Behaviour Abstract) and Web of Science (January 1980 to May 2015), as well as a manual search of the cited references of the selected articles and the search cited features of PubMed was performed. The search was limited to comparative analyses between individuals who had a TBI and non-injured individuals (control). The review included studies assessing prosodic processing outcomes after TBI has been formally diagnosed. Articles that measured communication disorders, prosodic impairments, aphasia, and recognition of various aspects of prosody were included. Methods of summary included study characteristics, sample characteristics, demographics, auditory processing task, age at injury, brain localization of the injury, time elapsed since TBI, reports between TBI and mental health, socialization and employment difficulties. There were no limitations to the population size, age or gender. Results were reported according to the PRISMA guidelines. Two raters evaluated the quality of the articles in the search, extracted data using data abstraction forms and assessed the external and internal validity of the studies included using STROBE criteria. Agreement between the two raters was very high (Cohen's kappa = .89, P < 0.001). Results are reported according to the PRISMA guidelines. A systematic review of 5212 records between 1980 and 2015
Full Text Available Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.
Chen, Wei; Guo, Yijun; Yang, Wenjin; Zheng, Ping; Zeng, Jinsong; Tong, Wusong
Oxidative stress is an important factor in the pathophysiologic changes after traumatic brain injury (TBI). Connexin43 (Cx43) was reported to contribute to cerebral damage. However, the impacts of Cx40 have not been investigated in detail. In the present study, we hypothesized that Cx40 was involved in oxidative stress-induced brain injury after TBI. The controlled cortical impact (CCI) model was introduced to Wistar rats as a TBI model. Neurological deficits, oxidative stress and Cx40 were evaluated in TBI rats and N-acetylcysteine (NAC)-treated TBI rats. Neurological severity score (NSS) was used to assess neurological deficits. Brain infarction was measured by histo-staining. Brain edema was evaluated by measuring the brain water content. Cortex samples were collected to measure the tissue levels of malonyldialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) and NADPH oxidase activity. Cx40 expression was determined by Western-blot. TBI-induced brain injuries gradually increased from 6 h to 24 h post CCI, and the severity remained till 72 h. The level of oxidative stress was consistent with the extent of neurological deficits. Cx40 was upregulated after TBI in a linear correlated manner with increased oxidative stress. With NAC intervention, both neurological deficits and oxidative stress were significantly attenuated. Meanwhile, elevated Cx40 expression in cortex was also prevented by NAC treatment. These studies revealed the relationship between levels of Cx40 and oxidative stress after TBI. The cortex Cx40 expression was positively correlated with the cerebral oxidative stress, indicating the involvement of Cx40 in the progress of brain damage.
Ryan C. Turner
Full Text Available The diagnosis of chronic traumatic encephalopathy (CTE upon autopsy in a growing number of athletes and soldiers alike has resulted in increased awareness, by both the scientific/medical and lay communities, of the potential for lasting effects of repetitive traumatic brain injury. While we have come to better understand the clinical presentation and underlying pathophysiology of CTE, the diagnosis of CTE remains autopsy-based, which prevents adequate monitoring and tracking of the disease. The lack of established biomarkers or imaging modalities for diagnostic and prognostic purposes also prevents the development and implementation of therapeutic protocols. In this work the clinical history and pathologic findings associated with CTE are reviewed as well as imaging modalities that have demonstrated some promise for future use in the diagnosis and/or tracking of CTE or repetitive brain injury. Biomarkers under investigation are also discussed with particular attention to the timing of release and potential utility in situations of repetitive traumatic brain injury. Further investigation into imaging modalities and biomarker elucidation for the diagnosis of CTE is clearly both needed as well as warranted.
Full Text Available Objective: The purpose of this study was to investigate the effect of prophylactic anticoagulation on the incidence of venous thromboembolic events (VTE in patients suffering from isolated severe traumatic brain injury (TBI. Materials and Methods: Retrospective matched case-control study in adult patients sustaining isolated severe TBI (head AIS ≥3, with extracranial AIS ≤2 receiving VTE prophylaxis while in the surgical intensive care unit from 1/2007 through 12/2009. Patients subjected to VTE prophylaxis were matched 1:1 by age, gender, glasgow coma scale (GCS score at admission, presence of hypotension on admission, injury severity score, and head abbreviated injury scale (AIS score, with patients who did not receive chemical VTE prophylaxis. The primary outcome measure was VTE. Secondary outcomes were SICU and hospital length of stay (HLOS, adverse effects of anticoagulation, and mortality. Results: After propensity matching, 37 matched pairs were analysed. Cases and controls had similar demographics, injury characteristics, rate of craniotomies/craniectomies, SICU LOS, and HLOS. The median time of commencement of VTE prophylaxis was 10 days. The incidence of VTE was increased 3.5-fold in the controls compared to the cases (95% CI 1.0-12.1, P=0.002. The mortality was higher in patients who did not receive anticoagulation (19% vs. 5%, P=0.001. No adverse outcomes were detected in the anticoagulated patients. Conclusion: Prophylactic anticoagulation decreases the overall risk for clinically significant VTE in patients with severe isolated TBI. Prospective validation of the timing and safety of chemical VTE prophylaxis in these instances is warranted.
Mohseni, Shahin; Talving, Peep; Lam, Lydia; Chan, Linda S; Ives, Crystal; Demetriades, Demetrios
The purpose of this study was to investigate the effect of prophylactic anticoagulation on the incidence of venous thromboembolic events (VTE) in patients suffering from isolated severe traumatic brain injury (TBI). Retrospective matched case-control study in adult patients sustaining isolated severe TBI (head AIS ≥3, with extracranial AIS ≤2) receiving VTE prophylaxis while in the surgical intensive care unit from 1/2007 through 12/2009. Patients subjected to VTE prophylaxis were matched 1:1 by age, gender, glasgow coma scale (GCS) score at admission, presence of hypotension on admission, injury severity score, and head abbreviated injury scale (AIS) score, with patients who did not receive chemical VTE prophylaxis. The primary outcome measure was VTE. Secondary outcomes were SICU and hospital length of stay (HLOS), adverse effects of anticoagulation, and mortality. After propensity matching, 37 matched pairs were analysed. Cases and controls had similar demographics, injury characteristics, rate of craniotomies/craniectomies, SICU LOS, and HLOS. The median time of commencement of VTE prophylaxis was 10 days. The incidence of VTE was increased 3.5-fold in the controls compared to the cases (95% CI 1.0-12.1, P=0.002). The mortality was higher in patients who did not receive anticoagulation (19% vs. 5%, P=0.001). No adverse outcomes were detected in the anticoagulated patients. Prophylactic anticoagulation decreases the overall risk for clinically significant VTE in patients with severe isolated TBI. Prospective validation of the timing and safety of chemical VTE prophylaxis in these instances is warranted.
Kaup, Allison R; Peltz, Carrie; Kenney, Kimbra; Kramer, Joel H; Diaz-Arrastia, Ramon; Yaffe, Kristine
The aim of this study was to characterize the neuropsychological profile of lifetime traumatic brain injury (TBI) in older Veterans. Participants were 169 older Veterans [mean age=79.1 years (range, 51-97 years), 89% male, 92% Caucasian], 88 with lifetime TBI and 81 without TBI, living in Veterans' retirement homes in independent residence. TBI history was ascertained with the Ohio State TBI Identification Method structured interview. Cognition was assessed with neuropsychological tests: Raw scores were converted to Z-scores compared to age-corrected normative data and combined into five domain composite Z-scores (attention/working memory, learning/memory, language, processing speed, executive functioning). We investigated the association between TBI and performance in each cognitive domain in linear mixed effects models, with and without adjustment for demographics, medical comorbidities, and psychiatric variables. Compared to those without TBI, older Veterans with TBI had greater deficits in processing speed (estimate=-.52; p=.01; f 2=.08 in fully adjusted model) and executive functioning (estimate=-.41; p=.02; f 2=.06 in fully adjusted model) but performed similarly in the attention/working memory, learning/memory, and language domains (all p>.05). TBI-associated deficits were most prominent among individuals with multiple mild TBIs and those with any moderate-to-severe TBI, but were not clearly present among those with single mild TBI. The neuropsychological profile of lifetime TBI in older Veterans is characterized by slowed processing speed and executive dysfunction, especially among those with greater injury burden. This pattern may reflect long-standing deficits or a TBI-associated cognitive decline process distinct from Alzheimer's disease. (JINS, 2017, 23, 56-64).
Nirula, Ram; Kaufman, Rob; Tencer, Allan
Traumatic brain injury (TBI) remains a major public health problem in the United States. Identifying and modifying vehicle designs associated with TBI will have a significant impact on the frequency and severity of TBI in motor vehicle crashes (MVCs). Our objective, therefore, was to identify interior vehicle contact points associated with severe TBI (head Abbreviated Injury Scale score > 3) among drivers and determine the extent to which modifications of these contact points impact the likelihood of severe TBI. We analyzed drivers in MVCs from the 1993 to 2001 National Automotive Sampling System database. The odds of severe TBI with respect to various vehicle contact points were estimated using multivariate logistic regression. Using computer simulation software, the magnitude of driver head deceleration was modeled while manipulating vehicle design features. The potential impact of this design modification on the frequency and hospital charges of TBI cases was estimated. There were 18,313 drivers involved who were victims of TBI, equating to a national sample size of 3,275,472 cases. The most frequent contact point associated with severe TBI was the roof rail (odds ratio, 2.0; 95% confidence interval, 1.2-3.3). Increasing roof rail padding thickness to 5.0 cm reduced the peak acceleration from 700 g to 218 g, which would potentially reduce the attributable number of severe TBI cases per year from 2,730 to 210, thereby reducing annual acute care charges from $136.5 million to $10.5 million US dollars. Contact with the roof rail significantly increases the likelihood of TBI in MVCs. Minor increases in padding at these points may reduce the frequency of severe TBI, which would have a substantial effect on health care costs.
Blume, Heidi K; Vavilala, Monica S; Jaffe, Kenneth M; Koepsell, Thomas D; Wang, Jin; Temkin, Nancy; Durbin, Dennis; Dorsch, Andrea; Rivara, Frederick P
To determine the prevalence of headache 3 and 12 months after pediatric traumatic brain injury (TBI). This is a prospective cohort study of children ages 5 to 17 years in which we analyzed the prevalence of headache 3 and 12 months after mild TBI (mTBI; n = 402) and moderate/severe TBI (n = 60) compared with controls with arm injury (AI; n = 122). The prevalence of headache 3 months after injury was significantly higher after mTBI than after AI overall (43% vs 26%, relative risk [RR]: 1.7 [95% confidence interval (CI): 1.2-2.3]), in adolescents (13-17 years; 46% vs 25%, RR: 1.8 [95% CI: 1.1-3.1]), and in girls (59% vs 24%, RR: 2.4 [95% CI: 1.4-4.2]). The prevalence of headache at 3 months was also higher after moderate/severe TBI than AI in younger children (5-12 years; 60% vs 27%; RR: 2.0 [95% CI: 1.2-3.4]). Twelve months after injury, TBI was not associated with a significantly increased frequency of headache. However, girls with mTBI reported serious headache (≥ 5 of 10 pain scale rating) more often than controls (27% vs 10%, RR: 2.2 [95% CI: 0.9-5.6]). Pediatric TBI is associated with headache. A substantial number of children suffer from headaches months after their head injury. The prevalence of headache during the year after injury is related to injury severity, time after injury, age, and gender. Girls and adolescents appear to be at highest risk of headache in the months after TBI.
Dayan, Peter S; Holmes, James F; Hoyle, John; Atabaki, Shireen; Tunik, Michael G; Lichenstein, Richard; Miskin, Michelle; Kuppermann, Nathan
To determine the risk of traumatic brain injuries (TBIs) in children with headaches after minor blunt head trauma, particularly when the headaches occur without other findings suggestive of TBIs (ie, isolated headaches). This was a secondary analysis of a prospective observational study of children 2 to 18 years with minor blunt head trauma (ie, Glasgow Coma Scale scores of 14-15). Clinicians assessed the history and characteristics of headaches at the time of initial evaluation, and documented findings onto case report forms. Our outcome measures were (1) clinically important TBI (ciTBI) and (2) TBI visible on computed tomography (CT). Of 27 495 eligible patients, 12 675 (46.1%) had headaches. Of the 12 567 patients who had complete data, 2462 (19.6%) had isolated headaches. ciTBIs occurred in 0 of 2462 patients (0%; 95% confidence interval [CI]: 0%-0.1%) in the isolated headache group versus 162 of 10 105 patients (1.6%; 95% CI: 1.4%-1.9%) in the nonisolated headache group (risk difference, 1.6%; 95% CI: 1.3%-1.9%). TBIs on CT occurred in 3 of 456 patients (0.7%; 95% CI: 0.1%-1.9%) in the isolated headache group versus 271 of 6089 patients (4.5%; 95% CI: 3.9%-5.0%) in the nonisolated headache group (risk difference, 3.8%; 95% CI: 2.3%-4.5%). We found no significant independent associations between the risk of ciTBI or TBI on CT with either headache severity or location. ciTBIs are rare and TBIs on CT are very uncommon in children with minor blunt head trauma when headaches are their only sign or symptom. Copyright © 2015 by the American Academy of Pediatrics.
Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin
Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI
Wammes, Jeffrey D; Good, Tyler J; Fernandes, Myra A
Those who have suffered a concussion, otherwise known as a mild traumatic brain injury (mTBI), often complain of lingering memory problems. However, there is little evidence in the behavioral literature reliably demonstrating memory deficits. Thus, in the present study, cognitive profiles including measures of general executive functioning and processing speed, as well as episodic and semantic memory were collected in younger and older adult participants with or without a remote (>1year prior to testing) mTBI. We first investigated whether there were observable episodic and autobiographical memory impairments associated with mTBI within an otherwise healthy young group. Next, because previous work had demonstrated some overlap in patterns of behavioral impairment in normally aging adults and younger adults with a history of mTBI (e.g. Ozen, Fernandes, Clark, & Roy, 2015), we sought to determine whether these groups displayed similar cognitive profiles. Lastly, we conducted an exploratory analysis to test whether having suffered an mTBI might exacerbate age-related cognitive decline. Results showed the expected age-related decline in episodic memory performance, coupled with a relative preservation of semantic memory in older adults. Importantly, this pattern was also present in younger adults with a history of remote mTBI. No differences were observed across older adult groups based on mTBI status. Logistic regression analyses, using each measure in our battery as a predictor, successfully classified mTBI status in younger participants with a high degree of specificity (79.5%). These results indicate that those who have had an mTBI demonstrate a distinct cognitive signature, characterized by impairment in episodic and autobiographical memory, coupled with a relative preservation of semantic memory. Copyright © 2016 Elsevier Inc. All rights reserved.
Lane, Peter L.; Skoretz, Terry G.; Doig, Gordon; Girotti, Murray J.
Objective Uncontrolled intracranial hypertension after traumatic brain injury (TBI) contributes significantly to the death rate and to poor functional outcome. There is no evidence that intracranial pressure (ICP) monitoring alters the outcome of TBI. The objective of this study was to test the hypothesis that insertion of ICP monitors in patients who have TBI is not associated with a decrease in the death rate. Design Study of case records. Methods The data files from the Ontario Trauma Registry from 1989 to 1995 were examined. Included were all cases with an Injury Severity Score (ISS) greater than 12 from the 14 trauma centres in Ontario. Cases identifying a Maximum Abbreviated Injury Scale score in the head region (MAIS head) greater than 3 were selected for further analysis. Logistic regression analyses were conducted to investigate the relationship between ICP and death. Results Of 9001 registered cases of TBI, an MAIS head greater than 3 was recorded in 5507. Of these patients, 541 (66.8% male, mean age 34.1 years) had an ICP monitor inserted. Their average ISS was 33.4 and 71.7% survived. There was wide variation among the institutions in the rate of insertion of ICP monitors in these patients (ranging from 0.4% to over 20%). Univariate logistic regression indicated that increased MAIS head, ISS, penetrating trauma and the insertion of an ICP monitor were each associated with an increased death rate. However, multivariate analyses controlling for MAIS head, ISS and injury mechanism indicated that ICP monitoring was associated with significantly improved survival (p < 0.015). Conclusions ICP monitor insertion rates vary widely in Ontario’s trauma hospitals. The insertion of an ICP monitor is associated with a statistically significant decrease in death rate among patients with severe TBI. This finding strongly supports the need for a prospective randomized trial of management protocols, including ICP monitoring, in patients with severe TBI. PMID:11129833
Ahmadi, Naser; Hajsadeghi, Fereshteh; Yehuda, Rachel; Anderson, Nils; Garfield, David; Ludmer, Charles; Vaidya, Nutan
Traumatic-brain-injury (TBI) is a devastating-condition resulting in cerebral edema and ischemia. This study investigates the association of mild-TBI (mTBI) to sub-clinical atherosclerosis and cardiovascular (CV) mortality. Five hundred and forty-three veterans without known coronary artery disease or diagnosed mental disorder, who underwent coronary artery calcium (CAC) scanning for clinical indications, were followed for a median of 4-years. Veterans' medical diagnoses and neuropsychiatric health status (mTBI vs non-mTBI) were evaluated using VA electronic medical records. CAC was defined as 0, 1-100, 101-400 and 400+. CAC was higher in mTBI, compared to without-mTBI (p mortality rate was 25% in mTBI and 10.5% in without-mTBI (p = 0.0001). Multivariable survival regression analyses revealed a significant-association between mTBI and CAC, with increased-risk of CV mortality (p mortality was 5.25 in mTBI & CAC > 0, compared to without-mTBI & CAC = 0 (p mortality was 2.25 for mTBI & CAC = 1-100, 4.93 for mTBI & CAC = 101-400 and 7.06 for mTBI & CAC ≥ 400, compared to matched CAC-categories without-mTBI (p mortality was 0.64 for mTBI, 0.69 for mTBI & PTSD, 0.85 for mTBI & CAC > 0 and 0.92 for the combination. The prognostication of mTBI to predict CV mortality is superior to the Framingham risk score. Also the combination of mTBI & PTSD provided incremental prognostic values to predict CV mortality (p atherosclerosis and independently predicts CV mortality.
Dennis, Emily L.; Rashid, Faisal; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Asarnow, Robert F.; Thompson, Paul M.
Outcome after a traumatic brain injury (TBI) is quite variable, and this variability is not solely accounted for by severity or demographics. Identifying sub-groups of patients who recover faster or more fully will help researchers and clinicians understand sources of this variability, and hopefully lead to new therapies for patients with a more prolonged recovery profile. We have previously identified two subgroups within the pediatric TBI patient population with different recovery profiles based on an ERP-derived (event-related potential) measure of interhemispheric transfer time (IHTT). Here we examine structural network topology across both patient groups and healthy controls, focusing on the `rich-club' - the core of the network, marked by high degree nodes. These analyses were done at two points post-injury - 2-5 months (post-acute), and 13-19 months (chronic). In the post-acute time-point, we found that the TBI-slow group, those showing longitudinal degeneration, showed hyperconnectivity within the rich-club nodes relative to the healthy controls, at the expense of local connectivity. There were minimal differences between the healthy controls and the TBI-normal group (those patients who show signs of recovery). At the chronic phase, these disruptions were no longer significant, but closer analysis showed that this was likely due to the loss of power from a smaller sample size at the chronic time-point, rather than a sign of recovery. We have previously shown disruptions to white matter (WM) integrity that persist and progress over time in the TBI-slow group, and here we again find differences in the TBI-slow group that fail to resolve over the first year post-injury.
Wright, Matthew J; Wong, Andrew L; Obermeit, Lisa C; Woo, Ellen; Schmitter-Edgecombe, Maureen; Fuster, Joaquín M
Traumatic brain injury (TBI) is associated with deficits in memory for the content of completed activities. However, TBI groups have shown variable memory for the temporal order of activities. We sought to clarify the conditions under which temporal order memory for activities is intact following TBI. Additionally, we evaluated activity source memory and the relationship between activity memory and functional outcome in TBI participants. Thus, we completed a study of activity memory with 18 severe TBI survivors and 18 healthy age- and education-matched comparison participants. Both groups performed eight activities and observed eight activities that were fashioned after routine daily tasks. Incidental encoding conditions for activities were utilized. The activities were drawn from two counterbalanced lists, and both performance and observation were randomly determined and interspersed. After all of the activities were completed, content memory (recall and recognition), source memory (conditional source identification), and temporal order memory (correlation between order reconstruction and actual order) for the activities were assessed. Functional ability was assessed via the Community Integration Questionnaire (CIQ). In terms of content memory, TBI participants recalled and recognized fewer activities than comparison participants. Recognition of performed and observed activities was strongly associated with social integration on the CIQ. There were no between- or within-group differences in temporal order or source memory, although source memory performances were near ceiling. The findings were interpreted as suggesting that temporal order memory following TBI is intact under conditions of both purposeful activity completion and incidental encoding, and that activity memory is related to functional outcomes following TBI.
Murry, Jason S; Hoang, David M; Barmparas, Galinos; Harada, Megan Y; Bukur, Marko; Bloom, Matthew B; Inaba, Kenji; Margulies, Daniel R; Salim, Ali; Ley, Eric J
Although beta-adrenergic receptor blockade may improve outcomes after traumatic brain injury (TBI), its early use is not routine. We hypothesize that judicious early low-dose propranolol after TBI (EPAT) will improve outcomes without altering bradycardia or hypotensive events. We conducted a prospective, observational study on all patients who presented with moderate-to-severe TBI from March 2010-August 2013. Ten initial patients did not receive propranolol (control). Subsequent patients received propranolol at 1-mg intravenous every 6 h starting within 12 h of intensive care unit (ICU) admission (EPAT) for a minimum of 48 h. Heart rate and blood pressure were recorded hourly for the first 72 h. Bradycardia and hypotensive events, mortality, and length of stay (LOS) were compared between cohorts to determine significant differences. Thirty-eight patients were enrolled; 10 control and 28 EPAT. The two cohorts were similar when compared by gender, emergency department (ED) systolic blood pressure, ED heart rate, and mortality. ED Glasgow coma scale was lower (4.2 versus 10.7, P propranolol. Hypotensive events were similar between cohorts, whereas bradycardia events were higher in control (5.8 versus 1.6, P = 0.05). ICU LOS (15.4 versus 30.4 d, P = 0.02) and hospital LOS (10 versus 19.1 d, P = 0.05) were lower in EPAT. Mortality rates were similar between groups (10% versus 10.7%, P = 0.9). The administration of propranolol led to no recorded complications. Although bradycardia and hypotensive events occur early after TBI, low-dose intravenous propranolol does not increase their number or severity. Early use of propranolol after TBI appears to be safe and may be associated with decreased ICU and hospital LOS. Copyright © 2016 Elsevier Inc. All rights reserved.
Keck, Casey S; Creaghead, Nancy A; Turkstra, Lyn S; Vaughn, Lisa M; Kelchner, Lisa N
The purpose of this study was to characterize pragmatic deficits after childhood traumatic brain injury (TBI) within the home environment social contexts where they occur. We used a descriptive qualitative approach to describe parents' experiences in communicating with their child with TBI. Participants were ten mothers of children ages 6-12 years who had sustained a moderate to severe TBI more than one year prior to the study. Mothers' experiences were collected through semi-structured interviews and questionnaires. Interviews were analyzed using a deductive framework to develop social contexts and pragmatic deficit themes for communication in the home. Overall, mothers primarily described their children with TBI as exhibiting average or near average pragmatic skills at home, but nine observed some pragmatic deficits and/or social behavior problems. There were four in-home social contexts in which pragmatic deficits were observed. Emergent themes also included outside-of-the home social contexts and social behavior problems. There was some overlap of pragmatic deficit and social behavior problem themes among contexts, but many deficits were context specific. This study's pragmatic deficit themes expanded on prior childhood TBI pragmatic investigations by identifying contexts in and outside of the home in which pragmatic deficits may occur after TBI. Learning Outcomes Readers will be able to describe the day-to-day social contexts that may be impacted by pragmatic deficits after childhood TBI. Readers will be able to compare the pragmatic deficit themes identified as occurring in the home to those occurring outside of the home. Copyright © 2017 Elsevier Inc. All rights reserved.
McDonald, Skye; Fisher, Alana; Flanagan, Sharon; Honan, Cynthia A
People with a severe traumatic brain injury (TBI) often experience problems understanding non-literal utterances such as sarcasm and lies in dyadic exchanges. This study aimed to investigate whether these problems extend to settings where speakers vary in their degree of sincerity and whether such problems are associated with deficits in social cognitive abilities (emotion perception, theory of mind, and self-reported empathy) or cognitive abilities (abstract reasoning, working memory, processing speed, attentional switching). Thirty-one adults with severe TBI (24 males) and 25 demographically matched controls (20 males) participated. They watched video vignettes depicting four actors volunteering for additional duties. Each speaker made a limited verbal response which literally suggested a willingness to be involved, but the sincerity with which the response was made was tempered by the actor's emotional demeanour. Participants rated each speaker in the vignettes for degree of sincerity (0-100%). Standardized measures of cognitive and social cognitive function were also taken. Control participants had excellent agreement (α = .90) in their rankings of actors according to sincerity. TBI participants were less consistent (α = .65). Overall, they were sensitive to decreasing sincerity but generally less accurate than control participants. They were poorer at differentiating between levels of sincerity and rated insincere expressions as more sincere, although they rated sincere expressions similarly. Poorer working memory and poorer social cognition were associated with poorer sincerity/sarcasm detection in the participants with TBI, but only social cognition was uniquely associated. Some adults with TBI have difficulty assessing the level of sincerity of speakers. Moreover, poorer social cognition abilities are associated with this difficulty. © 2015 The British Psychological Society.
Kleffelgaard, Ingerid; Soberg, Helene Lundgaard; Bruusgaard, Kari A; Tamber, Anne L; Langhammer, Birgitta
There has been an increasing focus on vestibular rehabilitation (VR) after traumatic brain injury (TBI) in recent years. However, detailed descriptions of the content of and patient responses to VR after TBI are limited. The purposes of this case series are (1) to describe a modified, group-based VR intervention and (2) to examine changes in self-reported and performance-based outcome measures. Two women and 2 men (aged 24-45 years) with mild TBI, dizziness, and balance problems participated in an 8-week intervention consisting of group sessions with guidance, individually modified VR exercises, a home exercise program, and an exercise diary. Self-reported and performance-based outcome measures were applied to assess the impact of dizziness and balance problems on functions related to activity and participation. The intervention caused no adverse effects. Three of the 4 patients reported reduced self-perceived disability because of dizziness, diminished frequency and severity of dizziness, improved health-related quality of life, reduced psychological distress, and improved performance-based balance. The change scores exceeded the minimal detectable change, indicating a clinically significant change or improvement in the direction of age-related norms. The fourth patient did not change or improve in most outcome measures. A modified, group-based VR intervention was safe and appeared to be viable and beneficial when addressing dizziness and balance problems after TBI. However, concurrent physical and psychological symptoms, other neurological deficits, and musculoskeletal problems might influence the course of central nervous system compensation and recovery. The present case series may be useful for tailoring VR interventions to patients with TBI. Future randomized controlled trials are warranted to evaluate the short- and long-term effects of VR after TBI. © 2016 American Physical Therapy Association.
Perron, Brian E; Howard, Matthew O
Delinquent youth frequently exhibit high-risk behaviours that can result in serious injury. However, little is known about traumatic brain injuries (TBIs) and their correlates in this population. To examine the period prevalence and correlates of TBIs in delinquent youths. Interviews were conducted with 720 (97.3%) residents of 27 Missouri Division of Youth Services rehabilitation facilities between March 1 and May 31, 2003. Participants [mean age (M age) = 15.5, standard deviation (SD) = 1.2, 87% male] completed measures assessing TBI, substance use, psychiatric symptoms, and antisocial traits/behaviours. TBI was defined as ever having sustained a head injury causing unconsciousness for more than 20 minutes. Nearly one-in-five youths (18.3%) reported a lifetime TBI. Youths with TBIs were significantly more likely than youths without to be male, have received a psychiatric diagnosis, report an earlier onset of criminal behaviour/substance use and more lifetime substance use problems and past-year criminal acts, evidence psychiatric symptoms, report lifetime suicidality, be impulsive, fearless, and external in locus of control and criminally victimized in the year preceding incarceration. Male gender and frequency of own criminal victimization were important predictors of TBI in multivariate analyses. Regression analyses adjusted for demographic factors, indicated that youths with TBIs were at significantly elevated risk for current depressive/anxious symptoms, antisocial behaviour, and substance abuse problems. TBI is common among delinquent youth and associated with wide ranging psychiatric dysfunction; however, the causal role of TBIs in the pathogenesis of co-morbid conditions remains unclear. Copyright (c) 2008 John Wiley & Sons, Ltd.
Daniel C Krawczyk
Full Text Available Individuals with traumatic brain injury (TBI exhibit deficits in executive control, which may impact their reasoning abilities. Analogical reasoning requires working memory and inhibitory abilities. In this study, we tested adolescents with moderate to severe TBI and typically-developing (TD controls on a set of picture analogy problems. Three factors were varied: complexity (number of relations in the problems, distraction (distractor item present or absent, and animacy (living or non-living items in the problems. We found that TD adolescents performed significantly better overall than TBI adolescents. There was also an age effect present in the TBI group where older participants performed better than younger ones. This age effect was not observed in the TD group. Performance was affected by complexity and distraction. Further, TBI participants exhibited lower performance with distractors present than TD participants. The reasoning deficits exhibited by the TBI participants were correlated with measures of executive function that required working memory updating, attention, and attentional screening. Using MRI-derived measures of cortical thickness, correlations were carried out between task accuracy and cortical thickness. The TD adolescents showed negative correlations between thickness and task accuracy in frontal and temporal regions consistent with cortical maturation in these regions. This study demonstrates that adolescent TBI results in impairments in analogical reasoning ability. Further, TBI youth have difficulty effectively screening out distraction, which may lead to failures in comprehension of the relations among items in visual scenes. Lastly, TBI youth fail to show robust cortical-behavior correlations as observed in TD individuals.
Full Text Available Beta-adrenergic blockade has been hypothesized to have a protective effect on intestinal dysfunction and increased intestinal permeability associated with the epinephrine surge after traumatic brain injury (TBI.Wister rats were subjected to either a weight drop TBI, and intraperitoneally injected or not with labetalol, or a sham procedure (18 rats per group. After 3, 6, or 12h (6 rats per subgroup, intestinal permeability to 4.4 kDa FITC-Dextran and plasma epinephrine levels were measured as was intestinal tight junction protein ZO-1 expression at 12h. Terminal ileum was harvested to measure levels of intestinal tumor necrosis factor (TNF-α and to evaluate histopathology.In TBI group vs. sham group, intestinal permeability (P<0.01 was significantly higher at all time-points, and intestinal ZO-1 expression was lower at 12h. In TBI with vs. without labetalol group, 1 intestinal permeability was significantly lower at 6 and 12h (94.31±7.64 vs. 102.16±6.40 μg/mL; 110.21±7.52 vs. 118.95±7.11 μg/mL, respectively; 2 levels of plasma epinephrine and intestinal TNF-α were significantly lower at 3, 6 and 12h; and 3 intestinal ZO-1 expression was higher at 3, 6 and 12h (p=0.018. Histopathological evaluation showed that labetalol use preserved intestinal architecture throughout.In a rat model of TBI, labetalol reduced TBI-induced sympathetic hyperactivity, and prevented histopathological intestinal injury accompanied by changes in gut permeability and gut TNF-α expression.
Olena Y Glushakova
Full Text Available As traumatic brain injury (TBI continues to affect children and young adults worldwide, research on reliable biomarkers grows as a possible aid in determining the severity of injury. However, many studies have revealed that diverse biomarkers such as S100B and myelin basic protein (MBP have many limitations, such as their elevated normative concentrations in young children. Therefore, the results of these studies have yet to be translated to clinical applications. However, despite the setbacks of research into S100B and MBP, investigators continue to research viable biomarkers, notably glial fibrillary acidic protein (GFAP and ubiquitin C-terminal hydrolase L1 (UCH-L1, as possible aids in medical decision making. Studies have revealed that GFAP and UCH-L1 actually are better predictors of injury progression than the before-mentioned biomarkers S100B and MBP. In addition, UCH-L1 has demonstrated an ability to detect injury while CT is negative, suggesting an ability to detect acute intracranial lesions. Here, we evaluate research testing levels of GFAP and UCH-L1 on children diagnosed with TBI and compare our results to those of other tested biomarkers. In a recent study done by Hayes et al., GFAP and UCH-L1 demonstrated the potential to recognize children with the possibility of poor outcome, allowing for more specialized treatments with clinical and laboratory applications. Although studies on GFAP and UCH-L1 have for the most part warranted positive results, further studies will be needed to confirm their role as reliable markers for pediatric TBI.
Edwards, George; Moreno-Gonzalez, Ines; Soto, Claudio
Neurodegenerative diseases are characterized by distinctive neuropathological alterations, including the cerebral accumulation of misfolded protein aggregates, neuroinflammation, synaptic dysfunction, and neuronal loss, along with behavioral impairments. Traumatic brain injury (TBI) is believed to be an important risk factor for certain neurodegenerative diseases, such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). TBI represents a ubiquitous problem in the world and could play a major role in the pathogenesis and etiology of AD or CTE later in life. TBI events appear to trigger and exacerbate some of the pathological processes in these diseases, in particular, the formation and accumulation of misfolded protein aggregates composed of amyloid-beta (Aβ) and tau. Here, we describe the relationship between repetitive mild TBI and the development of Aβ and tau pathology in patients affected by AD or CTE on the basis of epidemiological and pathological studies in human cases, and a thorough overview of data obtained in experimental animal models. We also discuss the possibility that TBI may contribute to initiate the formation of misfolded oligomeric species that may subsequently spread the pathology through a prion-like process of seeding of protein misfolding. Copyright © 2016 Elsevier Inc. All rights reserved.
Fouche, Pieter Francsois; Jennings, Paul Andrew; Smith, Karen; Boyle, Malcolm; Blecher, Gabriel; Knott, Jonathan; Raji, Mani; Rosengarten, Pamela; Augello, Michael Roberto; Bernard, Stephen
Rapid sequence intubation (RSI) is not only used in traumatic brain injuries in the out-of-hospital setting, but also for non-traumatic brain pathologies (NTBP) such as brain tumors, meningitis, encephalitis, hypoxic/anoxic brain injury, stroke, arteriovenous malformations, tumors, aneurysms, brain hemorrhage, as well as brain injury due to diabetes, seizures and toxicity, metabolic conditions, and alcohol and drug overdose. Previous research suggests that RSI is common in non-traumatic coma, but with an unknown prevalence of NTBP in those that receive RSI. If NTBP is common and if brain trauma RSI evidence is not valid for NTBP then a sizable proportion of NTBP receive this treatment without evidence of benefit. This study calculated the out-of-hospital NTBP prevalence in patients that had received RSI and explored factors that predicted survival. A retrospective cohort study based on data collected from an ambulance service and seven hospitals based in Melbourne, Australia. Non-traumatic brain pathologies were defined using ICD10-AM codes for the calculation of NTBP prevalence. Logistic regression modelled out-of-hospital predictors of survival to hospital discharge after adjustment for comorbidities. The seven participating hospitals treated 2,277 patients that received paramedic RSI for all illnesses and indications from January 1, 2008 to December 31, 2015, with survival data available for 1,940 (85%). Of the 1,940, 1,125 (58%) patients had at least one hospital-diagnosed NTBP. Sixty-nine percent all of NTBP survived to hospital discharge, compared to 65% for traumatic intracranial injury. Strokes were the most common and had poor survival to discharge (37%) compared to the second most common NTBP toxicity/toxic encephalopathy that had very high survival (98%). No out-of-hospital clinical intervention or prehospital time interval predicted survival. Factors that did predict survival include Glasgow Coma Scale (GCS), duration of mechanical ventilation, age, ICU
Full Text Available Traumatic brain injury is one of the major causes for invalidization in children. The research purpose is an integrated study of consequences of severe and moderate closed traumatic brain injury in children and evaluation of their dynamics during therapy by means of a no tropic medication — cerebrolysin (Ebewe Pharma, Austria. The total of 283 children aged from 4 to 14 years were examined in the longaterm period of severe and moderate closed traumatic brain injury, from 6 months to 4 years after injury. Their neurological status was characterized by nona specific focal symptoms along with evident motor coordination disturbances, elements of dynamic and staticoloa comotory ataxia, reduction in execution speed of serial movements. Statistically significant differences with ageamatched controls were confirmed for measures of acousticaverbal memory and sustained attention. Posttraumatic epilepsy developed in 16 (5,7% patients with the onset of secondarily generalized seizures in 4–12 months following the injury. Effectiveness of the no tropic medication was evaluated in 60 patients aged from 7 to 12 years, who were distributed into 2 equal groups. The research has confirmed a positive effect of no tropic medication in the treatment of traumatic brain injury consequences manifested in the regression of headaches, fatigue, motor coordination disturbances along with improvements of memory, attention, intellectual performance rates, as well as EEG characteristics.Key words: traumatic brain injury, consequences, children, therapy, nootropic medications.
Wagner, Amy K; Fabio, Anthony; Puccio, Ava M; Hirschberg, Ronald; Li, Wei; Zafonte, Ross D; Marion, Donald W
Female sex hormones appear to be neuroprotective after traumatic brain injury by attenuating multiple mechanisms of secondary insult, including excitotoxicity and ischemia. The purpose of this study was to evaluate associations between gender and cerebrospinal fluid glutamate and lactate/pyruvate production and the role of hypothermia with gender in attenuating these markers. Prospectively collected data were analyzed for adult patients with severe traumatic brain injury. Gender comparisons for cerebrospinal fluid glutamate and lactate/pyruvate production were determined using ventricular samples obtained over the first 48 hrs postinjury. University-based level I trauma center. There were 123 patients, male n = 93 and female n = 30 (n = 686 cerebrospinal fluid samples), with severe traumatic brain injury (Glasgow Coma Scale score fluid glutamate production for males compared with females (p = .0023) and a significant interaction between glutamate concentration, gender, and time (p = .0035) by 24 hrs postinjury. Females had lower lactate/pyruvate ratios than males (p = .0006), and there was a significant interaction between lactate/pyruvate, gender, and time (p = .0045) throughout the first 48 hrs postinjury. Hypothermia attenuated glutamate levels, particularly for males, over the time course studied. These data suggest significant gender differences with glutamate and lactate/pyruvate production after severe traumatic brain injury. Gender- and hormone-mediated differences in central nervous system pathophysiology should be considered with clinical trials in traumatic brain injury.
Li, Nan; Yang, Ya; Glover, David P; Zhang, Jiangyang; Saraswati, Manda; Robertson, Courtney; Pelled, Galit
The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating. We investigated the altered cortical plasticity 2-3 weeks after injury in a pediatric rat model of TBI. Significant decreases in neurophysiological responses across the depth of the noninjured, primary somatosensory cortex (S1) in TBI rats, compared to age-matched controls, were detected with electrophysiological measurements of multi-unit activity (86.4% decrease), local field potential (75.3% decrease), and functional magnetic resonance imaging (77.6% decrease). Because the corpus callosum is a clinically important white matter tract that was shown to be consistently involved in post-traumatic axonal injury, we investigated its anatomical and functional characteristics after TBI. Indeed, corpus callosum abnormalities in TBI rats were detected with diffusion tensor imaging (9.3% decrease in fractional anisotropy) and histopathological analysis (14% myelination volume decreases). Whole-cell patch clamp recordings further revealed that TBI results in significant decreases in spontaneous firing rate (57% decrease) and the potential to induce long-term potentiation in neurons located in layer V of the noninjured S1 by stimulation of the corpus callosum (82% decrease). The results suggest that post-TBI plasticity can translate into inappropriate neuronal connections and dramatic changes in the function of neuronal networks.
induced TBI causes progressive tau pathology in 2 lines of transgenic mice. First, we commissioned construction , shipping and assembly of a CHIMERA...AD_________________ Award Number: W81XWH-13-2-0016 TITLE: Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic...of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury 5b. GRANT NUMBER W81XWH-13-2-0016 5c. PROGRAM ELEMENT NUMBER 6
chronic neuronal cell loss, glial activation, and chronic traumatic encephalopathy (CTE) measure of β-amyloid and hyper-phosphorylated tau protein...Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury...30 Jun 2015 4. TITLE AND SUBTITLE Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After TBI 5a. CONTRACT NUMBER W81XWH-14-1
Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N; Post, Jeremy; Baldwin, Katherine; Hoffer, Barry; Balaban, Carey D; Barbacci, Damon; Schultz, J Albert; Gouty, Shawn; Cox, Brian M; Woods, Amina S
Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion. A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50μm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI. Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury. Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain. Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments. Copyright © 2016. Published by Elsevier B.V.
Panzer, Stephanie; Covaliov, Lidia; Augat, Peter; Peschel, Oliver
The aim of this study was to compare pathological findings after traumatic brain injury between autopsy and ante-mortem computed tomography (CT). A second aim was to identify changes in these findings between the primary posttraumatic CT and the last follow-up CT before death. Through the collaboration between clinical radiology and forensic medicine, 45 patients with traumatic brain injury were investigated. These patients had undergone ante-mortem CT as well as autopsy. During autopsy, the brain was cut in fronto-parallel slices directly after removal without additional fixation or subsequent histology. Typical findings of traumatic brain injury were compared between autopsy and radiology. Additionally, these findings were compared between the primary CT and the last follow-up CT before death. The comparison between autopsy and radiology revealed a high specificity (≥80%) in most of the findings. Sensitivity and positive predictive value were high (≥80%) in almost half of the findings. Sixteen patients had undergone craniotomy with subsequent follow-up CT. Thirteen conservatively treated patients had undergone a follow-up CT. Comparison between the primary CT and the last ante-mortem CT revealed marked changes in the presence and absence of findings, especially in patients with severe traumatic brain injury requiring decompression craniotomy. The main pathological findings of traumatic brain injury were comparable between clinical ante-mortem CT examinations and autopsy. Comparison between the primary CT after trauma and the last ante-mortem CT revealed marked changes in the findings, especially in patients with severe traumatic brain injury. Hence, clinically routine ante-mortem CT should be included in the process of autopsy interpretation. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Sandra A Acosta
Full Text Available Long-term consequences of traumatic brain injury (TBI are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD, yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long
Scheenen, Myrthe E.; Spikman, Jacoba M.; de Koning, Myrthe E.; van der Horn, Harm J.; Roks, Gerwin; Hageman, Gerard; van der Naalt, Joukje
Although most patients recover fully following mild traumatic brain injury (mTBI), a minority (15-25%) of all patients develop persistent post-traumatic complaints (PTC) that interfere with the resumption of previous activities. An early identification of patients who are at risk for PTC is
Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration after Traumatic Brain Injury...Purpose: The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will...objective of reducing blood levels of glutamate. This will produce a brain -to-blood gradient of glutamate which will enhance the removal of excess
Fotakopoulos, George; Makris, Demosthenes; Tsianaka, Eleni; Kotlia, Polikceni; Karakitsios, Paulos; Gatos, Charalabos; Tzannis, Alkiviadis; Fountas, Kostas
To identify the risk factors for post-traumatic amnesia (PTA) and to document the incidence of PTA after mild traumatic brain injuries. This was a prospective study, affecting mild TBI (mTBI) (Glasgow Coma Scale 14-15) cases attending to the Emergency Department between January 2009 and April 2012 (40 months duration). Patients were divided into two groups (Group A: without PTA, and Group B: with PTA, and they were assessed according to the risk factors. A total of 1762 patients (males: 1002, 56.8%) were meeting study inclusion criteria [Group A: n = 1678 (83.8%), Group B: n = 84 (4.2%)]. Age, CT findings: (traumatic focal HCs in the frontal and temporal lobes or more diffuse punctate HCs, and skull base fractures), anticoagulation therapy and seizures were independent factors of PTA. There was no statistically significant correlation between PTA and sex, convexity fractures, stroke event, mechanism of mTBI (fall +/or beating), hypertension, coronary heart disease, chronic smokers and diabetes (p > 0.005). CT findings: (traumatic focal HCs in the frontal and temporal lobes or more diffuse punctate HCs and skull base fractures), age, seizures and anticoagulation/antiplatelet therapy, were independent factors of PTA and could be used as predictive factors after mTBI.
Richard J Servatius
Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.
Mak, Calvin H K; Wong, Stephen K H; Wong, George K; Ng, Stephanie; Wang, Kevin K W; Lam, Ping Kuen; Poon, Wai Sang
Traumatic brain injury in elderly patients is a neglected global disease burden. The main cause is fall, followed by motor vehicle accidents. This review article summarizes different aspects of geriatric traumatic brain injury, including epidemiology, pathology, and effects of comorbidities and pre-injury medications such as antiplatelets and anticoagulants. Functional outcome with or without surgical intervention, cognitive outcome, and psychiatric complications are discussed. Animal models are also reviewed in attempt to explain the relationship of aging and outcome, together with advances in stem cell research. Though elderly people in general did fare worse after traumatic brain injury, certain "younger elderly" people, aged 65-75 years, could have a comparable outcome to younger adults after minor to moderate head injury.
Asht Mangal Mishra
Full Text Available Traumatic brain injury (TBI contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG-functional magnetic resonance imaging (fMRI was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and
Mishra, Asht Mangal; Bai, Xiaoxiao; Sanganahalli, Basavaraju G.; Waxman, Stephen G.; Shatillo, Olena; Grohn, Olli; Hyder, Fahmeed; Pitkänen, Asla; Blumenfeld, Hal
Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral
Sekhon, Mypinder S; Gooderham, Peter; Toyota, Brian; Kherzi, Navid; Hu, Vivien; Dhingra, Vinay K; Hameed, Morad S; Chittock, Dean R; Griesdale, Donald E
Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients. We conducted a single-center quasi-experimental uncontrolled pre- and post-NCC study in severe traumatic brain injury patients (Glasgow Coma Scale ≤8). The NCC program includes consultation with a neurointensivist and neurosurgeon and multimodal neuromonitoring. Demographic, injury severity metrics, neurophysiologic data, and therapeutic interventions were collected. Glasgow Outcome Scale (GOS) at 6 months was the primary outcome. Multivariable ordinal logistic regression was used to model the association between NCC implementation and GOS at 6 months. A total of 113 patients were identified: 76 pre-NCC and 37 post-NCC. Mean age was 39 years (standard deviation [SD], 2) and 87 of 113 (77%) patients were male. Median admission motor score was 3 (interquartile ratio, 1-4). Daily mean arterial pressure was higher (95 mmHg [SD, 10]) versus (88 mmHg [SD, 10], p<0.001) and daily mean core body temperature was lower (36.6°C [SD, 0.90]) versus (37.2°C [SD, 1.0], p=0.001) post-NCC compared with pre-NCC, respectively. Multivariable regression modelling revealed the NCC program was associated with a 2.5 increased odds (odds ratios, 2.5; 95% confidence interval, 1.1-5.3; p=0.022) of improved 6-month GOS. Implementation of a NCC program is associated with improved 6 month GOS in severe TBI patients.
Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate
Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial
Tkachenko, Nataliya; Singh, Kanwaljit; Hasanaj, Lisena; Serrano, Liliana; Kothare, Sanjeev V
Sleep problems affect 30% to 80% of patients with mild traumatic brain injury. We assessed the prevalence of sleep disorders after mild traumatic brain injury and its correlation with other symptoms. Individuals with mild traumatic brain injury were assessed at the New York University Concussion Center during 2013-2014 with the Sports Concussion Assessment Tool, third edition, data following mild traumatic brain injury. The relationship between sleep problems (drowsiness, difficulty falling asleep, fatigue or low energy), psychiatric symptoms (sadness, nervousness or anxiousness), headache, and dizziness were analyzed by Spearman correlation and logistic regression using moderate to severe versus none to mild categorization. Ninety-three patients were retrospectively considered. The most common injury causes were falls (34.4%) and motor vehicle accidents (21.5%). There was a positive correlation between dizziness, headache, psychiatric problems (sadness, anxiety, irritability), and sleep problems (fatigue, drowsiness, and difficulty falling asleep) (P brain injury to Sport Concussion Assessment Tool 3 administration (odds ratio = 1.005, 1.006, and 1.008, P brain injury and should be counseled and initiated with early interventions. Copyright © 2016 Elsevier Inc. All rights reserved.
Costanzo, Michelle E; Chou, Yi-Yu; Leaman, Suzanne; Pham, Dzung L; Keyser, David; Nathan, Dominic E; Coughlin, Mary; Rapp, Paul; Roy, Michael J
Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case-control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms. Published by Elsevier Ireland Ltd.
Logsdon, Aric F.; Lucke-Wold, Brandon P.; Turner, Ryan C.; Huber, Jason D.; Rosen, Charles L.; Simpkins, James W.
Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis. PMID:26140712
Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K.; Bernick, Charles; Ghosh, Chaitali; Bazarian, Jeffrey J.; Janigro, Damir
Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six post mortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772
Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir
Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (PCTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.
Hassett, Leanne; Moseley, Anne M; Harmer, Alison R
Reduced cardiorespiratory fitness (cardiorespiratory deconditioning) is a common consequence of traumatic brain injury (TBI). Fitness training may be implemented to address this impairment. The primary objective of this updated review was to evaluate whether fitness training improves cardiorespiratory fitness in people who have sustained a TBI. The secondary objectives were to evaluate whether fitness training improves body function and structure (physical and cognitive impairments, psychological responses resulting from the injury), activity limitations and participation restrictions in people who have sustained a TBI as well as to evaluate its safety, acceptance, feasibility and suitability. We searched 10 electronic databases (the Cochrane Injuries Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Embase; PubMed (MEDLINE); CINAHL; AMED; SPORTDiscus; PsycINFO; PEDro and PsycBITE) and the International Clinical Trials Registry Platform for relevant trials. In addition we screened reference lists from systematic reviews related to the topic that we identified from our search, and from the included studies, and contacted trialists to identify further studies. The search was run in August 2017. Randomised controlled studies with TBI participants were eligible if they compared an exercise programme incorporating cardiorespiratory fitness training to usual care, a non-exercise intervention, or no intervention. Two authors independently screened the search results, extracted data and assessed bias. We contacted all trialists for additional information. We calculated mean difference (MD) or standardised mean difference (SMD) and 95% confidence intervals (CI) for continuous data, and odds ratio with 95% CI for dichotomous data. We pooled data when there were sufficient studies with homogeneity. Two new studies incorporating 96 participants were identified in this update and were added to the six previously included studies. A total of
Full Text Available Abstract Introduction Traumatic brain injury is a form of acquired brain injury that results from sudden trauma to the head. Specifically, mild traumatic brain injury is a clinical diagnosis that can have significant effects on an individual's life, yet is difficult to identify through traditional imaging techniques. Case presentation This is the case of a 68-year-old previously healthy African American woman who was involved in a motor vehicle accident that resulted in significant head trauma. After the accident, she experienced symptoms indicative of mild traumatic brain injury and sought a neurological consultation when her symptoms did not subside. She was initially evaluated with a neurological examination, psychological evaluation, acute concussion evaluation and a third-party memory test using software from CNS Vital Signs for neurocognitive function. A diagnosis of post-concussion syndrome was suggested. Diffusion tensor imaging revealed decreased fractional anisotropy in the region immediately adjacent to both lateral ventricles, which was used to confirm the diagnosis. Fractional anisotropy is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. These results are indicative of post-traumatic gliosis and are undetectable by magnetic resonance imaging. Our patient was treated with cognitive therapy. Conclusion Minor traumatic brain injury is a common injury with variable clinical presentation. The system of diagnosis used in this case found a significant relationship between the clinical assessment and imaging results. This would not have been possible using traditional imaging techniques and highlights the benefits of using diffusion tensor imaging in the sub-acute assessment of minor traumatic brain injury.
Cadosch, Dieter; Toffoli, Andrew M; Gautschi, Oliver P; Frey, Sönke P; Zellweger, René; Skirving, Allan P; Filgueira, Luis
Traumatic brain injury is associated with an increased rate of heterotopic ossification within skeletal muscle, possibly as a result of humoral factors. In this study, we investigated whether cells from skeletal muscle adopt an osteoblastic phenotype in response to serum from patients with traumatic brain injury. Serum was collected from thirteen patients with severe traumatic brain injury, fourteen patients with a long-bone fracture, and ten control subjects. Primary cultures of skeletal muscle cells isolated from patients undergoing orthopaedic surgery were performed and characterized with use of immunofluorescence microscopy, reverse transcription-polymerase chain reaction, and Western blot analysis. Proliferation and osteoblastic differentiation were assessed with use of commercial cell assays, Western blot analysis (for Osterix protein), and the Villanueva bone stain. All serum-treated cell populations expressed the osteoblast marker Osterix after one week in culture. Cells treated with serum from all study groups in mineralization medium had increased alkaline phosphatase activity and mineralized nodules within the mesenchymal cell subpopulation after three weeks in culture. Serum from patients with traumatic brain injury induced a significant increase (p = 0.02) in the rate of proliferation of primary skeletal muscle cells (1.87 [95% confidence interval, 1.66 to 2.09]) compared with the rate induced by serum from patients with a fracture (1.42 [95% confidence interval, 1.21 to 1.58]) or by serum from controls (1.35 [95% confidence interval, 1.15 to 1.54]). Human serum supports the osteoblastic differentiation of cells derived from human skeletal muscle, and serum from patients with severe traumatic brain injury accelerates proliferation of these cells. These findings suggest the early presence of humoral factors following traumatic brain injury that stimulate the expansion of mesenchymal cells and osteoprogenitors within skeletal muscle.
Arnaud Messé; Sophie Caplain; Mélanie Pélégrini-Issac; Sophie Blancho; Richard Lévy; Nozar Aghakhani; Michèle Montreuil; Habib Benali; Stéphane Lehéricy
Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the D...
Monti, Daniel A; Tobia, Anna; Stoner, Marie; Wintering, Nancy; Matthews, Michael; He, Xiao-Song; Doucet, Gaelle; Chervoneva, Inna; Tracy, Joseph I; Newberg, Andrew B
The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms. We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI). The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET intervention and were associated with clinical improvement of symptoms associated with distressing recollections. This preliminary study suggests that the
Full Text Available The high prevalence of traumatic brain injuries (TBI among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI.We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption.Data were derived from the Centre for Addiction and Mental Health's 2013 Ontario Student Drug Use and Health Survey (OSDUHS. This population-based cross-sectional school survey included 10,272 7th to 12th graders (ages 11-20 who completed anonymous self-administered questionnaires in classrooms.Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed.Among all students, 22.4% (95% CI: 20.7, 24.1 reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year TBI (45.5%, 95% CI: 41.0, 50.1. Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months. Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers.TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol
Ilie, Gabriela; Boak, Angela; Mann, Robert E; Adlaf, Edward M; Hamilton, Hayley; Asbridge, Mark; Rehm, Jürgen; Cusimano, Michael D
The high prevalence of traumatic brain injuries (TBI) among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI. We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption. Data were derived from the Centre for Addiction and Mental Health's 2013 Ontario Student Drug Use and Health Survey (OSDUHS). This population-based cross-sectional school survey included 10,272 7th to 12th graders (ages 11-20) who completed anonymous self-administered questionnaires in classrooms. Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed. Among all students, 22.4% (95% CI: 20.7, 24.1) reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year) TBI (45.5%, 95% CI: 41.0, 50.1). Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months). Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers. TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol mixed with
Full Text Available Growth Mixture Modeling (GMM was used to investigate the longitudinal trajectory of groups (classes of depression symptoms, and how these groups were predicted by the covariates of age, sex, severity, and length of hospitalization following Traumatic Brain Injury (TBI in a group of 1074 individuals (696 males, and 378 females from the Royal Hobart Hospital, who sustained a TBI. The study began in late December 2003 and recruitment continued until early 2007. Ages ranged from 14 to 90 years, with a mean of 35.96 years (SD = 16.61. The study also examined the associations between the groups and causes of TBI. Symptoms of depression were assessed using the Hospital Anxiety and Depression Scale within 3 weeks of injury, and at 1, 3, 6, 12, and 24 months post-injury. The results revealed three groups: low, high, and delayed depression. In the low group depression scores remained below the clinical cut-off at all assessment points during the 24-months post-TBI, and in the high group, depression scores were above the clinical cut-off at all assessment points. The delayed group showed an increase in depression symptoms to 12 months after injury, followed by a return to initial assessment level during the following 12 months. Covariates were found to be differentially associated with the three groups. For example, relative to the low group, the high depression group was associated with more severe TBI, being female, and a shorter period of hospitalization. The delayed group also had a shorter period of hospitalization, were younger, and sustained less severe TBI. Our findings show considerable fluctuation of depression over time, and that a non-clinical level of depression at any one point in time does not necessarily mean that the person will continue to have non-clinical levels in the future. As we used GMM, we were able to show new findings and also bring clarity to contradictory past findings on depression and TBI. Consequently, we recommend the use
Maneewong, Jutaporn; Maneeton, Benchalak; Maneeton, Narong; Vaniyapong, Tanat; Traisathit, Patrinee; Sricharoen, Natthanidnan; Srisurapanont, Manit
Delirium in traumatic brain injury (TBI) is common, may be predictable, and has a multifaceted symptom complex. This study aimed to examine: 1) the sum score of Glasgow Coma Scale (GCS) and if its component scores could predict delirium in TBI patients, and 2) the prominent symptoms and their courses over the first days after TBI. TBI patients were recruited from neurosurgical ward inpatients. All participants were hospitalized within 24 hours after their TBI. Apart from the sum score of GCS, which was obtained at the emergency department (ED), the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for delirium were applied daily. The severity of delirium symptoms was assessed daily using the Delirium Rating Scale - Revised-98 (DRS-R-98). The participants were 54 TBI patients with a mean GCS score of 12.7 (standard deviation [SD] =2.9). A total of 25 patients (46.3%) met the diagnosis of delirium and had a mean age of 36.7 years (SD =14.8). Compared with 29 non-delirious patients, 25 delirious patients had a significantly lower mean GCS score (P=0.04), especially a significantly lower verbal component score (P=0.03). Among 18 delirious patients, four symptoms of the DRS-R-98 cognitive domain (orientation, attention, long-term memory, and visuospatial ability) were moderate symptoms (score ≥2) at the first day of admission. After follow-up, three cognitive (orientation, attention, and visuospatial ability) and two noncognitive symptoms (lability of affect and motor agitation) rapidly resolved. Almost half of patients with mild to moderate head injuries may develop delirium in the first 4 days after TBI. Those having a low GCS score, especially the verbal component score, at the ED were likely to have delirium in this period. Most cognitive domains of delirium described in the DRS-R-98 were prominent within the first 4 days of TBI with delirium. Three cognitive and two noncognitive symptoms of delirium decreased significantly.
Hammond, Flora M.; Barrett, Ryan S.; Shea, Timothy; Seel, Ronald T.; McAlister, Thomas W.; Kaelin, Darryl; Ryser, David; Corrigan, John D.; Cullen, Nora; Horn, Susan D.
Objective To describe psychotropic medication administration patterns during inpatient rehabilitation for traumatic brain injury (TBI) and their relationship to patient pre-injury and injury characteristics. Design Prospective observational cohort. Setting multiple acute inpatient rehabilitation units or hospitals. Participants 2,130 individuals with TBI (complicated mild, moderate, or severe) admitted for inpatient rehabilitation. Interventions NA Main Outcome Measure(s) NA Results Most frequently administered was narcotic analgesics (72% of sample) followed by antidepressants (67%), anticonvulsants (47%), antianxiolytics (33%), hypnotics (30%), stimulants (28%), antipsychotics (25%), antiparkinson agents (25%), and miscellaneous psychotropics (18%). The psychotropic agents studied were administered to 95% of the sample with 8.5% receiving only 1 and 31.8% receiving 6 or more. Degree of psychotropic medication administration varied widely between sites. Univariate analyses indicated younger patients were more likely to receive anxiolytics, antidepressants, antiparkinson agents, stimulants, antipsychotics, and narcotic analgesics, while those older were more likely to receive anticonvulsants and miscellaneous psychotropics. Men were more likely to receive antipsychotics. All medication classes were less likely administered to Asians, and more likely to those with more severe functional impairment. Use of anticonvulsants was associated with having seizures at some point during acute care or rehabilitation stays. Narcotic analgesics were more likely for those with history of drug abuse, history of anxiety and depression (premorbid or during acute care), and severe pain during rehabilitation. Psychotropic medication administration increased rather than decreased during the course of inpatient rehabilitation in each of the medication categories except for narcotics. This observation was also true for medication administration within admission functional levels (defined
Scheff, Stephen W.; Ansari, Mubeen A.; Roberts, Kelly N.
Traumatic brain injury (TBI) involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Oxidative stress is one of the most celebrated secondary injury mechanisms. A close relationship exists between levels of oxidative stress and the pathogenesis of TBI. However, other cascades, such as an increase in proinflammatory cytokines, also play important roles in the overall response to the trauma. Pharmacologic intervention, in order to be successful, requires a multifaceted approach. Naturally occurring flavonoids are unique in possessing not only tremendous free radical scavenging properties but also the ability to modulate cellular homeostasis leading to a reduction in inflammation and cell toxicity. This study evaluated the therapeutic role of Pycnogenol (PYC) a patented combinational bioflavonoid. Young adult Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion and treated post injury with PYC or vehicle. At either 48 or 96h post trauma, the animals were killed and the cortex and hippocampus analyzed for changes in enzymatic and non-enzymatic oxidative stress markers. In addition, possible changes in both pre and post synaptic proteins (synapsin-1, PSD-95, drebrin, synapse associated protein 97) were analyzed. Finally, a separate cohort of animals were used to evaluate two proinflammatory cytokines (IL-6, TNF-α). Following the trauma there was a significant increase in oxidative stress in both the injured cortex and the ipsilateral hippocampus. Animals treated with PYC significantly ameliorated levels of protein carbonyls, lipid peroxidation, and protein nitration. The PYC treatment also significantly reduced the loss of key pre and post synaptic proteins with some levels in the hippocampus of PYC treated animals not significantly different from sham operated controls. Although levels of the proinflammatory cytokines were significantly elevated in both injury groups, the cohort treated with PYC