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Find video protocols related to scientific articles indexed in Pubmed.
A Multi-Center Evaluation of Clinical and Radiographic Outcomes Following High-Grade Spondylolisthesis Reduction and Fusion.
J Spinal Disord Tech
PUBLISHED: 11-01-2014
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A retrospective review of the clinical and radiographic outcomes from a multi-center study of surgical treatment for high-grade spondylolisthesis (HGS) in adults. The objective was to assess the safety of surgical reduction, its ability to correct regional deformity, and its clinical effectiveness.
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Measurement of the GFAP-BDP Biomarker for the Detection of Traumatic Brain Injury Compared to CT and MRI.
J. Neurotrauma
PUBLISHED: 09-30-2014
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Glial Fibrillary Acidic Protein and its breakdown products (GFAP-BDP) are brain specific proteins released into serum as part of the pathophysiologic response following traumatic brain injury (TBI). We performed a multicenter trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multicenter, prospective cohort study included patients 16 to 93 years old presenting to 3 Level I trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, etc.). Serum GFAP-BDP levels were drawn within 24 hours and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission CT as well as delayed MRI was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; the mean age was 42.1± 18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score 2 (IQR 2)). GFAP-BDP demonstrated very good predictive ability (AUC= 0.87), and demonstrated significant discrimination of injury severity (OR 1.45, 95% CI 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12 to 30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity.
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Sideline assessment tools for the evaluation of concussion in athletes: a review.
Neurosurgery
PUBLISHED: 09-19-2014
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Sports-related concussions, which have become more prevalent in the past decade, are an extremely common phenomenon in organized athletics and create a substantial economic burden on the health care system. Furthermore, they can have devastating impacts on the athletic careers and long-term health of athletes. However, concussion evaluation remains a controversy with respect to diagnosis, management, and return-to-play guidelines for sports-related concussions. This is especially true of the immediate evaluation of sports-related concussion on the sidelines, where decisions must be made quickly and effectively with limited diagnostic resources. Considerable effort has been directed toward developing reliable and valid sidelines assessment modalities for concussion evaluation with a goal of accurately determining whether an athlete requires rapid removal from or is able to return to competition. This paper discusses the role of the concussion specialist on the sidelines during athletic competition and examines the current tools and resources available for the sidelines assessment of concussion. Additionally, new technologies, including electronic applications for Smartphones and tablets, as well as future directions in sidelines assessment of concussion are examined.
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Neurostimulation for traumatic brain injury.
J. Neurosurg.
PUBLISHED: 08-29-2014
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Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI.
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Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma.
Brain
PUBLISHED: 08-24-2014
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Cortical spreading depolarization causes a breakdown of electrochemical gradients following acute brain injury, and also elicits dynamic changes in regional cerebral blood flow that range from physiological neurovascular coupling (hyperaemia) to pathological inverse coupling (hypoperfusion). In this study, we determined whether pathological inverse neurovascular coupling occurred as a mechanism of secondary brain injury in 24 patients who underwent craniotomy for severe traumatic brain injury. After surgery, spreading depolarizations were monitored with subdural electrode strips and regional cerebral blood flow was measured with a parenchymal thermal diffusion probe. The status of cerebrovascular autoregulation was monitored as a correlation between blood pressure and regional cerebral blood flow. A total of 876 spreading depolarizations were recorded in 17 of 24 patients, but blood flow measurements were obtained for only 196 events because of technical limitations. Transient haemodynamic responses were observed in time-locked association with 82 of 196 (42%) spreading depolarizations in five patients. Spreading depolarizations induced only hyperaemic responses (794% increase) in one patient with intact cerebrovascular autoregulation; and only inverse responses (-24% decrease) in another patient with impaired autoregulation. In contrast, three patients exhibited dynamic changes in neurovascular coupling to depolarizations throughout the course of recordings. Severity of the pathological inverse response progressively increased (-14%, -29%, -79% decrease, P < 0.05) during progressive worsening of cerebrovascular autoregulation in one patient (Pearson coefficient 0.04, 0.14, 0.28, P < 0.05). A second patient showed transformation from physiological hyperaemic coupling (44% increase) to pathological inverse coupling (-30% decrease) (P < 0.05) coinciding with loss of autoregulation (Pearson coefficient 0.19 ? 0.32, P < 0.05). The third patient exhibited a similar transformation in brain tissue oxygenation, a surrogate of blood flow, from physiologic hyperoxic responses (20% increase) to pathological hypoxic responses (-14% decrease, P < 0.05). Pathological inverse coupling was only observed with electrodes placed in or adjacent to evolving lesions. Overall, 31% of the pathological inverse responses occurred during ischaemia (<18 ml/100 g/min) thus exacerbating perfusion deficits. Average perfusion was significantly higher in patients with good 6-month outcomes (46.8 ± 6.5 ml/100 g/min) than those with poor outcomes (32.2 ± 3.7 ml/100 g/min, P < 0.05). These results establish inverse neurovascular coupling to spreading depolarization as a novel mechanism of secondary brain injury and suggest that cortical spreading depolarization, the neurovascular response, cerebrovascular autoregulation, and ischaemia are critical processes to monitor and target therapeutically in the management of acute brain injury.
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Outcome Prediction After Mild and Complicated Mild Traumatic Brain Injury: External Validation of Existing Models and Identification of New Predictors Using the TRACK-TBI Pilot Study.
J. Neurotrauma
PUBLISHED: 07-16-2014
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Background Although the majority of patients with mild traumatic brain injury (mTBI) recover completely, some still suffer from disabling ailments at 3 or 6 months. We validated existing prognostic models for mTBI, and explored predictors of poor outcome after mTBI. Methods We selected patients with mTBI from TRACK-TBI Pilot; an unselected observational cohort of TBI patients from three centers in the United States. We validated two prognostic models for the Glasgow Outcome Scale Extended (GOS-E) at 6 months after injury. One model was based on the CRASH study data, and another from Nijmegen, the Netherlands. Possible predictors of 3 and 6-month GOS-E were analyzed with univariate and multivariable proportional odds regression models. Results Of the 386 out of 485 patients included in the study (median age 44 years (interquartile range: 27-58)), 75% (n=290) presented with a Glasgow Coma Score (GCS) of 15. In this mTBI population both previously developed models had a poor performance (AUC 0.49 to 0.56). In multivariable analyses, the strongest predictors of lower 3 and 6-month GOS-E were older age, pre-existing psychiatric conditions and lower education. Injury caused by assault, extracranial injuries and lower GCS were also predictive of lower GOS-E. Conclusion Existing models for mTBI performed unsatisfactorily. Our study shows that for mTBI different predictors are relevant as for moderate and severe TBI. These include age, pre-existing psychiatric conditions and lower education. Development of a valid prediction model for mTBI patients requires further research efforts.
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Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a TRACK-TBI study.
J. Neurotrauma
PUBLISHED: 07-09-2014
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We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ?1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ?1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history.
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Detection of white matter injury in concussion using high-definition fiber tractography.
Prog Neurol Surg
PUBLISHED: 06-06-2014
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Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients.
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Iatrogenic Pseudoaneurysm of the Middle Meningeal Artery after External Ventricular Drain Placement.
J Neuroimaging
PUBLISHED: 05-14-2014
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External ventricular drain (EVD) placement is often a routine but lifesaving neurosurgical procedure performed throughout the world. Misadventures involving the procedure are well documented throughout the literature. However, we present a unique case of middle meningeal artery pseudoaneurysm formation after EVD placement not before described and provide a review of the literature.
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The minimally invasive spinal deformity surgery algorithm: a reproducible rational framework for decision making in minimally invasive spinal deformity surgery.
Neurosurg Focus
PUBLISHED: 05-03-2014
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Minimally invasive surgery (MIS) is an alternative to open deformity surgery for the treatment of patients with adult spinal deformity. However, at this time MIS techniques are not as versatile as open deformity techniques, and MIS techniques have been reported to result in suboptimal sagittal plane correction or pseudarthrosis when used for severe deformities. The minimally invasive spinal deformity surgery (MISDEF) algorithm was created to provide a framework for rational decision making for surgeons who are considering MIS versus open spine surgery.
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Complications in adult spinal deformity surgery: an analysis of minimally invasive, hybrid, and open surgical techniques.
Neurosurg Focus
PUBLISHED: 05-03-2014
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It is hypothesized that minimally invasive surgical techniques lead to fewer complications than open surgery for adult spinal deformity (ASD). The goal of this study was to analyze matched patient cohorts in an attempt to isolate the impact of approach on adverse events.
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Comparison of radiographic results after minimally invasive, hybrid, and open surgery for adult spinal deformity: a multicenter study of 184 patients.
Neurosurg Focus
PUBLISHED: 05-03-2014
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Various surgical approaches, including open, minimally invasive, and hybrid techniques, have gained momentum in the management of adult spinal deformity. However, few data exist on the radiographic outcomes of different surgical techniques. The objective of this study was to compare the radiographic and clinical outcomes of the surgical techniques used in the treatment of adult spinal deformity.
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Less invasive surgery for treating adult spinal deformities: ceiling effects for deformity correction with 3 different techniques.
Neurosurg Focus
PUBLISHED: 05-03-2014
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Minimally invasive surgery (MIS) options for the treatment of adult spinal deformity (ASD) have advanced significantly over the past decade. However, a wide array of options have been described as being MIS or less invasive. In this study the authors investigated a multiinstitutional cohort of patients with ASD who were treated with less invasive methods to determine the extent of deformity correction achieved.
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Radiographic and clinical outcomes following combined lateral lumbar interbody fusion and posterior segmental stabilization in patients with adult degenerative scoliosis.
Neurosurg Focus
PUBLISHED: 05-03-2014
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A hybrid approach of minimally invasive lateral lumbar interbody fusion (LLIF) followed by supplementary open posterior segmental instrumented fusion (PSIF) has shown promising early results in the treatment of adult degenerative scoliosis. Studies assessing the impact of this combined approach on correction of segmental and regional coronal angulation, sagittal realignment, maximum Cobb angle, restoration of lumbar lordosis, and clinical outcomes are needed. The authors report their results of this approach for correction of adult degenerative scoliosis.
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ED disposition of the Glasgow Coma Scale 13 to 15 traumatic brain injury patient: analysis of the Transforming Research and Clinical Knowledge in TBI study.
Am J Emerg Med
PUBLISHED: 04-04-2014
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Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions. We evaluated factors associated with emergency department triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or intensive care unit (ICU).
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Lifetime Attributable Risk of Cancer From CT Among Patients Surviving Severe Traumatic Brain Injury.
AJR Am J Roentgenol
PUBLISHED: 12-26-2013
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OBJECTIVE. The purpose of this study was to determine the lifetime attributable risk of cancer from CT among patients surviving severe traumatic brain injury. MATERIALS AND METHODS. A retrospective cross-sectional study was conducted with prospectively collected data on patients 16 years old and older admitted with a Glasgow coma scale score of 8 or less to a single level 1 trauma center from 2007 to 2010. The effective dose of each CT examination the patients underwent was predicted with literature-accepted effective dose values of standard helical CT protocols. The lifetime attributable risk of cancer and related mortality incurred as a result of CT were estimated with the cumulative effective dose incurred from the time of injury to a 1-year follow-up evaluation and with the approach established by the Biologic Effects of Ionizing Radiation VII report. RESULTS. The average patient was a 34-year-old man. The median number of CT examinations received during the first 12 months after injury was 20, and the average cumulative effective dose was 87 ± 45 mSv. This resulted in increases in the lifetime incidence of all cancer types from 45.5% to 46.3% and in the lifetime incidence of cancer-related mortality from 22.1% to 22.5%. CONCLUSION. Radiation exposure from the use of CT in the evaluation and management of severe traumatic brain injury causes negligible increases in lifetime attributable risk of cancer and cancer-related mortality. Treating physicians should not allow the concern for future risk of radiation-induced cancer to influence decisions regarding radiographic evaluation in the acute treatment of traumatic brain injury.
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Mitochondrial Polymorphisms Impact Outcomes after Severe Traumatic Brain Injury.
J. Neurotrauma
PUBLISHED: 11-14-2013
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Abstract Patient outcomes are variable following severe traumatic brain injury (TBI); however, the biological underpinnings explaining this variability are unclear. Mitochondrial dysfunction after TBI is well documented, particularly in animal studies. The aim of this study was to investigate the role of mitochondrial polymorphisms on mitochondrial function and patient outcomes out to 1 year after a severe TBI in a human adult population. The Human MitoChip V2.0 was used to evaluate mitochondrial variants in an initial set of n=136 subjects. SNPs found to be significantly associated with patient outcomes [Glasgow Outcome Scale (GOS), Neurobehavioral Rating Scale (NRS), Disability Rating Scale (DRS), in-hospital mortality, and hospital length of stay] or neurochemical level (lactate:pyruvate ratio from cerebrospinal fluid) were further evaluated in an expanded sample of n=336 subjects. A10398G was associated with DRS at 6 and 12 months (p=0.02) and a significant time by SNP interaction for DRS was found (p=0.0013). The A10398 allele was associated with greater disability over time. There was a T195C by sex interaction for GOS (p=0.03) with the T195 allele associated with poorer outcomes in females. This is consistent with our findings that the T195 allele was associated with mitochondrial dysfunction (p=0.01), but only in females. This is the first study associating mitochondrial DNA variation with both mitochondrial function and neurobehavioral outcomes after TBI in humans. Our findings indicate that mitochondrial DNA variation may impact patient outcomes after a TBI potentially by influencing mitochondrial function, and that sex of the patient may be important in evaluating these associations in future studies.
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Symptomatology and Functional Outcome in Mild Traumatic Brain Injury: Results from the Prospective TRACK-TBI Study.
J. Neurotrauma
PUBLISHED: 10-31-2013
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Abstract Mild Traumatic Brain Injury (mTBI), or concussion, is a major public health concern. There is controversy in the literature regarding the true incidence of postconcussion syndrome (PCS), with the constellation of physical, cognitive, emotional, and sleep symptoms after mTBI. In the current study, we report on the incidence and evolution of PCS symptoms and patient outcomes after mTBI at 3, 6, and 12 months in a large, prospective cohort of mTBI patients. Participants were identified as part of the prospective, multi-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study. The study population was mTBI patients (Glasgow Coma Scale score of 13-15) presenting to the emergency department, including patients with a negative head computed tomography discharged to home without admission to hospital; 375 mTBI subjects were included in the analysis. At both 6 and 12 months after mTBI, 82% (n=250 of 305 and n=163 of 199, respectively) of patients reported at least one PCS symptom. Further, 44.5 and 40.3% of patients had significantly reduced Satisfaction With Life scores at 6 and 12 months, respectively. At 3 months after injury, 33% of the mTBI subjects were functionally impaired (Glasgow Outcome Scale-Extended score ?6); 22.4% of the mTBI subjects available for follow-up were still below full functional status at 1 year after injury. The term "mild" continues to be a misnomer for this patient population and underscores the critical need for evolving classification strategies for TBI for targeted therapy.
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The Impact of Previous Traumatic Brain Injury on Health and Functioning: A TRACK-TBI Study.
J. Neurotrauma
PUBLISHED: 10-23-2013
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Abstract The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed (?(2)=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75??(2)?24.16; p<0.05), and report substance use (16.35??(2)?27.57; p<0.01) before the acute injury, compared to those with no previous TBI history. Those with a previous TBI had less-severe acute injuries, but experienced worse outcomes at 6-month follow-up. Results of a series of regression analyses controlling for demographics and acute injury severity indicated that individuals with previous TBI reported more mood symptoms, more postconcussive symptoms, lower life satisfaction, and had slower processing speed and poorer verbal learning, compared to those with no previous TBI history. These findings suggest that history of TBI with LOC may have important implications for health and psychological functioning after TBI in community-based samples.
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Acute Biomarkers of Traumatic Brain Injury: Relationship between Plasma Levels of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein.
J. Neurotrauma
PUBLISHED: 10-09-2013
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Abstract Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. ( ClinicalTrials.gov Identifier NCT01565551).
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Transforming research and clinical knowledge in traumatic brain injury pilot: multicenter implementation of the common data elements for traumatic brain injury.
J. Neurotrauma
PUBLISHED: 09-24-2013
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Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide, with enormous negative social and economic impacts. The heterogeneity of TBI combined with the lack of precise outcome measures have been central to the discouraging results from clinical trials. Current approaches to the characterization of disease severity and outcome have not changed in more than three decades. This prospective multicenter observational pilot study aimed to validate the feasibility of implementing the TBI Common Data Elements (TBI-CDEs). A total of 650 subjects who underwent computed tomography (CT) scans in the emergency department within 24?h of injury were enrolled at three level I trauma centers and one rehabilitation center. The TBI-CDE components collected included: 1) demographic, social and clinical data; 2) biospecimens from blood drawn for genetic and proteomic biomarker analyses; 3) neuroimaging studies at 2 weeks using 3T magnetic resonance imaging (MRI); and 4) outcome assessments at 3 and 6 months. We describe how the infrastructure was established for building data repositories for clinical data, plasma biomarkers, genetics, neuroimaging, and multidimensional outcome measures to create a high quality and accessible information commons for TBI research. Risk factors for poor follow-up, TBI-CDE limitations, and implementation strategies are described. Having demonstrated the feasibility of implementing the TBI-CDEs through successful recruitment and multidimensional data collection, we aim to expand to additional study sites. Furthermore, interested researchers will be provided early access to the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data set for collaborative opportunities to more precisely characterize TBI and improve the design of future clinical treatment trials. (ClinicalTrials.gov Identifier NCT01565551.).
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Neurological outcome scale for traumatic brain injury: III. Criterion-related validity and sensitivity to change in the NABIS hypothermia-II clinical trial.
J. Neurotrauma
PUBLISHED: 08-02-2013
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The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16-45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearmans rank-order correlations were calculated between the NOS-TBI and the glasgow outcome scale (GOS), GOS-extended (GOS-E), disability rating scale (DRS), and neurobehavioral rating scale-revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxons signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.
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GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study.
J. Neurotrauma
PUBLISHED: 08-01-2013
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Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24?h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84-0.93). The optimal cutoff of 0.68?ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55-0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).
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Influence of ATP-binding cassette polymorphisms on neurological outcome after traumatic brain injury.
Neurocrit Care
PUBLISHED: 07-31-2013
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As important mediators of solute transport at the blood-brain and blood-cerebrospinal fluid barriers, ATP-binding cassette (ABC) transporters (including ABCB1, ABCC1, and ABCC2), impact the bioavailability of drugs and endogenous substrates in the brain. While several ABCB1, ABCC1, and ABCC2 single nucleotide polymorphisms (SNPs) have been identified, their impact on outcome after traumatic brain injury (TBI) is unknown.
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Prospective independent validation of IMPACT modeling as a prognostic tool in severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 12-01-2011
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Clinical trials in traumatic brain injury (TBI) have been fraught with failure due in part to heterogeneity in pathology and insensitive outcome measurements. The International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic model has been purposed as a means of risk adjustment and outcome prediction for use in trial design and analysis. The purpose of this study was to evaluate the performance of the IMPACT model in predicting 6-month functional outcome and mortality using prospectively collected data at a large, Level 1 neurotrauma center. This population-based cohort study included all TBI patients ?14 years of age admitted with a Glasgow Coma Scale (GCS) score of ?8 (severe TBI) to the University of Pittsburgh Medical Center between July 1994 and May 2009. Clinical data were prospectively collected and linked to 6-month functional outcome (Glasgow Outcome Scale [GOS]) and mortality. The discriminatory power and calibration of the three iterations of the IMPACT model (core, extended, and lab) were assessed using multiple regression analyses and indicated by the area under the receiver operating characteristic curve (AUC). A sample of 587 patients was available for analysis; the mean age was 37.8±17 years. The median 6-month GOS was 3 (IQR 3); 6-month mortality was 41%. The prognostic models were composed of age, motor score, and pupillary reactivity (core model), Marshall grade on head CT and secondary insults (extended), and laboratory values (lab); all of these displayed good prediction ability for unfavorable outcome and mortality (unfavorable outcome AUC=0.76, 0.79, 0.76; mortality AUC=0.78, 0.83, 0.83, respectively). All model iterations displayed adequate calibration for predicting unfavorable outcome and mortality. Prospective, independent validation supports the IMPACT prognostic models prediction of patient 6-month functional status and mortality after severe TBI. The IMPACT prognostic model is an effective instrument to assist TBI study design and analysis.
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Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study.
Lancet Neurol
PUBLISHED: 11-03-2011
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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 neurological outcome.
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Perioperative surgical complications of transforaminal lumbar interbody fusion: a single-center experience.
J Neurosurg Spine
PUBLISHED: 10-14-2011
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Since its original description in 1982, transforaminal lumbar interbody fusion (TLIF) has grown in popularity as a means for achieving circumferential fusion. The authors sought to define the perioperative complication rates of the TLIF procedure at a large academic medical center.
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Comparative effectiveness of using computed tomography alone to exclude cervical spine injuries in obtunded or intubated patients: meta-analysis of 14,327 patients with blunt trauma.
J. Neurosurg.
PUBLISHED: 05-27-2011
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The current standard of practice for clearance of the cervical spine in obtunded patients suffering blunt trauma is to use CT and an adjuvant imaging modality (such as MR imaging). The objective of this study was to determine the comparative effectiveness of multislice helical CT alone to diagnose acute unstable cervical spine injury following blunt trauma.
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Spreading depolarizations have prolonged direct current shifts and are associated with poor outcome in brain trauma.
Brain
PUBLISHED: 04-07-2011
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Cortical spreading depolarizations occur spontaneously after ischaemic, haemorrhagic and traumatic brain injury. Their effects vary spatially and temporally as graded phenomena, from infarction to complete recovery, and are reflected in the duration of depolarization measured by the negative direct current shift of electrocorticographic recordings. In the focal ischaemic penumbra, peri-infarct depolarizations have prolonged direct current shifts and cause progressive recruitment of the penumbra into the core infarct. In traumatic brain injury, the effects of spreading depolarizations are unknown, although prolonged events have not been observed in animal models. To determine whether detrimental penumbral-type depolarizations occur in human brain trauma, we analysed electrocorticographic recordings obtained by subdural electrode-strip monitoring during intensive care. Of 53 patients studied, 10 exhibited spreading depolarizations in an electrophysiologic penumbra (i.e. isoelectric cortex with no spontaneous activity). All 10 patients (100%) with isoelectric spreading depolarizations had poor outcomes, defined as death, vegetative state, or severe disability at 6 months. In contrast, poor outcomes were observed in 60% of patients (12/20) who had spreading depolarizations with depression of spontaneous activity and only 26% of patients (6/23) who had no depolarizations (?2, P<0.001). Spontaneous electrocorticographic activity and direct current shifts of depolarizations were further examined in nine patients. Direct current shift durations (n=295) were distributed with a significant positive skew (range 0:51-16:19?min:s), evidencing a normally distributed group of short events and a sub-group of prolonged events. Prolonged direct current shifts were more commonly associated with isoelectric depolarizations (median 2?min 36?s), whereas shorter depolarizations occurred with depression of spontaneous activity (median 2?min 10?s; P<0.001). In the latter group, direct current shift durations correlated with electrocorticographic depression periods, and were longer when preceded by periodic epileptiform discharges than by continuous delta (0.5-4.0?Hz) or higher frequency activity. Prolonged direct current shifts (>3?min) also occurred mainly within temporal clusters of events. Our results show for the first time that spreading depolarizations are associated with worse clinical outcome after traumatic brain injury. Furthermore, based on animal models of brain injury, the prolonged durations of depolarizations raise the possibility that these events may contribute to maturation of cortical lesions. Prolonged depolarizations, measured by negative direct current shifts, were associated with (i) isoelectricity or periodic epileptiform discharges; (ii) prolonged depression of spontaneous activity and (iii) occurrence in temporal clusters. Depolarizations with these characteristics are likely to reflect a worse prognosis.
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Fractures of the clivus and traumatic diastasis of the central skull base in the pediatric population.
J Neurosurg Pediatr
PUBLISHED: 03-03-2011
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Fractures of the clivus and traumatic diastases of the clival synchondroses are rare in the pediatric population. The incidence, outcome, and biomechanics associated with these fractures have been difficult to ascertain secondary to the lack of literature pertaining to their occurrence.
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Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial.
Lancet Neurol
PUBLISHED: 12-17-2010
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The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury.
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Translational systems biology of inflammation: potential applications to personalized medicine.
Per Med
PUBLISHED: 10-22-2010
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A central goal of industrialized nations is to provide personalized, preemptive and predictive medicine, while maintaining healthcare costs at a minimum. To do so, we must confront and gain an understanding of inflammation, a complex, nonlinear process central to many diseases that affect both industrialized and developing nations. Herein, we describe the work aimed at creating a rational, engineering-oriented and evidence-based synthesis of inflammation geared towards rapid clinical application. This comprehensive approach, which we call Translational Systems Biology, to date has been utilized for in silico studies of sepsis, trauma/hemorrhage/traumatic brain injury, acute liver failure and wound healing. This framework has now allowed us to suggest how to modulate acute inflammation in a rational and individually optimized fashion using engineering principles applied to a biohybrid device. We suggest that we are on the cusp of fulfilling the promise of in silico modeling for personalized medicine for inflammatory disease.
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Premorbid oral antithrombotic therapy and risk for reaccumulation, reoperation, and mortality in acute subdural hematomas.
J. Neurosurg.
PUBLISHED: 08-20-2010
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Acute subdural hematomas (SDHs) impart serious morbidity and mortality on the elderly population, with only 5% of those older than 65 years of age attaining functional independence. Despite its widespread use, oral antithrombotic therapy (OAT) in the context of acute SDH has not been extensively studied. The authors sought to evaluate the impact of premorbid OAT on recurrence of SDH, radiographic outcome, and mortality in patients undergoing surgical evacuation of an acute SDH.
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BCL2 genotypes: functional and neurobehavioral outcomes after severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 05-28-2010
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Traumatic brain injury (TBI) triggers a cascade of apoptotic-related events that include BCL2 expression, a pro-survival protein in the apoptosis pathway. The purpose of this study was to use tagging single nucleotide polymorphism (tSNP) genotypes to screen the BCL2 gene to determine if genetic variability in the BCL2 gene influences outcomes in 205 patients with severe TBI. Outcomes (Glasgow Outcome Scale [GOS], Disability Rating Scale [DRS], mortality, and Neurobehavioral Rating Scale-Revised [NRS-R]) were analyzed at 3, 6, 12, and 24 months. Multivariate analysis demonstrates that there were four tSNPs of significant interest: rs17759659, rs1801018, rs7236090, and rs949037. Presence of the variant allele for rs17759659 was associated with poorer outcomes (GOS p = 0.001; DRS p = 0.002), higher mortality (p = 0.02; OR = 4.23; CI 1.31,13.61), and worse NRS-R scores (p = 0.05). Presence of the variant allele for rs1801018 was associated with poorer outcomes (GOS p = 0.02; DRS p = 0.009), and mortality (p = 0.03; OR = 3.86; CI 1.18,12.59). Being homozygous for the wild-type allele for rs7236090 was associated with favorable outcomes on the NRS-R (p = 0.007), while homozygosity for the variant genotype was associated with favorable outcomes on the GOS (p = 0.007) and DRS (p = 0.006). The homozygous variant for rs949037 was associated with favorable outcomes (GOS p = 0.04; DRS p = 0.03), and the homozygous wild-type was associated with increased mortality at 3 months (p = 0.005; OR = 3.67; CI 1.08,12.49). The only finding that stood up to Bonferroni correction was rs17759659 for GOS. These data support the possibility that genetic variability for pro-survival proteins, particularly genetic variation in the BCL2 gene, impacts outcomes after severe TBI.
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Predictors of complications after spinal stabilization of thoracolumbar spine injuries.
J Trauma
PUBLISHED: 04-21-2010
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The management of complications after major traumatic spinal injury and surgical stabilization is a challenge. The purpose of this study is to identify factors predictive of a complication after surgical stabilization of thoracolumbar spine injuries.
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Neuroglobin genetic polymorphisms and their relationship to functional outcomes after traumatic brain injury.
J. Neurotrauma
PUBLISHED: 03-30-2010
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Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). However, to date an association between genetic variation within the human neuroglobin (NGB) gene and recovery post-TBI has not been reported. The purpose of this study was to explore the relationship between NGB genotypes and outcomes (as assessed by the Glasgow Outcome Scale [GOS], the Disability Rating Scale [DRS], and the Neurobehavioral Rating Scale-Revised [NRS-R]) after severe TBI. Genotyping using TaqMan allele discrimination for two tagging single nucleotide polymorphisms (tSNPs) that represent the two haplotype blocks for NGB (rs3783988 and rs10133981) was completed on DNA obtained from 196 Caucasian patients recovering from severe TBI. Patients were dichotomized based on the presence of the variant allele for each tSNP. Chi-square and Fishers exact tests were used to compare characteristics between groups. Multivariate linear regression was used to examine NGB tSNPs and recovery from severe TBI. Subjects with the TT genotype (wild-type) for rs3783988 were more likely to have better GOS and DRS scores at 3, 6, 12, and 24 months, while rs10133981 genotype was not significantly related to functional outcome. After controlling for age, gender, and Glasgow Coma Scale (GCS) score, those subjects with the rs3783988 TT genotype had more than a 2.65-times greater likelihood of better functional outcomes than individuals with genotypes harboring a variant allele. Data suggest that the haplotype block represented by rs3783988 in NGB appears to influence recovery after severe TBI. Represented within this haplotype block of NGB is the region that codes for the oxygen-binding portion of NGB.
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Complications and radiographic correction in adult scoliosis following combined transpsoas extreme lateral interbody fusion and posterior pedicle screw instrumentation.
Neurosurg Focus
PUBLISHED: 03-03-2010
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The authors recently used a combined approach of minimally invasive transpsoas extreme lateral interbody fusion (XLIF) and open posterior segmental pedicle screw instrumentation with transforaminal lumbar interbody fusion (TLIF) for the correction of coronal deformity. The complications and radiographic outcomes were compared with a posterior-only approach for scoliosis correction.
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Intraoperative computed tomography image-guided navigation for posterior thoracolumbar spinal instrumentation in spinal deformity surgery.
Neurosurg Focus
PUBLISHED: 03-03-2010
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Placement of thoracolumbar pedicle screws in spinal deformity surgery has a reported inaccuracy rate as high as 30%. At present, image-guided navigation systems designed to improve instrumentation accuracy typically use intraoperative fluoroscopy or preoperative CT scans. The authors report the prospective evaluation of the accuracy of posterior thoracolumbar spinal instrumentation using a new intraoperative CT operative suite with an integrated image guidance system. They compare the accuracy of thoracolumbar pedicle screw placement using intraoperative CT image guidance with instrumentation placement utilizing fluoroscopy.
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Translational systems approaches to the biology of inflammation and healing.
Immunopharmacol Immunotoxicol
PUBLISHED: 02-23-2010
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Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ impacts via tissue damage/dysfunction. This framework has now allowed us to suggest how to modulate acute inflammation in a rational, individually optimized fashion. This plethora of computational and intertwined experimental/engineering approaches is the cornerstone of Translational Systems Biology approaches for inflammatory diseases.
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Thoracolumbar spinal deformity: Part II. Developments from 1990 to today: historical vignette.
J Neurosurg Spine
PUBLISHED: 12-03-2009
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In the first part of this 2-part historical review, the authors outlined the early diagnostic and therapeutic strategies used in the management of spinal deformity. In this second part, they expand upon those early innovations and further detail the advances from 1990 to the modern era.
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Thoracolumbar spinal deformity: Part I. A historical passage to 1990: historical vignette.
J Neurosurg Spine
PUBLISHED: 12-03-2009
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Seven millennia of anthropological artifacts and historical tales reference human spinal deformity, its diagnosis, and treatment-many of the latter of which turned out to be worse than the deformity itself. From Hippocrates to Harrington to the 21st century, the literature base has expanded in exponential fashion to yield an imperfect but constantly improving body of evidence, experience, and understanding of this challenging disease phenomenon. This review details the pre-1990 innovations, whose failures and successes have equally contributed to the advancement and dissemination of the increasingly evidence-based field of spinal deformity.
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Fractures of the clivus: a contemporary series in the computed tomography era.
Neurosurgery
PUBLISHED: 11-26-2009
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We report the morbidity and mortality associated with fractures of the clivus and discuss management approaches specific to this unique diagnostic entity.
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Occipital condyle fractures: clinical decision rule and surgical management.
J Neurosurg Spine
PUBLISHED: 11-26-2009
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Occipital condyle fractures (OCFs) are rare injuries and their treatment remains controversial. Several classification systems have been proposed, first by Anderson and Montesano and more recently by Tuli and colleagues and Hanson and associates, who sought to stratify these fractures in a manner that would guide treatment that has typically ranged from semirigid collar immobilization to halo fixation or occipitocervical fusion. It has been the authors impression, based on experience with OCFs at their institution, that classification is cumbersome and contributes little to the clinical decision-making process, while the identification of craniocervical misalignment and neural element compromise is paramount, and sufficient, for the planning of treatment.
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Effect of short periods of normobaric hyperoxia on local brain tissue oxygenation and cerebrospinal fluid oxidative stress markers in severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 06-10-2009
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Preliminary evidence suggests local brain tissue oxygenation (PbtO(2)) values of or=20 mm Hg to avoid hypoxia. This study tested the impact of a short (2 h) trial of normobaric hyperoxia on measures of oxidative stress. We hypothesized this treatment would positively affect cerebral oxygenation but negatively affect the cellular environment via oxidative stress mechanisms. Cerebrospinal fluid (CSF) was serially assessed in 11 adults (9 male, 2 female), aged 26 +/- 1.8 years with severe TBI (Glasgow Coma Scale score, 6 +/- 1.4) before, during, and after a FiO(2) = 1.0 challenge for markers of oxidative stress, including lipid peroxidation (F(2)-isoprostane [ELISA]), protein oxidation (protein sulfhydryl [fluorescence]), and antioxidant defenses (total antioxidant reserve (AOR) [chemiluminescence] and glutathione [fluorescence]). Physiological parameters [PbtO(2), arterial oxygen content (PaO(2)), intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP)] were assessed at the same time points. Mean (+/-SD) PbtO(2) and PaO(2) levels significantly changed for each time point. Oxidative stress markers, antioxidant reserve defenses, and ICP, MAP, and CPP did not significantly change for any time period. These preliminary findings suggest that brief periods of normobaric hyperoxia do not produce oxidative stress and/or change antioxidant reserves in CSF. Additional studies are required to examine extended periods of normobaric hyperoxia in a larger sample.
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Reversal of sedation with flumazenil in a child after traumatic brain injury.
J Neurosurg Pediatr
PUBLISHED: 04-03-2009
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The authors report on a case of successful reversal of sedation with flumazenil, a benzodiazepine antagonist, in a child following a moderate traumatic brain injury and demonstrate the utility of flumazenil to reverse benzodiazepine effects in traumatically injured children.
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Minimal-access technique for distal catheter insertion during ventricular peritoneal shunt procedures: a review of 100 cases.
J. Neurosurg.
PUBLISHED: 03-17-2009
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The authors report the safety and efficacy of using a percutaneous minimal-access insertion technique for distal shunt catheter placement in 100 cases. From June 2007 to March 2008, they attempted 100 minimal-access insertions of distal shunt catheters in 91 patients who required ventriculoperitoneal shunting. Using the minimal-access approach, they avoided utilizing laparoscopic assistance or a mini-laparotomy in 91% of the cases. There were no bowel injuries or misplaced distal catheters. Additional outcomes in terms of operative times, cases that required conversion to open or laparoscopically assisted implantation, and infection rates are presented. They conclude that intraperitoneal shunt catheter placement can be safely and effectively accomplished using a simplified percutaneous minimal-access insertion method that does not require direct laparoscopic visualization.
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Multicenter trial of early hypothermia in severe brain injury.
J. Neurotrauma
PUBLISHED: 02-28-2009
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The North American Brain Injury Study: Hypothermia IIR (NABIS:H IIR) is a randomized clinical trial designed to enroll 240 patients with severe brain injury between the ages of 16 and 45 years. The primary outcome measure is the dichotomized Glasgow Outcome Scale (GOS) at 6 months after injury. The study has the power to detect a 17.5% absolute difference in the percentage of patients with a good outcome with a power of 80%. All patients are randomized by waiver of consent unless family is immediately available. Enrollment is within 2.5 h of injury. Patients may be enrolled in the field by emergency medical services personnel affiliated with the study or by study personnel when the patient arrives at the emergency department. Patients who do not follow commands and have no exclusion criteria and who are enrolled in the hypothermia arm of the study are cooled to 35 degrees C as rapidly as possible by intravenous administration of up to 2 liters of chilled crystalloid. Those patients who meet the criteria for the second phase of the protocol (primarily a post-resuscitation GCS 3-8 without hypotension and without severe associated injuries) are cooled to 33 degrees C. Patients enrolled in the normothermia arm receive standard management at normothermia. As of December 2007, 74 patients had been randomized into phase II of the protocol. Patients in the hypothermia arm reached 35 degrees C in 2.7 +/- 1.1 (SD) h after injury and reached 33 degrees C at 4.4 +/- 1.5 h after injury.
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Induced normothermia attenuates intracranial hypertension and reduces fever burden after severe traumatic brain injury.
Neurocrit Care
PUBLISHED: 02-22-2009
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Hyperthermia following a severe traumatic brain injury (TBI) is common, potentiates secondary injury, and worsens neurological outcome. Conventional fever treatment is often ineffective. An induced normothermia protocol, utilizing intravascular cooling, was used to assess the impact on fever incidence and intracranial pressure (ICP) in patients with severe TBI.
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Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury.
Ann. Neurol.
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To determine the clinical relevance, if any, of traumatic intracranial findings on early head computed tomography (CT) and brain magnetic resonance imaging (MRI) to 3-month outcome in mild traumatic brain injury (MTBI).
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Magnetoencephalographic virtual recording: a novel diagnostic tool for concussion.
Neurosurg Focus
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Heightened recognition of the prevalence and significance of head injury in sports and in combat veterans has brought increased attention to the physiological and behavioral consequences of concussion. Current clinical practice is in part dependent on patient self-report as the basis for medical decisions and treatment. Magnetoencephalography (MEG) shows promise in the assessment of the pathophysiological derangements in concussion. The authors have developed a novel MEG-based neuroimaging strategy to provide objective, noninvasive, diagnostic information in neurological disorders. In the current study the authors demonstrate a novel task protocol and then assess MEG virtual recordings obtained during task performance as a diagnostic tool for concussion.
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Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury.
Nat. Neurosci.
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The brain contains a highly diversified complement of molecular species of a mitochondria-specific phospholipid, cardiolipin, which, because of its polyunsaturation, can readily undergo oxygenation. Using global lipidomics analysis in experimental traumatic brain injury (TBI), we found that TBI was accompanied by oxidative consumption of polyunsaturated cardiolipin and the accumulation of more than 150 new oxygenated molecular species of cardiolipin. RNAi-based manipulations of cardiolipin synthase and cardiolipin levels conferred resistance to mechanical stretch, an in vitro model of traumatic neuronal injury, in primary rat cortical neurons. By applying a brain-permeable mitochondria-targeted electron scavenger, we prevented cardiolipin oxidation in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, and markedly reduced behavioral deficits and cortical lesion volume. We conclude that cardiolipin oxygenation generates neuronal death signals and that prevention of it by mitochondria-targeted small molecule inhibitors represents a new target for neuro-drug discovery.
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Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials.
J. Neurosurg.
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The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes.
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Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury.
Brain
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Spreading depolarizations are waves of mass neuronal and glial depolarization that propagate across the injured human cortex. They can occur with depression of neuronal activity as spreading depressions or isoelectric spreading depolarizations on a background of absent or minimal electroencephalogram activity. Spreading depolarizations are characterized by the loss of neuronal ion homeostasis and are believed to damage functional neurons, leading to neuronal necrosis or neurological degeneration and poor outcome. Analgesics and sedatives influence activity-dependent neuronal ion homeostasis and therefore represent potential modulators of spreading depolarizations. In this exploratory retrospective international multicentre analysis, we investigated the influence of midazolam, propofol, fentanyl, sufentanil, ketamine and morphine on the occurrence of spreading depolarizations in 115 brain-injured patients. A surface electrode strip was placed on the cortex, and continuous electrocorticographical recordings were obtained. We used multivariable binary logistic regression to quantify associations between the investigated drugs and the hours of electrocorticographical recordings with and without spreading depolarizations or clusters of spreading depolarizations. We found that administration of ketamine was associated with a reduction of spreading depolarizations and spreading depolarization clusters (P?
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High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage.
J. Neurosurg.
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For patients with traumatic brain injury (TBI), current clinical imaging methods generally do not provide highly detailed information about the location of axonal injury, severity of injury, or expected recovery. In a case of severe TBI, the authors applied a novel high-definition fiber tracking (HDFT) to directly visualize and quantify the degree of axonal fiber damage and predict functional deficits due to traumatic axonal injury and loss of cortical projections. This 32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an area of hemorrhage in the basal ganglia with mass effect, but no specific information on the location of axonal injury could be obtained from these studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed motor weaknesses of the left extremities. Four months postinjury, 257-direction diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree of axonal damage in the motor pathway and quantify asymmetries in the left and right axonal pathways. High-definition fiber tracking was used to follow corticospinal and corona radiata pathways from the cortical surface to the midbrain and quantify projections from motor areas. Axonal damage was then localized by assessing the number of descending fibers at the level of the cortex, internal capsule, and midbrain. The motor deficit apparent in the clinical examinations correlated with the axonal losses visualized using HDFT. Fiber loss estimates at 4 months postinjury accurately predicted the nature of the motor deficits (severe, focal left-hand weakness) when other standard clinical imaging modalities did not. A repeat scan at 10 months postinjury, when edema and hemorrhage had receded, replicated the fiber loss. Using HDFT, the authors accurately identified the presence and location of damage to the underlying white matter in this patient with TBI. Detailed information of injury provided by this novel technique holds future potential for precise neuroimaging assessment of TBI.
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The brain in vivo expresses the 2,3-cAMP-adenosine pathway.
J. Neurochem.
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Although multiple biochemical pathways produce adenosine, studies suggest that the 2,3-cAMP-adenosine pathway (2,3-cAMP?2-AMP/3-AMP?adenosine) contributes to adenosine production in some cells/tissues/organs. To determine whether the 2,3-cAMP-adenosine pathway exists in vivo in the brain, we delivered to the brain (gray matter and white matter separately) via the inflow perfusate of a microdialysis probe either 2,3-cAMP, 3,5-cAMP, 2-AMP, 3-AMP, or 5-AMP and measured the recovered metabolites in the microdialysis outflow perfusate with mass spectrometry. In both gray and white matter, 2,3-cAMP increased 2-AMP, 3-AMP and adenosine, and 3,5-cAMP increased 5-AMP and adenosine. In both brain regions, 2-AMP, 3-AMP and 5-AMP were converted to adenosine. Microdialysis experiments in 2,3-cyclic nucleotide-3-phosphodiesterase (CNPase) wild-type mice demonstrated that traumatic brain injury (controlled cortical impact model) activated the brain 2,3-cAMP-adenosine pathway; similar experiments in CNPase knockout mice indicated that CNPase was involved in the metabolism of endogenous 2,3-cAMP to 2-AMP and to adenosine. In CSF from traumatic brain injury patients, 2,3-cAMP was significantly increased in the initial 12 h after injury and strongly correlated with CSF levels of 2-AMP, 3-AMP, adenosine and inosine. We conclude that in vivo, 2,3-cAMP is converted to 2-AMP/3-AMP, and these AMPs are metabolized to adenosine. This pathway exists endogenously in both mice and humans.
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Intermittent Versus Continuous Cerebrospinal Fluid Drainage Management in Adult Severe Traumatic Brain Injury: Assessment of Intracranial Pressure Burden.
Neurocrit Care
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There is clinical equipoise regarding whether neurointensive care unit management of external ventricular drains (EVD) in severe traumatic brain injury (TBI) should involve an open EVD, with continuous drainage of cerebrospinal fluid (CSF), versus a closed EVD, with intermittent opening as necessary to drain CSF. In a matched cohort design, we assessed the relative impact of continuous versus intermittent CSF drainage on intracranial pressure in the management of adult severe TBI.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.