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Sung C. Choi, John D. Ward, and Donald P. Becker

✓ An analysis of clinical and demographic data of 264 patients with severe head injury showed that a combination of the Glasgow Coma Scale (GCS) score, oculocephalic responses, and age can provide a simple but reliable prediction of outcome in severe head injury. Addition of other clinical data, excluding intracranial pressure and evoked potentials, improved the predictability only negligibly. A simple chart, which is constructed from the application of the logistic regression model, can be used to determine the odds of a good outcome from the combination of the three factors. A method is given by which the GCS score of a patient with a missing verbal response score can be accurately approximated in order to complete the chart. Among other values, the odds of a good outcome provide the clinician with a reliable measure of the relative severity of a patient's injury. The accuracy of the chart in prediction is expected to be 80% or above.

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Sung C. Choi, Raj K. Narayan, Randy L. Anderson, and John D. Ward

✓ Data from 523 patients admitted to the Medical College of Virginia with severe head injury and known 6-month outcomes were analyzed in order to determine the optimal combination of early-available prognostic factors. Twenty-one prognostic indicators noted in the emergency room at admission were used to predict outcomes into four categories: good, moderately disabled, severely disabled, or vegetative/dead. A combination of the patient's age (in years), the best motor response (graded in the usual six-point scale), and pupillary response (in both eyes) was found to be the most accurate indicator. The model correctly predicted outcome into one of the four outcome categories in 78% of cases (“specifically accurate predictions”). If predictions into an outcome category adjacent to the actual outcome were accepted, this model was accurate in 90% of cases (“grossly accurate predictions”). A set of three simple graphs based on this model can be used for rapid early estimation of probable outcome in a severely head-injured patient at admission.

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Ross Bullock, Alois Zauner, John J. Woodward, John Myseros, Sung C. Choi, John D. Ward, Anthony Marmarou, and Harold F. Young

Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury.

In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27 ± 22 μmol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 μmol/L; p < 0.01).

The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

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Ross Bullock, Alois Zauner, John J. Woodward, John Myseros, Sung C. Choi, John D. Ward, Anthony Marmarou, and Harold F. Young

Object. Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury.

Methods. In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27 ± 22 µmol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 µmol/L; p < 0.01).

Conclusions. The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

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Eric R. Trumble, J. Paul Muizelaar, John S. Myseros, Sung C. Choi, and Brian B. Warren

✓ The use of colloid agents to achieve hypervolemia in the prevention and treatment of postsubarachnoid hemorrhage (post-SAH) vasospasm is included in the standard of care at many institutions. Risk profiles are necessary to ensure appropriate use of these agents. In a series of 85 patients with recent aneurysmal SAH, 26 developed clinical symptoms of vasospasm. Fourteen of the 26 were treated with hetastarch for volume expansion while the other 12 received plasma protein fraction (PPF). Clinically significant bleeding pathologies were noted in six patients who received hetastarch as a continuous intravenous infusion. Hetastarch increased partial thromboplastin time from a mean of 23.9 seconds to a mean of 33.1 seconds (p < 0.001) in all patients who received infusions of this agent, while no effect was noted in the 12 patients who received PPF infusions. No other coagulation parameters were altered. This study shows an increase in coagulopathy with the use of hetastarch as compared with the use of PPF for the treatment of postaneurysmal vasospasm.

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R. John Hurlbert, Neil R. Crawford, Won Gyu Choi, and Curtis A. Dickman

Object. The purpose of this study was to compare cable techniques used in occipitocervical fixation with two types of screw fixation. The authors hypothesized that screw fixation would provide superior immobilization compared with cable methods.

Methods. Ten cadaveric specimens were prepared for biomechanical analyses by using standard techniques. Angular and linear displacement data were recorded from the occiput to C-6 with infrared optical sensors after conditioning runs. Specimens underwent retesting after fatiguing. Six methods of fixation were analyzed: Steinmann pin with and without C-1 incorporation; Cotrel-Dubousett horseshoe with and without C-1 incorporation; Mayfield loop with C1–2 transarticular screw fixation; and a custom-designed occipitocervical transarticular screw-plate system. Sublaminar techniques were extended to include C-3 in the fusion construct, whereas transarticular techniques incorporated the occiput, C-1, and C-2 only.

All methods of fixation provided significant immobilization in all specimens compared with the nonconstrained destabilized state. Despite incorporation of an additional vertebral segment, sublaminar techniques performed worse as a function of applied load than screw fixation techniques. Following fatiguing, these differences were more pronounced. The sublaminar techniques failed most prominently in flexion—extension and in axial rotation. On gross inspection, increased angular displacement associated with loosening of the sublaminar cables was observed.

Conclusion. Occipitocervical fixation can be performed using a variety of techniques; all bestow significant immobilization compared with the destabilized spine. All methods tested in this study were susceptible to fatigue and loss of reduction and were weakest in resisting vertical settling. Screw fixation of the occiput—C2 reduces the number of vertebral segments that are necessary to incorporate into the fusion construct while providing superior immobilization and resistance to fatigue and vertical settling compared with sublaminar methods.

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Outcome after severe head injury

Relationship to mass lesions, diffuse injury, and ICP course in pediatric and adult patients

Anthony M. Alberico, John D. Ward, Sung C. Choi, Anthony Marmarou, and Harold F. Young

✓ A consecutive series of 330 severely head-injured patients was studied prospectively. All of the patients were treated with the same protocols by the same physicians and staff in the same intensive care unit. All of the patients had intracranial pressure (ICP) monitoring. Of the 330 patients, 100 were in the pediatric age group (0 to 19 years of age) and 230 were in the adult group (20 to 80 years of age). Statistical analyses were performed with regard to outcome, Glasgow Coma Scale (GCS) score, ICP course, and incidence of surgical lesions. The average emergency room GCS score as well as the 24-hour GCS score for each group was the same. The percentage of patients having ICP that was normal, increased but reducible, and increased but not reducible in each group was the same.

The pediatric patients had a significantly higher percentage of good outcomes (43%) than the adult patients (28%) (p < 0.01). They also had a significantly lower mortality rate (24%) than the adult patients (45%) (p < 0.01). At 1 year following injury, 55% of pediatric patients had a good outcome compared to 21% of adults (p < 0.001); this trend was evident at 3 months, with the same p value. Pediatric patients with normal ICP had a higher percentage of good outcomes (70%) than the adult patients with normal ICP (48%) (p < 0.05). There was no significant difference in outcome in pediatric and adult patients with mass lesions or with increased ICP, regardless of whether or not the pressure was reducible. There was a much higher incidence of surgical mass lesions in adult patients (46%) than in pediatric patients (24%) (p < 0.001).

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Joseph E. Levasseur, John L. Patterson Jr., Nitya R. Ghatak, Hermes A. Kontos, and Surg C. Choi

✓ The function-specific enzyme superoxide dismutase (SOD) was tested for its protective effect in severe experimental fluid-percussion brain injury (4.45 ± 0.10 atm) in 30 of 60 randomly selected male Sprague-Dawley rats. A respirator was used only in the event of need. The number of animals with permanent resumption of spontaneous breathing (Type I respiratory response) remained essentially the same in each group. However, when Type II apnea (cannot maintain recovery) and Type III apnea (never recovers from the initial apnea) were terminated with a respirator, all rats with Type II responses from each group were successfully converted to a state of sustained spontaneous breathing. In contrast, only five (41.7%) of the 12 rats with Type III response were salvaged in the control group while five (83.3%) of six Type III rats in the SOD-treated group were saved. The results reveal the nature of the therapeutic effectiveness of superoxide radical scavengers in the overall outcome of head injury in this animal model. While SOD alone did not increase the number of spontaneous survivors, the drug shifted a number of animals from the critically injured rats with Type III respiratory response to the less critical Type II condition. Whereas induced respiration as the sole therapy in the control group lowered the mortality rate to 23.3%, respiratory assistance together with SOD treatment reduced the “mortality” to a single animal with Type III apnea (3.3%) which was alive but still required the respirator after 2 hours (p < 0.001). The results show that respiratory assistance alone accounted for a 33% decrease in mortality rate and that SOD, given in addition to induced ventilation, further decreased mortality by 20%. Since SOD enzymes are reactively specific for superoxide, the increased survival rate of the brain-injured rat must have been due either to preventing or to minimizing pathophysiological changes, probably in the brain stem, caused by oxygen free radicals.

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Bryan D. Choi, Michael R. DeLong, David M. DeLong, Allan H. Friedman, and John H. Sampson

Object

The purpose of this study was to report the prevalence of neurosurgeons with both medical degrees (MDs) and doctorates (PhDs) at top-ranked US academic institutions and to assess whether the additional doctorate education is associated with substantive career involvement in academia as well as greater success in procuring National Institutes of Health (NIH) research funding compared with an MD-only degree.

Methods

The authors reviewed the training of neurosurgeons across the top 10 neurosurgery departments chosen according to academic impact (h index) to examine whether MD-PhD training correlated significantly with career outcomes in academia.

Results

Six hundred thirteen neurosurgery graduates and residents between the years 1990 and 2012 were identified for inclusion in this analysis. Both MD and PhD degrees were held by 121 neurosurgeons (19.7%), and an MD alone was held by 492. Over the past 2 decades, MD-PhD trainees represented a gradually increasing percentage of neurosurgeons, from 10.2% to 25.7% (p < 0.01). Of the neurosurgeons with MD-PhD training, a greater proportion had appointments in academic medicine compared with their MD-only peers (73.7% vs 52.3%, p < 0.001). Academic neurosurgeons with both degrees were also more likely to have received NIH funding (51.9% vs 31.8%, p < 0.05) than their single-degree counterparts in academia. In a national analysis of all active NIH R01 grants awarded in neurosurgery, MD-PhD investigators held a disproportionate number, more than 4-fold greater than their representation in the field.

Conclusions

Dual MD-PhD training is a significant factor that may predict active participation in and funding for research careers among neurological surgeons at top-ranked academic institutions. These findings and their implications are of increasing relevance as the population of neurosurgeons with dual-degree training continues to rise.

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Tiffany R. Hodges, Bryan D. Choi, Darell D. Bigner, Hai Yan, and John H. Sampson

Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered to be frequent and highly conserved in secondary glioblastoma multiforme and lower-grade gliomas. Although IDH1 mutations confer a unique genotype that has been associated with a favorable prognosis, the role of the mutated IDH1 enzyme and its metabolites in tumor initiation and maintenance remains unresolved. However, given that IDH1 mutations are homogeneously expressed and are limited solely to tumor tissue, targeting this mutation could potentially yield novel treatment strategies for patients with glioblastoma multiforme.