Christopher J Madden

University of Texas Southwestern Medical Center, Dallas, Texas, United States

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Publications (53)235.22 Total impact

  • Elizabeth A Dawson · Puneet K Gupta · Christopher J Madden · Joe Pacheco · DaiWai M Olson
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    ABSTRACT: Nurses who work with patients at risk for seizures should be informed that both adult and pediatric patients are at risk for sudden unexpected death in epilepsy (SUDEP). Although the exact pathophysiology of SUDEP is not determined, patients with mesial temporal lobe epilepsy represent an at-risk population because of autonomic dysregulation. With prompt treatment, patients with near-SUDEP can continue to lead normal productive lives. This case series presents three patients with near-SUDEP diagnosed with temporal lobe epilepsy.
    04/2015; 47(3). DOI:10.1097/JNN.0000000000000139
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    ABSTRACT: OBJECT Screening, management, and follow-up of Grade 3 and 4 blunt carotid artery injuries (BCAIs) remain controversial. These high-grade BCAIs were analyzed to define their natural history and establish a rational management plan based on lesion progression and cerebral infarction. METHODS A retrospective review of a prospectively maintained database of all blunt traumatic carotid and vertebral artery injuries from August 2003 to April 2013 was performed, and Grade 3 and 4 BCAIs were identified. The authors define Grade 3 injuries as stenosis of the vessel greater than 50%, or the development of a pseudoaneurysm, and Grade 4 injuries as complete vessel occlusion. Demographic information, imaging findings, number of images obtained per individual, length of radiographic follow-up examination, radiographic outcome at end of follow-up period, treatment(s), and documentation of ischemic stroke or transient ischemic attack (TIA) were recorded. RESULTS Fifty-three Grade 3 BCAIs in 44 patients and 5 Grade 4 BCAIs in 5 patients were identified and had available follow-up information. The mean follow-up duration for Grade 3 BCAIs was 113 days, and the mean follow-up for Grade 4 BCAIs was 78 days. Final imaging of Grade 3 BCAIs showed that 53% of cases were radiographically stable, 11% had resolved, and 11% were improved, whereas 25% had radiographically worsened. In terms of treatment, 75% of patients received aspirin (ASA) alone, 5% received various medications, and 2% received no treatment. Eighteen percent of the patients in the Grade 3 BCAI group underwent endovascular intervention, and in all of these cases, treatment with ASA was continued after the procedure. Final imaging of the Grade 4 BCAIs showed that 60% remained stable (with persistent occlusion), whereas the remaining arteries improved (with recanalization of the vessel). All patients in the Grade 4 BCAI follow-up group were treated with ASA, although in 1 patient treatment was transitioned to Coumadin. There were 3 cases of cerebral infarction that appeared to be related to Grade 3 BCAIs (7% of 44 patients in the Grade 3 group), and 1 case of stroke that appeared to be related to a Grade 4 BCAI. All identified cases of stroke developed soon after hospital admission. CONCLUSIONS Although the posttraumatic cerebral infarction rate may be overestimated, the results of this study suggest that the Grade 3 and 4 BCAIs carry the highest stroke risk of the blunt cerebrovascular injuries, and those infarctions were identified on or shortly after hospital admission. Despite a 40% recanalization rate in the Grade 4 BCAI group and an 89% rate of persistent pseudoaneurysm in the Grade 3 BCAI group, follow-up imaging showed progressive worsening without radiographic improvement in only a small number of patients, and these findings alone did not correlate with adverse clinical outcome. Follow-up protocols may require amending; however, further prospective studies are needed to make conclusive changes as they relate to management.
    Journal of Neurosurgery 12/2014; 122(3):1-6. DOI:10.3171/2014.10.JNS14875 · 3.23 Impact Factor
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    ABSTRACT: Traditional cranioplasty methods focus on pre-operative or intraoperative hand molding. Recently, CT guided polyether ether ketone (PEEK) plate reconstruction enables precise, time-saving reconstruction. This case series aims to show a single institution experience with use of PEEK cranioplasty as an effective, safe, precise, reusable, and time-saving cranioplasty technique in large, complex cranial defects.Methods We performed a 6-year retrospective review of cranioplasty procedures performed at our affiliated hospitals using PEEK implants. A total of nineteen patients underwent twenty-two cranioplasty procedures. Pre-operative, intra-operative, and post-operative data was collected.ResultsNineteen patients underwent twenty-two procedures. Time interval from injury to loss of primary cranioplasty averaged 57.7 months (0-336 mo); 4.0 months (n=10, range 0-19) in cases of trauma. Time interval from primary cranioplasty loss to PEEK cranioplasty was 11.8 months for infection (n=11, range 6-25 mo.), 12.2 months for trauma (n=5, range 2-27 mo.), and 0.3 months for cosmetic or functional reconstructions (n=3, range 0-1). Similar surgical techniques were used in all patients. Drains were placed in 11/22 procedures. Varying techniques were used in skin closure, including adjacent tissue transfer (4/22) and free tissue transfer (1/22). The PEEK plate required modification in four procedures. Three patients had reoperation following PEEK plate reconstruction.Conclusion Cranioplasty utilizing CT-guided PEEK plate allows easy inset, anatomic accuracy, mirror image aesthetics, simplification of complex 3D defects, and potential time savings. Additionally, it’s easily manipulated in the operating room, and can be easily re-utilized in cases of intraoperative course changes or infection.
    Journal of Plastic Reconstructive & Aesthetic Surgery 11/2014; 68(3). DOI:10.1016/j.bjps.2014.11.001 · 1.47 Impact Factor
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    ABSTRACT: Objective To help define the perioperative risk related to commonly used non-aspirin NSAIDs with whole blood platelet aggregometry. Methods Twelve healthy volunteers were recruited. Two COX-1 inhibitors (ibuprofen and naproxen), and 2 COX-2 inhibitors (meloxicam and celecoxib) were administered, and daily whole blood platelet aggregometry (WBPA) studies were obtained until studies showed no platelet inhibition. Aspirin (ASA) was studied at the conclusion of the study. Results Ibuprofen had no inhibitory effect on platelet aggregation in all women and no inhibitory effect in 83% of men at 24 hours. All platelet function had returned to normal at 48 hours. The inhibitory effect of naproxen on platelets was absent at 48 hours in 83% of the women and 50% of men. By 72 hours all platelet studies had returned to normal. Meloxicam and Celecoxib did not cause any overall inhibitory effect on platelet aggregation. Conclusion Ibuprofen and naproxen have a mild inhibitory effect on platelet aggregation as compared to aspirin and this effect is undetectable by 48 hours and 72 hours, respectively. Meloxicam and celecoxib show essentially no inhibitory effect on platelet aggregation. These findings suggest that there is little bleeding risk related to platelet aggregation at 24 hours in patients who take COX-2 inhibitors and at 72 hours for those who take COX-1 inhibitor medications.
    World Neurosurgery 11/2014; 82(5). DOI:10.1016/j.wneu.2014.03.043 · 2.42 Impact Factor
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    ABSTRACT: OBJECT Grade 3 and 4 blunt vertebral artery (VA) injuries may carry a different natural course from that of lower-grade blunt VA injuries. Proper screening, management, and follow-up of these injuries remain controversial. Grade 3 and 4 blunt VA injuries were analyzed to define their natural history and establish a rational management plan based on lesion progression and cerebral infarction. METHODS A retrospective review of a prospectively maintained database of all blunt traumatic carotid and vertebral artery injuries from August 2003 to April 2013 was performed, and Grade 3 and 4 blunt VA injuries were identified. Grade 3 injuries were defined as stenosis of the vessel greater than 50% or the development of a pseudoaneurysm, and Grade 4 injuries were defined as complete vessel occlusion. Demographic information, radiographic imaging findings, number of imaging sessions performed per individual, length of radiographic follow-up, radiographic outcome at end of follow-up, treatment(s) provided, and documentation of ischemic stroke or transient ischemic attack were recorded. RESULTS A total of 79 high-grade (Grade 3 and 4) blunt VA injuries in 67 patients were identified. Fifty-nine patients with 66 high-grade blunt VA injuries were available for follow-up. There were 17 patients with 23 Grade 3 injuries and 42 patients with 43 Grade 4 injuries. The mean follow-up duration was 58 days for Grade 3 and 67 days for Grade 4 blunt VA injuries. Repeat imaging of Grade 3 blunt VA injuries showed that 39% of injuries were radiographically stable, 43% resolved, and 13% improved, while 1 injury radiographically worsened. Repeat imaging of the Grade 4 blunt VA injuries showed that 65% of injuries were radiographically stable (persistent occlusion), 30% improved (recanalization of the vessel), and in 2 cases (5%) the injury resolved. All Grade 3 injuries that were treated were managed with aspirin or clopidogrel alone, as were the majority of Grade 4 injuries. There were 3 cerebral infarctions thought to be related to Grade 4 blunt VA injuries, which were likely present on admission. All 3 of these patients died at a mean of 13.7 days after hospital admission. No cerebral infarctions directly related to Grade 3 blunt VA injuries were identified. CONCLUSIONS The majority of high-grade blunt VA injuries remain stable or are improved at final follow-up. Despite a 4% rate of radiographic worsening in the Grade 3 blunt VA injury group and a 35% recanalization rate in the Grade 4 blunt VA injury group, there were no adverse clinical outcomes associated with these radiographic changes. No cerebral infarctions were noted in the Grade 3 group. A 7% stroke rate was identified in the Grade 4 blunt VA injury group; however, this was confined to the immediate postinjury period and was associated with 100% mortality. While these data suggest that these high-grade vertebral artery injuries may require less intensive radiographic follow-up, future prospective studies are needed to make conclusive changes related to treatment and management.
    Journal of Neurosurgery 10/2014; 122(5):1-6. DOI:10.3171/2014.9.JNS1461 · 3.23 Impact Factor
  • Journal of Neurotrauma 07/2014; · 3.97 Impact Factor
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    ABSTRACT: As a basis for venous thromboembolism (VTE) prophylaxis after traumatic brain injury (TBI), we have previously published an algorithm known as the Parkland Protocol. Patients are classified by risk for spontaneous progression of hemorrhage with chemoprophylaxis regimens tailored to each tier. We sought to validate this schema. In our algorithm, patients with any of the following are classified "Low-risk" for spontaneous progression: subdural hemorrhage <8 mm thick; epidural hemorrhage <8 mm thick; contusions <20 mm in diameter; a single contusion per lobe; any amount of subarachnoid hemorrhage; or any amount of intraventricular hemorrhage. Patients with any injury exceeding these are "Moderate-risk" for progression, and any patient receiving a monitor or craniotomy is "High-risk." From 2/2010 to 11/2012, TBI patients were entered into a dedicated database tracking injury types and sizes, risk category at presentation, and progression on subsequent CTs. The cohort (n=414) was classified as Low-risk (n=200), Moderate-risk (n=75), or High-risk (n=139) after first CT. After repeat CT scan, radiographic progression was noted in 27% of Low-risk subjects, 53% of Moderate-risk, and 58% of High-risk. Omnibus ANOVA test for differences in progression rates was highly significant (p<0.0001). Tukey's post-hoc test showed the Low-risk progression rate to be significantly different than both the Moderate and the High-risk arms; no difference was seen between the Moderate and High-risk arms themselves. These criteria are a valid tool for classifying TBI patients into two categories of risk for spontaneous progression. This supports tailored chemoprophylaxis regimens for each arm. Key words: TBI, progression, validation, venous thromboembolism.
    Journal of Neurotrauma 06/2014; 31(20). DOI:10.1089/neu.2014.3366 · 3.97 Impact Factor
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    ABSTRACT: Evidence is emerging that isolated traumatic subarachnoid hemorrhage (ITSAH) may be a milder form of traumatic brain injury (TBI). If true, ITSAH may not benefit from intensive care unit (ICU) admission which would in turn decrease resource utilization. We conducted a retrospective review of all TBI admissions to our institution between 2/2010 and 11/2012 to compare the presentation and clinical course of subjects with ITSAH to all other TBI. We then performed descriptive statistics on the subset of ITSAH subjects presenting with a Glasgow Coma Score (GCS) of 13 to 15. Of 698 subjects, 102 had ITSAH and 596 had any other intracranial hemorrhage pattern. Compared to all other TBI, ITSAH had significantly lower injury severity scores (p<0.0001), lower head abbreviated injury scores (p<0.0001), higher emergency department GCS (p<0.0001), shorter ICU stays (p=0.007), higher discharge GCS (p=0.005), lower mortality (p=0.003), and significantly fewer head CT scans (p<0.0001). Of those ITSAH subjects presenting with a GCS of 13 to 15 (n=77), none underwent placement of an intracranial monitor nor craniotomy. One subject (1.3%) demonstrated a change in exam (worsened headache and dizziness) concomitant with a progression of his intracranial injury. His symptoms resolved with readmission to the ICU and continued observation. Our results suggest that ITSAH are less severe brain injuries than other TBI. ITSAH patients with GCS scores of 13 to 15 demonstrate low rates of clinical progression, and when progression occurs it resolves without further intervention. This subset of TBI patients does not appear to benefit from ICU admission. Key words: isolated; traumatic; subarachnoid; progression; sequelae.
    Journal of Neurotrauma 06/2014; 31(20). DOI:10.1089/neu.2014.3377 · 3.97 Impact Factor
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    ABSTRACT: Object Screening of blunt vertebral artery (VA) injuries has increased since research has shown that they occur at a higher incidence than originally reported. Grade 1 and 2 injuries are the most common form of blunt VA injury. Proper screening, management, and follow-up of these injuries remain controversial. In this report, imaging, progression, treatment, and outcomes of Grade 1 and 2 blunt VA injuries were analyzed to better define their natural history and to establish a rational management plan based upon their risk of progression and cerebral infarct. Methods A retrospective review of all blunt traumatic carotid artery and VA injuries from December 2003 to April 2013 was performed. For the purposes of this report, focus was given to Grade 1 and 2 VA injuries. Grade 1 injuries were defined as a vessel lumen stenosis of less than 25%, and Grade 2 injuries were defined as vessel lumen stenosis between 25% and 50%. Demographic information, radiological imaging, number of images performed per individual, length of radiological follow-up, radiological outcome at the end of follow-up, treatment provided, and documentation of stroke or transient ischemic attack were recorded. Results One hundred eighty-seven Grade 1 and 2 VA injuries in 143 patients were identified. Of these 143 patients, 120 with 152 Grade 1 or 2 blunt VA injuries were available for follow-up. The mean duration of follow-up was 40 days. Repeat imaging showed that 148 (97.4%) Grade 1 or 2 blunt VA injuries were stable, improved, or resolved on final follow-up imaging. Seventy-nine patients (66%) were treated with aspirin, whereas 35 patients (29%) received no treatment. The remaining patients were treated with other antiplatelet agents or anticoagulant medication. Neuroimaging demonstrated 2 cases (1.7%) with posterior circulation infarcts that were believed to be related to their blunt VA injuries, both of which occurred during the initial hospitalization and within the first 4 days after injury. Conclusions Although follow-up imaging showed progressive worsening without radiological improvement in only a small number of patients with low-grade blunt VA injuries, these findings did not correlate with adverse clinical outcome. The posttraumatic cerebral infarction rate of 1.7% may be overestimated, and the use of acetylsalicylic acid or other antiplatelet or anticoagulant medication did not correlate with radiological changes or rate of cerebral infarction. While these data suggest the possibility that these low-grade VA injuries may not require treatment or follow-up, future prospective studies are needed to make conclusive changes related to management.
    Journal of Neurosurgery 06/2014; 121(2):1-7. DOI:10.3171/2014.4.JNS132235 · 3.23 Impact Factor
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    ABSTRACT: Purpose: Post-traumatic epilepsy (PTE) is a consequence of traumatic brain injury (TBI), occurring in 10-25% of patients with moderate to severe injuries. The development of animal models for testing antiepileptogenic therapies and validation of biomarkers to follow epileptogenesis in humans requires sophisticated understanding of the subtypes of PTE, which is the objective of this study. Methods: Retrospective review was done of patients with moderate or severe TBI with subsequent development of medically-refractory epilepsy referred for video-EEG monitoring at a single center over a 10-year period. Information regarding details of injury, neuroimaging studies, seizures, video-EEG, and surgery outcomes were collected and analyzed. Key Findings: One hundred twenty-three patients with PTE were identified, representing 4.3% of all patients evaluated in the EMU. Most of them had localization-related epilepsy, of which 57% had temporal lobe epilepsy (TLE), 35% had frontal lobe epilepsy (FLE), and 3% each had parietal and occipital lobe epilepsy. Of patients with TLE, 44% had mesial temporal sclerosis (MTS), 26% had temporal neocortical lesions, and 30% were nonlesional. There was no difference in age at injury between the different PTE subtypes. Twenty-two patients, 13 of which had MTS, proceeded to surgical resection. At a mean follow-up of 2.5 years, Engel Class I outcomes were seen in 69% of those with TLE and 33% of those with FLE. Significance: PTE is a heterogeneous condition, and careful evaluation with video-EEG monitoring and high resolution MRI can identify distinct syndromes. These results have implications for the design of clinical trials of antiepileptogenic therapies for PTE.
    Journal of neurotrauma 04/2014; 31(16). DOI:10.1089/neu.2013.3221 · 3.97 Impact Factor
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    ABSTRACT: Endometriosis is a common disease; however, ectopic müllerian tissue within the spine is a rare entity with the potential for producing significant neurological compromise. There are several postulated etiologies for this phenomenon, and only a few case reports are available in the world literature. Knowledge of this rare phenomenon is of paramount importance, since early diagnosis can lead to lessened neurological morbidity. In this manuscript, we present a case report, discuss gynecological and neurosurgical perspectives relating to the treatment strategies for managing this entity, and propose an alternative explanation for such an occurrence from a neurogenetic standpoint. We present a case of spinal müllerianosis within the conus medullaris which was managed symptomatically for several years with an intracystic drain and subcutaneous reservoir. Over the years, it became clear that there was a cyclical presentation to her clinical malady, which at times was severe. Ultimately, she required surgical resection which aided in her diagnosis and subsequent treatment. Intraspinal müllerianosis is a rare location for an otherwise common disease in women and has the potential to create significant neurological morbidity by creating a mass lesion. Although the exact etiology remains unclear, the histogenic theories of embryologic origin appear most plausible. Treatment strategies for this condition may include hormonal therapy, obstetrical surgery, or open spinal surgery. This unusual and poorly understood disease should be considered in the differential diagnosis for intraspinal lesions presenting with hemorrhage in the clinical context of cyclical neurological symptoms.
    Child s Nervous System 10/2013; DOI:10.1007/s00381-013-2291-5 · 1.16 Impact Factor
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    ABSTRACT: EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in-frame deletion in the extracellular domain of EGFR, does not bind ligand and is thought to be constitutively active. Although EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood. Here we present a new model of EGFRvIII activation and propose that oncogenic activation of EGFRvIII in glioma cells is driven by co-expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a striking increase in EGFRvIII tyrosine phosphorylation and activation while silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB-EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this study, we show that HB-EGF is induced by EGFRvIII only when EGFRwt is present. Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed-forward loop regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking inhibition of EGFRvIII-induced tumorigenicity, while increasing EGFRwt or HB-EGF levels resulted in accelerated EGFRvIII-mediated oncogenicity in an orthotopic mouse model. Furthermore, we demonstrate the existence of this loop in human GBM. Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely maintained by a continuous EGFRwt-EGFRvIII-HB-EGF loop, potentially an attractive target for therapeutic intervention.Oncogene advance online publication, 30 September 2013; doi:10.1038/onc.2013.400.
    Oncogene 09/2013; 33(33). DOI:10.1038/onc.2013.400 · 8.56 Impact Factor
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    ABSTRACT: Object Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (Aβ) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Methods Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecular-weight β-amyloid oligomers were measured using Western blot analysis. Results Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Conclusions Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.
    Journal of Neurosurgery 03/2013; 118(6). DOI:10.3171/2013.2.JNS121771 · 3.15 Impact Factor
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    ABSTRACT: Object Coagulopathy and thrombocytopenia are common after traumatic brain injury (TBI), yet transfusion thresholds for mildly to moderately abnormal ranges of international normalized ratio and platelet count remain controversial. This study evaluates associations between fresh frozen plasma (FFP) and platelet transfusions with long-term functional outcome and survival in TBI patients with moderate hemostatic laboratory abnormalities. Methods This study is a retrospective review of prospectively collected data of patients with mild to severe TBI. Data include patient demographics, several initial injury severity metrics, daily laboratory values, Glasgow Outcome Score- Extended (GOSE) scores, Functional Status Examination (FSE) scores, and survival to 6 months. Correlations were evaluated between these variables and transfusion of FFP, platelets, packed red blood cells (RBCs), cryoprecipitate, recombinant factor VIIa, and albumin. Ordinal regression was performed to account for potential confounding variables to further define relationships between transfusion status and long-term outcome. By analyzing collected data, mild to moderate coagulopathy was defined as an international normalized ratio 1.4-2.0, moderate thrombocytopenia as platelet count 50 × 10(9)/L to 107 × 10(9)/L, and moderate anemia as 21%-30% hematocrit. Results In patients with mild to moderate laboratory hematological abnormalities, univariate analysis shows significant correlations between poor outcome scores and FFP, platelet, or packed RBC transfusion; the volume of FFP or packed RBCs transfused also correlated with poor outcome. Several measures of initial injury and laboratory abnormalities also correlated with poor outcome. Patient age, initial Glasgow Coma Scale score, and highest recorded serum sodium were included in the ordinal regression model using backward variable selection. In the moderate coagulopathy subgroup, patients transfused with FFP were more likely to have a lower GOSE score relative to those who did not receive a transfusion (OR 5.20 [95% CI 1.72-15.73]). Patients with moderate coagulopathy who received FFP and packed RBCs were even more likely to be have a lower GOSE score (OR 7.17 [95% CI 2.12-24.12]). Moderately anemic patients who received packed RBCs alone were more likely to have a worse long-term functional outcome as determined by GOSE and FSE scores (GOSE: OR 2.41 [95% CI 1.51-3.85]; and FSE: OR 3.27 [95% CI 2.00-5.35]). No transfusion types or combinations were noted to significantly correlate with the 6-month mortality in ordinal regression. Conclusions In TBI patients with moderate coagulopathy, FFP transfusions alone or a combination of FFP and packed RBCs were associated with poorer long-term functional outcomes as measured by the GOSE. Red blood cell transfusions were associated with poor long-term functional outcome in TBI patients with moderate anemia. Platelet transfusion in patients with moderate thrombocytopenia was not significantly associated with outcome. Although transfusion is beneficial to many patients with severe hematological abnormalities, it is not without risk, and the indications for transfusion should be carefully considered in patients with moderate hematological abnormalities.
    Journal of Neurosurgery 12/2012; 118(3). DOI:10.3171/2012.11.JNS12622 · 3.15 Impact Factor
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    ABSTRACT: Glioblastomas and brain metastases demonstrate avid uptake of 2-[(18) F]fluoro-2-deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by (1) H MRS. These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. 2-[(18) F]Fluoro-2-deoxyglucose-positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation relative to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid cycle is unknown. Here, we studied the metabolism of human brain tumors in situ. [U-(13)  C]Glucose (uniformly labeled glucose, i.e. d-glucose labeled with (13)  C in all six carbons) was infused during surgical resection, and tumor samples were subsequently subjected to (13) C NMR spectroscopy. The analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-coenzyme A pool was derived from blood-borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of (13) C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment. Copyright © 2012 John Wiley & Sons, Ltd.
    NMR in Biomedicine 11/2012; 25(11):1234-44. DOI:10.1002/nbm.2794 · 3.56 Impact Factor
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    ABSTRACT: Scheduled repeat head computed tomography after mild traumatic brain injury has been shown to have limited use for predicting the need for an intervention. We hypothesized that repeat computed tomography in persons with intracranial hemorrhage and a Glasgow Coma Scale (GCS) score of 13 to 15, without clinical progression of neurologic symptoms, does not impact the need for neurosurgical intervention or discharge GCS scores. This prospective cohort study followed all patients presenting to our urban Level I trauma center with intracranial hemorrhage and a GCS score of 13 to 15 from February 2010 to December 2010. Subjects were divided into two groups: those in whom repeat CT scans were performed routinely (ROUTINE) and those in whom they were performed selectively (SELECTIVE) based on changes in clinical examination. CT scanning decisions were made at the discretion of the neurosurgical service attending physician. One hundred forty-five patients met the inclusion criteria (ROUTINE, n = 92; SELECTIVE, n = 53). Group demographics, including age, sex, and presenting GCS score were not significantly different. Of SELECTIVE patients, six (11%) required a repeat head computed tomography for a neurologic change, with one having a radiographic progression of hemorrhage (16%) versus 26 (28%) of 92 in the ROUTINE group showing a radiographic progression. No patient in either group required medical or neurosurgical intervention based on repeat scan. The number of CT scans performed differed between the two groups (three scans in ROUTINE vs. one scan in SELECTIVE, p < 0.001), as did the intensive care unit (2 days vs. 1 day, p < 0.001) and hospital (5 days vs. 2 days, p < 0.001) lengths of stay. Discharge GCS score was similar for both groups (15 vs. 15, p = 0.37). One death occurred in the SELECTIVE group, unrelated to intracranial findings. The negative predictive value of a repeat CT scan leading to neurosurgical intervention with no change in clinical examination was 100% for both groups. A practice of selective repeat head CT scans in patients with traumatic brain injury admitted with a GCS score of 13 to 15 decreases use of the test and is associated with decreased hospital length of stay, without impacting discharge GCS scores. Diagnostic study, level II.
    09/2012; 73(3):685-8. DOI:10.1097/TA.0b013e318265ccd9
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    ABSTRACT: BACKGROUND: Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm. METHODS: In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications. RESULTS: A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9% (95% confidence interval [CI], 0.7-19.7%) for enoxaparin and 3.6% (95% CI, 0.1-18.3%) for placebo, a treatment effect difference of 2.3% (95% CI, -14.42-16.5%). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm. CONCLUSION: TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm. LEVEL OF EVIDENCE: Therapeutic study, level II.
    08/2012; 73(6). DOI:10.1097/TA.0b013e31825ac49e
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    ABSTRACT: We have created a theoretical algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI) known as the Parkland Protocol, which stratifies patients into low-, medium-, and high-risk categories for spontaneous progression of hemorrhage. This prospective study characterizes the incidence and timing of radiographic progression of the TBI patterns in these categories. Inclusion criterion was presentation with intracranial blood between February 2010 and March 2011; exclusion was receipt of only one computed tomographic scan of the head during the inpatient stay or preinjury warfarin. At admission, all patients were preliminarily categorized per the Parkland Protocol as follows: low risk (LR), patients meeting the modified Berne-Norwood criteria; moderate risk (MR), injuries larger than the modified Berne-Norwood criteria without requiring a neurosurgical procedure; high risk (HR), any patient with a craniotomy/monitor. A total of 245 patients with intracranial hemorrhage were enrolled during the 13-month study period. Of patients preliminarily classified as LR at admission (n = 136), progression was seen in 25.0%. Spontaneous worsening was seen in 7.4% of LR patients at 24 hours after injury, and no LR patients progressed at 72 hours after injury. In patients initially classified as MR at admission (n = 42), progression was seen in 42.9%, with 91.5% of patients demonstrating stable computed tomographic head scans at 72 hours after injury. In patients initially classified as HR (n = 67), 64.2% demonstrated spontaneous progression of their TBI patterns, with 10.5% continuing to progress at 72 hours after injury. Most repeat scans were performed as routinely scheduled studies (81-91%). Increases in the incidence of spontaneous worsening were seen as severities of injury progressed from the Parkland Protocol's LR to MR to HR arms. The time frames for these spontaneous worsenings seem to be such that the protocol's theoretical recommendations for venous thromboembolism prophylaxis are worth pursuing as future points of investigation.
    08/2012; 73(2 Suppl 1):S122-7. DOI:10.1097/TA.0b013e3182606327
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    ABSTRACT: Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.
    Nature medicine 01/2012; 18(4):624-9. DOI:10.1038/nm.2682 · 28.05 Impact Factor

Publication Stats

1k Citations
235.22 Total Impact Points

Institutions

  • 2005–2014
    • University of Texas Southwestern Medical Center
      • Department of Neurological Surgery
      Dallas, Texas, United States
  • 2008–2012
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2009–2010
    • Parkland Memorial Hospital
      Dallas, Texas, United States
    • University of North Texas at Dallas
      Dallas, Texas, United States