Christopher Madden

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

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Publications (47)203.81 Total impact

  • Journal of Neurotrauma 07/2014; · 4.30 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;
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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;
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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;
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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; · 4.25 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 01/2014; · 1.77 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; · 1.24 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; · 7.36 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; · 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; · 3.15 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.
    The journal of trauma and acute care surgery. 09/2012; 73(3):685-8.
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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.
    The journal of trauma and acute care surgery. 08/2012;
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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.
    The journal of trauma and acute care surgery. 08/2012; 73(2 Suppl 1):S122-7.
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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 03/2012; 25(11):1234-44. · 3.45 Impact Factor
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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. · 27.14 Impact Factor
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    ABSTRACT: Intracerebral hemorrhage (ICH) is the most serious bleeding complication of vitamin K antagonist (VKA) therapy, carrying a high mortality. Rapid reversal of VKA in ICH is critical. Plasma therapy, the standard of care in the US, is not optimal. The ideal prothrombin complex concentrate (PCC) containing all vitamin K-dependent factors (VKDFs) is not available in the US. Therefore, the authors developed a Trauma Coumadin Protocol (TCP) consisting of a 3-factor PCC available in the US (which contains insufficient factor VII [FVII]) with a low-dose recombinant FVIIa to rapidly reverse VKA. Forty-six patients treated with the TCP were retrospectively analyzed. Fourteen patients had pre- and post-TCP plasma samples collected to assess their VKDF increment. Eleven patients had measurable intraparenchymal hematomas, which were evaluated for expansion. The mean pre- and post-TCP international normalized ratios (INRs) were 3.4 (median 2.9) and 1.0 (median 0.9), respectively. Once corrected, INR was maintained at < 1.3 during a patient's hospital stay. The pre-TCP median values of FII, FVII, FIX, and FX were 28%, 21%, 45%, and 20%, respectively; post-TCP median values increased to 144%, 417%, 102%, and 143%, respectively. Four of the 11 patients with measurable intraparenchymal hemorrhage had expansion at 24 hours after TCP. One patient probably (8 hours post-TCP) and 1 patient possibly (3 days post-TCP) had thrombotic complications. The TCP was very effective in rapidly reversing VKA-associated coagulopathy; however, this protocol should be used cautiously in patients at high risk for thrombosis.
    Journal of Neurosurgery 12/2011; 116(3):491-7. · 3.15 Impact Factor
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    ABSTRACT: The incidence of small vestibular schwannomas in patients with serviceable hearing is increasing because of the widespread use of MRI. The middle fossa approach provides the patient with an opportunity for tumor removal with hearing preservation. To determine the rate of hearing preservation and facial nerve outcomes after removal of a vestibular schwannoma with the use of the middle fossa approach. A retrospective case review at a tertiary, academic medical center was performed identifying patients from 1998 through 2008 that underwent removal of a vestibular schwannoma by the middle fossa approach. Preoperative and postoperative audiograms were compared to determine hearing preservation rates. In addition, facial nerve outcomes at last follow-up were recorded. Forty-six patients underwent a middle fossa craniotomy for the removal of a vestibular schwannoma. Of the 38 patients that had class A or class B hearing preoperatively, 24 (63.2%) retained class A or B hearing and 29 (76.3%) retained class A, B, or C hearing. When tumors were 10 mm or less in patients with class A or B preoperative hearing, 22 of 30 patients (73.3%) retained class A or B hearing. When the tumor size was greater than 10 mm in patients with class A or B preoperative hearing, 2 of 8 patients (25%) retained class A or B hearing. At most recent follow-up, 76.1% of patients had House-Brackmann grade I facial function, 13.0% had House-Brackmann grade II facial function, and 10.9% had House-Brackmann grade III facial function. Hearing preservation rates are excellent using the middle fossa approach, especially for smaller tumors. No patient experienced long-term facial nerve function worse than House-Brackmann grade III.
    Neurosurgery 08/2011; 70(2):334-40; discussion 340-1. · 2.53 Impact Factor
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    ABSTRACT: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome. The participants were 28 patients with mild to severe traumatic axonal injury and 20 age- and sex-matched healthy control subjects. Neuroimaging was obtained 0-9 days postinjury for acute scans and 6-14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used. Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients' long-term outcome. Acute tractography measurements were able to predict patients' learning and memory performance; chronic measurements also determined performance on processing speed and executive function. Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients' long-term outcome.
    Neurology 08/2011; 77(9):818-26. · 8.25 Impact Factor
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    ABSTRACT: To describe a patient who developed a thyrotropin (TSH)-secreting adenoma in the setting of primary hypothyroidism. We report the clinical, laboratory, and radiologic findings of a patient with a history of primary hypothyroidism who presented with headache, a bitemporal visual field deficit, and elevated TSH despite long-term levothyroxine therapy. We discuss the diagnostic challenges of this case and review the relevant literature. A 54 year old woman with a history of primary hypothyroidism presented with a 3-year history of headache and a week of worsening vision. Imaging revealed a heterogeneous sellar mass elevating the optic chiasm. Her serum TSH was 46.5 mIU/L and free thyroxine concentration was 0.1 ng/dL. The differential diagnosis included pituitary hyperplasia and a TSH-secreting adenoma in a patient with primary hypothyroidism. The pathologic characteristics of the tumor were consistent with the latter. In a patient with an elevated TSH concentration and a previous diagnosis of hypothyroidism, it is important to consider other entities besides medication noncompliance. TSH-secreting adenomas can also cause elevated levels of TSH.
    Endocrine Practice 07/2011; 17(6):e135-9. · 2.49 Impact Factor

Publication Stats

679 Citations
203.81 Total Impact Points

Institutions

  • 2005–2014
    • University of Texas Southwestern Medical Center
      • • Division of Neuro-oncology
      • • Department of Physical Medicine and Rehabilitation
      Dallas, Texas, United States
  • 2008–2011
    • University of Texas at Dallas
      • • Center for BrainHealth
      • • Cognition and Neuroscience
      Dallas, TX, United States
  • 2010
    • Parkland Memorial Hospital
      Dallas, Texas, United States