The biportal transorbital approach: quantitative comparison of the anterior subfrontal craniotomy, bilateral transorbital endoscopic, and microscopic approaches.

OBJECTIVE: The aim of this study was to assess the surgical use and applicability of a biportal bitransorbital approach. Single-portal transorbital and combined transorbital transnasal approaches have been used in clinical practice, but no study has assessed the surgical use and applicability of a biportal bitransorbital approach. METHODS: Ten cadaver specimens underwent midline anterior subfrontal (ASub), bilateral transorbital microsurgery (bTMS), and bilateral transorbital neuroendoscopic surgery (bTONES) approaches. Morphometric analyses included the length of the bilateral cranial nerves I and II, the optic tract, and A1; the area of exposure of the anterior cranial fossa floor; craniocaudal and mediolateral angles of attack (AOAs); and volume of surgical freedom (VSF; maximal available working volume for a specific surgical corridor and surgical target structure normalized to a height of 10 mm) of the bilateral paraclinoid internal carotid arteries (ICAs), bilateral terminal ICAs, and anterior communicating artery (ACoA). Analyses were conducted to determine whether the biportal approach was associated with greater instrument freedom. RESULTS: The bTMS and bTONES approaches provided limited access to the bilateral A1 segments and the ACoA, which were inaccessible in 30% (bTMS) and 60% (bTONES) of exposures. The average total frontal lobe area of exposure (AOE) was 1648.4 mm2 (range 1516.6-1958.8 mm2) for ASub, 1658.9 mm2 (1274.6-1988.2 mm2) for bTMS, and 1914.9 mm2 (1834.2-2014.2 mm2) for bTONES exposures, with no statistically significant superiority between any of the 3 approaches (p = 0.28). The bTMS and bTONES approaches were significantly associated with decreases of 8.7 mm3 normalized volume (p = 0.005) and 14.3 mm3 normalized volume (p < 0.001) for VSF of the right paraclinoid ICA compared with the ASub approach. No statistically significant difference in surgical freedom was noted between all 3 approaches when targeting the bilateral terminal ICA. The bTONES approach was significantly associated with a decrease of 105% in the (log) VSF of the ACoA compared with the ASub (p = 0.009). CONCLUSIONS: Although the biportal approach is intended to improve maneuverability within these minimally invasive approaches, these results illustrate the pertinent issue of surgical corridor crowding and the importance of surgical trajectory planning. A biportal transorbital approach provides improved visualization but does not improve surgical freedom. Furthermore, although it affords impressive anterior cranial fossa AOE, it is unsuitable for addressing midline lesions because the preserved orbital rim restricts lateral movement. Further comparative studies will elucidate whether a combined transorbital transnasal route is preferable to minimize skull base destruction and maximize instrument access.

Improving the metric of surgical freedom in the laboratory based on a novel concept of volume.

BACKGROUND: In laboratory-based neuroanatomical studies, surgical freedom, the most important metric of instrument maneuverability, has been based on Heron's formula. Inaccuracies and limitations hinder this study design's applicability. A new methodology, volume of surgical freedom (VSF), may produce a more realistic qualitative and quantitative representation of a surgical corridor. METHODS: Overall, 297 data set measurements assessing surgical freedom were completed for cadaveric brain neurosurgical approach dissections. Heron's formula and VSF were calculated specifically to different surgical anatomical targets. Quantitative accuracy and the results of an analysis of human error were compared. RESULTS: Heron's formula for irregularly shaped surgical corridors resulted in overestimation of the respective areas (minimum overestimation 31.3%). In 92% (188/204) of data sets reviewed for influence of offset, areas calculated on the basis of measured data points were larger than areas calculated on the basis of the translated best-fit plane points (mean [SD] overestimation of 2.14% [2.62%]). Variability in the probe length attributable to human error was small (mean [SD] calculated probe length 190.26 mm [5.57 mm]). CONCLUSIONS: VSF is an innovative concept that can develop a model of a surgical corridor producing better assessment and prediction of the ability to maneuver and manipulate surgical instruments. VSF corrects for deficits in Heron's method by generating the correct area for an irregular shape using the shoelace formula, adjusting the data points to account for offset, and attempting to correct for human error. VSF produces 3-dimensional models and, therefore, is a preferable standard for assessing surgical freedom.

Toward "bigger" data for neurosurgical anatomical research: a single centralized quantitative neurosurgical anatomy platform.

Quantitative neurosurgical anatomy research aims to produce surgically applicable knowledge for improving operative decision-making using measurements from anatomical dissection and tools such as stereotaxis. Although such studies attempt to answer similar research questions, there is little standardization between them, offering minimal comparability. Modern technology has been incorporated into the research methodology, but many scientific principles are lacking, and results are not broadly applicable or suitable for evaluating big-data trends. Advances in information technology and the concept of big data permit more accessible and robust means of producing valuable, standardized, reliable research. A technology project, "Inchin," is presented to address these needs for neurosurgical anatomy research. This study applies the concept of big data to neurosurgical anatomy research, specifically in quantifying surgical metrics. A remote-hosted web application was developed for computing standard neurosurgical metrics and storing measurement data. An online portal (Inchin) was developed to produce a database to facilitate and promote neurosurgical anatomical research, applying optimal scientific methodology and big-data principles to this recent and evolving field of research. Individual data sets are not insignificant, but a collective of data sets present advantages. Large data sets allow confidence in data trends that are usually obscured in smaller numbers of samples. Inchin, a single centralized software platform, can act as a global database of results of neurosurgical anatomy studies. A calculation tool ensuring standardized peer-reviewed methodology, Inchin is applied to the analysis of neurosurgical metrics and may promote efficient study collaboration within and among neurosurgical laboratories.

Volumetric 3-Dimensional Analysis of the Supraorbital vs Pterional Approach to Paramedian Vascular Structures: Comprehensive Assessment of Surgical Maneuverability.

BACKGROUND: Both the pterional and supraorbital approaches have been proposed as optimal access corridors to deep and paramedian anatomy. OBJECTIVE: To assess key intracranial structures accessed through the surgical approaches using the angle of attack (AOA) and the volume of surgical freedom (VSF) methodologies. METHODS: Ten pterional and 10 supraorbital craniotomies were completed. Data points were measured using a neuronavigation system. A comparative analysis of the craniocaudal AOA, mediolateral AOA, and VSF of the ipsilateral paraclinoid internal carotid artery (ICA), terminal ICA, and anterior communicating artery (ACoA) complex was completed. RESULTS: For the paraclinoid ICA, the pterional approach produced larger craniocaudal AOA, mediolateral AOA, and VSF than the supraorbital approach (28.06° vs 10.52°, 33.76° vs 23.95°, and 68.73 vs 22.59 mm3 normalized unit [NU], respectively; P < .001). The terminal ICA showed similar superiority of the pterional approach in all quantitative parameters (27.43° vs 11.65°, 30.62° vs 25.31°, and 57.41 vs 17.36 mm3 NU; P < .05). For the ACoA, there were statistically significant differences between the results obtained using the pterional and supraorbital approaches (18.45° vs 10.11°, 29.68° vs 21.01°, and 26.81 vs 16.53 mm3 NU; P < .005). CONCLUSION: The pterional craniotomy was significantly superior in all instrument maneuverability parameters for approaching the ipsilateral paraclinoid ICA, terminal ICA, and ACoA. This global evaluation of 2-dimensional and 3-dimensional surgical freedom and instrument maneuverability by amalgamating the craniocaudal AOA, mediolateral AOA, and VSF produces a comprehensive assessment while generating spatially and anatomically accurate corridor models that provide improved visual depiction for preoperative planning and surgical decision-making.

Development and implementation of an ultralow-dose CT protocol for the assessment of cerebrospinal shunts in adult hydrocephalus.

BACKGROUND: Cerebrospinal fluid shunts in the treatment of hydrocephalus, although associated with clinical benefit, have a high failure rate with repeat computed tomography (CT) imaging resulting in a substantial cumulative radiation dose. Therefore, we sought to develop a whole-body ultralow-dose (ULD) CT protocol for the investigation of shunt malfunction and compare it with the reference standard, plain radiographic shunt series (PRSS). METHODS: Following ethical approval, using an anthropomorphic phantom and a human cadaveric ventriculoperitoneal shunt model, a whole-body ULD-CT protocol incorporating two iterative reconstruction (IR) algorithms, pure IR and hybrid IR, including 60% filtered back projection and 40% IR was evaluated in 18 adult patients post new shunt implantation or where shunt malfunction was suspected. Effective dose (ED) and image quality were analysed. RESULTS: ULD-CT permitted a 36% radiation dose reduction (median ED 0.16 mSv, range 0.07-0.17, versus 0.25 mSv (0.06-1.69 mSv) for PRSS (p = 0.002). Shunt visualisation in the thoracoabdominal cavities was improved with ULD-CT with pure IR (p = 0.004 and p = 0.031, respectively) and, in contrast to PRSS, permitted visualisation of the entire shunt course (p < 0.001), the distal shunt entry point and location of the shunt tip in all cases. For shunt complications, ULD-CT had a perfect specificity. False positives (3/22, 13.6%) were observed with PRSS. CONCLUSIONS: At a significantly reduced radiation dose, whole body ULD-CT with pure IR demonstrated diagnostic superiority over PRSS in the evaluation of cerebrospinal fluid shunt malfunction.

Transorbital Neuroendoscopic Surgery as a Mainstream Neurosurgical Corridor: A Systematic Review.

BACKGROUND: Transorbital neuroendoscopic surgery (TONES) offers a new level of minimally invasive, minimally disfiguring skull base surgery with maximal surgical visualization. METHODS: This review systematically assesses the body of published anatomic (cadaveric) and clinical evidence for the approach. PubMed, Cochrane Library, Ovid MEDLINE, and Embase were systematically searched for articles in which the TONES surgical technique was used in an anatomic, clinical, or combined study. The outcomes of interest included identification of the diseases, operative outcomes, and complication rates. RESULTS: Twenty-three articles were selected for this systematic review: 10 were purely anatomic, 10 were clinical, and 3 had both clinical and cadaveric components. The articles reported 69 patients undergoing transorbital or combined transorbital and transnasal intervention. A total of 30 cases of cerebrospinal fluid leak were documented; of these, 28 (93%) had successful resolution, 2 (7%) had recurrence, and 5 (15%) experienced complications. A total of 31 tumors were biopsied (n = 1), resected (n = 22), or debulked (n = 8). Meningiomas were the most common lesion managed via TONES, with 5 of 7 patients with meningioma who reported preoperative neurologic deficits experiencing an improvement in extraocular movement impairment, visual acuity, proptosis, and ptosis. Transient postoperative clinical sequelae, including diplopia and ptosis, were increasingly associated with the superior lid crease incision and the sole transorbital approach. CONCLUSIONS: TONES is a significant development in transorbital skull base surgery. However, comprehensive, robust, comparative analyses and increasing use and generalizability of this technique in skull base surgery are awaited.

From Krönlein, through madness, to a useful modern surgery: the journey of the transorbital corridor to enter the neurosurgical armamentarium.

Transorbital surgery has gained recent notoriety because of its incorporation into endoscopic skull base surgery. The use of this surgical corridor has been pervasive throughout the 20th century. It has been utilized by multiple disciplines for both clinical and experimental purposes, although its historical origin is medically and ethically controversial. Hermann Knapp first introduced the orbital surgical technique in 1874, and Rudolf Krönlein introduced his procedure in 1889. Rivalry between Walter Dandy in neurosurgery and Raynold Berke in ophthalmology further influenced methods of tackling intracranial and intraorbital pathologies. In 1946, Walter Freeman revolutionized psychosurgery by completing seemingly successful transorbital leucotomies and promoting their minimally invasive and benign surgical characteristics. However, as Freeman's legacy came into disrepute, so did the transorbital brain access corridor, again resulting in its stunted evolution. Microsurgery and endoscopy further influenced the use, or lack thereof, of the transorbital corridor in neurosurgical approaches. Historical analysis of present goals in modern skull base surgery echoes the principles established through an approach described almost 150 years ago: minimal invasion, minimal morbidity, and priority of patient satisfaction. The progression of the transorbital approach not only reflects psychosocial influences on medical therapy, as well as the competition of surgical pioneers for supremacy, but also describes the diversification of skull base techniques, the impact of microsurgical mastery on circumferential neurosurgical corridors, the influence of technology on modernizing skull base surgery, and the advancing trend of multidisciplinary surgical excellence.

Biopsychosocial variations in quality of life outcome following microdiscectomy.

BACKGROUND: Lumbar microdiscectomy is one of the most frequently performed neurosurgical procedures. In this review, we ask why patients' outcomes vary so widely even within the same unit, with the same surgeon performing the procedure and utilizing the technique? METHODS: In a cohort of 87 patients, we investigated how/whether multiple patient variables impacted outcomes following single-level lumbar microdiscectomy. We studied whether early surgical intervention improved the patients' quality of life (QOL) versus late intervention. Furthermore, we assessed other variables that could influence patient-perceived improvement. Preoperatively and postoperatively, we additionally utilized the following internationally standardized questionnaires (EQ-5D, Oswestry, and Core Outcome Measures Index [COMI]). RESULTS: A generalized substantial improvement in QOL was identified throughout the cohort population (<0.05). There was no difference in health measurement scores for those undergoing early versus late surgery. However, there was a statistically significant improvement in all QOL scores for privately insured patients versus publicly insured patients (e.g., on COMI, EQ-5D, and ODI Scores). CONCLUSION: There was no objective statistically significant difference in QOL health scores between patients undergoing early versus late surgical lumbar microdiscectomy. This would suggest that the length of time patients is symptomatic before surgery did not significantly impact postoperative outcome. Of interest, however, was the difference in QOL health scores for private versus public patients suggesting that there are more subjective, complex, and psychosocial issues that influence outcome.

Deceptive Features on Surveillance Imaging of Intraneural Metastatic Deposits in Metastatic Renal Cell Cancer.

BACKGROUND: Spinal renal cell metastases are a common insidious pathological manifestation of the oncological process but less common are intramedullary and intraneural spinal metastases. The differential diagnosis of such pathological features can be difficult in the presence of conflicting radiological evidence. CASE DESCRIPTION: In the present case report, we have detailed the clinical, diagnostic, surgical, and therapeutic progression of a 54-year-old man diagnosed with metastatic renal cell carcinoma. After the initial presentation and treatment, he had presented with symptomatic right lower limb radiculopathy. Magnetic resonance imaging identified a well-defined cystic lesion expanding in the right exit foramina at L5-S1, suggestive of a benign schwannoma. After a multidisciplinary review, he was treated symptomatically and imaging surveillance for a 19-month period, with static lesion findings. Failure of symptomatic management resulted in operative intervention and subsequent histological diagnosis of the metastatic deposit. CONCLUSION: To the best of our knowledge, the present report is the first documented case of intraneural metastatic deposits from renal cell carcinoma that showed benign radiographic features and demonstrated a stable appearance on surveillance imaging studies for a significant period. These findings suggest that clinicians should have a high index of suspicion for a metastatic process in symptomatic patients with a known renal cell cancer regardless of the lesion's radiographic or temporal characteristics.

Intra-operative imaging for spinal level localisation in lumbar surgery.

Study Design: Retrospective review of the practice of 3 surgeons in a single centre during a 1-year period. Objective: We aimed to investigate our adherence to the Society of British Neurological Surgeons (SBNS) guidelines regarding intra-operative imaging during lumbar surgery and to determine if this has any impact on length of surgery or complications rates, in particular rates of wrong-level surgery. Background: The SBNS recommends three x-rays for intra-operative spinal localisation - one prior to incision, the second after exposure of the laminae and before the commencement of decompression, and the third at the end of the operation to confirm the adequacy of decompression. At our centre, surgeon A performs x-rays 1 and 3 routinely, and x-ray 2 in cases where the anatomy is uncertain, surgeon B performs x-ray 2 only, and the practice of surgeon C varies depending on the complexity of cases. Method: We reviewed the surgical logbooks of 3 consultant neurosurgeons in our centre for the 1-year period between October 2015 and October 2016. Our study included 301 patients who had undergone lumbar decompression or lumbar discectomy during this period. Results: There were no cases of wrong-level surgery. The incorrect spinal level was initially exposed in 13 cases (4.3%). 10 of these had x-ray 2 only, 1 had x-ray 1, 1 had x-rays 1 and 2, and 1 had all 3 x-rays. Surgeon B performed 8 of these cases, four were performed by surgeon C, and 1 by surgeon A. The median duration of surgery was 80 minutes for lumbar decompression and 67.5 minutes for lumbar discectomy. The median duration of surgery in patients in whom the wrong level was initially exposed was 85 minutes for lumbar decompression and 80 minutes for lumbar discectomy. Conclusion: Performance of the 3 recommended x-rays may increase the identification of wrong-level exposures before the commencement of decompression and may reduce the length of surgery.

(S)-N'-Nitrosonornicotine, a constituent of smokeless tobacco, is a powerful oral cavity carcinogen in rats.

Currently, smokeless tobacco products are being proposed as an alternative mode of tobacco use associated with less harm. All of these products contain the tobacco-specific carcinogen N'-nitrosonornicotine (NNN). The major form of NNN in tobacco products is (S)-NNN, shown in this study to induce a total of 89 benign and malignant oral cavity tumors in a group of 20 male F-344 rats treated chronically with 14 p.p.m. in the drinking water. The opposite enantiomer (R)-NNN was weakly active, but synergistically enhanced the carcinogenicity of (S)-NNN. Thus, (S)-NNN is identified for the first time as a strong oral cavity carcinogen in smokeless tobacco products and should be significantly reduced or removed from these products without delay in order to prevent debilitating and deadly oral cavity cancer in people who use them.

Reduction in colon cancer risk by consumption of kava or kava fractions in carcinogen-treated rats.

Epidemiological studies suggest that kava reduces colon cancer risk. However, no experimental studies of the chemopreventive properties of kava toward colon cancer have been reported. Further, there are concerns regarding hepatotoxicity of kava. The goal of this study was to determine whether kava consumption reduces markers of colon cancer in an animal model and to study the safety of kava. An ethanolic extract and polar and nonpolar fractions of the kava extract were fed to rats for 12 days prior to, during, and after administration of dimethylhydrazine, a colon-specific carcinogen. After 14 wk, rats fed the nonpolar extract had a significant reduction in precancerous lesions [aberrant crypt (AC) foci (ACF)] as well as large (≥ 4 AC/ACF) sialomucin-only expressing foci, an indicator of greater tumorigenic potential, compared to the control group. Groups fed the ethanolic extract and polar kava fraction trended toward reductions in ACF and large sialomucin-only expressing foci. The combined kava groups had significantly fewer total AC, ACF, large ACF, and large sialomucin-only expressing foci compared to the control group. Histological examination found no hepatic lesions in animals consuming the kava diets, suggesting that kava is safe to consume. Our results support that kava may reduce colon cancer risk.

Runx1 is a tumor suppressor gene in the mouse gastrointestinal tract.

The Runx1 transcription factor plays an important role in tissue homeostasis through its effects on stem/progenitor cell populations and differentiation. The effect of Runx1 on epithelial differentiation of the secretory cell lineage of the colon was recently demonstrated. This study aimed to examine the role of Runx1 in tumor development in epithelial cells of the gastrointestinal tract. Conditional knockout mice that lacked Runx1 expression in epithelial cells of the GI tract were generated. These mice were crossed onto the Apc(Min) background, killed and their intestinal tumor phenotypes were compared with Apc(Min) Runx1 wild-type control mice. Apc-wild-type Runx1-mutant mice were also examined for tumor development. Colons from Runx1 knockout and wild-type mice were used for genome-wide mRNA expression analyses followed by gene-specific quantitative RT-PCR of whole colon and colon epithelium to identify Runx1 target genes. Runx1 deficiency in intestinal epithelial cells significantly enhanced tumorigenesis in Apc(Min) mice. Notably, epithelial Runx1 deficiency in Apc-wild-type mice was sufficient to cause tumor development. Absence of Runx1 was associated with global changes in the expression of genes involved in inflammation and intestinal metabolism, and with gene sets indicative of a metastatic phenotype and poor prognosis. Gene-specific analysis of Runx1-deficient colon epithelium revealed increased expression of genes linked to an expansion of the stem/progenitor cell population. These results identify Runx1 as a novel tumor suppressor gene for gastrointestinal tumors and support a role for Runx1 in maintaining the balance between the intestinal stem/progenitor cell population and epithelial differentiation of the GI tract.

Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice.

Lung cancer is the most deadly malignancy in the US. Chemoprevention is potentially a complementary approach to smoking cessation for lung cancer control. Recently, we reported that a commercially available form of kava extract significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice at a dose of 10 mg per gram diet. In the present study, we examined the dose-dependent lung tumor inhibitory activities of kava and investigated potential active constituent(s). Mice treated with carcinogen alone contained 12.1±5.8 lung adenomas per mouse 22 weeks after final carcinogen administration. Mice that were fed diets containing kava at dosages of 1.25, 2.5, 5, and 10 mg/g of diet had 8.4±3.5, 6.6±3.5, 4.3±2.4, and 3.8±2.3 lung adenomas per mouse, respectively. This corresponds to a reduction of 31%, 46%, 65% and 69% in tumor multiplicity, which were all statistically significant (p < 0.05). Analyses of lung adenoma tissues derived from kava-treated animals revealed that kava significantly inhibited adenoma cell proliferation while it had no detectable effect on cell death, indicating that kava primarily suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation. Flavokawains A, B, and C, three chalcone-based components from kava, demonstrated greatly reduced chemopreventive efficacies even at concentrations much higher than their natural abundance, suggesting that they alone were unlikely to be responsible for kava's chemopreventive activity. Kava at all dosages and treatment regimens did not induce detectable adverse effects, particularly with respect to liver. Specifically, kava treatment showed no effect on liver integrity indicator enzymes or liver weight, indicating that kava may be potentially safe for long-term chemopreventive application.

Pla2g2a attenuates colon tumorigenesis in azoxymethane-treated C57BL/6 mice; expression studies reveal Pla2g2a target genes and pathways.

BACKGROUND: The group IIA secretory phospholipase A2 gene, Pla2g2a, confers resistance to intestinal tumorigenesis in the Apc(Min/+) mouse model. However, it is unclear how Pla2g2a exerts its tumor-suppressive effects and whether its mode of action depends on Apc-germline mutations. METHODS: We tested whether expression of a Pla2g2a transgene provides protection against carcinogen-induced colon tumors, and examined whether the normal colon microenvironment is modulated by Pla2g2a expression. RESULTS: Pla2g2a strongly inhibited colon tumorigenesis in mice following treatment with the DNA alkylating agent azoxymethane (AOM). Moreover, AOM-induced duodenal tumors were also attenuated by Pla2g2a expression. These tumors demonstrated upregulation of beta-catenin, indicative of involvement of the Wnt signaling pathway. Comparison of genome-wide microarray expression profiles of healthy (non-pathologic) colon tissues from Pla2g2a-transgenic to non-transgenic mice revealed 382 genes that were differentially expressed, comprising clusters of genes involved in inflammation and microbial defense, cell signaling and cell cycle, transactivation, apoptosis and mitochondrial function, DNA repair, and lipid and energy metabolism. Pathway analysis using Gene Set Enrichment Analysis (GSEA) indicated that Pla2g2a suppresses the expression of interferon-induced genes. CONCLUSION: Our results demonstrate that Pla2g2a attenuates colon tumorigenesis independent of Apc-germline mutations, and reveal Pla2g2a target genes and pathways in non-pathologic colon microenvironment that influence conditions for colorectal cancer development.

Effect of midazolam versus propofol sedation on markers of neurological injury and outcome after isolated severe head injury: a pilot study.

BACKGROUND: Midazolam and propofol are sedative agents commonly administered to patients with brain injury. We compared plasma concentrations of glial cell S100beta protein and nitric oxide (NO) between patients who received midazolam and those who received propofol sedation after severe brain injury, and investigated the association between S100beta and NO concentrations and neurological outcome. DESIGN: 28 patients with severe head injury (Glasgow Coma Score <9) who required sedation and ventilation were randomly assigned to receive midazolam (n =15) or propofol (n = 13) based sedation. Blood samples were drawn daily for 5 days for estimation of S100beta and NO concentrations. Neurological outcome was assessed 3 months later as good (Glasgow Outcome Score [GOS], 4-5) or poor (GOS, 1-3). RESULTS: A good neurological outcome was observed in 8/15 patients (53%) in the midazolam group and 7/13 patients (54%) in the propofol group. Patients with a poor outcome had higher serum S100beta concentrations on ICU admission and on Days 1-4 in the ICU than those with a good outcome (mean [SD] on Day 1, 0.99 [0.81] v 0.41 [0.4] microg/L; Day 2, 0.80 [0.81] v 0.41 [0.24] microg/L; Day 3, 0.52 [0.55] v 0.24 [0.25] microg/L; and Day 4, 0.54 [0.43] v 0.24 [0.35] microg/L; P<0.05). There was no significant difference on Day 5. Plasma NO concentrations were not associated with outcome. In subgroup analysis, there was no difference in S100beta and NO concentrations between patients with a good outcome versus those with a poor outcome in either the midazolam or propofol group. CONCLUSIONS: Plasma concentrations of markers of neurological injury in patients with severe head injury were similar in those who received midazolam sedation and those who received propofol. Patients who had a poor neurological outcome at 3 months had consistently higher serum S100beta concentrations during the initial 4 days after injury than patients who had a good outcome.

Epithelioid hemangioendothelioma of the spine. Report of two cases.

Epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin. The authors describe two cases of spinal EH, one involving the T-10 vertebra and the second involving the upper cervical spine. In the first case the patient underwent resection of the tumor; this case represents the longest reported follow-up period for spinal EH. In the second case, extensive involvement of C-2, C-3, and C-4 as well as encasement of both vertebral arteries precluded safe tumor resection, and posterior occipitocervical stabilization was performed. The patient subsequently died of metastatic disease. The findings in these two cases underscore the difficulty in predicting the clinical behavior of spinal EH based solely on histological and clinical features as well as the uncertainty of the roles of surgery, chemotherapy, and radiotherapy in the oncological management of a spinal tumor for which clinical data are very limited.