Microparticles Impair Hypotensive Cerebrovasodilation and Cause Hippocampal Neuronal Cell Injury after Traumatic Brain Injury.

Endothelin-1 (ET-1), tissue plasminogen activator (tPA), and extracellular signal-regulated kinases-mitogen activated protein kinase (ERK-MAPK) are mediators of impaired cerebral hemodynamics after fluid percussion brain injury (FPI) in piglets. Microparticles (MPs) are released into the circulation from a variety of cells during stress, are pro-thrombotic and pro-inflammatory, and may be lysed with polyethylene glycol telomere B (PEG-TB). We hypothesized that MPs released after traumatic brain injury impair hypotensive cerebrovasodilation and that PEG-TB protects the vascular response via MP lysis, and we investigated the relationship between MPs, tPA, ET-1, and ERK-MAPK in that process. FPI was induced in piglets equipped with a closed cranial window. Animals received PEG-TB or saline (vehicle) 30-minutes post-injury. Serum and cerebrospinal fluid (CSF) were sampled and pial arteries were measured pre- and post-injury. MPs were quantified by flow cytometry. CSF samples were analyzed with enzyme-linked immunosorbent assay. MP levels, vasodilatory responses, and CSF signaling assays were similar in all animals prior to injury and treatment. After injury, MP levels were elevated in the serum of vehicle but not in PEG-TB-treated animals. Pial artery dilation in response to hypotension was impaired after injury but protected in PEG-TB-treated animals. After injury, CSF levels of tPA, ET-1, and ERK-MAPK were all elevated, but not in PEG-TB-treated animals. PEG-TB-treated animals also showed reduction in neuronal injury in CA1 and CA3 hippocampus, compared with control animals. These results show that serum MP levels are elevated after FPI and lead to impaired hypotensive cerebrovasodilation via over-expression of tPA, ET-1, and ERK-MAPK. Treatment with PEG-TB after injury reduces MP levels and protects hypotensive cerebrovasodilation and limits hippocampal neuronal cell injury.

Lateral Transorbital Endoscopic Access to the Hippocampus, Amygdala, and Entorhinal Cortex: Initial Clinical Experience.

BACKGROUND/AIMS: Transorbital approaches traditionally have focused on skull base and cavernous sinus lesions medial to the globe. Lateral orbital approaches to the temporal lobe have not been widely explored despite several theoretical advantages compared to open craniotomy. Recently, we demonstrated the feasibility of the lateral transorbital technique in cadaveric specimens with endoscopic visualization. We describe our initial clinical experience with the endoscope-assisted lateral transorbital approach to lesions in the temporal lobe. METHODS: Two patients with mesial temporal lobe pathology presenting with seizures underwent surgery. The use of a transpalpebral or Stallard-Wright eyebrow incision enabled access to the intraorbital compartment, and a lateral orbital wall 'keyhole' opening permitted visualization of the anterior temporal pole. RESULTS: This approach afforded adequate access to the surgical target and surrounding structures and was well tolerated by the patients. To the best of our knowledge, this report constitutes the first case series describing the endoscope-assisted lateral transorbital approach to the temporal lobe. We discuss the limits of exposure, the nuances of opening and closing, and comparisons to open craniotomy. CONCLUSION: Further prospective investigation of this approach is warranted for comparison to traditional approaches to the mesial temporal lobe.

Fully endoscopic microvascular decompression for trigeminal neuralgia: technique review and early outcomes.

OBJECT: Fully endoscopicmicrovascular decompression (E-MVD) of the trigeminal nerve was initially described more than 1 decade ago, but has not yet gained wide acceptance. The authors present the experience of their first 47 consecutive E-MVDs for trigeminal neuralgia (TN). METHODS: All surgeries were performed by a single surgeon (J.Y.K.L.) at the Pennsylvania Hospital at the University of Pennsylvania. Patients prospectively completed pain scales before and after surgery by using the Brief Pain Inventory-Facial outcomes tool. All patients were called on the telephone, and the same outcome tool was administered without reference to their preoperative pain status. RESULTS: Forty-seven patients (17 men) were identified and enrolled. Forty (85%) had Burchiel Type 1 TN. Vascular compression was observed at surgery in 42 patients (89%). No surgery was aborted or converted to microscope. One patient suffered permanent hearing loss, for a permanent neurological morbidity rate of 2%. Overall improvement in pain outcomes was excellent, with a median maximum pain intensity preoperatively of 10 and postoperatively of 0 (p< 0.0001). The mean interference with global function scores were 6.2 preoperatively and reduced to 1.0 at last follow-up (p < 0.0001). The mean interference with facial function was 7.3 preoperatively and reduced to 1.2 at last follow-up (p < 0.0001). The mean follow-up period after surgery was 15 ± 8 months. CONCLUSIONS: In experienced hands, E-MVD offers superb visualization and illumination and is both safe and effective, at least in the short term. Further longer-term study is needed to compare E-MVD to traditional microscopic MVD.

Skull base chordoma and chondrosarcoma: influence of clinical and demographic factors on prognosis: a SEER analysis.

OBJECTIVE: Chordomas and chondrosarcomas are rare skull base tumors, with similar radiographic and clinical presentations. We investigated factors influencing long-term survival in these 2 tumors using the Surveillance Epidemiology and End Results (SEER) database. METHODS: Patients with chordoma (n = 416) and chondrosarcoma (n = 269) within the skull base from 1983 to 2009 were identified within the SEER database. Kaplan-Meier curves and Cox proportional hazards models were used to test associations with survival. t tests and χ(2) tests were used to compare groups. RESULTS: Chordoma and chondrosarcoma patients were similar demographically. Survival at 5 years was 65% for chordomas and 81.8% (P < 0.0001) for chondrosarcomas and at 10 years was 32.3% and 49.5% (P = 0.004). Multivariate analysis demonstrated chordomas had a worse prognosis even when we controlled for age and tumor size (hazard ratio 3.0, 95% confidence interval 1.9-4.7, P < 0.0001). For chordomas, multivariate analysis demonstrated increasing age and tumor size were significantly associated with reduced survival. For chondrosarcomas, multivariate analysis demonstrated older age, earlier decade of diagnosis, and mesenchymal subtype were significantly associated with reduced survival. Postoperative radiation was given to 42% and 41% of patients with chordomas and chondrosarcomas, respectively. The addition of radiation did not improve survival. CONCLUSION: Consistent with previous case series, skull base chordomas have significantly worse prognosis than chondrosarcomas. Patients in the SEER database had worse survival overall compared with existing case series for both chordomas and chondrosarcomas, suggesting selection bias in the existing literature.

Cerebrospinal fluid leaks and their management after anterior cervical discectomy and fusion: a report of 13 cases and a review of the literature.

STUDY DESIGN: Retrospective medical record review and literature review. OBJECTIVE: To identify cases where a cerebrospinal fluid (CSF) leak occurred during an anterior cervical discectomy and fusion (ACDF) and to create a management algorithm based on the findings. SUMMARY OF BACKGROUND DATA: ACDF is a commonly performed spinal operation. It is effective with very low complication rates. One rare complication of ACDF is a CSF leak. There is limited information on the management of CSF leaks after ACDF and management is on a surgeon-by-surgeon basis. METHODS: We reviewed 3 surgeons' case logs and identified cases where a CSF leak was encountered during ACDF and reviewed the patients' medical records, operative reports and imaging to determine how these leaks were managed. We also performed a PubMed search for articles about the presentation and management of CSF leaks after ACDF. RESULTS: Thirteen CSF leaks were identified in 1223 ACDFs, corresponding to a CSF leak rate of 1%. Of these, 9 were successfully treated with intraoperative repair. Postoperative lumbar drainage was used in the remaining 4 patients and was successful in 1 patient. Three patients underwent neck re-exploration and attempted delayed repair. Three patients, including one who was found to have hydrocephalus, ultimately required continuous CSF diversion via shunting. We identified 7 case reports of CSF leak in ADCF in the literature and 1 article that reviewed the prevalence and management of this complication. CONCLUSION: CSF leak after ACDF is an uncommon complication that can usually be repaired. We provide a stepwise management strategy for CSF leaks in ACDF.

Transorbital endoscopic amygdalohippocampectomy: a feasibility investigation.

OBJECT: Resection of the hippocampus is the standard of care for medically intractable epilepsy in patients with mesial temporal sclerosis. Although temporal craniotomy in this setting is highly successful, the procedure carries certain immutable risks and may be associated with cognitive deficits related to cortical and white matter disruption. Alternative surgical approaches may reduce some of these risks by preserving the lateral temporal lobe. This study examined the feasibility of transorbital endoscopic amygdalohippocampectomy (TEA) as an alternative to open craniotomy in cadaveric specimens. METHODS: TEA dissections were performed in 4 hemispheres from 2 injected cadaveric specimens fixed in alcohol. Quantitative predictions of the limits of exposure based on predissection imaging were compared with intradissection measurements. The extent of resection and angles of exposure during the dissection and on postdissection imaging were recorded. These measurements were validated with MRI studies from 10 epilepsy patients undergoing standard surgical evaluations. RESULTS: The transorbital approach permitted direct access to the mesial temporal structures through the lateral orbital wall. Up to 97% of the hippocampal formation was resected with no brain retraction and minimal (mean 6.0 ± 1.4 mm) globe displacement. Lateral temporal lobe white matter tracts were preserved. CONCLUSIONS: TEA permits hippocampectomy comparable to standard surgical approaches without disrupting the lateral temporal cortex or white matter. This novel approach is feasible in cadaveric specimens and warrants clinical investigation in carefully selected cases.

Fever and therapeutic normothermia in severe brain injury: an update.

PURPOSE OF REVIEW: Fever is common in the ICU among patients with severe brain injury. Fever has been consistently shown to exacerbate brain injuries in animal models and has been consistently associated with poor outcome in human studies. However, whether fever control improves outcome and the ideal means of fever control remain unknown. This review will address recent literature on the impact of fever on severe brain injury and on interventions to maintain normothermia. RECENT FINDINGS: Current guidelines generally recommend maintenance of normothermia after brain injury but have scant recommendations on methods to do this. Observational trials have continued to demonstrate the association between fever and poor outcome after severe brain injury. Recent trials have shown the efficacy of more aggressive approaches to fever reduction, whereas a large randomized trial showed the relative ineffectiveness of acetaminophen alone for fever control. Several studies have also described the impact of fever and of fever control on brain physiology. SUMMARY: The value of therapeutic normothermia in the neurocritical care unit (NCCU) is increasingly accepted, yet prospective trials that demonstrate a functional benefit to patients are lacking.

Contemporary neurosurgical techniques for pituitary tumor resection.

Approximately 5,000 trans-sphenoidal surgeries are performed for resection of pituitary tumors each year in the United States. The rise in popularity of the trans-spehnoidal approach, though described nearly a century ago, has been facilitated over the last decades by advances in technique and technology. In this review, we discuss the relative strengths of microscopic and endoscopic techniques for pituitary tumor resection. However, despite being the standard of care for patients with most pituitary tumors, cure rates for many subtypes of pituitary lesions, such as secretory macroadenomas or tumors with significant cavernous sinus invasion, remain unsatisfactory. We also describe two more recent advances in neurosurgical technique which may offer promise of increased rates of surgical cure: pseudocapsular resection and cavernous sinus approaches.

Decompressive craniectomy for management of traumatic brain injury: an update.

Decompressive craniectomy (DC) for the management of severe traumatic brain injury (TBI) has a long history but remains controversial. Although DC has been shown to improve both survival and functional outcome in patients with malignant cerebral infarctions, evidence of benefit in patients with TBI is decidedly more mixed. Craniectomy can clearly be life-saving in the presence of medically intractable elevations of intracranial pressure. Craniectomy also has been consistently demonstrated to reduce "therapeutic intensity" in the ICU, to reduce the need for intracranial-pressure-directed and brain-oxygen-directed interventions, and to reduce ICU length of stay. Still, the only randomized trial of DC in TBI failed to demonstrate any benefit. Studies of therapies for TBI, including hemicraniectomy, are challenging owing to the inherent heterogeneity in the pathophysiology observed in this disease. Craniectomy can be life-saving for patients with severe TBI, but many questions remain regarding its ideal application, and the outcome remains highly correlated with the severity of the initial injury.

Implementation of a departmental picture archiving and communication system: a productivity and cost analysis.

BACKGROUND: Digital radiology enhances productivity and results in long-term cost savings. However, the viewing, storage, and sharing of outside imaging studies on compact discs at ambulatory offices and hospitals pose a number of unique challenges to a surgeon's efficiency and clinical workflow. OBJECTIVE: To improve the efficiency and clinical workflow of an academic neurosurgical practice when evaluating patients with outside radiological studies. METHODS: Open-source software and commercial hardware were used to design and implement a departmental picture archiving and communications system (PACS). RESULTS: The implementation of a departmental PACS system significantly improved productivity and enhanced collaboration in a variety of clinical settings. Using published data on the rate of information technology problems associated with outside studies on compact discs, this system produced a cost savings ranging from $6250 to $33600 and from $43200 to $72000 for 2 cohorts, urgent transfer and spine clinic patients, respectively, therefore justifying the costs of the system in less than a year. CONCLUSION: The implementation of a departmental PACS system using open-source software is straightforward and cost-effective and results in significant gains in surgeon productivity when evaluating patients with outside imaging studies.

Response of brain oxygen to therapy correlates with long-term outcome after subarachnoid hemorrhage.

BACKGROUND: Brain oxygen (PbtO2) monitoring can help guide care of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients. The relationship between PbtO2-directed therapy and long-term outcome is unclear. We hypothesized that responsiveness to PbtO2-directed interventions is associated with outcome. METHODS: Seventy-six aSAH patients who underwent PbtO2 monitoring were included. Long-term outcome [Glasgow Outcome Score-Extended (GOS-E) and modified Rankin Scale (mRS)] was ascertained using the social security death database and structured telephone interviews. Univariate and multivariate regression were used to identify variables that correlated with outcome. RESULTS: Data from 64 patients were analyzed (12 were lost to follow-up). There were 530 episodes of compromised PbtO2 (<20 mmHg) during a total of 7,174 h of monitor time treated with 1,052 interventions. Forty-two patients (66 %) survived to discharge. Median follow-up was 8.5 months (range 0.1-87). At most recent follow-up 35 (55 %) patients were alive, and 28 (44 %) had a favorable outcome (mRS ≤3). In multivariate ordinal regression analysis, only age and response to PbtO2-directed intervention correlated significantly with outcome. Increased age was associated with worse outcome (coeff. 0.8, 95 % CI 0.3-1.3, p = 0.003), and response to PbtO2-directed intervention was associated with improved outcome (coeff. -2.12, 95 % CI -4.0 to -0.26, p = 0.03). Patients with favorable outcomes had a 70 % mean rate of response to PbtO2-directed interventions whereas patients with poor outcomes had a 45 % response rate (p = 0.005). CONCLUSIONS: Response to PbtO2-directed intervention is associated with improved long-term functional outcome in aSAH patients.

tPA-S(481)A prevents impairment of cerebrovascular autoregulation by endogenous tPA after traumatic brain injury by upregulating p38 MAPK and inhibiting ET-1.

Traumatic brain injury (TBI) is associated with loss of cerebrovascular autoregulation, which leads to cerebral hypoperfusion. Mitogen activated protein kinase (MAPK) isoforms ERK, p38, and JNK and endothelin-1 (ET-1) are mediators of impaired cerebral hemodynamics after TBI. Excessive tissue plasminogen activator (tPA) released after TBI may cause loss of cerebrovascular autoregulation either by over-activating N-methyl-D-aspartate receptors (NMDA-Rs) or by predisposing to intracranial hemorrhage. Our recent work shows that a catalytically inactive tPA variant (tPA-S(481)A) that competes with endogenous wild type (wt) tPA for binding to NMDA-R through its receptor docking site but that cannot activate it, prevents activation of ERK by wt tPA and impairment of autoregulation when administered 30 min after fluid percussion injury (FPI). We investigated the ability of variants that lack proteolytic activity but bind/block activation of NMDA-Rs by wt tPA (tPA-S(481)A), do not bind/block activation of NMDA-Rs but are proteolytic (tPA-A(296-299)), or neither bind/block NMDA-Rs nor are proteolytic (tPA-A(296-299)S(481)A) to prevent impairment of autoregulation after TBI and the role of MAPK and ET-1 in such effects. Results show that tPA-S(481)A given 3 h post-TBI, but not tPA-A(296-299) or tPA-A(296-299)S(481)A prevents impaired autoregulation by upregulating p38 and inhibiting ET-1, suggesting that tPA-S(481)A has a realistic therapeutic window and focuses intervention on NMDA-Rs to improve outcome.

Endoscopic versus open resection of tuberculum sellae meningiomas: a decision analysis.

BACKGROUND/AIMS: Tuberculum sellae meningiomas (TSMs) are challenging tumors for surgical resection. Endoscopic endonasal (EE) approaches to these lesions have not been directly compared to open craniotomy in a controlled trial. METHODS: We searched Medline and Embase online databases for English-language articles containing key words related to TSMs. Data were pooled, including 5 of our own patients reported here for the first time. Metaregression was used and a decision-analytical model was constructed to compare outcomes between open microsurgery and EE approaches. RESULTS: The overall quality of life (QOL) was not significantly different between the approaches (p = 0.410); however, there were large differences in individual complication rates. The Monte Carlo simulation yielded an overall average QOL in craniotomy patients of 0.915 and in endoscopic patients of 0.952. Endoscopy had a higher CSF leak rate (26.8 vs. 3.5%, p < 0.001) but a lower rate of injury to the optic apparatus (1.4 vs. 9.2%, p < 0.001) compared with craniotomy. The 3-year recurrence rates were not statistically different (p = 0.529). CONCLUSION: EE resection of TSMs appears to be a comparable alternative to traditional open microsurgical resection with respect to overall QOL based on available publications. A meaningful comparison of recurrence rates will require a longer follow-up.

Temporal dynamics of microparticle elevation following subarachnoid hemorrhage.

OBJECT: Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH. METHODS: On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden. RESULTS: When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)-, CD66b+(neutrophil)-, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])-associated MPs and CD146+(endothelial cell)-associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH. CONCLUSIONS: Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)-associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma.

Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFadden's ρ(2) = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (A(z) = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI-derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.

Medical management of compromised brain oxygen in patients with severe traumatic brain injury.

BACKGROUND: Brain tissue oxygen (PbtO(2)) monitoring is used in severe traumatic brain injury (TBI) patients. How brain reduced PbtO(2) should be treated and its response to treatment is not clearly defined. We examined which medical therapies restore normal PbtO(2) in TBI patients. METHODS: Forty-nine (mean age 40 ± 19 years) patients with severe TBI (Glasgow Coma Scale [GCS] ≤ 8) admitted to a University-affiliated, Level I trauma center who had at least one episode of compromised brain oxygen (PbtO(2) <25 mmHg for >10 min), were retrospectively identified from a prospective observational cohort study. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO(2) were monitored continuously. Episodes of compromised PbtO(2) and brain hypoxia (PbtO(2) <15 mmHg for >10 min) and the medical interventions that improved PbtO(2) were identified. RESULTS: Five hundred and sixty-four episodes of compromised PbtO2 were identified from 260 days of PbtO2 monitoring. Medical management used in a "cause-directed" manner successfully reversed 72% of the episodes of compromised PbtO(2), defined as restoration of a "normal" PbtO(2) (i.e. ≥ 25 mmHg). Ventilator manipulation, CPP augmentation, and sedation were the most frequent interventions. Increasing FiO(2) restored PbtO(2) 80% of the time. CPP augmentation and sedation were effective in 73 and 66% of episodes of compromised brain oxygen, respectively. ICP reduction using mannitol was effective in 73% of treated episodes, though was used only when PbtO(2) was compromised in the setting of elevated ICP. Successful medical treatment of brain hypoxia was associated with decreased mortality. Survivors (n = 38) had a 71% rate of response to treatment and non-survivors (n = 11) had a 44% rate of response (P = 0.01). CONCLUSION: Reduced PbtO(2) may occur in TBI patients despite efforts to maintain CPP. Medical interventions other than those to treat ICP and CPP can improve PbtO(2). This may increase the number of therapies for severe TBI in the ICU.

Magnetic resonance imaging characteristics of glioblastoma multiforme: implications for understanding glioma ontogeny.

BACKGROUND: Identifying the origin of gliomas carries important implications for advancing the treatment of these recalcitrant tumors. Recent research promotes the hypothesis of a subventricular zone (SVZ) origin for the stemlike gliomagenic cells identified within human glioma specimens. However, conflicting evidence suggests that SVZ-like cells are not uniquely gliomagenic but this capacity may be shared by cycling progenitors distributed throughout the subcortical white matter (SCWM). OBJECTIVE: To review radiological evidence in glioblastoma multiforme (GBM) patients to provide insight into the question of glioma ontogeny. METHODS: We explored whether GBMs at first diagnosis demonstrated a pattern of anatomic distribution consistent with origin at the SVZ through retrospective analysis of preoperative contrast-enhanced T1-weighted magnetic resonance images in 63 patients. We then examined the relationship of tumor volume, point of origin, and proximity to the ventricles using a computer model of glioma growth. RESULTS: Fewer than half of the GBMs analyzed had contrast-enhancing portions that contacted the ventricle on preoperative imaging. A strong correlation was found between tumor volume and the distance between the contrast-enhancing edge of the tumor and the ventricle, demonstrating that tumors abutting the ventricle are significantly larger than those that do not. The lesions simulated by the computer model validated our assumption that tumors that are radiographically distant from the ventricles are unlikely to have originated in the SVZ and supported our hypothesis that as they grow, the edges of all tumors will near the ventricles, regardless of their point of origin. CONCLUSION: This work offers further support for the hypothesis that the origins of GBMs are at sites distributed throughout the white matter and are not limited to the region of the SVZ.

The survival impact of postoperative infection in patients with glioblastoma multiforme.

OBJECTIVE: The capacity for local infection to prolong survival in patients with cancer is a widely accepted but unsubstantiated principle. The neurosurgical literature contains anecdotal reports of patients with malignant gliomas who experienced prolonged remission of their tumors after a bacterial infection. This association has not been explored in a larger series of patients with malignant glioma with postoperative infections. METHODS: A single-center operative experience accumulated over 10 years was examined to evaluate whether postoperative infections conferred a survival advantage in patients with glioblastoma multiforme. A total of 382 patients were examined, and 18 bacterial infections were identified. The vast majority (17 cases, 94%) of these were gram-positive infections. Cases were compared with age-matched controls. Survival differences were evaluated using Kaplan-Meier curves, and other differences were tested using the Mann-Whitney U test. RESULTS: Cases and controls were younger and survived longer than the overall study sample, but cases and controls were similar at baseline. A moderate, statistically insignificant survival advantage was seen in the case group (Kaplan-Meier P = 0.27). However, when patients with infections in the first quarter and first half of their postoperative survival were examined, this survival advantage disappeared. There was no significant survival difference in any subgroup analyzed, including deep infections, bone flap infections, or infections caused by any specific organism. CONCLUSION: In this single-center study, postoperative infection did not confer any survival advantage in patients with glioblastoma multiforme.

Comparison of endoscopic and microscopic removal of pituitary adenomas: single-surgeon experience and the learning curve.

OBJECT: The endoscopic endonasal approach for resection of pituitary lesions is an effective surgical option for tumors of the sella turcica. In this study the authors compared outcomes after either purely endoscopic resection or traditional microscope-aided resection. They also attempted to determine the learning curve associated with a surgical team converting to endoscopic techniques. METHODS: Retrospective data were collected on patients who were surgically treated for a pituitary lesion at the Hospital of the University of Pennsylvania between July 2003 and May 2008. Age, sex, race, presenting symptoms, length of hospital stay, surgical approach, duration of surgery, tumor pathological features, gross-total resection (GTR) of tumor, recurrence of the lesion, and intraoperative and postoperative complications were noted. All procedures were performed by the same senior neurosurgeon, who was initially unfamiliar with the endoscopic endonasal approach. RESULTS: A total of 25 patients underwent microscopic resection and 25 patients underwent endoscopic resection performed by a single skull base team consisting of the same senior neurosurgeon and otorhinolaryngologist (M.S.G. and B.W.O.). In the microscopically treated cohort, there were 8 intra- or postoperative complications, 6 intraoperative CSF leaks, 17 (77%) of 22 patients had GTR on postoperative imaging, 5 patients underwent >or= 2 operations, and 10 (59%) of 17 patients reported total symptom resolution at follow-up. The endoscopically treated group had 7 intraor postoperative complications and 7 intraoperative CSF leaks. Of the patients who had pre- and postoperative imaging studies, 14 (66%) of 21 endoscopically treated patients had GTR; 4 patients had >or= 2 operations, and 10 (66%) of 15 patients reported complete symptom resolution at follow-up. The first 9 patients who were treated endoscopically had a mean surgical time of 3.42 hours and a mean hospital stay of 4.67 days. The next 8 patients treated had a mean surgical time of 3.11 hours and a mean hospital stay of 3.13 days. The final 8 patients treated endoscopically had a mean surgical time of 2.22 hours and a mean hospital stay of 3.88 days. The difference in length of operation between the first 9 and the last 8 patients treated endoscopically was significantly different. There was a trend toward decreased CSF leaks and other complications from the first 2 groups compared with the third group. CONCLUSIONS: In this subset of patients, the use of endoscopic endonasal resection results in a similar complication and symptom resolution rate compared with traditional techniques. The authors postulate that the learning curve for endoscopic resection can be

Surgical treatment of moyamoya syndrome in patients with sickle cell anemia: outcome following encephaloduroarteriosynangiosis.

OBJECTIVES: Children with sickle cell anemia (SCA) and moyamoya syndrome carry a significant risk of ischemic stroke. Given the success of encephaloduroarteriosynangiosis (EDAS) or pial synangiosis in the treatment of moyamoya disease, the purpose of this study was to examine whether it reliably and durably protected children with SCA and moyamoya syndrome against cerebrovascular complications. METHODS: The authors retrospectively reviewed a series of 12 patients with SCA who developed clinical and/or radiological evidence of moyamoya syndrome and underwent EDAS. RESULTS: Eleven patients (92%) presented following a cerebrovascular accident (CVA), transient ischemic attack (TIA), or seizure. Magnetic resonance (MR) imaging or angiography suggested moyamoya vascular changes, and cerebral angiography confirmed the diagnosis in all 12 patients. At the time of surgery, the median age was 12.3 years (range 6.8-19.4 years). Ten (83%) of 12 patients had a history of CVA, and 4 of these patients were compliant with a transfusion protocol at the time of their CVA. Bilateral (7 patients) or unilateral (5 patients) EDAS was performed without complications. The mean follow-up period was 46.8 months (range 8.1-106 months). During the follow-up period, 2 patients (16.7%) suffered cerebrovascular events. One patient, who was stroke-free preoperatively, suffered a CVA 3 weeks after the procedure. The other patient suffered a single left lower-extremity TIA 18 months following right-sided EDAS. She returned to her neurological baseline condition and remains stable 53 months postoperatively. Seven patients underwent follow-up angiography or MR angiography, and evidence of revascularization was noted in all cases. At this time, no patient has developed progressive disease requiring a contralateral procedure after unilateral EDAS. CONCLUSIONS: The EDAS procedure is a safe and effective treatment option in patients with SCA who develop moyamoya syndrome.