Neurosurgical management of adult diffuse low grade gliomas in Canada: a multi-center survey.

Adult diffuse low-grade gliomas are slow growing, World Health Organization grade II lesions with insidious onset and ultimate anaplastic transformation. The timing of surgery remains controversial with polarized practices continuing to govern patient management. As a result, the management of these patients is variable. The goal of this questionnaire was to evaluate practice patterns in Canada. An online invitation for a questionnaire including diagnostic, preoperative, perioperative, and postoperative parameters and three cases with magnetic resonance imaging data with questions to various treatment options in these patients was sent to practicing neurosurgeons and trainees. Survey was sent to 356 email addresses with 87 (24.7%) responses collected. The range of years of practice was less than 10 years 36% (n = 23), 11-20 years 28% (n = 18), over 21 years 37% (n = 24). Twenty-two neurosurgery students of various years of training completed the survey. 94% (n = 47) of surgeons and trainees (n = 20) believe that we do not know the "right treatment". 90% of surgeons do not obtain formal preoperative neurocognitive assessments. 21% (n = 13) of surgeons and 23% of trainees (n = 5) perform a biopsy upon first presentation. A gross total resection was believed to increase progression free survival (surgeons: 75%, n = 46; trainees: 95%, n = 21) and to increase overall survival (surgeons: 64%, n = 39, trainees: 68%, n = 15). Intraoperative MRI was only used by 8% of surgeons. Awake craniotomy was the procedure of choice for eloquent tumors by 80% (n = 48) of surgeons and 100% of trainees. Of those surgeons who perform awake craniotomy 93% perform cortical stimulation and 38% performed subcortical stimulation. Using the aid of three hypothetical cases with progressive complexities in tumor eloquence there was a trend for younger surgeons to operate earlier, and use awake craniotomy to obtain greater extent of resection with the aid of cortical stimulation when compared to senior surgeons who still more often preferred a "wait-and-see" approach. Despite the limitations of an online survey study, it has offered insights into the variability in surgeon practice patterns in Canada and the need for a consensus on the workup and surgical management of this disease.

The role of left inferior fronto-occipital fascicle in verbal perseveration: a brain electrostimulation mapping study.

The subcortical connectivity underlying verbal perseveration (VP) remains poorly understood. We have previously reported that intraoperative electrical stimulation of the caudate nucleus during awake surgery resulted in VP. Here, our purpose is to study the white matter pathway underlying VP using subcortical stimulation mapping in a series of patients who underwent glioma resection. Eleven patients with a left hemispheric low grade glioma were operated on while awake. Intraoperative direct electrical stimulation was used both at cortical and subcortical levels while the patients carried out motor and naming tasks during the resection. All patients experienced VP during electrical stimulation performed at the level of different subcortical locations, which corresponded in the 11 cases to different parts of the left inferior fronto-occipital fascicle. Perseveration persisted into the postoperative days, but resolved completely by three months.Our original findings provide further insight into the neuroanatomical basis of VP, by supporting the role of left inferior fronto-occipital fascicle. Such data may have both fundamental and clinical implications.

Endoscopic endonasal resection of skull base meningiomas: the significance of a "cortical cuff" and brain edema compared with careful case selection and surgical experience in predicting morbidity and extent of resection.

OBJECT: This paper describes a consecutive series of skull base meningiomas resected using an endoscopic endonasal approach through various corridors at a single institution over 7 years. The impact of case selection and experience, the presence of a cortical cuff between the tumor and surrounding vessels, and brain edema on morbidity and rates of gross-total resection (GTR) were examined. METHODS: A retrospective review of a series of 46 skull base meningiomas from a prospective database was conducted. The series of cases were divided by location: olfactory groove (n = 15), tuberculum and planum (n = 20), sellar/cavernous (n = 9) and petroclival (n = 2). Gross-total resection was never intended in the sellar/cavernous tumors, which generally invaded the cavernous sinus. Clinical charts, volumetric imaging, and pathology were reviewed to assess the extent of resection and complications. Cases were divided based on a time point in which surgical technique and case selection improved into Group 1 (surgery prior to June 2008; n = 21) and Group 2 (surgery after June 2008; n = 25) and into those with and without a cortical cuff and with and without brain edema. RESULTS: Improved case selection had the greatest impact on extent of resection. For the entire cohort, rates of GTR went from 38% to 76% (p = 0.02), and for cases in which GTR was the intent, the rates went from 63% to 84% (not significant), which was mostly driven by the planum and tuberculum meningiomas, which went from 75% to 91.7 % (nonsignificant difference). The presence of a cortical cuff and brain edema had no impact on outcomes. There were 3 CSF leaks (6.5%) but all were in Group 1. Hence, CSF leak improved from 14.2% to 0% with surgical experience. Lessons learned for optimal case selection are discussed. CONCLUSIONS: Surgical outcome for endonasal endoscopic resection of skull base meningiomas depends mostly on careful case selection and surgical experience. Imaging criteria such as the presence of a cortical cuff or brain edema are less important.

Predictors of salvage therapy for parasagittal meningiomas treated with primary surgery, radiosurgery, or surgery plus adjuvant radiotherapy.

OBJECTIVE: Parasagittal meningiomas (PM) are treated with primary microsurgery, radiosurgery (SRS), or surgery with adjuvant radiation. We investigated predictors of tumor progression requiring salvage surgery or radiation treatment. We sought to determine whether primary treatment modality, or radiologic, histologic, and clinical variables were associated with tumor progression requiring salvage treatment. METHODS: Retrospective study of 109 consecutive patients with PMs treated with primary surgery, radiation (RT), or surgery plus adjuvant RT (2000-2017) and minimum 5 years follow-up. Patient, radiologic, histologic, and treatment data were analyzed using standard statistical methods. RESULTS: Median follow up was 8.5 years. Primary treatment for PM was surgery in 76 patients, radiation in 16 patients, and surgery plus adjuvant radiation in 17 patients. Forty percent of parasagittal meningiomas in our cohort required some form of salvage treatment. On univariate analysis, brain invasion (OR: 6.93, p < 0.01), WHO grade 2/3 (OR: 4.54, p < 0.01), peritumoral edema (OR: 2.81, p = 0.01), sagittal sinus invasion (OR: 6.36, p < 0.01), sagittal sinus occlusion (OR: 4.86, p < 0.01), and non-spherical shape (OR: 3.89, p < 0.01) were significantly associated with receiving salvage treatment. On multivariate analysis, superior sagittal sinus invasion (OR: 8.22, p = 0.01) and WHO grade 2&3 (OR: 7.58, p < 0.01) were independently associated with receiving salvage treatment. There was no difference in time to salvage therapy (p = 0.11) or time to progression (p = 0.43) between patients receiving primary surgery alone, RT alone, or surgery plus adjuvant RT. Patients who had initial surgery were more likely to have peritumoral edema on preoperative imaging (p = 0.01). Median tumor volume was 19.0 cm3 in patients receiving primary surgery, 5.3 cm3 for RT, and 24.4 cm3 for surgery plus adjuvant RT (p < 0.01). CONCLUSION: Superior sagittal sinus invasion and WHO grade 2/3 are independently associated with PM progression requiring salvage therapy regardless of extent of resection or primary treatment modality. Parasagittal meningiomas have a high rate of recurrence with 80.0% of patients with WHO grade 2/3 tumors with sinus invasion requiring salvage treatment whereas only 13.6% of the WHO grade 1 tumors without sinus invasion required salvage treatment. This information is useful when counseling patients about disease management and setting expectations.

Building Team Medicine in the Management of CNS Metastases.

CNS metastases are often terminal for cancer patients and occur at an approximately 10-fold higher rate than primary CNS tumors. The incidence of these tumors is approximately 70,000-400,000 cases annually in the US. Advances that have occurred over the past two decades have led to more personalized treatment approaches. Newer surgical and radiation techniques, as well as targeted and immune therapies, have enanled patient to live longer, thus increasing the risk for the development of CNS, brain, and leptomeningeal metastases (BM and LM). Patients who develop CNS metastases have often been heavily treated, and options for future treatment could best be addressed by multidisciplinary teams. Studies have indicated that patients with brain metastases have improved survival outcomes when cared for in high-volume academic institutions using multidisciplinary teams. This manuscript discusses a multidisciplinary approach for both parenchymal brain metastases as well as leptomeningeal metastases implemented in three academic institutions. Additionally, with the increasing development of healthcare systems, we discuss optimizing the management of CNS metastases across healthcare systems and integrating basic and translational science into our clinical care to further improve outcomes. This paper summarizes the existing therapeutic approaches to the treatment of BM and LM and discusses novel and emerging approaches to optimizing access to neuro-oncologic care while simultaneously integrating multidisciplinary teams in the care of patients with BM and LM.

Secondary CNS myeloma with remission after systemic CNS-penetrating agents.

Background: CNS myeloma is a rare manifestation of multiple myeloma and is often associated with a dismal prognosis; however, cases are increasing in frequency as overall survival improves for MM. There is currently no standardized treatment for CNS myeloma; however, different chemotherapy and radiotherapy regimens have been described. Methods: We had previously reported on the efficacy of proton-based craniospinal irradiation in a patient with CNS myeloma; here we present a patient with a history of extramedullary plasmacytoma, 10 years in remission status post standard systemic chemotherapy, with biopsy-proven CNS myeloma successfully treated with systemic chemotherapy as a first-line treatment. Results: The patient achieved clinical and radiographic remission on 2 separate occasions with systemic chemotherapy alone. Conclusions: This case demonstrates that systemically administered agents may have activity in CNS myeloma. Further investigations are necessary to establish the optimal combination of agents and treatment schedules.

Practice patterns in the management of recurrent and residual non-functioning pituitary adenomas: Results from a Canada-wide survey.

BACKGROUND: There is no consensus regarding the management and postoperative follow-up of non-functioning pituitary adenomas (NFAs) in the setting of recurrent or residual disease. Subsequent treatment options include continued follow-up, re-resection or radiotherapy. To address this gap and better understand current practice patterns, we surveyed neurosurgeons and radiation oncologists in Canada. METHODS: Neurosurgeons and radiation oncologists (ROs) across Canada were invited to complete a standardized online questionnaire. Summary statistics were computed, and Fisher's Exact tests were performed to assess significance. Qualitative analyses were performed through open and axial coding. RESULTS: Thirty-three participants completed the questionnaires, with neurosurgeons representing a majority of respondents (n = 20 vs n = 13). When treating giant (>3 cm) tumors, 90.9% of neurosurgeons in practice for less than 10 years reported using an endoscopic approach, as compared to only 66.7% of neurosurgeons in practice for 10 years of more. Additionally, neurosurgeons who were newer to practice had a greater tendency to advocate for stereotactic radiosurgery (SRS) or re-resection (54.5% and 36.4%, respectively), as compared to older surgeons who showed a higher propensity (22.2%) to advocate for observation. The presence of cavernous sinus extension appeared to encourage ROs to offer radiotherapy sooner (61.4%), as compared to 40% of neurosurgeons. CONCLUSIONS: Our results identified both variations and commonalities in practice amongst Canadian neurosurgeons. Approaches deviated in the setting of residual tumor based on years of practice. This work provides a critical foundation for future studies aiming to define evidence-based best practices in the management of NFAs.

Unilateral Lumbar Facet Dislocation: Case Report and Review of the Literature.

BACKGROUND: Facet dislocations of the lumbar spine, particularly without neurologic injury, are rare occurrences after major trauma. Although there are documented cases of lumbosacral dislocation in the published literature, strictly lumbar unilateral facet dislocation is rare. CASE DESCRIPTION: We report a case of a unilateral facet dislocation at L4-L5 after a single vehicle motorcycle accident. This injury was treated with posterior open reduction and instrumented stabilization with good results. CONCLUSIONS: Given the rarity of this injury pattern, the management of this type of injury is not established. Careful imaging to make the diagnosis is crucial, and we recommend a surgical treatment in the form of an open reduction and instrumented stabilization. In our case, we achieved good outcomes with a posterior approach.

Whole-Brain Radiotherapy for Brain Metastases: Evolution or Revolution?

An estimated 20% of patients with cancer will develop brain metastases. Approximately 200,000 individuals in the United States alone receive whole-brain radiotherapy (WBRT) each year to treat brain metastases. Historically, the prognosis of patients with brain metastases has been poor; however, with new therapies, this is changing. Because patients are living longer following the diagnosis and treatment of brain metastases, there has been rising concern about treatment-related toxicities associated with WBRT, including neurocognitive toxicity. In addition, recent clinical trials have raised questions about the use of WBRT. To better understand this rapidly changing landscape, this review outlines the treatment roles and toxicities of WBRT and alternative therapies for the management of brain metastases.

Calcium antagonism in neonatal rats with kaolin-induced hydrocephalus.

Juvenile rats with kaolin-induced hydrocephalus have reduced brain injury if treated with nimodipine or magnesium sulfate. Experiments were conducted to determine if the neuroprotective effects could be replicated in neonatal rats with experimental hydrocephalus at an age comparable to prematurely born humans. In a blinded and randomized manner, drugs were administered for 14 days beginning 7 days after induction of hydrocephalus. Nimodipine was given twice daily by subcutaneous injections. Daily doses greater than 38 mg/kg of body weight were fatal. Daily doses of 3.8 to 30 mg/kg were not associated with behavioral, structural, or biochemical improvements. Magnesium chloride was administered via daily subcutaneous minipump infusion (0.87 or 1.74 mM/kg) along with twice daily injections of 0.74 or 1.48 mM/kg. Magnesium sulfate was administered by twice daily subcutaneous doses of 1.54 or 7.72 mM/kg. Sedation occurred, but there was no statistically significant protection in regard to behavior, brain structure, or brain composition in any of the magnesium experiments. Developmental alterations in calcium channels of the neonatal rat brain could account for differences from prior experiments in young hydrocephalic rats.

Draf III Extension in the Endoscopic Endonasal Transethmoidal, Transcribriform Approach Through the Back Wall of the Frontal Sinus: A Cadaveric Study.

BACKGROUND: The Draf III (modified endoscopic Lothrop) procedure has been proposed to extend the endonasal transethmoidal, transfovea ethmoidalis, and transcribriform approach through the back wall of the frontal sinus. The exposure is time-consuming and increases the risk of cerebrospinal fluid leak, and the indications for use are not well described. There are few data quantifying the advantage it conveys over the approach without the Draf III procedure. METHODS: An endoscopic, endonasal transfovea, transcribriform approach was performed in 5 fresh, injected cadaveric heads. Anatomic boundaries and measurements of the exposure were compared before and after addition of a Draf III procedure. Computed tomography scans were performed before and after dissection, and additional radiographic measurements were made to quantify the additional exposure provided by the Draf III procedure. Also, 2 clinical cases are presented in which a Draf III procedure was used. RESULTS: The mean anterior to posterior boundary from the frontal sinus to the planum sphenoidale before the Draf III procedure was 3.0 cm and after the Draf III procedure was 3.8 cm with an average change of 0.8 cm. After the Draf III procedure, the mean anterior to posterior boundary from the posterior wall of frontal sinus to the planum sphenoidale increased from 3.0 cm to 4.3 cm. There was an average increase of 1.3 cm with an average increased area of view of 1.79 cm(2). CONCLUSIONS: This study quantifies the increased field of view provided by the Draf III procedure during anterior skull base dissection. Recommendations for preoperative examination of radiographic evidence are provided to help identify which individuals would benefit from the additional exposure.

Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non-skull base meningiomas.

OBJECTIVE The objective of this study was to identify the natural history and clinical predictors of postoperative recurrence of skull base and non-skull base meningiomas. METHODS The authors performed a retrospective hospital-based study of all patients with meningioma referred to their institution from September 1993 to January 2014. The cohort constituted both patients with a first-time presentation and those with evidence of recurrence. Kaplan-Meier curves were constructed for analysis of recurrence and differences were assessed using the log-rank test. Cox proportional hazard regression was used to identify potential predictors of recurrence. RESULTS Overall, 398 intracranial meningiomas were reviewed, including 269 (68%) non-skull base and 129 (32%) skull base meningiomas (median follow-up 30.2 months, interquartile range [IQR] 8.5-76 months). The 10-year recurrence-free survival rates for patients with gross-total resection (GTR) and subtotal resection (STR) were 90% and 43%, respectively. Skull base tumors were associated with a lower proliferation index (0.041 vs 0.062, p = 0.001), higher likelihood of WHO Grade I (85.3% vs 69.1%, p = 0.003), and younger patient age (55.2 vs 58.3 years, p = 0.01). Meningiomas in all locations demonstrated an average recurrence rate of 30% at 100 months of follow-up. Subsequently, the recurrence of skull base meningiomas plateaued whereas non-skull base lesions had an 80% recurrence rate at 230 months follow-up (p = 0.02). On univariate analysis, a prior history of recurrence (p < 0.001), initial WHO grade following resection (p < 0.001), and the inability to obtain GTR (p < 0.001) were predictors of future recurrence. On multivariate analysis a prior history of recurrence (p = 0.02) and an STR (p < 0.01) were independent predictors of a recurrence. Assessing only patients with primary presentations, STR and WHO Grades II and III were independent predictors of recurrence (p < 0.001 for both). CONCLUSIONS Patients with skull base meningiomas present at a younger age and have less aggressive lesions overall. Extent of resection is a key predictor of recurrence and long-term follow-up of meningiomas is necessary, especially for non-skull base tumors. In skull base meningiomas, recurrence risk plateaus approximately 100 months after surgery, suggesting that for this specific cohort, follow-up after 100 months can be less frequent.

Serum lactate as a potential biomarker of malignancy in primary adult brain tumours.

Lactate, a by-product of glycolysis, is an indicator of poor tissue perfusion and is a useful biomarker with prognostic value in risk-stratifying patients in several diseases. Furthermore, elevated lactate production is observed in tumour glycolysis, also known as the Warburg effect, and is essential in promoting tumour cell invasion, metastasis, and immune system evasion, promoting resistance to cell death. However, there are no studies of elevated serum lactate in brain tumour patients as a potential biomarker, to our knowledge. The aim of this study is to determine possible correlations between the malignancy of tumours and pre- and intraoperative serum lactate elevation in patients undergoing craniotomy for tumour resection. We provide initial evidence that a rise in serum lactate can be used as a non-invasive biomarker that correlates with brain tumour grade. The results from this study and future prospective studies may allow for determination of tumour progression and response to therapy using serum lactate as a biomarker.

Endoscopic endonasal resection of suprasellar meningiomas: the importance of case selection and experience in determining extent of resection, visual improvement, and complications.

OBJECTIVE: Suprasellar meningiomas have been resected via various open cranial approaches. During the past 2 decades, the endoscopic endonasal approach has been shown to be an option in selected patients. We wished to examine the learning curve for parameters such as extent of resection, visual outcome, and complications. METHODS: We retrospectively reviewed a consecutive series of patients in whom suprasellar meningiomas were resected via an endonasal endoscopic approach between 2005 and 2013 at our institution. After June 2008, our surgical technique matured. Using this time point, we divided our case series into 2 chronological groups, group 1 (n=8) and group 2 (n=12). This cut-off also was used to examine rates of gross total resection (GTR) and visual improvement. Case selection criteria in successful and unsuccessful cases were examined to determine important principals for case selection. RESULTS: Mean patient age at surgery was 57.05 years (range, 31-81 years). Mean tumor volume was 11.98 cm3 (range, 0.43-28.93 cm3). Overall, GTR was achieved in 80%, and vision improved or normalized in 14 patients (82.4%) with no occurrence of postoperative visual deterioration. Rates of GTR increased from 62.5% (group 1) to 91.7% (group 2). Visual improvement increased from 75% (group 1) to 88.9% (group 2). Rates of cerebrospinal fluid leak were 25% in group 1 and 0% in group 2. Average follow-up was 51.5 month (range, 3-96 months). CONCLUSION: Once the learning curve is overcome, surgeons performing endonasal endoscopic resection of suprasellar meningiomas can achieve high rates of GTR with low complication rates in well-selected cases.

Pediatric awake craniotomy and intra-operative stimulation mapping.

The indications for operating on lesions in or near areas of cortical eloquence balance the benefit of resection with the risk of permanent neurological deficit. In adults, awake craniotomy has become a versatile tool in tumor, epilepsy and functional neurosurgery, permitting intra-operative stimulation mapping particularly for language, sensory and motor cortical pathways. This allows for maximal tumor resection with considerable reduction in the risk of post-operative speech and motor deficits. We report our experience of awake craniotomy and cortical stimulation for epilepsy and supratentorial tumors located in and around eloquent areas in a pediatric population (n=10, five females). The presenting symptom was mainly seizures and all children had normal neurological examinations. Neuroimaging showed lesions in the left opercular (n=4) and precentral or peri-sylvian regions (n=6). Three right-sided and seven left-sided awake craniotomies were performed. Two patients had a history of prior craniotomy. All patients had intra-operative mapping for either speech or motor or both using cortical stimulation. The surgical goal for tumor patients was gross total resection, while for all epilepsy procedures, focal cortical resections were completed without any difficulty. None of the patients had permanent post-operative neurologic deficits. The patient with an epileptic focus over the speech area in the left frontal lobe had a mild word finding difficulty post-operatively but this improved progressively. Follow-up ranged from 6 to 27 months. Pediatric awake craniotomy with intra-operative mapping is a precise, safe and reliable method allowing for resection of lesions in eloquent areas. Further validations on larger number of patients will be needed to verify the utility of this technique in the pediatric population.

Pure endoscopic expanded endonasal approach for olfactory groove and tuberculum sellae meningiomas.

The expanded endoscopic endonasal (EEE) approach for the removal of olfactory groove (OGM) and tuberculum sellae (TSM) meningiomas is currently becoming an acceptable surgical approach in neurosurgical practice, although it is still controversial with respect to its outcomes, indications and limitations. Here we provide a review of the available literature reporting results with use of the EEE approach for these lesions together with our experience with the use of the endoscope as the sole means of visualization in a series of patients with no prior surgical biopsy or resection. Surgical cases between May 2006 and January 2013 were retrospectively reviewed. Twenty-three patients (OGM n=6; TSM n=17) were identified. In our series gross total resection (GTR) was achieved in 4/6 OGM (66.7%) and 11/17 (64.7%) TSM patients. Vision improved in the OGM group (2/2) and 8/11 improved in the TSM group with no change in visual status in the remaining three patients. Post-operative cerebrospinal fluid (CSF) leak occurred in 2/6 (33%) OGM and 2/17 (11.8%) TSM patients. The literature review revealed a total of 19 OGM and 174 TSM cases which were reviewed. GTR rate was 73% for OGM and 56.3% for TSM. Post-operative CSF leak was 30% for OGM and 14% for TSM. With careful patient selection and a clear understanding of its limitations, the EEE technique is both feasible and safe. However, longer follow-ups are necessary to better define the appropriate indications and ideal patient population that will benefit from the use of these newer techniques.

Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas: institutional experience and predictors of extent of resection.

UNLABELLED: OBJECT.: While the use of endoscopic approaches has become increasingly accepted in the resection of pituitary adenomas, limited evidence exists regarding the success of this technique for patients with large and giant pituitary adenomas. This study reviews the outcomes of a large cohort of patients with large and giant pituitary adenomas who underwent endoscopic endonasal transsphenoidal surgery at the authors' institution and focuses on identifying factors that can predict extent of resection and hence aid in developing guidelines and indications for the use of endoscopic endonasal transsphenoidal surgery versus open craniotomy approaches to large and giant pituitary adenomas. METHODS: The authors reviewed 487 patients who underwent endoscopic endonasal transsphenoidal resection of sellar masses. From this group, 73 consecutive patients with large and giant pituitary adenomas (defined as maximum diameter ≥ 3 cm and tumor volume ≥ 10 cm(3)) who underwent endoscopic endonasal transsphenoidal surgery between January 1, 2006, and June 6, 2012, were included in the study. Clinical presentation, radiological studies, laboratory investigations, tumor pathology data, clinical outcomes, extent of resection measured by volumetric analysis, and complications were analyzed. RESULTS: The mean preoperative tumor diameter in this series was 4.1 cm and the volume was 18 cm(3). The average resection rate was 82.9%, corresponding with a mean residual volume of 3 cm(3). Gross-total resection was achieved in 16 patients (24%), near-total in 11 (17%), subtotal in 24 (36%), and partial in 15 (23%). Seventy-three percent of patients experienced improvement in visual acuity, while 24% were unchanged. Visual fields were improved in 61.8% and unchanged in 5.5%. Overall, 27 patients (37%) experienced a total of 32 complications. The most common complications were sinusitis (14%) and CSF leak (10%). Six patients underwent subsequent radiation therapy because of aggressive tumor histopathology. No deaths occurred in this cohort of patients. Statistically significant predictors of extent of resection included highest Knosp grade (p = 0.001), preoperative tumor volume (p = 0.025), preoperative maximum tumor diameter (p = 0.002), hemorrhagic component (p = 0.027), posterior extension (p = 0.001), and sphenoid sinus invasion (p = 0.005). CONCLUSIONS: Endoscopic endonasal transsphenoidal surgery is an effective treatment method for patients with large and giant pituitary adenomas, which results in high (> 80%) rates of resection and improvement in visual function. It is not associated with high rates of major complications and is safe when performed by experienced surgeons. The preoperative Knosp grade, tumor volume, tumor diameter, hemorrhagic components on MRI, posterior extension, and sphenoid sinus invasion may allow a prediction of extent of resection and in these patients a staged operation may be required to maximize extent of resection.

Transclival pseudomeningocele secondary to ecchordosis physaliphora: case report and literature review.

We describe a 52-year-old woman who presented with meningitis secondary to a pseudomeningocele within the sphenoid sinus derived from a bony defect in the clivus. The bony defect was radiologically characteristic of an ecchordosis physaliphora (EP). She underwent surgical repair of the defect and had resolution of her symptoms. This case report will discuss the second case of transclival pseudomeningocele in the English literature and present EP as a cause.

Cerebral white matter oxidation and nitrosylation in young rodents with kaolin-induced hydrocephalus.

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1α was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.