HFE polymorphisms affect survival of brain tumor patients.

The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.

HFE polymorphisms influence the response to chemotherapeutic agents via induction of p16INK4A.

HFE is a protein that impacts cellular iron uptake. HFE gene variants are identified as risk factors or modifiers for multiple diseases. Using HFE stably transfected human neuroblastoma cells, we found that cells carrying the C282Y HFE variant do not differentiate when exposed to retinoic acid. Therefore, we hypothesized HFE variants would impact response to therapeutic agents. Both the human neuroblastoma and glioma cells that express the C282Y HFE variant are resistant to Temodar, geldanamycin and γ-radiation. A gene array analysis revealed that p16INK4A (p16) expression was increased in association with C282Y expression. Decreasing p16 protein by siRNA resulted in increased vulnerability to all of the therapeutic agents suggesting that p16 is responsible for the resistance. Decreasing HFE expression by siRNA resulted in a 85% decrease in p16 expression in the neuroblastoma cells but not the astrocytoma cells. These data suggest a potential direct relationship between HFE and p16 that may be cell specific or mediated by different pathways in the different cell types. In conclusion, the C282Y HFE variant impacts the vulnerability of cancer cells to current treatment strategies apparently by increasing expression of p16. Although best known as a tumor suppressor, there are multiple reports that p16 is elevated in some forms of cancer. Given the frequency of the HFE gene variants, as high as 10% of the Caucasian population, these data provide compelling evidence that the C282Y HFE variant should be part of a pharmacogenetic strategy for evaluating treatment efficacy in cancer cells.

Efficacy of interleukin-13 receptor-targeted liposomal doxorubicin in the intracranial brain tumor model.

Human glioblastoma tumors selectively express receptors for interleukin 13 (IL-13). In a previous study, we showed that liposomes, when conjugated with IL-13, will deliver chemotherapeutics to a subcutaneous glioma tumor model in mice much more effectively than conventional unconjugated liposomes. Based on this observation, we developed an intracranial brain tumor model in nude mice using human U87 glioma cells. Mice receiving weekly i.p. injections of 15 mg/kg of doxorubicin encapsulated in IL-13-conjugated liposomes had a 5-fold reduction in the intracranial tumor volume over 6 weeks and four of seven animals survived >200 days after tumor implantation. In contrast, the animals receiving unconjugated liposomes with the same doxorubicin concentration did not survive beyond 35 days and there was no evidence of tumor size reduction. The presence of liposomes with doxorubicin in the tumor was shown by taking advantage of the selective expression of IL-13 receptors on the tumor cells and the endogenous fluorescence of doxorubicin. There was no increase in the indices of toxicity in animals receiving the doxorubicin-containing liposomes. Finally, a model of the blood-brain barrier was used to show that the nanovesicles do not harm the endothelial cells yet maintain their toxicity to astrocytoma cells. This approach is necessary to show the efficacy of this targeting platform for tumors in which the blood-brain barrier is not compromised and as a potential use of the nanovesicle system as a surveillance mechanism to prevent recurrence. These data show that IL-13 targeted nanovesicles are a viable option for the treatment of brain tumors.

Brain magnetic resonance imaging changes after sorafenib and sunitinib chemotherapy in patients with advanced renal cell and breast carcinoma.

OBJECT: The authors report novel imaging findings associated with the treatment of sorafenib (Nexavar) and sunitinib (Sutant), 2 agents used in the treatment of advanced metastatic disease. METHODS: Patients with renal cell and breast carcinoma metastases to the brain were identified from the prospective database at the Penn State Hershey Medical Center and Penn State Cancer Institute. RESULTS: Four patients who received sorafenib or sunitinib after surgical or radiosurgical treatment of their metastases were identified from the database. Clinical and/or radiographic changes consisting of seizures and cognitive or motor changes were described, associated with an increase in peritumoral edema and enhancement. These findings were observed to improve with discontinuation of the medications. CONCLUSIONS: The administration of sorafenib and sunitinib in patients with metastatic breast and renal cell carcinoma may lead to reversible clinical and imaging changes following surgical or radiosurgical treatment of their brain lesions. The authors hypothesize that leakage of the drug across a locally impaired blood-brain barrier contributes to peritumoral edema and inflammation, which may be erroneously interpreted as disease progression.

The Honest Palm Sign: Detecting Incomplete Effort on Physical Examination.

BACKGROUND: We investigated a simple, novel diagnostic test for detecting incomplete effort during the motor portion of the neurological examination. METHODS: The results from the honest palm sign (HPS) were evaluated for 162 consecutive neuro-oncology patients who had undergone upper extremity strength testing. Deltoid, bicep, and wrist extensor strength was assessed in all patients. During the examination, patients were repeatedly encouraged to "try as hard as possible" and to "resist with all your strength." The absence of nail prints on the palms constituted a positive HPS test result (i.e., indicative of incomplete effort). The presence of nail prints constituted a negative HPS test result (i.e., indicative of full effort). RESULTS: A total of 162 patients were tested. Their mean age was 55.5 ± 14.9 years, the median Karnofsky performance scale score was 80 (range, 60-100), and 63 patients (39%) were men. Of the 162 patients, 102 (63%) had malignant gliomas, 28 (17%) had brain metastases, 21 (13%) had other primary brain tumors, and 11 (6.8%) had primary central nervous system lymphomas. Of the 162 patients, 48 (30%) had positive HPS test results. The test sensitivity (84.6%), specificity (75.2%), positive likelihood ratio (3.41), and negative likelihood ratio (0.205) were good. After excluding 33 patients with characteristics that rendered them unsuitable for testing, the results from the remaining 129 patients were analyzed. The sensitivity was unchanged (84.6%), but the specificity (96.6%), positive likelihood ratio (24.5), and negative likelihood ratio (0.16) improved dramatically. CONCLUSIONS: The HPS test is a simple, sensitive, and very specific test for detecting incomplete effort during the motor portion of neurological evaluations.

Idiopathic temporal bone encephaloceles in the obese patient.

OBJECTIVES: Our aims were to introduce temporal bone encephalocele (TBE) to the differential diagnosis of persistent middle ear effusion, cerebrospinal fluid otorrhea, or chronic otitis media in obese adults and to demonstrate the basic pathophysiologic principles of morbid obesity as it may lead to the cascade of increased intra-abdominal pressure, increased central venous pressure, benign increased intracranial pressure, and TBE. METHODS: A retrospective review of the medical records was performed to determine the location, nature, and etiology of the encephaloceles identified at our institution from 1989 to 2005. Body mass index was calculated from the patient height and weight data. RESULTS: Eight patients with spontaneous, idiopathic TBE were identified. Body mass index values ranged from 32.0 to 67.5 kg/m(2) with a mean of 48.6 kg/m(2). All patients identified with a spontaneous, idiopathic TBE were obese. CONCLUSION: TBE is associated with morbid obesity in our population and should be considered in the differential diagnosis when evaluating mastoid and middle ear disease in the morbidly obese.

Surgical management of brain metastases.

Metastatic brain tumors continue to increase in incidence as patients with cancer live longer. The options for management continue to evolve as well, with advances in radiation-based treatment, chemotherapy, and surgery. Although metastatic brain tumors are frequently treated without surgical intervention, there continues to be a significant role for surgery in caring for patients with these lesions. Study data have proven that surgery has a positive effect on survival and quality of life in properly selected patients. Those with a suitable age, functional status, systemic disease control, and several metastases may be suitable for surgical treatment. Advances in preoperative imaging and planning as well as intraoperative surgical adjuncts have lowered the morbidity associated with resection. With proper patient selection and operative and postoperative management, resection continues to play a significant and evolving role in the care of patients with metastatic brain tumor.

Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme.

The difficulties associated with treatment of malignant brain tumors are well documented. For example, local infiltration of high-grade astrocytomas prevents the complete resection of all malignant cells. It is, therefore, critical to develop delivery systems for chemotherapeutic agents that ablate individual cancer cells without causing diffuse damage to surrounding brain tissue. Here, we describe sterically stable human interleukin-13 (IL-13)-conjugated liposomes, which efficiently bind to the brain cancer cells that overexpress the IL-13 receptor alpha2 protein. The conjugated liposomes bind to glioblastoma multiforme tissue specimens but not to normal cortex. Conjugating the liposomes with human IL-13 allows for specific binding to glioma cells and uptake of the liposomes via endocytosis. Delivering doxorubicin to glioma cells by IL-13-conjugated liposomes results in enhanced cytotoxicity and increased accumulation and retention of drug in the glioma cells compared with delivery of free drug. The therapeutic potential and targeting efficacy of the IL-13-conjugated liposomes carrying doxorubicin was tested in vivo using a s.c. glioma tumor mouse model. Animals receiving i.p. injections of IL-13-conjugated liposomes carrying doxorubicin for 7 weeks had a mean tumor volume of 37 mm3 compared with a mean volume of 192 mm3 in animals injected with nontargeted liposomes. These results strongly suggest that IL-13-conjugated liposomes carrying cytotoxic agents are a feasible approach for creating a nanovesicle drug delivery system for brain tumor therapy.

The Impact of Neurophysiological Intraoperative Monitoring during Spinal Cord and Spine Surgery: A Critical Analysis of 121 Cases.

Neuromonitoring has been utilized during spinal surgery to assess the function of the spinal cord in an effort to prevent intraoperative injury. Although its use is widespread, no clear benefit has been demonstrated. Our goal in this study was to interrogate the value of intraoperative neuromonitoring in decreasing the severity and rate of neurological injury during and after spinal surgery. Here we describe our experience of 121 patients who underwent spinal cord procedures with the combination of intraoperative neuromonitoring, to determine its ability to detect neurological changes and the specificity and sensitivity in this setting. The data for the 121 patients who underwent neurophysiological monitoring during various spinal procedures was collected retrospectively. The patients were classified into one of four groups according to the findings of intraoperative monitoring and the clinical outcomes on postoperative neurological exam. Intraoperative monitoring was evaluated for its specificity, sensitivity, and predictive value. In our cohort of 121 patients, the use of intraoperative neuromonitoring had a low sensitivity, which may produce an excessive number of false negatives. Based on these findings, neuromonitoring seems to have a poor positive predictive value and is thus an inappropriate test to prevent harm to patients.

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.

BACKGROUND: Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. METHODS: The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. RESULTS: The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. CONCLUSIONS: IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI.

Multi-modality management of craniopharyngioma: a review of various treatments and their outcomes.

Craniopharyngioma is a rare tumor that is expected to occur in ∼400 patients/year in the United States. While surgical resection is considered to be the primary treatment when a patient presents with a craniopharyngioma, only 30% of such tumors present in locations that permit complete resection. Radiotherapy has been used as both primary and adjuvant therapy in the treatment of craniopharyngiomas for over 50 years. Modern radiotherapeutic techniques, via the use of CT-based treatment planning and MRI fusion, have permitted tighter treatment volumes that allow for better tumor control while limiting complications. Modern radiotherapeutic series have shown high control rates with lower doses than traditionally used in the two-dimensional treatment era. Intracavitary radiotherapy with radio-isotopes and stereotactic radiosurgery may have a role in the treatment of recurrent cystic and solid recurrences, respectively. Recently, due to the exclusive expression of the Beta-catenin clonal mutations and the exclusive expression of BRAF V600E clonal mutations in the overwhelming majority of adamantinomatous and papillary tumors respectively, it is felt that inhibitors of each pathway may play a role in the future treatment of these rare tumors.

Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium.

OBJECT: Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas. METHODS: Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas. A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low. CONCLUSIONS: Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.

Distinguishing grade I meningioma from higher grade meningiomas without biopsy.

BACKGROUND: Many meningiomas are identified by imaging and followed, with an assumption that they are WHO Grade I tumors. The purpose of our investigation is to find clinical or imaging predictors of WHO Grade II/III tumors to distinguish them from Grade I meningiomas. METHODS: Patients with a pathologic diagnosis of meningioma from 2002-2009 were included if they had pre-operative MRI studies and pathology for review. A Neuro-Pathologist reviewed and classified all tumors by WHO 2007. All Brain MRI imaging was reviewed by a Neuro-radiologist. Pathology and Radiology reviews were blinded from each other and clinical course. Recursive partitioning was used to create predictive models for identifying meningioma grades. RESULTS: Factors significantly correlating with a diagnosis of WHO Grade II-III tumors in univariate analysis: prior CVA (p = 0.005), CABG (p = 0.010), paresis (p = 0.008), vascularity index = 4/4: (p = 0.009), convexity vs other (p = 0.014), metabolic syndrome (p = 0.025), non-skull base (p = 0.041) and non-postmenopausal female (p = 0.045). Recursive partitioning analysis identified four categories: 1. prior CVA, 2. vascular index (vi) = 4 (no CVA), 3. premenopausal or male, vi < 4, no CVA. 4. Postmenopausal, vi < 4, no CVA with corresponding rates of 73, 54, 35 and 10% of being Grade II-III meningiomas. CONCLUSIONS: Meningioma patients with prior CVA and those grade 4/4 vascularity are the most likely to have WHO Grade II-III tumors while post-menopausal women without these features are the most likely to have Grade I meningiomas. Further study of the associations of clinical and imaging factors with grade and clinical behavior are needed to better predict behavior of these tumors without biopsy.

Thoracic diastematomyelia with concurrent intradural epidermoid spinal cord tumor and cervical syrinx in an adult. Case report.

Diastematomyelia is a rare entity in which some portion of the spinal cord is split into two by a midline septum. Most cases occur in childhood, but some develop in adulthood. A variety of concurrent spinal anomalies may be found in patients with diastematomyelia. The authors describe a 38-year-old right-handed woman who presented with a 7-month history of lower-extremity pain and weakness on the right side. She denied recent trauma or illness. Sensorimotor deficits, hyperreflexia, and a positive Babinski reflex in the right lower extremity were demonstrated on examination. Neuroimaging revealed diastematomyelia extending from T-1 to T-3, an expanded right hemicord from T-2 to T-4, and a C6-7 syrinx. The patient underwent T1-3 total laminectomies, resection of the septum, untethering of the cord, and excision of the hemicord lesion. The hemicord mass was determined to be an intramedullary epidermoid cyst; on microscopic evaluation the diastematomyelia cleft was shown to contain fibroadipose connective tissue with nerve twigs and ganglion cells. Postoperatively, the right lower-extremity pain, weakness, and sensory deficits improved. Diastematomyelia can present after a long, relatively asymptomatic period and should be kept in the differential diagnosis for radiculopathy, myelopathy, tethered cord syndrome, or cauda equina syndrome. Numerous spinal lesions can be found in conjunction with diastematomyelia. To the authors' knowledge, this is the first case in which a thoracic epidermoid cyst and cervical syrinx occurred concurrently with an upper thoracic diastematomyelia. Thorough neuraxis radiographic evaluation and surgical treatment are usually indicated.

The safety and utility of recombinant human bone morphogenetic protein-2 for cranial procedures in a nonhuman primate model.

OBJECT: The goal of this study was to evaluate the safety and efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in cranial applications. METHODS: Critical-sized calvarial defects were created bilaterally in four rhesus monkeys, and bilateral rectangular bone flaps were created in six others. Control and rhBMP-2-treated sides were randomly chosen for each animal, and an absorbable collagen sponge was used to deliver the growth factor. Over a 6-month period postoperatively, the animals were serially evaluated for bone healing and adverse BMP-related consequences by using the following methods: computerized tomography (CT) scanning, magnetic resonance (MR) imaging, electroencephalography, histological investigations, and cerebrospinal fluid (CSF) analysis. The critical-sized defects for the rhBMP-2-treated and control sides attained 71 +/- 12% and 28 +/- 11% closure, respectively (four animals; p = 0.04). The CT scans demonstrated that the bone flaps treated with rhBMP-2 had complete osteointegration in five of six animals, whereas scans of the untreated bone flaps demonstrated uniformly poor osteointegration with the intact skull. Histological analysis confirmed well-formed bridges of bone on the rhBMP-2-treated sides. No epileptogenic activity was detected in any of the animals, and MR imaging revealed no evidence of adverse effects on the brain parenchyma. Meningitic irritation was not found on postoperative CSF sample analysis. CONCLUSIONS: Treatment of bone flaps and critical-sized cranial defects with rhBMP-2 leads to improved bone formation and osteointegration in nonhuman primates. Initial evaluation of rhBMP-2 appears to indicate a good safety profile for use in cranial procedures in primates.

Intramedullary spinal cysticercosis. Case report and review of the literature.

Cysticercosis is the most common parasitic infection of the central nervous system. It infrequently affects the spine, but when it does, it can present with symptoms similar to other more common spinal diseases. The authors present a case of isolated intramedullary cysticercosis of the cervical spine and review the literature.

Pediculotomy as an adjunct to posterior cervical hemilaminectomy, foraminotomy, and discectomy.

Currently the posterior approach undertaken to perform cervical hemilaminectomy and foraminotomy provides sufficient exposure to treat the majority of lateral soft-disc herniations or osteophytes causing radiculopathy. Limitations imposed by the surgical field, however, often necessitate excessive retraction of the nerve root and epidural venous plexus, which may potentially exacerbate a preexisting radiculopathy or increase intraoperative blood loss. Partial resection of the inferior pedicle augments exposure and enlarges the neural foramen, thus facilitating decompression while minimizing manipulation of the nerve root and epidural venous plexus. With the patient in the prone position, partial hemilaminectomy and foraminotomy are performed using a highspeed 3-mm diamond burr with continuous irrigation. The thecal sac and nerve root are exposed, and the overlying fibroareolar layer is coagulated and incised. With the nerve root protected and under direct vision, the superomedial portion of the inferior pedicle is removed. Nerve root decompression is then performed through this augmented exposure. Partial excision of the pedicle allows for more expeditious removal of the pathological elements causing cervical radiculopathy and requires minimal manipulation of the nerve root and epidural venous plexus. This procedure results in a potential decrease in transient postoperative radiculopathy and minimization of intraoperative blood loss. In addition, the resulting foraminal enlargement enhances the decompression provided by traditional foraminotomy, even if discectomy is not performed.

Stress fracture of the pedicle after extensive decompression and contralateral posterior fusion for lumbar stenosis. Report of three cases.

Lumbar spinal stenosis can be effectively treated by performing an extensive ipsilateral spinal decompression, including a partial pediculotomy, and contralateral posterior bone fusion. Infrequently, complications can arise following radical decompression to alleviate symptoms of stenosis, and one such complication is a pedicle fracture. Three reports of pedicle fractures following extensive spinal decompression and contralateral posterior fusion are detailed. This complication is emphasized, and interventions are discussed. Three patients presented with symptoms attributable to lumbar stenosis; they were initially treated with an ipsilateral decompression, achieved in part, through a partial pediculotomy followed by contralateral autologous bone fusion. Initially, all three patients improved postoperatively; however, they later developed neurological symptoms ipsilateral to the side of spinal decompression. Computerized tomography scanning demonstrated pedicle fractures on the decompressed side. This complication has not yet been reported in association with decompression and fusion for lumbar stenosis. Two of the patients developed leg pain necessitating reoperation whereas the third experienced only mild transient symptoms. The fractured pedicle was removed in one patient; laminar and spinous process fusion was performed again. Another patient underwent a total laminectomy, removal of the fractured pedicle, and bilateral transverse process fusion. Reoperation yielded satisfactory outcomes. The third patient's symptoms resolved without intervention. Pedicle fractures are a potential complication of extensive lumbar decompression and contralateral posterior fusion. Loading forces from the facets or transverse processes are possibly the cause of such fractures. Removal of the fractured pedicle, additional decompression, and enhanced bone fusion are recommended when the symptoms warrant surgical intervention.

Esthesioneuroblastoma: clinical presentation, radiological, and pathological features, treatment, review of the literature, and the University of Virginia experience.

Esthesioneuroblastoma is a rare and malignant upper nasal cavity neoplasm involving the anterior skull base. Treatment includes surgery, radiotherapy, chemotherapy, or a combination. The ideal treatment modality has yet to be determined. Esthesioneuroblastoma often lies in proximity to the optic nerves, optic chiasm, and the orbit. Resection risks damaging these critical structures, and radiotherapeutic techniques, similar to those applied for paranasal sinus tumors, may damage these vital structures and result in late sequelae such as blindness and cortical necrosis. Management strategies for this neoplasm lack uniformity, and there is no universally accepted staging system. In this paper the authors discuss the clinical presentation, radiological and pathological features, and treatment of this rare, malignant skull base neoplasm, as well as review the literature. They also present their results and treatment regimen, which includes preoperative radio- and chemotherapy or 1) craniofacial resection if the lesion has a significant intracerebral component, or 2) frontal sinus resection if little intracranial extension exists.

Acute and long-term management of sports-related closed head injuries.

Aggressive participation in athletics is rewarded in many ways in our society. As long as there is such strong impetus for participation in athletics, the risks of head injuries for participants will remain. Important strides made in understanding of the pathophysiology of head injuries may lead to improved treatment strategies in the future. In light of the current lack of effective therapies, however, the best options remain injury prevention, early and appropriate recognition, and limitation of subsequent, further injury. Frequently the medical staff is encouraged to allow the athlete to return to play based on the desires of the coach, team, fans, parents, and even the athlete himself. A thorough understanding of the potentially serious risks of repetitive injury, however, mandates that only a proper conservative period of observation and evaluation will best serve the competitor.