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Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffective effective in triggering cancer cell death. To address these issues, we have made several chemical modifications in fenofibrate structure to increase its stability, water solubility, tissue penetration, and ultimately anticancer potential. Our data show that, in comparison to fenofibrate, four new compounds designated here as PP1, PP2, PP3, and PP4 have improved anticancer activity in vitro. Like fenofibrate, the compounds block mitochondrial respiration and trigger massive glioblastoma cell death in vitro. In addition, one of the lead compounds, PP1, has improved water solubility and is significantly more stable when exposed to human blood in comparison to fenofibrate. Importantly, mice bearing large intracranial glioblastoma tumors demonstrated extensive areas of tumor cell death within the tumor mass following oral administration of PP1, and the treated mice did not show any major signs of distress, and accumulated PP1 at therapeutically relevant concentrations in several tissues, including brain and intracranial tumors.

Background The practice of surgeons running overlapping operating rooms has recently come under scrutiny. Objective To examine the impact of hospital policy allowing overlapping rooms in the case of patients admitted to a tertiary care, safety-net hospital for urgent neurosurgical procedures. Methods The neurosurgery service at the hospital being studied transitioned from routinely allowing 1 room per day (period 1) to overlapping rooms (period 2), with the second room being staffed by the same attending surgeon. Patients undergoing neurosurgical intervention in each period were retrospectively compared. Demographics, indication, case type, complications, outcomes, and total charges were tracked. Results There were 59 urgent cases in period 1 and 63 in period 2. In the case of these patients, the length of stay was significantly decreased in period 2 (13.09 d vs 19.52; P = .006). The time from admission to surgery (wait time) was also significantly decreased in period 2 (5.12 d vs 7.00; P = .04). Total charges also trended towards less in period 2 (${\$}$150 942 vs ${\$}$200 075; P = .05). Surgical complications were no different between the groups (16.9% vs 14.3%; P = .59), but medical complications were significantly decreased in period 2 (14.3% vs 30.5%; P = .009). Significantly more patients were discharged to home in period 2 (69.8% vs 42.4%; P = .003). Conclusion As a matter of policy, allowing overlapping rooms significantly reduces the length of stay in the case of a vulnerable population in need of urgent surgery at a single safety-net academic institution. This may be due to a reduction in medical complications in these patients.

Historically, the surgical management of gunshot wounds to the spine has been controversial. Repair of a persistent cerebrospinal fluid (CSF) leak is a generally agreed upon indication. The management of such CSF leaks typically involves lumbar drainage or direct surgical repair. Here, the authors report two cases of CSF diversion with an external ventricular drain (EVD) in patients with cervical gunshot wounds. Both patients had spinal canal obliteration or physiologic myelographic block at or below the level of injury. To the best of the author’s knowledge, these are the first two reports of successful EVD treatment of persistent CSF leaks related cervical gunshot wounds. The authors also propose a CSF treatment algorithm for cervical gunshot wounds that includes EVD.

Rationale: Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of angiotensin-converting enzyme type 2 (ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated. Objective: To assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process. Methods and Results: Using a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting angiotensin II into angiotensin-(1–7) in human cerebrospinal fluid. We also observed an increase in ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor-α in those cerebrospinal fluid samples confirmed that ADAM17 was upregulated in the brain of hypertensive patients. To further assess the interaction between brain renin–angiotensin system and ADAM17, we generated mice lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 upregulation during deoxycorticosterone acetate–salt hypertension occurs selectively on neurons, and neuronal angiotensin II type 1 receptors are indispensable to this process. Mechanistically, reactive oxygen species and extracellular signal-regulated kinase were found to mediate ADAM17 activation. Conclusions: Our data demonstrate that angiotensin II type 1 receptors promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.

The effect of intoxicating substances on assessment of Glasgow Coma Scale (GCS) in the trauma setting has not been completely elucidated.A trauma registry was queried for patients with blunt head trauma in 2013-2017. Initial GCS score and toxicology screening from the database were reviewed. Next recorded GCS score from the neurosurgery evaluation and change in GCS score (ΔGCS) were compared.We reviewed 468 patients. In 217 (46.4%) patients, no toxic substances were found, whereas1 toxic substance was found in 104 (22.2%) patients. Alcohol level above the legal limit was found in 109 (23.3%) patients, marijuana was found in 105 (22.4%) patients, benzodiazepines were found in 94 (20.1%) patients, opiates were found in 48 (10.3%) patients, and cocaine was found in 41 (8.8%) patients. Mean change in GCS score was significantly higher in impaired patients compared with patients with a negative screening test (1.74 ± 2.4 vs. 0.75 ± 2.7, P0.001); this is despite both groups having a similar initial GCS score (6.23 ± 3.86 in impaired group vs. 6.47 ± 3.52 in sober group, P = 0.677). Initial GCS score was 3 in 187 patients, of whom 150 had a positive toxicology screen. Change in GCS score was significantly higher in the impaired group (2.75 ± 2.7 vs. 1.19 ± 1.8, P 0.001).Intoxicating substances can confound GCS assessment in trauma patients. This can have effects on patient care as well as performance metrics and predictive analytics. These patients should be screened, and intoxicating substances should be reversed or allowed to wear off before GCS score is recorded for benchmarking or quality reporting.

Aluminum is a ubiquitous neurotoxin highly enriched in our biosphere, and has been implicated in the etiology and pathology of multiple neurological diseases that involve inflammatory neural degeneration, behavioral impairment and cognitive decline. Over the last 36 years our group has analyzed the aluminum content of the temporal lobe neocortex of 511 high quality coded human brain samples from 18 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Brodmann anatomical areas including the inferior, medial and superior temporal gyrus (A20-A22) were selected for analysis: (i) because of their essential functions in massive neural information processing operations including cognition and memory formation; and (ii) because subareas of these anatomical regions are unique to humans and are amongst the earliest areas affected by progressive neurodegenerative disorders such as Alzheimer's disease (AD). Coded brain tissue samples were analyzed using the analytical technique of: (i) Zeeman-type electrothermal atomic absorption spectrophotometry (ETAAS) combined with (ii) an experimental multi-elemental analysis using the advanced photon source (APS) ultra-bright storage ring-generated hard X-ray beam (7 GeV) and fluorescence raster scanning (XRFR) spectroscopy device at the Argonne National Laboratory, US Department of Energy, University of Chicago IL, USA. These data represent the largest study of aluminum concentration in the brains of human neurological and neurodegenerative disease ever undertaken. Neurological diseases examined were AD (N=186), ataxia Friedreich's type (AFT; N=6), amyotrophic lateral sclerosis (ALS; N=16), autism spectrum disorder (ASD; N=26), dialysis dementia syndrome (DDS; N=27), Down's syndrome (DS; trisomy21; N=24), Huntington's chorea (HC; N=15), multiple infarct dementia (MID; N=19), multiple sclerosis (MS; N=23), Parkinson's disease (PD; N=27), prion disease (PrD; N=11) including bovine spongiform encephalopathy (BSE; 'mad cow disease'), Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Sheinker syndrome (GSS), progressive multifocal leukoencephalopathy (PML; N=11), progressive supranuclear palsy (PSP; N=24), schizophrenia (SCZ; N=21), a young control group (YCG; N=22) and an aged control group (ACG; N=53). Amongst these 18 common neurological conditions and controls we report a statistically significant trend for aluminum to be increased only in AD, DS and DDS compared to age- and gender-matched brains from the same anatomical region. The results continue to suggest that aluminum's association with AD, DDS and DS brain tissues may contribute to the neuropathology of these neurological diseases but appear not to be a significant factor in other common disorders of the human central nervous system (CNS).

BACKGROUND Diabetes mellitus affects 9.3% of the US population and increases risks of surgery and complications. Diabetic neuropathic pain (DNP), one of the main consequences of diabetes mellitus, is extremely difficult to treat. Current medications yield limited benefits and/or have severe adverse effects. Therefore, new, effective treatment is needed. METHODS Streptozotocin at 55 mg/kg was injected intraperitoneally in rats to induce diabetes mellitus. Diabetic rats exhibiting neuropathic pain underwent intrathecal injection of purified agrin proteins at various doses and were then tested for tactile allodynia to evaluate whether DNP was inhibited. The agrin effects were also analyzed with patch-clamp recording on spinal cord slices. RESULTS Fifty-kilo Dalton agrin (Agr50) at 0.2 and 2 ng suppressed DNP when given intrathecally, while 25- and 75-kDa agrin (Agr25, Agr75) had little effect. The suppressive effect of Agr50 lasted 4 hours after a single bolus injection. The difference in effects of Agr50 on mean withdrawal threshold (4.6 ± 2.2 g before treatment to 26 ± 0 g after treatment) compared with that of Agr25 (4.9 ± 2.0 g to 4.9 ± 2.0 g) and Agr75 (5.3 ± 2.3 g to 9.2 ± 2.5 g) was highly significant (P < .01). On spinal cord slices, Agr50 increased spontaneous GABAergic current activities, suggesting increased spontaneous inhibitory postsynaptic currents and action potential firing rate from GABA neurons, whereas Agr25 and Agr75 had no such effect. CONCLUSIONS Agr50 had a potent suppressive effect on DNP and increased spontaneous inhibitory postsynaptic currents and action potential firing rate from GABA neurons. Therefore, Agr50 may provide a potential therapy for DNP.

Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of angiotensin-converting enzyme type 2 (ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated.To assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process.Using a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting angiotensin II into angiotensin-(1-7) in human cerebrospinal fluid. We also observed an increase in ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor-α in those cerebrospinal fluid samples confirmed that ADAM17 was upregulated in the brain of hypertensive patients. To further assess the interaction between brain renin-angiotensin system and ADAM17, we generated mice lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 upregulation during deoxycorticosterone acetate-salt hypertension occurs selectively on neurons, and neuronal angiotensin II type 1 receptors are indispensable to this process. Mechanistically, reactive oxygen species and extracellular signal-regulated kinase were found to mediate ADAM17 activation.Our data demonstrate that angiotensin II type 1 receptors promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.

Alzheimer’s disease (AD) is a uniquely human, age-related central nervous system (CNS) disorder for which there is no adequate experimental model. While well over 100 transgenic murine models of AD (TgAD) have been developed that recapitulate many of the neuropathological features of AD, key pathological features of AD such as progressive neuronal atrophy, neuron cell loss, and neurofibrillary tangle (NFT) formation have not been observed in any TgAD model to date. To more completely analyze and understand the neuropathology, altered neuro-inflammatory and innate-immune signaling pathways, and the complex molecular-genetics and epigenetics of AD, it is therefore necessary to rigorously examine short post-mortem interval (PMI) human brain tissues to gain a deeper and more thorough insight into the neuropathological mechanisms that characterize the AD process. This perspective-methods paper will highlight some important recent findings on the utilization of short PMI tissues in sporadic (idiopathic; of unknown origin) AD research with focus on the extraction and quantification of RNA, and in particular microRNA (miRNA) and messenger RNA (mRNA) and analytical strategies, drawing on the authors’ combined 125 years of laboratory experience into this investigative research area. We sincerely hope that new investigators in the field of “gene expression analysis in neurological disease” will benefit from the observations presented here and incorporate these recent findings and observations into their future experimental planning and design.

Fenofibrate (FF) is a common lipid-lowering drug and a potent agonist of the peroxisome proliferator-activated receptor alpha (PPARα). FF and several other agonists of PPARα have interesting anticancer properties, and our recent studies demonstrate that FF is very effective against tumor cells of neuroectodermal origin. In spite of these promising anticancer effects, the molecular mechanism(s) of FF-induced tumor cell toxicity remains to be elucidated. Here we report a novel PPARα-independent mechanism explaining FF's cytotoxicity in vitro and in an intracranial mouse model of glioblastoma. The mechanism involves accumulation of FF in the mitochondrial fraction, followed by immediate impairment of mitochondrial respiration at the level of complex I of the electron transport chain. This mitochondrial action sensitizes tested glioblastoma cells to the PPARα-dependent metabolic switch from glycolysis to fatty acid β-oxidation. As a consequence, prolonged exposure to FF depletes intracellular ATP, activates the AMP-activated protein kinase–mammalian target of rapamycin–autophagy pathway, and results in extensive tumor cell death. Interestingly, autophagy activators attenuate and autophagy inhibitors enhance FF-induced glioblastoma cytotoxicity. Our results explain the molecular basis of FF-induced glioblastoma cytotoxicity and reveal a new supplemental therapeutic approach in which intracranial infusion of FF could selectively trigger metabolic catastrophe in glioblastoma cells.

Objectives:(1) Examine the efficacy of quick-setting, hydrophilic formulation of hydroxyapatite cement (HAC) used in cranioplasty for the prevention of cerebrospinal fluid (CSF) leaks and long-term wound complications following translabyrinthine acoustic neuroma (TLAN) surgery. (2) Review evolution of HAC cranioplasty.Methods:Retrospective case review from 2006 to 2013 in atertiary referral center. Consecutive patients undergoing translabyrinthine approach for acoustic neuroma tumors were operated on by the senior author. Intervention: Therapeutic: Cranioplasty combining a medial abdominal fat graft with hydrophilic hydroxyapatite cement filling the mastoid. Main outcome measures: Incidence of cerebrospinal fluid (CSF) leaks and any wound complications.Results:Forty-four patients met inclusion criteria. There were no CSF leaks or other wound complications in this series.Conclusions:Hydrophilic HAC appears to be safe and efficacious for cranioplasty following translabyrinthine acoustic neuroma surgery.

ACE2 (Angiotensin Converting Enzyme type 2) is involved in the conversion of the vasoconstrictor peptide Angiotensin (Ang)-II into its vasodilatory metabolite Ang-(1-7), thereby offering a new perspective for the treatment of cardiovascular diseases associated with over-activity of the renin-angiotensin system. Our group recently reported that ACE2 shedding, a process by which ACE2 is cleaved from the plasma membrane and secreted into the surrounding milieu, contributes to the loss of the enzyme’s compensatory activity in the central nervous system (CNS) during the development of experimental hypertension. The objective of this study was to determine whether ACE2 shedding is taking place in the CNS of patients during hypertension. Unused cerebrospinal fluid, collected from patients (17 males and 27 females, aged 22-66) for diagnostic purposes, was divided in 3 groups: normotensive (n=23), hypertensive (n=9), and hypertensive controlled with medication (n=12). In addition, blood pressure values and current medications were recorded. While ELISA lacked sensitivity, soluble levels of hACE2 (sACE2) could be detected by Mass spectrometry-based RAS-Fingerprint™ in all patients. Validation experiments (n=16) indicated that pre-treatment with MLN4760 (ACE2 inhibitor) abolished the conversion of Ang-II to Ang-(1-7) by 76 ±3 %, suggesting that ACE2 is the main enzyme converting Ang-II to Ang-(1-7) in human CSF. In hypertensive patients not taking blood pressure medications, (Systolic: 157 ±10, Diastolic: 95 ±7 mmHg; n=6) CSF sACE2 activity was significantly higher (21.7 ±8.3 AU; P

Once biologically available aluminum bypasses gastrointestinal and blood-brain barriers, this environmentally-abundant neurotoxin has an exceedingly high affinity for the large pyramidal neurons of the human brain hippocampus. This same anatomical region of the brain is also targeted by the earliest evidence of Alzheimer's disease (AD) neuropathology. The mechanism for the selective targeting and transport of aluminum into the hippocampus of the human brain is not well understood. In an effort to improve our understanding of a pathological aluminum entry system into the brain, this study examined the aluminum content of 8 arteries that supply blood to the hippocampus, including the aorta and several cerebral arteries. In contrast to age-matched controls, in AD patients we found a gradient of increasing aluminum concentration from the aorta to the posterior cerebral artery that supplies blood to the hippocampus. Primary cultures of human brain endothelial cells were found to have an extremely high affinity for aluminum when compared to other types of brain cells. Together, these results suggest for the first time that endothelial cells that line the cerebral vasculature may have biochemical attributes conducive to binding and targeting aluminum to selective anatomical regions of the brain, such as the hippocampus, with potential downstream pro-inflammatory and pathogenic consequences.

INTRODUCTION: Vasospasm following aneurysmal subarachnoid hemorrhage is a very extensively studied source of morbidity and mortality. Numerous treatment regiments have been investigated and published. A recently published article discussed the use of prolonged infusion of verapamil through an indwelling catheter as an effective treatment for medically refractory severe vasospasm. The goal of our study is to report our institution's experience with this method of treatment. METHODS & MATERIALS: All patients with medically refractory vasospasm from July 2009 through August 2011 were included in the study. A retrospective review of data was compiled. In particular, age, sex, aneurysm location, aneurysm treatment, intra-arterial treatment fo vasospasm, dosages and times of medication infusion, and presence of new ischemia or progression of ischemia on CT scan were investigated. RESULTS: A total of 13 treatments were administered. Nicardipine was used in two treatments, and verapamil was used in the remaining eleven treatments. The doses of nicardipine were 10mg and 49 mg, and were infused over 20 min and 75 min respectively. The doses of verapamil ranged from 41 mg to 200 mg. One patient was treated with both nicardipine and verapamil at one treatment session. The infusion times ranged from 25 min to 22 hr. Between 1 and 3 vessels were treated per patient resulting in a total of 19 vessels treated. The number of treatments per patient ranged from one to two. Review of pre- and post-treatment CT scans revealed worsening of ischemic changes in 9 of the 13 treatments, while the remaining 4 treatments showed no change or progression of ischemic changes on imaging. One patient had a conversion to a hemorrhagic infarct from an inschemic infarct after a treatment. CONCLUSIONS: Upon reviewing our data we have come to the conclusion that prolonged infusion of calcium channel blockers is not an effective treatment for medically refractory severe vasospasm. After 13 treatments we have decided to not continue with this treatment. Therefore, we believe that angioplasty is still the gold standard for treatment of medically refractory vasospasm.

Cancers of the brain comprise a genetically and morphologically heterogeneous class of proliferating neural cells derived from incompletely differentiated brain tumor stem cells (BTSCs). The molecular and genetic mechanisms that contribute to their development and propagation are incompletely understood, however, current research is expanding our knowledge as to what specific gene activation and deactivation mechanisms are triggered during the onset of brain cell neoplasia. Apparently, only relatively small populations of BTSCs are capable of driving the proliferative and invasive nature of these cancers, and the intrinsic ability to reinitiate and propagate aberrant cell growth at any metabolic cost. This chapter provides a current overview of gene expression patterns in glioma and glioblastoma multiforme (GBM), with special emphasis on messenger RNA (mRNA) and micro RNA (miRNA) speciation and abundance, and how our recent understanding of specific mRNA–miRNA interactions have increased our comprehension of this insidious neoplastic process.

analyzed. A lod score of 4.5 was calculated under a dominant model on chromosome 3 at rs10510224, which is in CNTN4, encoding a neuronal membrane protein. Under the dominant model, 5 additional SNPs, on chromosomes 6 and 1, had lod scores >4.0. Five other SNPs, on chromosomes 2 and 9, had lod scores >4.0 under the recessive model. Another 26 SNPs had lod scores >3.6 under either a dominant or recessive model. In addition, we are performing simulation studies to evaluate approaches toward subsetting the pedigree for optimal linkage analysis. Conclusions: Our linkage results suggest several novel non-APOE genetic effects, with the most compelling evidence on chromosomes 1, 2, 3, 6, and 9, for LOAD in the Amish. Computationally intensive multipoint linkage analysis is ongoing and will help further localize these signals.

Micro RNAs (miRNAs) are post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNAs (mRNAs). Here we report that the levels of a human brain-enriched miRNA-125b are up-regulated in interleukin-6 (IL-6)-stressed normal human astrocytes (NHA), a treatment known to induce astrogliosis. In vitro, anti-miRNA-125b added exogenously to IL-6-stressed NHA cultures attenuated both glial cell proliferation and increased the expression of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a miRNA-125b target and negative regulator of cell growth. A strong positive correlation between miRNA-125b abundance and the glial cell markers glial fibrillary acidic protein (GFAP) and vimentin, and CDKN2A down-regulation was noted in advanced Alzheimer's disease (AD) and in Down's syndrome (DS) brain, chronic neurological disorders associated with astrogliosis. The results suggest that miRNA-125b up-regulation contributes to astrogliosis and to defects in the cell cycle that are characteristic of degenerating brain tissues.

Recurrent stenosis of the carotid arteries after a carotid endarterectomy for atherosclerosis can occur as a result of myointimal hyperplasia. This condition was treated by percutaneous transluminal angioplasty. Excellent dilatation of the vessel lumen was documented after balloon dilatation. A 6-month follow-up angiographic study, however, demonstrated recurrent high-grade stenosis at the same level in both carotid arteries. Presumably, the failure of percutaneous transluminal angioplasty and the treatment of myointimal hyperplasia of the internal carotid artery results in the same condition after the original endarterectomy, that is, additional myointimal hyperplasia.

Glioma and glioblastoma multiforme constitute rapidly proliferating glial cell tumors whose pathogenic mechanisms are not well understood. This study examined proinflammatory and neurodegenerative gene expression in five American Tissue Culture Collection glioma and glioblastoma multiforme tumor cell lines and in 14 glioma and glioblastoma samples obtained from human brain biopsy. Expression of the low-abundance cyclooxygenase-1 and the high-abundance cytoskeletal element beta-actin were found not to significantly change in any cells or tissues studied and were used as internal controls. In contrast, proinflammatory cyclooxygenase-2, cytosolic phospholipase A2, IL-1beta, and beta-amyloid precursor protein expression levels were found to be significantly upregulated. These studies suggest that glioma and glioblastoma exhibit robust upregulation of proinflammatory and neurodegenerative genetic markers that may contribute to the pathobiology, phenotype, and proliferation of glial cell growth.

A case of eosinophilic granuloma of the cervical spine is described. Cervical radiography and computed tomography demonstrated destruction of pedicles and posterior portions of the neural arch. Vertebral body heights were essentially preserved and the importance of this finding is underscored. Computed tomography played an important role in evaluating the extent of this disease.

Patients with malignant gliomas are at increased risk for deep vein thrombophlebitis (DVT) and pulmonary embolism (PE). Difficult anticoagulation in cancer patients undergoing surgery, chemotherapy, or radiotherapy limit the choices of therapy for DVT. Interruption of the inferior vena cava with a Greenfield filter is a safe method of treating patients who have malignant gliomas and DVT with PE. We studied 23 patients treated for malignant gliomas; 16 were men and seven were women, with a mean age of 51 years (range, 26 to 78). Five patients had DVT shown by noninvasive blood flow studies, and four subsequently had PE, as demonstrated by ventilation perfusion lung scan; in one patient PE was diagnosed at autopsy. Of the 23 patients, four with postoperative craniotomy had DVT and all four had PE. Two of the five patients who received preoperative chemotherapy had DVT and three had PE. All patients with PE had a Greenfield filter placed in the inferior vena cava via the internal jugular vein without adverse sequelae.