bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrum of subdural fluid collections in spontaneous intracranial hypotension
Authors: Schievink Wouter I. , Maya M. Marcel , Moser Franklin G. , Tourje James
Published: May 2009

Object. Spontaneous intracranial hypotension is a noteworthy but commonly misdiagnosed cause of new daily persistent headaches. Subdural fluid collections are frequent radiographic findings, but they can be interpreted as primary rather than secondary pathological entities, and uncertainties exist regarding their optimal management. The authors therefore reviewed their experience with subdural fluid collections in 40 consecutive patients with spontaneous spinal cerebrospinal fluid (CSF) leaks and intracranial hypotension.

Methods. The mean age of the 26 female and 14 male patients was 43 years (range 13–72 years). Subdural fluid collections were present in 20 patients (50%); 12 of these patients (60%) had subdural hygromas alone, and eight (40%) had subacute to chronic subdural hematomas (SDHs) associated with significant mass effect. The subdural hygromas resolved within several days to weeks following treatment of the underlying CSF leak. Three patients with SDHs underwent evacuation of the hematoma prior to the establishment of the diagnosis of spontaneous intracranial hypotension, but the SDHs did not resolve until the underlying spinal CSF leak was treated. In the remaining five patients, the CSF leak was treated primarily and the SDHs resolved over a 1- to 3-month period without the need for evacuation.

Conclusions. Subdural fluid collections are common in spontaneous intracranial hypotension, varying in appearance from thin subdural hygromas to large SDHs associated with significant mass effect. These collections can be safely managed by directing treatment at the underlying CSF leak without the need for hematoma evacuation.
Stereotactic interstitial radiosurgery for cerebral metastases
Authors: Curry William T. , Cosgrove Garth Rees , Hochberg Fred H. , Loeffler Jay , Zervas Nicholas T.
Published: May 2009

Object. The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique.

Methods. Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging.

Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10–20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of 11 months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery.

Conclusions. Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy.
Mental health, anxiety, and depression in patients with cerebral aneurysms
Authors: King Joseph T. , Kassam Amin B. , Yonas Howard , Horowitz Michael B. , Roberts Mark S.
Published: May 2009

Object. Aneurysm disease and its treatment can have an adverse impact on mental health, yet the affects of cerebral aneurysms on general mental health, anxiety, and depression are poorly understood.

Methods. Patients with cerebral aneurysms who were seen at a neurosurgery clinic underwent a structured interview, completed the Hospital Anxiety and Depression Scale and the Medical Outcomes Study 12-item Short Form Health Survey (providing a mental component summary [MCS] score for general mental health), and were assigned functional status scores based on the Glasgow Outcome Scale (GOS), Rankin Scale, and Barthel Index. Rank-order methods were used to assess the relationship between mental health, aneurysm characteristics and history, and functional status. Data were collected in 166 patients (71% women) with a mean age of 53.7 years. Depression was present in 8% of the study population and an anxiety disorder in 17%. Patients with both an unsecured aneurysm and a history of subarachnoid hemorrhage (SAH) tended toward higher anxiety scores (p = 0.086). Higher depression scores were associated with a decreased functional status on the GOS (p = 0.015) and Rankin Scale (p = 0.010). The mean 6 standard deviation adjusted MCS score (37.9 ± 7.1) was significantly less than that of the US population (p < 0.001). Lower MCS scores were associated with a decreased functional status on the GOS (p = 0.052), Rankin Scale (p < 0.001), and Barthel Index (p = 0.002).

Conclusions. Patients with cerebral aneurysms have increased levels of anxiety and depression and poor general mental health. Those who have experienced an SAH and harbor an unsecured cerebral aneurysm demonstrate increased levels of anxiety. A lower functional status in patients with aneurysms is associated with depression and decreased general mental health.
Testing the radiosurgery-based arteriovenous malformation score and the modified Spetzler—Martin grading system to predict radiosurgical outcome
Authors: Andrade-Souza Yuri M. , Zadeh Gelareh , Ramani Meera , Scora Daryl , Tsao May N. , Schwartz Michael L.
Published: May 2009

Object. The aim of this study was to validate the radiosurgery-based arteriovenous malformation (AVM) score and the modified Spetzler—Martin grading system to predict radiosurgical outcome.

Methods. One hundred thirty-six patients with brain AVMs were randomly selected. These patients had undergone a linear accelerator radiosurgical procedure at a single center between 1989 and 2000. Patients were divided into four groups according to an AVM score, which was calculated from the lesion volume, lesion location, and patient age (Group 1, AVM score < 1; Group 2, AVM score 1–1.49; Group 3, AVM score 1.5–2; and Group 4, AVM score > 2). Patients with a Spetzler—Martin Grade III AVM were divided into Grades IIIA (lesion > 3 cm) and IIIB (lesion < 3 cm). Sixty-two female (45.6%) and 74 male (54.4%) patients with a median age of 37.5 years (mean 37.5 years, range 5–77 years) were followed up for a median of 40 months. The median tumor margin dose was 15 Gy (mean 17.23 Gy, range 15–25 Gy). The proportions of excellent outcomes according to the AVM score were as follows: 91.7% for Group 1, 74.1% for Group 2, 60% for Group 3, and 33.3% for Group 4 (chi-square test, degrees of freedom (df) = 3, p < 0.001). Based on the modified Spetzler—Martin system, Grade I lesions had 88.9% excellent results; Grade II, 69.6%; Grade IIIB, 61.5%; and Grades IIIA and IV, 44.8% (chi-square test, df = 3, p = 0.047).

Conclusions. The radiosurgery-based AVM score can be used accurately to predict excellent results following a single radiosurgical treatment for AVM. The modified Spetzler—Martin system can also predict radiosurgical results for AVMs, thus making it possible to use this system while deciding between surgery and radiosurgery.
Endovascular management of dissecting vertebrobasilar artery aneurysms in patients presenting with acute subarachnoid hemorrhage
Authors: Yuki Ichiro , Murayama Yuichi , Viñuela Fernando
Published: May 2009

Object. The authors report on a series of 29 patients presenting with acute subarachnoid hemorrhage (SAH) related to the rupture of a vertebrobasilar dissecting aneurysm. Special attention was focused on embolization techniques and immediate and midterm anatomical and clinical outcomes.

Methods. Between March 1994 and January 2003, 29 patients presented with acute SAH caused by the rupture of a vertebrobasilar dissecting aneurysm. Eleven patients (37.9%) had Hunt and Hess Grade I SAH, four (13.8%) Grade II, six (20.7%) Grade III, five (17.2%) Grade IV, and three (10.3%) Grade V. Aneurysms were classified into five groups based on lesion location, and treatment courses were decided. All patients except two were treated by endovascular trapping of the aneurysm with concomitant occlusion of the involved vertebral artery (VA). No technical or clinical complication was observed in 28 patients (97%). Aneurysm perforation occurred during the procedure in one patient (3%). There was evidence of aneurysm recanalization in one patient. One patient with Hunt and Hess Grade IV SAH and two patients with Grade V SAH died. One patient died of respiratory infection 1 year after aneurysm trapping. One patient presented with a recurrent hemorrhage 1 month after treatment and died. Overall morbidity and mortality rates were 13.8 and 17.2%, respectively.

Conclusions. Twenty-nine patients with acute SAH due to rupturing of vertebrobasilar dissecting aneurysms were treated using endovascular techniques. In most cases, endovascular trapping of the aneurysm and concomitant occlusion of the VA was technically and clinically successful.
A proposed parent vessel geometry—based categorization of saccular intracranial aneurysms: computational flow dynamics analysis of the risk factors for lesion rupture
Authors: Hassan Tamer , Timofeev Eugene V. , Saito Tsutomu , Shimizu Hiroaki , Ezura Masayuki , Matsumoto Yasushi , Takayama Kazuyoshi , Tominaga Teiji , Takahashi Akira
Published: May 2009

Object. The authors created a simple, broadly applicable classification of saccular intracranial aneurysms into three categories: sidewall (SW), sidewall with branching vessel (SWBV), and endwall (EW) according to the angiographically documented patterns of their parent arteries. Using computational flow dynamics analysis (CFDA) of simple models representing the three aneurysm categories, the authors analyzed geometry-related risk factors such as neck width, parent artery curvature, and angulation of the branching vessels.

Methods. The authors performed CFDAs of 68 aneurysmal geometric formations documented on angiograms that had been obtained in patients with 45 ruptured and 23 unruptured lesions. In successfully studied CFDA cases, the wall shear stress, blood velocity, and pressure maps were examined and correlated with aneurysm rupture points. Statistical analysis of the cases involving aneurysm rupture revealed a statistically significant correlation between aneurysm depth and both neck size (p < 0.0001) and caliber of draining arteries (p < 0.0001).

Wider-necked aneurysms or those with wider-caliber draining vessels were found to be high-flow lesions that tended to rupture at larger sizes. Smaller-necked aneurysms or those with smaller-caliber draining vessels were found to be low-flow lesions that tended to rupture at smaller sizes. The incidence of ruptured aneurysms with an aspect ratio (depth/neck) exceeding 1.6 was 100% in the SW and SWBV categories, whereas the incidence was only 28.75% for the EW aneurysms.

Conclusions. The application of standardized categories enables the comparison of results for various aneurysms' geometric formations, thus assisting in their management. The proposed classification system may provide a promising means of understanding the natural history of saccular intracranial aneurysms.
Influence of age on stroke outcome following transient focal ischemia
Authors: Rosen Charles L. , Dinapoli Vincent A. , Nagamine Tomoaki , Crocco Todd
Published: May 2009

Object. More than 100 clinical trials based on animal models have failed to identify a clinically effective neuroprotectant for stroke. Current models of stroke do not account adequately for aging nor do they incorporate the use of female animals. The authors evaluated the pathological and physiological differences in stroke in young, adult, and elderly female rats.

Methods. Three groups of female Sprague—Dawley rats were studied. Nine rats were divided into three groups: young (3 months); adult (9 months); and elderly (18 months). Intraluminal filament occlusion was performed for 120 minutes while cerebral blood flow was monitored. Physiological parameters were assessed. Infarction volumes were quantified at 24 hours.

The mean arterial pressure increased in the young animals (103 ± 3.51 mm Hg; p < 0.001) during occlusion and decreased in the elderly group (65.56 ± 3.03 mm Hg; p < 0.01). Cortical and striatal infarction volumes in the elderly animals were substantially larger (p < 0.05). Young animals exhibited a lesser decrement in cerebral blood flow (p < 0.05) during ischemia.

Conclusions. This study reinforces the importance of using older animals for the researching and treatment of stroke. Elderly animals show differences in response mechanisms, ischemic consequences, and histological changes. These differences may partially explain the current lack of success involved in using young-animal models to predict the clinical efficacy of neuroprotective agents.
Gliomatosis cerebri: quantitative proof of vessel recruitment by cooptation instead of angiogenesis
Authors: Bernsen Hans , van der Laak Jeroen , Küsters Benno , van der Ven Abel , Wesseling Pieter
Published: May 2009

Object. Gliomas are the most common primary brain tumors, many of which (especially astrocytic and oligodendroglial neoplasms) are characterized by diffuse infiltrative growth in the preexisting brain tissue. Gliomatosis cerebri is a rare glial tumor and represents an extreme example of such diffuse infiltrative growth. This growth pattern not only hampers curative treatment but also allows for vessel cooptation rather than tumor angiogenesis as a way of vessel recruitment by the tumor tissue. The goal of this study was to establish the extent to which tumor angiogenesis occurs in gliomatosis cerebri.

Methods. Computerized image analysis was performed to assess quantitatively two microvascular parameters (vessel density and diameter) in different areas of a brain harboring a gliomatosis cerebri. These regions were the cerebral white and gray matter in which there was a diffuse infiltrative tumor, cerebral white and gray matter in which there was a more compact growth pattern of tumor cells, and normal cerebral white and gray matter. In addition, the authors performed immunohistochemical stainings for blood—brain barrier (BBB) characteristics (Glut-1 and PgP) on samples obtained in these different areas.

The results of the quantitative analysis strongly indicated that in gliomatosis cerebri tumor, angiogenesis was completely absent, a finding that is corroborated by the fact that the microvasculature in gliomatosis cerebri persists in exhibiting immunohistochemical characteristics of the BBB.

Conclusions. The results of this study may help resolve the difficulties in radiological detection and delineation of the diffuse infiltrative part of glial brain tumors and put the expectations for antiangiogenic treatment of such tumors into perspective.
Effect of perfluorocarbons on brain oxygenation and ischemic damage in an acute subdural hematoma model in rats
Authors: Kwon Taek Hyun , Sun Dong , Daugherty Wilson P. , Spiess Bruce D. , Bullock M. Ross
Published: May 2009

Object. This study was conducted to determine whether perfluorocarbons (PFCs) improve brain oxygenation and reduce ischemic brain damage in an acute subdural hematoma (SDH) model in rats.

Methods. Forty adult male Sprague—Dawley rats were allocated to four groups: 1) controls, acute SDH treated with saline and 30% O2; 2) 30-PFC group, acute SDH treated with PFC infusion in 30% O2; 3) 100-O2 group, acute SDH treated with 100% O2; and 4) 100-PFC group, acute SDH treated with PFC plus 100% O2. Ten minutes after the induction of acute SDH, a single dose of PFC was infused and 30% or 100% O2 was administered simultaneously. Four hours later, half of the rats were killed by perfusion for histological study to assess the extent of ischemic brain damage. The other half were used to measure brain tissue oxygen tension (PO2). The volume of ischemic brain damage was 162.4 ± 7.6 mm3 in controls, 165.3 ± 11.3 mm3 in the 30-PFC group, 153.4 ± 17.3 mm3 in the 100-O2 group, and 95.9 ± 12.8 mm3 in the 100-PFC group (41% reduction compared with controls, p = 0.002). Baseline brain tissue PO2 values were approximately 20 mm Hg, and after induction of acute SDH, PO2 rapidly decreased and remained at 1 to 2 mm Hg. Treatment with either PFC or 100% O2 improved brain tissue PO2, with final values of 5.14 and 7.02 mm Hg, respectively. Infusion of PFC with 100% O2 improved brain tissue PO2 the most, with a final value of 15.16 mm Hg.

Conclusions. Data from the current study demonstrated that PFC infusion along with 100% O2 can significantly improve brain oxygenation and reduce ischemic brain damage in acute SDH.
A triple bifurcation aneurysm model for evaluating complex endovascular therapies in dogs
Authors: Boulos Alan S. , Deshaies Eric M. , Fessler Richard D. , Aketa Shuta , Standard Scott , Miskolczi Lazlo , Guterman Lee R. , Hopkins L. Nelson
Published: May 2009

Object. Animal aneurysm models are required for the study of the hemodynamics and pathophysiology of intracranial aneurysms in humans and so that experimental treatments can be tested prior to clinical trials. The authors developed a canine model that consistently produces up to three bifurcation aneurysms similar in morphological features and hemodynamics to human intracranial aneurysms.

Methods. In 10 mongrel dogs, a harvested segment of the external jugular vein was anastamosed to an external carotid artery (CA)—lingual artery bifurcation arteriotomy site to create a lateral bifurcation aneurysm. The surgery was repeated on the contralateral side in each animal to form a second lateral bifurcation aneurysm and, in five dogs, a CA—CA crossover anastomosis was also performed to create a terminal bifurcation aneurysm.

Nineteen of 20 lateral bifurcation aneurysms were confirmed in 10 dogs by diagnostic angiography 7 to 14 days after surgery. Aneurysm fundus-to-neck ratios ranged from 1 to 2, depending on the size of the arteriotomy. The terminal bifurcation aneurysms were confirmed in all five dogs by diagnostic angiography 7 to 14 days after the procedure. The authors later tested endovascular techniques for embolizing the aneurysms.

Conclusions. Three bifurcation aneurysms of sufficient size for endovascular access can be created in a reproducible fashion in the same animal. This model is useful for studying complex endovascular procedures in aneurysms that mimic the human condition and for testing new devices and techniques.
Controlled release of a nitric oxide donor for the prevention of delayed cerebral vasospasm following experimental subarachnoid hemorrhage in nonhuman primates
Authors: Clatterbuck Richard E. , Gailloud Philippe , Tierney Travis , Clatterbuck Victoria M. , Murphy Kieran J. , Tamargo Rafael J.
Published: May 2009

Object. Results of prior studies in rats and rabbits show that the alteration of vasomotor tone in vasospasm following periadventitial blood exposure may be reversed, at least in part, by the administration of compounds releasing nitric oxide (NO). The authors have now generalized this finding to nonhuman primates.

Methods. Ten cynomolgus monkeys underwent cerebral angiography before and 7 days following the induction of subarachnoid hemorrhage (SAH) by the placement of 2 to 3 ml clotted autologous blood around the supraclinoid carotid, proximal anterior cerebral, and proximal middle cerebral arteries. An ethylene vinyl acetate copolymer, either blank (five animals) or containing 20% w/w (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO, 4.3 mg/kg; five animals) was placed adjacent to the vessels at the time of surgery. Animals were killed on Day 7 post-SAH following repeated cerebral angiography. The mean percentage of control vascular areal fraction was calculated from angiograms. Cerebral vessels were sectioned and the mean percentage of lumen patency was calculated.

One animal that had received the DETA/NO polymer died prior to repeated angiography. In the remaining animals, DETA/NO caused a significant decrease in vasospasm compared with controls, according to both angiographic (84.8 ± 8.6 compared with 56.6 ± 5.2%, respectively, p < 0.05) and histological studies (internal carotid artery 99.3 ± 1.8 compared with 60.1 ± 4.4%, respectively, p < 0.001; middle cerebral artery 98.4 ± 3 compared with 56.1 ± 3.7%, respectively, p < 0.001; and anterior cerebral artery 89.2 ± 8.5 compared with 55.8 ± 6.3%, respectively, p < 0.05).

Conclusions. The controlled release of DETA/NO is effective in preventing delayed cerebral vasospasm in an SAH model in nonhuman primates. The death of one animal in the treatment group indicates that the present dosage is at the threshold between therapeutic efficacy and toxicity.
Endoscopic aqueductoplasty through a tailored craniocervical approach
Authors: Gawish Islam , Reisch Robert , Perneczky Axel
Published: May 2009

Object. Neuroendoscopy has an essential role in the management of occlusive hydrocephalus due to a membranous obstruction of the sylvian aqueduct. Well-known endoscopic methods include endoscopic third ventriculostomy (ETV) and endoscopic aqueductoplasty through a frontal burr hole. Building on their experience in the endoscopic management of hydrocephalus, the authors realized that not all of their patients with aqueductal obstruction were eligible for the aforementioned lines of treatment. Certain anatomical situations made it impossible to perform ETV or endoscopic aqueductoplasty through a frontal burr hole. Long-term complications of the shunt system led the authors to seek an alternative form of treatment for these patients. In this study, they present a new endoscopic approach to performing aqueductoplasty through the fourth ventricle.

Methods. Endoscopic aqueductoplasty was performed in five patients by using a tailored craniocervical approach. In all patients a caudally located membranous obstruction of the sylvian aqueduct was present, and the authors were able to relieve the membranous obstruction in all patients without complications. All patients experienced improvement, which was demonstrated clinically and on imaging studies.

Conclusions. Caudal endoscopic aqueductoplasty is a safe and effective method of treatment in the management of a caudally located membranous obstruction of the sylvian aqueduct. This should be considered as an alternative endoscopic method when other endoscopic solutions are not suitable.
Posterior subtemporal transtentorial approach to intraparenchymal lesions of the anteromedial region of the superior cerebellum
Authors: Ammerman Joshua M. , Lonser Russell R. , Oldfield Edward H.
Published: May 2009

Object. To overcome the limitations associated with surgical approaches that have been described for accessing intraparenchymal lesions of the anteromedial region of the superior cerebellum, the authors used a posterior subtemporal transtentorial approach to remove tumors in this region. In this paper they describe the surgical technique that they used as well as the operative findings and clinical outcomes observed in patients who underwent resection of tumors in the anteromedial superior cerebellum.

Methods. The consecutive patients with anteromedial superior cerebellar tumors who underwent resection performed using the posterior subtemporal transtentorial approach at the National Institutes of Health were included in this study. Clinical, neuroimaging, and operative results were analyzed.

Three patients (two men and one woman) with anteromedial superior cerebellar tumors (two hemangioblastomas and one pilocytic astrocytoma) underwent resection via this approach. All the tumors were larger than 3 cm in diameter (range 3.1–3.5 cm). This approach provided excellent surgical access and permitted complete tumor resection in each case. The patients remained neurologically unchanged compared with preoperative baseline findings at the last follow-up examination (conducted at 4, 18, and 42 months postoperatively). One patient displayed a mild transient confusion immediately after surgery, but it resolved within 6 days.

Conclusions. The posterior subtemporal transtentorial approach provides excellent access to the anteromedial superior cerebellar region. This approach permits resection of large lesions in this location, while avoiding many of the limitations associated with other approaches to this site.
Primary empty sella syndrome in a series of 142 patients
Authors: Maira Giulio , Anile Carmelo , Mangiola Annunziato
Published: May 2009

Object. The primary empty sella syndrome (ESS) represents a heterogeneous clinical picture characterized by endocrine disturbances and signs of intracranial hypertension. An increase in intracranial pressure (ICP) is proposed to be one of the involved pathogenetic factors.

Methods. The series included 142 patients who were observed during a period of 20 years. All patients underwent an ICP and cerebrospinal fluid (CSF) dynamics evaluation through the use of a lumbar constant-rate infusion test.

Impairment of ICP and CSF dynamics was observed in 109 patients (76.8%). In 35 of the 36 patients affected by severe intracranial hypertension without rhinorrhea, improvement in adverse neurological symptoms was achieved after implanting a CSF shunt. Visual function, already seriously compromised before surgery, remained severely altered in one patient. In the group of 34 patients affected by rhinorrhea, CSF leakage was controlled using different surgical treatments: CSF shunt placement in 16 cases, surgical repair of the sellar floor in three, and both procedures in the remaining 13. Two patients refused any surgical treatment.

Conclusions. The role of increased ICP in the pathogenesis and perpetuation of primary ESS has been confirmed. Adverse neurological signs and a CSF leak are correlated with an actual increase in ICP and are relieved after CSF shunt insertion. Cerebrospinal fluid rhinorrhea is more common than generally thought. Its resolution can be achieved using a careful diagnostic protocol and sometimes may require different surgical procedures.
Depression and functional outcome in patients with brain tumors: a population-based 1-year follow-up study
Authors: Mainio Arja , Hakko Helinä , Niemelä Asko , Koivukangas John , Räsänen Pirkko
Published: May 2009

Object. The authors analyzed changes in depression and contemporary functional states by using valid tools in a population-based study sample during a 1-year follow-up period.

Methods. The study population consisted of 77 patients with a solitary primary brain tumor treated surgically at the Oulu Clinic for Neurosurgery. Each patient's depressive status, according to the Beck Depression Inventory (BDI), and functional outcome, based on the Karnofsky Performance Scale (KPS), were evaluated before the tumor was surgically treated as well as 3 months and 1 year after surgery. Before surgery 27 patients (35%) had BDI scores indicating the presence of depression. These scores were significantly higher in patients with a history of depression (p = 0.017) and in those with a lower functional outcome (p = 0.015). In the entire study sample the severity of depression decreased statistically significantly (p = 0.031) at 3 months postsurgery. A lower functional status (KPS score ≤ 70) in patients was significantly associated with high depression scores at the 3-month (p = 0.000) and 1-year (p = 0.005) assessments. The decrease in the level of depression was significant in patients with an anterior tumor (p = 0.049) and those with a pituitary adenoma (p = 0.019).

Conclusions. Affective disorders among patients with brain tumors must be considered immediately after surgery, especially in persons with a depression history and in those with a coincident physical disability.
A reassessment of vascular endothelial growth factor in central nervous system pathology
Authors: Merrill Marsha J. , Oldfield Edward H.
Published: May 2009

✓ Overexpression of vascular endothelial growth factor (VEGF) is associated with several central nervous system (CNS) diseases and abnormalities, and is often postulated as a causative factor and promising therapeutic target in these settings. The authors' goal was to reassess the contribution of VEGF to the biology and pathology of the CNS.

The authors review the literature relating to the following aspects of VEGF: 1) the biology of VEGF in normal brain; 2) the involvement of VEGF in CNS disorders other than tumors (traumatic and ischemic injuries, arteriovenous malformations, inflammation); and 3) the role of VEGF in brain tumor biology (gliomas and the associated vasogenic edema, and hemangioblastomas).

The authors conclude the following: first, that VEGF overexpression contributes to the phenotype associated with many CNS disorders, but VEGF is a reactive rather than a causative factor in many cases; and second, that use of VEGF as a therapeutic agent or target is complicated by the effects of VEGF not only on the cerebral vasculature, but also on astrocytes, neurons, and inflammatory cells. In many cases, therapeutic interventions targeting the VEGF/VEGF receptor axis are likely to be ineffective or even detrimental. Clinical manipulation of VEGF levels in the CNS must be approached with caution.
Expression of the tumor necrosis factor receptor—associated factors 1 and 2 and regulation of the nuclear factor—kB antiapoptotic activity in human gliomas
Authors: Conti Alfredo , Aguennouz M'Hammed , La Torre Domenico , Cardali Salvatore , Angileri Filippo Flavio , Buemi Catia , Tomasello Chiara , Iacopino Domenico Gerardo , D'Avella Domenico , Vita Giuseppe , Tomasello Francesco
Published: May 2009

Object. Tumor necrosis factor receptor (TNFR)—associated factors (TRAFs) are a recently established group of proteins involved in the intracellular signaling of the TNFR superfamily members. The TRAFs have been implicated in promoting cell survival through the activation of transcription factor nuclear factor (NF)—κB. The authors investigated the expression of NF-κB, caspase 3, TRAF1, TRAF2, and TRAF-associated NF-κB activator/TRAF—interacting protein (TANK/I-TRAF), a regulator of TRAF activity, in human gliomas.

Methods. Tumor samples were obtained in 27 adult patients harboring seven low-grade gliomas, nine anaplastic astrocytomas, and 11 glioblastomas multiforme. The NF-κB activation was analyzed using the electrophoresis mobility shift assay; TRAF1, TRAF2, TANK/I-TRAF, and caspase 3 expression were studied using Western blot analysis.

Upregulated NF-κB DNA—binding activity, compared with that in normal brain tissue, was detected in all tumor samples (p = 0.002). The level of NF-κB activity showed some correlation with World Health Organization tumor grades (p = 0.01), even though variable activity levels were demonstrated in relation to tissue heterogeneity, which resulted in a substantial number of outliers in the quantitative analysis. Increased levels of TRAF1, TRAF2, and TANK/I-TRAF were expressed in astrocytomas compared with levels in normal brain tissue (p = 0.02, 0.006, and 0.01, respectively).

Conclusions. Data in this study confirm the upregulation of NF-κB in gliomas and reveal a correlation between levels of this transcription factor and tumor grade. A constitutive expression of TRAF1, TRAF2, and TANK/I-TRAF in human gliomas was documented. These proteins are involved in the intracellular signal transduction of the TNFR superfamily and in the control of NF-κB expression and its antiapoptotic activity.
Ultrastructural characteristics of hemorrhagic, nonhemorrhagic, and recurrent cavernous malformations
Authors: Tu Jian , Stoodley Marcus A. , Morgan Michael K. , Storer Kingsley P.
Published: May 2009

Object. Ultrastructural characteristics of hemorrhagic, nonhemorrhagic, primary, and recurrent central nervous system cavernous malformations (CMs) were examined in an attempt to clarify their pathological mechanisms.

Methods. Thirteen specimens (nine from samples of CMs and four from healthy control tissue) were processed for ultrastructural study immediately after surgical or postmortem removal, by fixation in glutaraldehyde/formalin and postfixation in OsO4. Transmission electron microscopy was used to examine the vascular walls, endothelium, subendothelium, and cytoplasmic organelles.

The vascular walls in CMs demonstrated abnormal ultrastructure with no basement membranes and astrocytic foot processes. Pericytes were rarely seen. Single-layer lining endothelial cells showed fenestrated luminal surfaces. Large gaps were observed at intercellular junctions between endothelial cells, and large vesicles with extremely thin plasma membranes bordering the lumen were common in the lesions that had previously hemorrhaged. Endothelial cells of recurrent CMs had more Weibel—Palade bodies, filopodia, cytoplasmic processes, micropinocytotic vesicles, and filaments than those in primary lesions and normal control tissues.

Conclusions. The absence of the blood–brain barrier, normal supporting wall structure, and large vesicles bordering the lumen of CM vessels may explain leakage of red blood cells into surrounding brain in the absence of major hemorrhage. Proliferation of residual abnormal endothelial cells may contribute to the recurrence of surgically removed CMs.
Functional magnetic resonance imaging in adult craniopagus for presurgical evaluation
Authors: Ho Yi-Ching Lynn , Goh Keith Yu-Ching , Golay Xavier , Hong Wee-Tin , Lim Shih-Hui , Pan Andrew Beng-Siong , Chua Violet Gek-Eng , Hui Francis , Sitoh Yih-Yian
Published: May 2009

✓ Cranially conjoined twins are rare and pose unique challenges in the preoperative evaluation of cerebral language function. The authors report on their experience in the functional magnetic resonance (fMR) imaging evaluation of adult craniopagus (temporoparietooccipital fusion) to evaluate hemispheric language dominance and the eloquent language areas in the preoperative planning stages. Conventional clinical imaging hardware originally designed for individuals was adapted and tailored for use in the twins. They were assigned a selection of language tasks while undergoing fMR imaging. Significant blood oxygen level—dependent activations were detected in the main language regions in each twin, that is, the inferior frontal gyrus (around the Broca area), the middle and superior temporal lobes (around the Wernicke area) together with the inferior parietal lobe, and the middle and superior frontal gyri. Overall, the right-handed twin was strongly left lateralized for language, whereas the left-handed twin showed more bilateral activation during language tasks. Noninvasive language mapping with the aid of fMR imaging has been demonstrated for the first time in total craniopagus.
Prospective evaluation of surgical microscope—integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery
Authors: Raabe Andreas , Nakaji Peter , Beck Jürgen , Kim Louis J. , Hsu Frank P. K. , Kamerman Jonathan D. , Seifert Volker , Spetzler Robert F.
Published: May 2009

Object. The authors prospectively compared a new technique of surgical microscope-based indocyanine green (ICG) videoangiography with intraoperative or postoperative digital subtraction (DS) angiography.

Method. The technique was performed during 187 surgical procedures in which 124 aneurysms in 114 patients were clipped. Using a newly developed setup, the ICG technique has been integrated into an operating microscope (Carl Zeiss Co., Oberkochen, Germany). A microscope-integrated light source containing infrared excitation light illuminates the operating field. The dye is injected intravenously into the patient, and intravascular fluorescence from within the blood vessels is imaged using a video camera attached to the microscope. The patency of parent, branching, and perforating arteries and documentation of clip occlusion of the aneurysm as shown by ICG videoangiography were compared with intraoperative or postoperative findings on DS angiography.

The results of ICG videoangiography corresponded with intra- or postoperative DS angiography in 90% of cases. The ICG technique missed mild but hemodynamically irrelevant stenosis that was evident on DS angiography in 7.3% of cases. The ICG technique missed angiographically relevant findings in three cases (one hemodynamically relevant stenosis and two residual aneurysm necks [2.7% of cases]). In two cases the missed findings were clinically and surgically inconsequential; in the third case, a 4-mm residual neck may require a second procedure. Indocyanine green videoangiography provided significant information for the surgeon in 9% of cases, most of which led to clip correction.

Conclusions. Microscope-based ICG videoangiography is simple and provides real-time information about the patency of vessels of all sizes and about the aneurysm sac. This technique may be useful during routine aneurysm surgery as an independent form of angiography or as an adjunct to intra- or postoperative DS angiography.
Connectivity of the human periventricular—periaqueductal gray region
Authors: Sillery Emma , Bittar Richard G. , Robson Matthew D. , Behrens Timothy E. J. , Stein John , Aziz Tipu Z. , Johansen-Berg Heidi
Published: May 2009

Object. The periventricular gray (PVG) zone and its continuation, the periaqueductal gray (PAG) substance, have been targets for deep brain stimulation (DBS) in the alleviation of intractable pain for longer than two decades. Nevertheless, the anatomical connectivity of this region has been fairly poorly defined. The effects of DBS in this region are probably related to the release of endogenous endorphins, but until the connectivity of this region is better understood the mechanisms will remain unclear.

Methods. Diffusion tractography was used to trace the pathways of the PVG—PAG region in seven healthy human volunteers. Images were acquired with the aid of a 1.5-tesla magnetic resonance imaging system. The region of interest was located just lateral to the posterior commissure and extended caudally to the level of the superior colliculus. Probabilistic diffusion tractography was performed from each voxel in each patient's PVG—PAG region.

The PVG—PAG region was found to yield descending projections to the spinal cord and cerebellum. Ascending projections to the thalamus and frontal lobes were also observed.

Conclusions. These findings suggest that the PVG—PAG region may modulate pain by two mechanisms: one involving the antinociceptive system in the spinal cord and the other involving influences on the central pain network.
Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part I: experimental study of the effect of oophorectomy in rats
Authors: Jamous Mohammad A. , Nagahiro Shinji , Kitazato Keiko T. , Satomi Junichiro , Satoh Koichi
Published: May 2009

Object. Estrogen has been shown to play a central role in vascular biology. Although it may exert beneficial vascular effects, its role in the pathogenesis of cerebral aneurysms remains to be determined. To elucidate the role of hormones further, the authors examined the effects of bilateral oophorectomy on the formation and progression of cerebral aneurysms in rats.

Methods. Forty-five female, 7-week-old Sprague—Dawley rats were divided into three equal groups. Group I consisted of intact rats (controls). To induce cerebral aneurysms, the animals in Groups II and III were subjected to ligation of the right common carotid and bilateral posterior renal arteries. One month later, the rats in Group II underwent bilateral oophorectomy. Three months after the experiment began all animals were killed and cerebral vascular corrosion casts were prepared and screened for cerebral aneurysms by using a scanning electron microscope. Plasma was used to determine the level of estradiol and the gelatinase activity.

Hypertension developed in all rats except those in the control group. The estradiol level was significantly lower in Group II than in the other groups (p < 0.01). The incidence of cerebral aneurysm formation in Group II (60%) was three times higher than that in Group III (20%), and the mean size of aneurysms in Group II (76 ± 27 µm, mean ± standard deviation) was larger than that in Group III (28 ± 4.6 µm) (p < 0.05). No aneurysm developed in control animals (Group I), and there was no significant difference in plasma gelatinase activity among the three groups.

Conclusions. The cerebral aneurysm model was highly reproducible in rats. Bilateral oophorectomy increased the susceptibility of rats to aneurysm formation, indicating that hormones play a role in the pathogenesis of cerebral aneurysms.
Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II: experimental study of the effects of hormone replacement therapy in rats
Authors: Jamous Mohammad A. , Nagahiro Shinji , Kitazato Keiko T. , Tamura Tetsuya , Kuwayama Kazuyuki , Satoh Koichi
Published: May 2009

Object. The increased incidence of cerebral aneurysms in postmenopausal women appears to be related to low levels of circulating estrogen. Using a rat model of aneurysm induction, the authors found that oophorectomy increased the incidence of experimental cerebral aneurysms (Part I in this issue). In the current study they examined the effects of hormone replacement therapy (HRT) on the formation of cerebral aneurysms in rats.

Methods. Forty-five female Sprague—Dawley rats were divided into three equal groups. The animals in Groups A and B were subjected to a cerebral aneurysm induction procedure (renal hypertension and right common carotid artery ligation) followed 1 month later by bilateral oophorectomy. After an additional week the rats in Group A received 17β estradiol continuous-release pellets. The rats in Group C served as controls. Three months after the aneurysm induction procedure, all the rats were killed and vascular corrosion casts of their cerebral arteries were prepared and checked for aneurysmal changes. Using a scanning electron microscope, the authors recorded aneurysmal changes as endothelial changes alone (Stage I), endothelial changes with intimal pad elevation (Stage II), and saccular aneurysm formation (Stage III). Aneurysmal changes (Stages I, II, and III) occurred in one third of rats that had undergone oophorectomy and were receiving HRT (Group A), compared with 87% of the rats that had undergone oophorectomy but did not receive HRT (Group B). Although most of the aneurysmal changes identified in Group A rats were limited to Stage I or II, most changes in Group B animals were identified as saccular dilation (Stage III).

Conclusions. The findings demonstrated the significant protective role of estrogen against the formation and progression of cerebral aneurysms. It appears to be related to the beneficial effects of estrogen on the function and growth of endothelial cells, which play a major role in preserving the integrity of the vascular wall.
Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy
Authors: Wang Weijun , Zhu Nian-Ling , Chua Jason , Swenson Steve , Costa Fritz K. , Schmitmeier Stephanie , Sosnowski Barbara A. , Shichinohe Toshiaki , Kasahara Noriyuki , Chen Thomas C.
Published: May 2009

Object. Adenovirus vector (AdV)—mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression.

Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis.

Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.
Rapid expansion of a previously asymptomatic subependymoma
Authors: Laxton Adrian W. , Shannon Patrick , Nag Sukriti , Farb Richard I. , Bernstein Mark
Published: May 2009

✓ This 39-year-old man presented with a 6-month history of occipital headaches. Magnetic resonance imaging revealed an irregularly shaped fourth ventricle mass. One month after his initial presentation, he was admitted to the hospital with significant tumor expansion and clinical deterioration. A posterior fossa craniectomy was performed and the mass was resected. Histopathological analysis of this tumor showed central necrosis with associated edema in an otherwise typical and benign-appearing subependymoma. To the authors' knowledge, this is the first reported case of rapid, nonhemorrhagic expansion associated with necrosis in a previously asymptomatic subependymoma.
Arachnoid cyst with associated arachnoiditis developing after subarachnoid hemorrhage
Authors: Tumialán Luis M. , Cawley C. Michael , Barrow Daniel L.
Published: May 2009

✓ The authors report the case of a 53-year-old woman in whom a T1–T2 spinal arachnoid cyst with associated arachnoiditis developed, compressing the thoracic spinal cord 1 year after the patient had suffered a Hunt and Hess Grade IV subarachnoid hemorrhage (SAH). Development of spinal arachnoiditis with or without an arachnoid cyst is a rare complication of aneurysmal SAH. Risk factors may include posterior circulation aneurysms, the extent and severity of the hemorrhage, and the need for cerebrospinal fluid diversion. Surgical drainage, shunt placement, or cyst excision, when possible, is the mainstay of treatment.