bluuebunny/crossref_metadata_2025 huggingface dataset:
Medulloblastoma with extensive nodularity: a variant with favorable prognosis
Authors: Giangaspero Felice , Perilongo Giorgio , Fondelli Maria Paola , Brisigotti Massimo , Carollo Carla , Burnelli Roberta , Burger Peter C. , Garrè Maria Luisa
Published: May 2009

Object. Some medulloblastomas (MBs) are characterized by extreme nodularity and intranodular nuclear uniformity in a fine fibrillary background. These lesions have also been designated as “cerebellar neuroblastoma.” Although numerous reports have been published in which their morphological features have been investigated, only a few studies have been focused on their neuroradiological appearance, biological behavior, and response to therapy. The goal of this study was to gather more information about these lesions.

Methods. The authors present 11 cases of MB with extensive nodularity. Five patients were boys and six were girls; all but one were 24 months of age or younger at diagnosis. Magnetic resonance imaging disclosed a peculiar grapelike architecture in eight cases. Surgical tumor removal was complete in nine cases and partial in one. In the other case a biopsy sample of the tumor was obtained after a preoperative course of chemotherapy. After surgery, two children were treated with radiotherapy alone and one with craniospinal irradiation followed by systemic chemotherapy. Eight patients were treated with chemotherapy only. All the patients in the study are presently alive with a median follow up of 66 months. Eight patients (73%) are in complete remission at 35 to 156 months. Three patients treated with chemotherapy alone postsurgery relapsed; however, all underwent successful retreatment (two with craniospinal irradiation and one with further surgery plus high-dose chemotherapy) and are in complete remission. A review of the literature revealed that patients in 11 of 12 reported cases were younger than 3 years of age and that seven of eight in whom follow-up information was available were alive and well, with survival times ranging from 6 to 84 months.

Conclusions. Medulloblastomas with extensive nodularity represent a variant that is characterized by: 1) occurrence in very young children; 2) a peculiar grapelike appearance on neuroimaging; and 3) an apparently favorable outcome.
Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels
Authors: Bell Helen S. , Wharton Stephen B. , Leaver H. Anne , Whittle Ian R.
Published: May 2009

Object. Intracranial infusions of gamma-linolenic acid (GLA), an essential fatty acid, have been used as an adjuvant therapy following malignant glioma resection; however, little is known about the dose response of glioma cells to this therapy. In this in vitro study the authors address this important pharmacological question.

Methods. Glioma spheroids derived from U87, U373, MOG-G-CCM, and C6 cell lines were grown in collagen gel and exposed to a range of GLA concentrations (0–1 mM) for 5 days. The diameter of glioma spheroids was measured, the apoptotic index was assessed using both the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling technique and cell morphological testing, and the levels of proliferating cell nuclear antigen were also measured.

Conclusions. The dose—response patterns were similar for all four glioma spheroids. Low concentrations of GLA (< 100 µM) increased both apoptosis and proliferation with a net increase in tumor growth and invasion, whereas high-dose GLA (> 100 µM) significantly impaired spheroid cell growth. The proliferative effects of low-dose GLA could be a hazard in the clinical treatment of malignant glioma; however, because of the low toxicity of GLA against normal cells, local delivery of millimolar doses of GLA could significantly reduce tumor size.
Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction
Authors: Broaddus William C. , Liu Yue , Steele Laura L. , Gillies George T. , Lin Peck-Sun , Loudon William G. , Valerie Kristoffer , Schmidt-Ullrich Rupert K. , Fillmore Helen L.
Published: May 2009

Object. The goal of this study was to determine whether adenoviral vector—mediated expression of human wildtype p53 can enhance the radiosensitivity of malignant glioma cells that express native wild-type p53.

The p53 gene is thought to function abnormally in the majority of malignant gliomas, although it has been demonstrated to be mutated in only approximately 30%. This has led to studies in which adenoviral transduction with wild-type human p53 has been investigated in an attempt to slow tumor cell growth. Recent studies suggest that reconstitution of wild-type p53 can render cells more susceptible to radiation-mediated death, primarily by p53-mediated apoptosis.

Methods. Rat RT2 glioma cells were analyzed for native p53 status by reverse transcriptase—polymerase chain reaction and sequence analysis and for p53 expression by Western blot analysis. Clonogenic survival and the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling assay were used to characterize RT2 cell radiosensitivity and apoptosis, respectively, with and without prior transduction with p53-containing and control adenoviral vectors. Animal survival length was monitored after intracerebral implantation with transduced and nontransduced RT2 cells, with and without cranial radiation.

The RT2 cells were demonstrated to express native rat wild-type p53 and to markedly overexpress human p53 following adenoviral p53 transduction. The combination of p53 transduction followed by radiation resulted in marked decreases in RT2 cell survival and increases in apoptosis at radiation doses from 2 to 6 Gy. Animals receiving cranial radiation after intracerebral implantation with RT2 cells previously transduced with p53 survived significantly longer than control animals (p < 0.01).

Conclusions. The ability to enhance the radiosensitivity of malignant glioma cells that express wild-type p53 by using adenoviral transduction to induce overexpression of p53 offers hope for this approach as a therapeutic strategy, not only in human gliomas that express mutant p53, but also in those that express wild-type p53.
Quantification of increased exposure resulting from orbital rim and orbitozygomatic osteotomy via the frontotemporal transsylvian approach
Authors: Schwartz Marc S. , Anderson Gregory J. , Horgan Michael A. , Kellogg Jordi X. , McMenomey Sean O. , Delashaw Johnny B.
Published: May 2009

Object. Use of orbital rim and orbitozygomatic osteotomy has been extensively reported to increase exposure in neurosurgical procedures. However, there have been few attempts to quantify the extent of additional exposure gained by these maneuvers. Using a novel laboratory technique, the authors have attempted to measure the increase in the “area of exposure” that is gained by removal of the orbital rim and zygomatic arch via the frontotemporal transsylvian approach.

Methods. The authors dissected five cadavers bilaterally. The area of exposure provided by the frontotemporal transsylvian approach was determined by using a frameless stereotactic device. With the tip of a microdissector placed on targets deep within the exposure, the position of the end of the microdissector handle was measured in three-dimensional space as the microdissector was rotated around the periphery of the operative field. This maneuver was performed via the frontotemporal approach alone as well as with orbital rim and orbitozygomatic osteotomy approaches. After data manipulation, the areas of exposure corresponding to the polygons used to define these handle positions were calculated and directly compared. On average, the area of exposure provided by the frontotemporal transsylvian approach was increased 26 to 39% (p < 0.05) by adding orbital rim osteotomy and an additional 13 to 22% (not significant) with removal of the zygomatic arch.

Conclusions. Significant and consistent increases in surgical exposure were obtained by using orbital osteotomy, whereas zygomatic arch removal produced less consistent gains. Both maneuvers may be expected to improve surgical access. However, because larger and more consistent gains were afforded by orbital rim removal, the threshold for removal of this portion of the orbitozygomatic complex should be lower.
The anatomy of the Berrettini branch: implications for carpal tunnel release
Authors: Stančić Marin F. , Mićović Vladimir , Potoćnjak Mark
Published: May 2009

Object. Dissections were performed in 100 fresh cadaver palms to determine the frequency with which superficial palmar communication between the median and ulnar nerves occurs and to what extent it might incur iatrogenic injury during endoscopic carpal tunnel release.

Methods. Superficial palmar communication between the median and ulnar nerves was present in 81% of the dissected hands. Superficial palmar communication, also known as the Berrettini branch, has been classified into four distinct types by Ferrari and Gilbert. Twelve hands were classified as Group 1 (communication in an oblique course from the ulnar to the median nerve originating > 4 mm above the distal margin of the transverse carpal ligament [TCL]), 16 hands were classified as Group 2 (communication parallel to the distal margin of the TCL), and 53 hands were classified as Group 3 (communication in an oblique course from the ulnar nerve to the third common digital nerve, originating below the distal margin of the TCL). No hand fit the Group 4 classification (atypical communication).

Conclusions. The Berrettini branch can be considered a normal anatomical finding. In 28% of the hands in this study, the branch was proximal to the edge of the distal ligament and, therefore, prone to iatrogenic injury in both one-portal and two-portal endoscopic surgery.
Ruptured cerebral pseudoaneurysm caused by the removal of a ventricular catheter
Authors: Shirane Reizo , Kondo Takeo , Yoshida Yasuko K. , Furuta Susumu , Yoshimoto Takashi
Published: May 2009

✓ A rare case of cerebral pseudoaneurysm located at the internal carotid artery (ICA) was caused by the removal of a ventricular catheter in an infant. This 4-month-old girl underwent ventriculoperitoneal shunt revision, during which the old ventricular catheter was removed from the posterior horn of the left lateral ventricle, but the choroid plexus was pulled out by the tip of the catheter. Intraventricular hemorrhage (IVH) and subarachnoid hemorrhage were observed postoperatively. Magnetic resonance (MR) angiography performed on the 12th postoperative day revealed ICA stenosis and aneurysm formation at the C1 portion of the left ICA. Contrast-enhanced computerized tomography (CT) scans obtained on the 21st postoperative day revealed recurrent IVH and enlargement of the lesion. The patient underwent surgery for treatment of the aneurysm. Operative findings revealed a pseudoaneurysm arising from the left ICA at the proximal end of the anterior choroidal artery (AChA). The aneurysm was removed and the wall of the ICA was reconstructed. Postoperative three-dimensional CT scanning and MR angiography demonstrated disappearance of the aneurysm and preservation of the ICA. The patient was discharged without additional neurological deficits.

Many complications, including IVH, are associated with removal of a ventricular catheter. This case shows that pseudoaneurysm formation can occur in a remote region due to avulsion of the AChA from the ICA. In most circumstances a ventricular catheter can be removed without difficulty. However, precision and caution should be exercised when removing a ventricular catheter.
Histiocytic lesion mimicking intrinsic brainstem neoplasm
Authors: Weaver Kyle D. , Armao Diane , Wiley Joseph M. , Ewend Matthew G.
Published: May 2009

✓ This 10-year-old girl presented with a 1-month history of progressive bulbar palsy and a solitary enhancing mass originating within the floor of the fourth ventricle. Results of initial imaging studies and presentation were suggestive of neoplasia. Subtotal resection was performed and pathological examination revealed the mass to be a histiocytic lesion, with no evidence of a glioma. The patient had no other stigmata of histiocytosis and was treated with steroid medications, resulting in prolonged resolution of the lesion. This case demonstrates that for discrete brainstem lesions the differential diagnosis includes entities other than glioma for which treatment is available. Biopsy sampling should be considered when technically feasible.
Pure sylvian fissure arteriovenous malformations
Authors: Zimmerman Gary , Lewis Adam I. , Tew John M.
Published: May 2009

Object. Pure sylvian fissure arteriovenous malformations (AVMs) are vascular malformations confined to the sylvian fissure without parenchymal involvement. Because the branches of the middle cerebral artery are arteries of passage and the margins between the AVM and the insula cortex may be ill defined, many surgeons regard pure sylvian fissure AVMs as inoperable. The authors reviewed their surgical experience with eight patients harboring pure sylvian fissure AVMs to determine the incidence of operative morbidity.

Methods. All eight patients experienced seizures, five (63%) had headaches, and three (38%) experienced hemorrhages. Preoperatively, six patients (75%) were normal neurologically and two (25%) had neurological deficits. Five (63%) of eight sylvian fissure AVMs were located in the dominant hemisphere. The size of the nidus ranged from 6 to 27 cm3 (mean 14 cm3).

Complete removal of the AVM was documented by postoperative angiography in every case. Seizures were reduced or eliminated and headaches were relieved in all affected patients. Transient neurological deficits, which included aphasia, short-term memory loss, and hemiparesis, occurred in four patients (50%). Within 3 months, all patients were functioning independently with no new neurological deficits. The status of two patients who had had preoperative neurological deficits improved postoperatively. Neuropsychological testing showed no new cognitive deficits.

Conclusions. With appreciation for transient instances of postoperative morbidity, the outcome was excellent in all patients. The authors thus advocate microsurgery as the primary treatment for pure sylvian fissure AVMs.
Somatosensory representation in patients who have undergone hemispherectomy: a functional magnetic resonance study imaging
Authors: Bittar Richard G. , Ptito Alain , Reutens David C.
Published: May 2009

Object. Removal or disconnection of an entire cerebral hemisphere is occasionally used to treat refractory seizures. Patients who have undergone a hemispherectomy provide useful models to study the reorganization of cortical somatosensory representation. This plasticity may be a consequence of the pathological lesion, the hemispherectomy itself, or both.

Methods. Three patients who had undergone hemispherectomy were studied with functional magnetic resonance (fMR) imaging. Responses to sensory stimulation in normal hands and hands opposite the lesioned hemisphere were studied. Multislice T2*-weighted gradient-echo echoplanar images were obtained using a 1.5-tesla MR imager. The activation condition consisted of somatosensory stimulation of the index finger. A T1-weighted anatomical MR image was acquired. The fMR and anatomical MR images were coregistered, and statistically significant activation foci (p < 0.01) were identified. Stimulation of the normal hand produced activation in the primary somatosensory cortex (SI) in all patients. Stimulation of the impaired hand resulted in activation of the ipsilateral parietal operculum (second somatosensory area [SII]) and posterior parietal lobe (Brodmann's Area 7) in all cases, but no activation was elicited in the SI in any patient. In addition, other areas within the ipsilateral frontal and parietal lobes were activated in some individuals.

Conclusions. Residual somatosensory function in the hand opposite the lesioned hemisphere is mediated by the SII and other cortical regions in the intact hemisphere, without involvement of the SI.
Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study
Authors: Davis Karen D. , Taub Ethan , Duffner Frank , Lozano Andres M. , Tasker Ronald R. , Houle Sylvain , Dostrovsky Jonathan O.
Published: May 2009

Object. Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.

Methods. The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.

Conclusions. The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.
Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia
Authors: Huh Pil W. , Belayev Ludmila , Zhao Weizhao , Koch Sebastian , Busto Raul , Ginsberg Myron D.
Published: May 2009

Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats.

Methods. Male Sprague—Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-l-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89% and 88%, respectively) and total infarct volume (by 54% and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64% and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level.

Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.
Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure
Authors: Benveniste Helene , Kim Katie R. , Hedlund Laurence W. , Kim John W. , Friedman Allan H.
Published: May 2009

Object. It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model.

Methods. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons.

There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups.

Conclusions. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.
Intracerebral administration of interleukin-1β and induction of inflammation, apoptosis, and vasogenic edema
Authors: Holmin Staffan , Mathiesen Tiit
Published: May 2009

Object. The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor—α (TNFα) are produced intracerebrally in brain disorders such as trauma, ischemia, meningitis, and multiple sclerosis. This investigation was undertaken to analyze the effect of intracerebral administration of IL-1β and TNFα on inflammatory response, cell death, and edema development.

Methods. Intracerebral microinjections of these cytokines were administered to rats. The animals were killed 24 or 72 hours after the injections, and their brains were analyzed by using deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) with digoxigenin-labeled deoxyuridine triphosphate, immunohistochemical studies, and brain-specific gravity measurement. The IL-1β induced a transient inflammatory response (p < 0.001) and TUNEL staining (p < 0.001), indicating cell death, in intrinsic central nervous system (CNS) cells and infiltrating inflammatory cells. In 73.8 ± 6.77% of the TUNEL-positive cells, small, fragmented nuclei were found. All TUNEL-positive cells expressed the proapoptotic gene Bax, and 69.6 ± 4.6% of the TUNEL-positive cells expressed the antiapoptotic gene Bcl-2; the Bax expression was stronger than the Bcl-2 expression. Taken together, the data indicate that cell death occurred via the apoptotic pathway. The TNFα did not induce inflammation or DNA fragmentation within the analyzed time period. Both IL-1β (p < 0.001) and TNFα (p < 0.01) caused vasogenic edema, as measured by specific gravity and albumin staining. The edematous effect of TNFα persisted 72 hours after injection (p < 0.01), whereas the IL-1β—treated animals had normalized by that time.

Conclusions. Intracerebral inflammation, death of intrinsic CNS cells, and vasogenic edema can be mediated by IL-1β, and TNFα can cause vasogenic edema. Suppression of these cytokines in the clinical setting may improve outcome.
Reduced xenograft rejection in rat striatum after pretransplant photodynamic therapy of murine neural xenografts
Authors: Honey Christopher R. , Obochi Modestus O. K. , Shen Hao , Margaron Philippe , Yip Stephen , Levy Julia G.
Published: May 2009

Object. The goal of this study was to develop a method of reducing neural xenograft rejection by pretreating the graft with photodynamic therapy (PDT).

Methods. Xenograft cell suspensions were prepared from fetal mouse mesencephalon, after which they were incubated for 30 minutes with various concentrations of a photosensitizer, verteporfin for injection, and light exposure. The xenograft cell suspensions were injected into the dopamine-depleted striata of 40 hemiparkinsonian rats assigned to different treatment groups. Four weeks after transplantation, xenograft function (determined by methamphetamine-induced rotation) and survival (determined by immunohistochemical staining for murine neurons) were compared. Group 1 animals (xenografts pretreated with 25 ng/ml verteporfin) and Group 3 animals (no verteporfin pretreatment, but daily administration of cyclosporin A) had significantly better xenograft survival and function compared with control animals (no pretreatment with verteporfin). Group 2 animals (xenografts pretreated with 250 ng/ml verteporfin) had no significant improvement.

Conclusions. This work demonstrates improved neural xenograft survival and function when using pretransplant PDT of the graft in a rodent model. The potential benefits of this new therapy are its convenience (one pretransplant treatment) and its compatibility with host immunosuppression.
Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo
Authors: Pu Peiyu , Liu Xuwen , Liu Aixue , Cui Jianling , Zhang Yunting
Published: May 2009

Object. The goal of this study was to evaluate the effect of antisense epidermal growth factor receptor (EGFR) RNA on the growth of rat glioma cells in vitro and in vivo and to determine the feasibility of targeting the EGFR gene for gene therapy in gliomas.

Methods. Antisense EGFR complementary (c)DNA was transfected into C6 glioma cells by using lipofectamine. In vitro studies, Southern and Northern blot analyses, in situ hybridization, and immunohistochemical staining were designed to examine the integration and expression of antisense EGFR constructs. The 3′(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay and the average number of argyrophilic nuclear organizer regions (Ag-NORs) were used to evaluate cell proliferation, whereas the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and microscopy were used to observe cell apoptosis. As part of the in vivo studies, parental C6 cells and C6 cells transfected with EGFR antisense cDNA were implanted stereotactically into the right caudate nucleus of Wistar rats (C6-injected animals and transfected C6-injected animals). Rats with well-established cerebral C6 glioma foci were treated intratumorally with either antisense EGFR cDNA or empty-vector DNA by using lipofectamine (treated-C6 and control treated group). The general behavior and survival of the rats, findings on magnetic resonance images of their brains, histopathological changes, proliferation activity, and apoptosis of the cerebral gliomas in each group of rats were examined.

Exogenous antisense EGFR cDNA was integrated into the genome of C6 cells and expressed. In clones with a high expression of the antisense construct, there was a dramatic decrease in endogenous EGFR messenger RNA and protein levels, reduced proliferation activity, and induction of apoptosis in vitro. The mean survival time of rats injected with C6 cells was 17.3 days. The mean survival time of rats injected with C6 cells followed by treatment with empty vector in lipofectamine was 15.4 days. Survival time was significantly prolonged in 100% of the rats injected with antisense-transfected C6 cells and in two thirds of the rats injected with C6 cells followed by antisense EGFR cDNA. Magnetic resonance imaging revealed distinct cerebral tumor foci in C6-injected rats and in control rats of the treated group, but none were found in the rats injected with transfected C6 cells. Furthermore, tumor foci disappeared completely in C6-injected rats treated with antisense EGFR cDNA. The cerebral gliomas of the rats treated by injection of antisense EGFR RNA were characterized by reduced proliferation activity and the induction of apoptosis.

Conclusions. The results of this study indicate that EGFR plays an important role in the genesis of malignant gliomas. It may, therefore, be an effective target of antisense gene therapy in patients with gliomas.
Ganglioglioma in a patient with Turcot syndrome
Authors: Tamiya Takashi , Hamazaki Shuji , Ono Yasuhiro , Tokunaga Koji , Matsumoto Kengo , Furuta Tomohisa , Ohmoto Takashi
Published: May 2009

✓ A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor—polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.
New concept for the pressure setting of a programmable pressure valve and measurement of in vivo shunt flow performed using microflow meter
Authors: Miyake Hiroji , Ohta Tomio , Kajimoto Yoshinaga , Nagao Kohji
Published: May 2009

✓ The aim of this study was to establish a standard method for determining the pressure setting of the Codman Hakim valve (CHV) in patients with hydrocephalus.

The authors' investigation was twofold. It focused on: 1) the relationships among CHV setting, intracranial pressure (ICP), intraabdominal pressure (IAP), hydrostatic pressure (HP), and perfusion pressure (PP); and 2) the shunt flow in 18 patients with normal-pressure hydrocephalus.

With the patient in a sitting position, the pressure environment around the ventriculoperitoneal shunt stabilized when PP became equal to the CHV setting. The lower the CHV setting, the lower the ICP obtained in patients in a sitting position (ICPsit) settled. This indicated the possibility of calculating the CHV setting by the equation CHV setting = HP + ideal ICPsit − IAP, where the ideal ICPsit was estimated to be between −70 and −140 mm H2O. The CHV setting was individually determined for 18 patients by using this method. The ICPsit was controlled at a level equal to the estimated ICPsit in most cases, which supported the rationality of our concept. Shunt flow was intermittent or very low when the patient assumed a supine position and between 200 and 600 µl/minute when the patient was seated.

Determining the CHV setting by using the equation CHV setting = HP + ideal ICPsit − IAP was found to be useful when directly measuring HP and IAP in patients and estimating the ideal ICPsit to be between −70 and −140 mm H2O. Postoperative shunt control performed using this method was satisfactory, and shunt complications and the number of CHV resettings were lower than in those published in previous reports.

Shunt-flow measurement performed in vivo and in real time by using a microflowmeter should be useful not only in testing the functioning of shunt systems, but also in clarifying the pathophysiology of hydrocephalus.
Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector—producer cells followed by intravenous ganciclovir administration
Authors: Packer Roger J. , Raffel Cory , Villablanca Judith G. , Tonn Jörg-Christian , Burdach Stefan E. , Burger Klaus , LaFond Deborah , McComb J. Gordon , Cogen Philip H. , Vezina Gilbert , Kapcala Leonard P.
Published: May 2009

Object. The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors.

Methods. After optimal repeated tumor resection, multiple injections of murine vector—producing cells shedding murine replication—defective retroviral vectors coding the herpes simplex virus thymidine kinase type 1 (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector-producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSV-Tk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2–15 years). Treated brain tumors included seven malignant gliomas, two ependymomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings.

Conclusions. This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector—producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.
Efficacy of transluminal angioplasty for the management of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Authors: Polin Richard S. , Coenen Volker A. , Hansen Carolyn Apperson , Shin Peter , Baskaya Mustafa K. , Nanda Anil , Kassell Neal F.
Published: May 2009

Object. Transluminal angioplasty has become a widely used adjunct therapy to medical management of symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH). Despite anecdotal reports of universal, angiographically confirmed reversal of vasospasm and high rates of clinical improvement, no rigorous examination of the efficacy of this procedure has been conducted. In this study the authors assess the efficacy of the aforementioned procedure.

Methods. Thirty-eight patients enrolled as part of the North American trial of tirilazad in aneurysmal SAH underwent transluminal angioplasty for symptomatic cerebral vasospasm. Fifty-three percent of these patients showed good recovery or moderate disability based on their 3-month Glasgow Outcome Scale score.

Among the 38 patients who underwent angioplasty, the severity and type of vasospasm, use of papaverine in addition to balloon angioplasty, timing of treatment, and dose of study drug did not have an effect on the outcome. The results of their neurological examinations improved in only four of the 38 patients immediately after the procedure. A conditional logistic regression analysis was performed in which these patients were compared with individuals matched for age, sex, dose of study drug, admission neurological grade, and modified Glasgow Coma Scale score at the time of angioplasty. No effect on favorable outcomes was found for this procedure.

Conclusions. Transluminal cerebral angioplasty is very effective in reversing angiographically confirmed vasospasm, and anecdotal reports of its clinical utility are numerous. However, in this report the authors conclude that its superiority to medical management for symptomatic cerebral vasospasm is questionable.
Clinical outcomes after carotid endarterectomy: comparison of the use of regional and general anesthetics
Authors: Papavasiliou Achilles K. , Magnadottir Hulda B. , Gonda Tamas , Franz Douglas , Harbaugh Robert E.
Published: May 2009

Object. The authors analyzed their series of carotid endarterectomies (CEAs), which were performed after administration of either a general or regional anesthetic, to determine whether the choice of anesthetic affected patients' clinical outcomes and length of hospital stay.

Methods. A series of 803 consecutive CEAs performed between July 1990 and February 1999 was reviewed. Cases were analyzed for patient demographics, comorbid medical states, and perioperative complications. Contingency-table statistical analysis was used to compare the incidence of comorbid medical states and perioperative complications between patients who underwent CEA in which either a regional or general anesthetic was used. Student's t-test was used to compare the length of hospital stay and mean patient age.

A regional anesthetic was used for 632 CEAs, and a general anesthetic was used for 171 operations. There were no statistically significant intergroup differences in demographics or comorbid medical states. The incidence of perioperative stroke and death did not differ significantly between the regional (2.7%) and the general anesthetic groups (2.3%). However, the incidence of nonneurological, nonfatal complications was significantly less in the regional anesthetic (1.6%) than in the general anesthetic group (14 .6%, p < 0.0001). Patients undergoing CEA in which a regional anesthetic was used had a significantly lower incidence of cardiopulmonary complications (myocardial infarction and postoperative intubation), cervical complications (neck hematomas and cranial nerve injuries), and urological complications (urinary retention) than patients who underwent surgery after receiving a general anesthetic.

Conclusions. Patients undergoing CEA in which a regional anesthetic was used had significantly fewer nonneurological, nonfatal complications, particularly cardiopulmonary complications, than similar patients surgically treated after induction of general anesthesia.
Marked inhibition of glioblastoma target cell tumorigenicity in vitro by retrovirus-mediated transfer of a hairpin ribozyme against deletion-mutant epidermal growth factor messenger RNA
Authors: Halatsch Marc-Eric , Schmidt Ursula , Bötefür Ingolf C. , Holland James F. , Ohnuma Takao
Published: May 2009

Object. The goal of this study was to evaluate the activity of certain hairpin ribozymes against deletion-mutant epidermal growth factor receptor (ΔEGFR) messenger (m)RNA in glioblastomas multiforme (GBMs). A distinct 801-bp deletion mutation associated with amplification of the EGFR gene is present in a large subgroup of primary GBMs and confers enhanced tumorigenicity in vivo. As a result of the deletion mutation, the fusion junction of the gene is created directly upstream of a GTA triplet, which is subsequently transcribed into a ribozyme target codon (GUA).

Methods. In attempts to intercept ΔEGFR gene expression at the mRNA level, the authors designed three different hairpin ribozymes derived from the negative strands of satellite RNAs in tobacco ringspot virus, chicory yellow mottle virus (sCYMV1), and arabis mosaic virus against this target and evaluated their efficiency and specificity in a cell-free system. The sCYMV1, identified as the most active anti-ΔEGFR hairpin ribozyme motif, was cloned into the retroviral plasmid N2A+tRNAimet. High-titer recombinant retrovirus-containing supernatants (> 105 colony-forming units/ml) derived from an amphotropic GP+envAM 12 packaging cell line transfected with the N2A+tRNAimet-anti-ΔEGFR-sCYMV1 construct were used to introduce the sCYMV1 hairpin ribozyme into U-87MG.ΔEGFR glioblastoma cells, which overexpress exogenous ΔEGFR. Using a virus/target cell ratio of 40:1 in the absence of drug selection, the ribozyme transfer resulted in a greater than 90% reduction of ΔEGFR mRNA levels, a 69% inhibition of ΔEGFR-mediated proliferation advantage, and a greater than 95% decrease of colony formation in soft agar under relative serum starvation conditions in vitro; transfer of a control mutant ribozyme that was rendered incapable of cleaving its target yielded none of these effects.

Conclusions. These findings indicate that the anti-ΔEGFR-sCYMV1 hairpin ribozyme is capable of specifically inhibiting the expression of ΔEGFR and reversing the ΔEGFR-associated malignant phenotype of GBM cells. This strategy may constitute a promising gene therapy approach for a molecularly defined subgroup of GBMs.
Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth
Authors: McCutcheon Ian E. , Friend Keith E. , Gerdes Tammy M. , Zhang Bing-Mei , Wildrick David M. , Fuller Gregory N.
Published: May 2009

Object. Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice.

Methods. Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (106/10 µl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth.

Conclusions. The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.
Malignant intracerebral nerve sheath tumor with intratumoral calcification
Authors: Tanaka Minoru , Shibui Soichiro , Nomura Kazuhiro , Nakanishi Yukihiro , Hasegawa Tadashi , Hirose Takanori
Published: May 2009

✓ The authors present the clinical, radiological, and pathological features of a malignant intracerebral nerve sheath tumor that occurred in the right parietooccipital lobe of a 4-year-old girl. Computerized tomography scanning and magnetic resonance imaging demonstrated a 5 × 5 × 4—cm multiloculated mass with considerable enhancement of the irregularly shaped septa and clearly calcified areas within the mass. Among five cases reported in the literature, this patient is the youngest and represents the first case in which there is radiological evidence of intratumoral calcification.
Continuous intrathecal pump infusion of baclofen with antibiotic drugs for treatment of pump-associated meningitis
Authors: Zed Peter J. , Stiver H. grant , Devonshire Virginia , Jewesson Peter J. , Marra Fawziah
Published: May 2009

✓ Intrathecal baclofen administered by means of an implantable pump is being increasingly used for successful treatment of spasticity. Meningitis following intrathecally administered baclofen is a rare but serious complication that is difficult to treat without removal of the pump. Because success rates with intravenously administered antibiotic drugs for the treatment of meningitis have been low, intrathecal administration of antibiotic agents is often required to eradicate the pathogen. The authors report the case of a patient in whom Staphylococcus epidermidis meningitis developed after insertion of an intrathecal baclofen pump. The patient was successfully treated by intrathecal coadministration of vancomycin and baclofen.
Visual loss associated with fibrous dysplasia of the anterior skull base
Authors: Michael Christopher B. , Lee Andrew G. , Patrinely James R. , Stal Samuel , Blacklock J. Bob
Published: May 2009

✓ The authors present a case of visual loss associated with fibrous dysplasia of the anterior skull base and the surgical management of this case. Preoperative computerized tomography scanning in this patient demonstrated a patent optic foramen and a rapidly growing cystic mass within the orbit, which was responsible for the patient's visual loss. A literature review revealed that this case is typical, in that cystic mass lesions of various types are frequently responsible for visual loss associated with fibrous dysplasia. The authors did not find significant evidence in the literature to support the notion that visual loss associated with fibrous dysplasia is the result of progressive optic canal stenosis, thus raising questions about the value of prophylactic optic canal decompression. Instead, as demonstrated by this case and those uncovered in the literature review, most instances of visual loss result from the rapid growth of mass lesions of cystic fibrous dysplasia, mucoceles, or hemorrhage. Findings of the literature review and the present case of fibrous dysplasia of the anterior skull base support a role for extensive surgical resection in these cases and indicate a need for additional prospective analysis of a larger number of patients with this disease.
Modification of a nasal speculum for transsphenoidal surgery
Authors: Miyake Hiroji , Ohta Tomio
Published: May 2009

✓ The authors modified a Hardy nasal speculum to improve the access to surgical fields and the handling of various instruments during transsphenoidal surgery. A section of the inferior edge of the speculum was cut out 2 cm from its orifice on both sides. The thickness of the tip of the speculum was also reduced. The authors are prepared to operate using a variety of speculum lengths (the distance between the tip and the cutting level), and this length is selected depending on the distance between the anterior wall of the sphenoid sinus and the surface of the gingiva in the individual patient.

A modified nasal speculum was used in transsphenoidal surgery for a pituitary adenoma. With use of this device, the protrusion of the speculum above the gingiva was markedly decreased. Because most instruments are inserted into the inferior portion of the speculum orifice, this approach facilitated the handling of all surgical instruments through the modified nasal speculum. The actual surgical field became shallow and wide, and the long surgical instruments that are generally used for transsphenoidal surgery were unnecessary in most cases.