bluuebunny/crossref_metadata_2025 huggingface dataset:
Participation of an abnormality in the transforming growth factor–β signaling pathway in resistance of malignant glioma cells to growth inhibition induced by that factor
Authors: Zhang Lei , Sato Eiji , Amagasaki Kenichi , Nakao Atsuhito , Naganuma Hirofumi
Published: January 2008

Object

Malignant glioma cells secrete and activate transforming growth factor–β (TGFβ) and are resistant to growth inhibition by that factor. Nevertheless, the mechanism underlying this effect remains poorly understood. In this study, the mechanism of the resistance to growth inhibition induced by TGFβ was investigated.

Methods

The authors examined the expression of downstream components of the TGFβ receptor, including Smad2, Smad3, Smad4, and Smad7, and the effect of TGFβ1 treatment on the phosphorylation of Smad2 and the nuclear translocation of Smad2 and Smad3 by using 10 glioma cell lines and the A549 cell line, which is sensitive to TGFβ-mediated growth inhibition. The expression of two transcriptional corepressor proteins, SnoN and Ski, and the effect of TGFβ1 treatment on the expression of the SnoN protein and the cell cycle regulators p21, p15, cyclin-dependent kinase–4 (CDK4), and cyclin D1 were also examined.

Expression of the Smad2 and Smad3 proteins was lower in the glioma cell lines than in the A549 cell line and in normal astrocytes. In particular, Smad3 expression was low or very low in nine of the 10 malignant glioma cell lines. Expression of Smad4 was low in four glioma cell lines, and expression of the Smad7 protein was similar when compared with protein expression in the A549 cell line and in normal astrocytes. The levels of Smad2 phosphorylation after TGFβ1 treatment were lower in glioma cell lines than in the A549 cell line, except for one glioma cell line. Seven of the 10 glioma cell lines exhibited lower levels of nuclear translocation of Smad2 and Smad3, and two cell lines that expressed very low levels of Smad3 protein showed no nuclear translocation. All glioma cell lines expressed the SnoN protein and its expression was unaltered by treatment with TGFβ1. Three glioma cell lines expressed high levels of the Ski protein. The expression of the p21cip1, p15INK4B, CDK4, and cyclin D1 proteins was not altered by TGFβ1 treatment, except in one cell line that displayed a slight increase in p21 protein. Overall, the expression of the Smad2 and Smad3 proteins was low in the glioma cell lines, the phosphorylation and nuclear translocation of Smad2 and Smad3 were impaired, and the TGFβ receptor signal did not affect the expression of the SnoN, p21, p15, cyclin D1, and CDK4 proteins.

Conclusions

These results suggest that the ability to resist TGFβ-mediated growth inhibition in malignant glioma cells is due to abnormalities in the TGFβ signaling pathway.
Fourth ventricle rosette-forming glioneuronal tumor
Authors: Johnson Mahlon , Pace John , Burroughs Judy F.
Published: January 2008

✓ The authors describe a rosette-forming glioneuronal tumor of the fourth ventricle in a 29-year-old woman. She had been experiencing dizziness for 1 year and headaches for 1 month. Cranial computed tomography revealed a relatively circumscribed mass involving the inferior cerebellum and floor of the fourth ventricle with extension into the ventricle. Histologically, much of the tumor was piloid with Rosenthal fibers as well as telangiectatic blood vessels; other areas contained complete or incomplete neurocytic rosettes. This tumor type must be differentiated from pilocytic astrocytomas, other gliomas with a piloid glial component, and glioneuronal tumors arising from the floor of the fourth ventricle or inferior cerebellum. Recognition of, and long-term follow up for, this recently described pathological entity may clarify the nature of this lesion and strategies for its optimal management.
Dural involvement in primary extradural meningiomas of the cranial vault
Authors: Bassiouni Hischam , Asgari Siamak , Hübschen Uwe , König Hermann-Josef , Stolke Dietmar
Published: January 2008

Object

The authors retrospectively analyzed a consecutive series of patients with cranial vault primary extradural meningioma (PEM), with particular regard to the tumor’s dural involvement. The pertinent literature was reviewed.

Methods

Clinical data were retrospectively obtained in a consecutive series of 16 patients treated for a PEM at two institutions between 1992 and 2004. The authors created a classification system based on dural involvement of the tumors.

Nine women and six men (mean age 55 years) presented with a painless, slowly progressive swelling. Preoperative magnetic resonance (MR) imaging revealed dural enhancement at the site of tumor in 11 patients. On surgical inspection, the tumor infiltrated the dura in all but three patients. Histological examination of tissue samples demonstrated tumor infiltration of the dura in all 14 patients in whom the dura had been resected. Three recurrent tumors were observed on follow-up examination during a mean period of 5.8 years (range 1.5–13 years) and required extirpation. In addition to one patient in whom there was histological evidence of malignancy, the other two cases involved two patients in whom no apparent dural involvement was observed during the first surgery. In a review of the literature, the authors found that histological examination showed dural involvement in 22%; the dura was not histologically evaluated in the remaining patients (78%). Postoperative follow-up data exceeding 2 years were only provided in two of the reported cases.

Conclusions

Tumor infiltration of the dura should be assumed in PEMs of the cranial vault, and resection of the dura at the site of craniotomy is recommended to prevent tumor recurrence.
Apoptosis in human glioblastoma cells produced using embryonic stem cell–derived astrocytes expressing tumor necrosis factor–related apoptosis-inducing ligand
Authors: Germano Isabelle M. , Uzzaman Mahmud , Benveniste Ronald J. , Zaurova Milana , Keller Gordon
Published: January 2008

Object

Embryonic stem (ES) cell–derived astrocytes have several theoretical and practical advantages as gene therapy vectors in the treatment of malignant gliomas. The aim of this study was to test the proapoptotic effects of ES cell–derived astrocytes expressing transgenic tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in human malignant glioma cells.

Methods

Mouse ES cells containing a doxycycline-inducible transgene were engineered with human TRAIL (hTRAIL) and then directed to differentiate into astrocytes. The ES cell-derived–TRAIL-expressing astrocytes were cocultured with human malignant glioma cells. Reverse transcriptase polymerase chain reaction, immunocytochemistry, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling, and flow cytometry were used to quantify results.

In vitro coculture of ES cell–derived astrocytes expressing hTRAIL with A172 human malignant glioma cells after doxycycline induction caused a significant decrease in cell viability from 85 ± 2% at baseline to 8 ± 2% posttreatment (p < 0.001). Labeling with apoptotic markers showed that cell death occurred by means of apoptosis. A significant increase in apoptotic rate (88 ± 3%) from baseline (4 ± 2%) was found in A172 cells after doxycycline induction (p < 0.005). This effect was superior to the apoptotic rate seen after treatment with recombinant TRAIL (57 ± 2%). A decrease in cell viability and an increase in the apoptotic rate were not found in TRAIL-expressing–ES cell-derived astrocytes after induction with doxycycline or in A172 cells exposed to doxycycline alone.

Conclusions

Engineering of transgenic hTRAIL by using ES cell–derived astrocytes induced apoptosis in human malignant glioma cells while sparing nontumor astrocytes. The apoptotic effects of transgenic hTRAIL are greater than those of recombinant hTRAIL. Analysis of these results suggests that hTRAIL-expressing–ES cell-derived astrocytes should be considered in the development of new in vivo strategies to treat malignant human gliomas.
Survival and early differentiation of human neural stem cells transplanted in a nonhuman primate model of stroke
Authors: Roitberg Ben Z. , Mangubat Erwin , Chen Er-Yun , Sugaya Kiminobu , Thulborn Keith R. , Kordower Jeffrey H. , Pawar Ambarish , Konecny Todd , Emborg Marina E.
Published: January 2008

Object

Neural cell transplantation has been proposed as a treatment after stroke. The purpose of this study was to establish if human neural stem cells (HNSCs) could survive in the nonhuman primate brain after an ischemic event.

Methods

Three adult cynomolgus monkeys received a unilateral occlusion of the M1 segment of the right middle cerebral artery (MCA). One week later each animal received five magnetic resonance (MR) image–guided stereotactic intracerebral injections of HNSC neurospheres labeled with bromodeoxyuridine (BrdU) in the areas surrounding the ischemic lesion as defined in T1- and T2-weighted images. On the day of transplantation and throughout the study the monkeys received oral cyclosporine (10 mg/kg twice a day), and plasma levels were monitored routinely. The animals were killed at 45, 75, or 105 days after transplantation. Magnetic resonance images revealed a cortical and subcortical infarction in the MCA distribution area. Postmortem morphological brain analyses confirmed the distribution of the infarcted area seen in the MR images, with loss of tissue and necrosis in the ischemic region. Cells that were positive for BrdU were present in the three experimental monkeys, mainly along injection tracks. Double-label immuno-fluorescence for BrdU and βIII-tubulin (a marker of young neurons) revealed colocalization of few HNSCs, most of which were observed outside the immediate injection site. Colocalization with nestin was also observed, indicating an early neural/glial fate.

Conclusions

In a model of stroke in nonhuman primates, HNSCs can survive up to 105 days when transplanted 1 week after an ischemic event and can partly undergo neuronal differentiation.
Magnetic resonance angiography and clinical evaluation of third nerve palsies and posterior communicating artery aneurysms
Authors: Kupersmith Mark J. , Heller Gordon , Cox Terry A.
Published: January 2008

Object

The authors conducted a study to determine the utility of the clinical profile and magnetic resonance (MR) angiography in evaluating patients with isolated third cranial nerve palsies or posterior communicating artery (PCoA) aneurysms.

Methods

Three-dimensional time-of-flight MR angiography was performed in a consecutive series of patients with isolated acute third cranial nerve palsy not due to a ruptured aneurysm and in patients with unruptured PCoA aneurysms. A neuroradiologist, masked to the identities of the patients, interpreted reformatted maximum intensity projection (MIP) and source images of the PCoAs and aneurysms. The investigators assessed clinical features of oculomotor nerve dysfunction and focal head pain. Cases involving cranial third nerve palsy without aneurysms were classified as Group 1 (no case entailed catheter-based angiography), and cases involving PCoA aneurysms seen on MR angiography (42 cases confirmed by catheter-based angiography) were classified as Group 2.

The mean age of the 73 patients in Group 1 was 60.1 years and that of the 45 patients in Group 2 was 59.1 years (p = 0.37). The pattern and severity of oculomotor (p = 0.61) and lid (p = 0.83) dysfunction and pain frequency (p = 0.2) were similar for the 73 patients with vasculopathy in Group 1 and the 15 symptomatic patients in Group 2. Abnormal pupils were observed in 38% of the patients in Group 1 and 80% of those in Group 2 (p = 0.016). In cases of complete external third nerve palsy, nine of 22 in Group 1 and none of four in Group 2 had normal pupil function. For all patients, source imaging showed 206 PCoAs (85%) and MIP imaging demonstrated 120 PCoAs (49%). Of 48 aneurysms (three bilateral), MIP imaging showed 44 (92%) and source imaging showed 47 (98%). Only a 2-mm aneurysm seen on catheter-based angiography was missed by MR angiography. Symptomatic aneurysms were equal or greater than 4 mm in size.

Conclusions

Only the presence of complete external third nerve palsy and normal pupil function allowed ischemia to be clinically distinguished from a PCoA aneurysm in a patient with isolated third nerve palsy and no subarachnoid hemorrhage. When source image MR angiography demonstrates normal findings, catheter-based angiography need not be performed in these patients, even if pupil function is abnormal.
Effect of subthalamic nucleus lesions in a 6-hydroxydopamine–induced rat parkinsonian model: behavioral and biochemical studies
Authors: Hwang Yong Sup , Shim Insop , Lee Bom Bee , Chang Jin Woo
Published: January 2008

Object

The purpose of this study was to determine whether subthalamic nucleus (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission and improve motor deficits in a 6-hydroxydopamine (6-OHDA)–induced hemiparkinsonian model.

Methods

The authors investigated behavioral changes in rats displaying parkinsonian symptoms (6-OHDA–lesioned rats) after an STN lesion was created using kainic acid. They also measured levels of dopamine and its metabolites following tissue dissection. The results of this study showed that STN ablation led to behavioral improvement in parkinsonian motor deficits. Increased levels of dopamine were also observed in the striatum and globus pallidus externus (GPE).

Conclusions

The results indicate that creation of an STN lesion in this hemiparkinsonian rat model may counteract some of the neurochemical changes within the striatum and GPE caused by the 6-OHDA, and influence striatal dopaminergic metabolism.
Anatomical analysis of transoral surgical approaches to the clivus
Authors: Balasingam Vijayabalan , Anderson Gregory J. , Gross Neil D. , Cheng Cheng-Mao , Noguchi Akio , Dogan Aclan , McMenomey Sean O. , Delashaw Johnny B. , Andersen Peter E.
Published: January 2008

Object

The authors conducted a cadaveric anatomical study to quantify and compare the area of surgical exposure and the freedom available for instrument manipulation provided by the following four surgical approaches to the extracranial periclival region: simple transoral (STO), transoral with a palate split (TOPS), Le Fort I osteotomy (LFO), and median labioglossomandibulotomy (MLM).

Methods

Twelve unembalmed cadaveric heads with normal mouth opening capacity were serially dissected. For each approach, quantitation of extracranial periclival exposure and freedom for instrument manipulation (known here as surgical freedom) was accomplished by stereotactic localization. To quantify the extent of extracranial clival exposure obtained, anatomical measurements of the extracranial clivus were performed on 17 dry skull bases.

The values (means ± standard deviations in mm2) for periclival exposure and surgical freedom, respectively, for the surgical approaches studied were as follows: STO = 492 ± 229 and 3164 ± 1900; TOPS = 743 ± 319 and 3478 ± 2363; LFO = 689 ± 248 and 2760 ± 1922; and MLM 1312 ± 384 and 8074 ± 6451. The extent of linear midline clival exposure and the percentage of linear midline clival exposure relative to the total linear midline exposure were as follows, respectively: STO = 0.6 ± 4.9 mm and 7.8 ± 11%; TOPS = 8.9 ± 5.5 mm and 24.2 ± 16.7%; LFO = 32.9 ± 10.2 mm and 85.0 ± 18.7%; and MLM = 2.1 ± 4.4 mm and 6.7 ± 11.1%.

Conclusions

The choice of approach and the resulting degree of complexity and associated morbidity depends on the location of the pathological entity. The authors found that the MLM approach, like the STO approach, provided good exposure of the craniocervical junction but limited exposure of the clivus. The TOPS approach, an approach attended by a lesser risk of morbidity, provided adequate exposure of the extracranial inferior clivus. Maximal exposure of the extracranial clivus proper was provided by the LFO approach.
Subdural hemorrhage in the posterior fossa caused by a ruptured cavernous carotid artery aneurysm after a balloon occlusion test
Authors: Andaluz Norberto , Tomsick Thomas A. , Keller Jeffrey T. , Zuccarello Mario
Published: January 2008

✓Given the relatively benign natural history of cavernous carotid artery aneurysms and based on anecdotal reports in the literature of subarachnoid hemorrhage (SAH) or subdural hemorrhage (SDH) from these aneurysms, observation is warranted and typically recommended. In this case report, the authors describe a woman who harbored a partially thrombosed, giant cavernous aneurysm that ruptured after she underwent a balloon occlusion test (BOT) and predominately led to an SDH. The authors believe that this occurrence is the first such report in the English literature. They discuss possible mechanisms for this event and the literature related to SAH or SDH from cavernous aneurysms, including why cavernous aneurysms cause such hemorrhages. The authors also recommend that attention be paid to such lesions regarding the possibility of aneurysmal rupture following a BOT.
Gamma Knife surgery–induced meningioma
Authors: Sheehan Jason , Yen Chun PO , Steiner Ladislau
Published: January 2008

✓Gamma Knife surgery (GKS) is a minimally invasive neurosurgical technique. During the past 30 years, radiosurgery has been performed for a number of intracranial disorders with a generally low incidence of side effects. Although radiation-induced neoplasia following radiotherapy is well documented, there are few reports of this complication following radiosurgery.

The authors are engaged in an ongoing project in which they are studying the delayed adverse effects of radiosurgical changes in 2500 patients with arteriovenous malformations (AVMs) treated within a 30-year period. The cases of 1333 patients treated by the senior author (L.S.) have been reviewed thus far. A subset of 288 patients in this group underwent neuroimaging and participated in clinical follow up for at least 10 years.

The authors report two cases of radiosurgically induced neoplasia. In both cases the patient was treated with GKS for an AVM. Longer than 10 years after GKS, each of the patients was found to have an incidental, uniformly enhancing, dura-based mass lesion near the site of the AVM. These lesions displayed the imaging characteristics of a meningioma. Because in both cases the lesion has displayed no evidence of a mass effect, they continue to be followed using serial neuroimaging. These are the fifth and sixth cases meeting the criteria for radiation-induced neoplasms defined by Cahan, et al., in 1998.

Although radiosurgery is generally considered quite safe, the incidence of radiation-induced neoplasms is not known. These cases and the few others detailed in the literature emphasize the need for long-term neurosurgical follow-up review in patients after radiosurgery.
Primary cerebellopontine angle craniopharyngioma in a patient with Gardner syndrome
Authors: Aquilina Kristian , O’Brien Donncha F. , Farrell Michael A. , Bolger Ciaran
Published: January 2008

✓The authors report on the case of a craniopharyngioma arising in the cerebellopontine angle (CPA) in a patient with Gardner syndrome. Although familial adenomatous polyposis (FAP) is associated with intracranial neoplasms, the current case is only the third reported craniopharyngioma in a patient with Gardner syndrome. Two of these tumors, including that of the current case, originated in the CPA, an unusual location for craniopharyngiomas. The literature concerning FAP and its associations with intracranial neoplasia, as well as the pathogenesis of craniopharyngiomas in the posterior fossa, is discussed.
Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat
Authors: Vikman Petter , Beg Saema , Khurana Tejvir , Hansen-Schwartz Jacob , Edvinsson Lars
Published: January 2008

Object

The authors investigated early changes in the cerebral arteries of rats that occur after subarachnoid hemorrhage (SAH).

Methods

Messenger RNA was investigated by performing microarray and quantitative real-time polymerase chain reaction (PCR) analyses, and protein expression was shown by performing immunohistochemical studies. The array data indicated that the initial processes that occur after SAH involve activation of genes involved in angiogenesis, inflammation, and extracellular matrix (ECM) remodeling. The real-time PCR investigation confirmed upregulation of genes that were observed using the microarray to be regulated, including iNOS, MMP13, and cxcl2. The authors also verified the upregulation of previously implicated genes for G-protein–coupled receptors (endothelin B [ETB], angiotensin 1 [AT1], and AT2) and metalloproteinase 9. The results of an immunohistochemical study confirmed that receptor genes that were seen to be regulated produced an increase in protein expression. Double immunostaining of rat cerebral arteries with endothelial cell– or smooth-muscle cell–specific antibodies verified that an increase in ETB, 5-hydrotryptamine (5-HT1B), and 5-HT1D receptor expression occurs in smooth-muscle cells.

Conclusions

Processes occurring after SAH lead to enhanced arterial contractility and ECM remodeling either directly or through angiogenesis and inflammation. These processes are active via an increase in metalloproteinase expression, the presence of proangiogenic factors, and the expression of proinflammatory genes.
Establishing tumor cell lines from aggressive telomerase-positive chordomas of the skull base
Authors: Ricci-Vitiani Lucia , Pierconti Francesco , Falchetti Maria Laura , Petrucci Giovanna , Maira Giulio , De Maria Ruggero , Larocca Luigi Maria , Pallini Roberto
Published: January 2008

✓ Permanent cell cultures are invaluable tools for understanding the biological characteristics of tumors. In the present study the authors report on the establishment of permanent human cell lines from three cases of aggressive chordomas of the clival region. All of the parental tumors showed telomerase activity. Cultured chordoma cells had a doubling time of 5 to 7 days and grew as a monolayer of cells that retained both the immunophenotype and the p53 status of the parental tumor. In vitro, chordoma cells overexpressed telomerase, supporting the hypothesis that this enzyme is required for the immortalization process.
Gamma Knife surgery for metastatic brain tumors from renal cell carcinoma
Authors: Shuto Takashi , Inomori Shigeo , Fujino Hideyo , Nagano Hisato
Published: January 2008

Object

The authors evaluated the results of Gamma Knife surgery (GKS) for the treatment of metastatic brain tumors from renal cell carcinoma (RCC).

Methods

The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 69 patients with metastatic brain tumors from RCC who underwent GKS at the authors’ institution. Fifty-one patients were men, and 18 were women. The mean patient age was 64.2 years (range 45–85 years).

The 69 patients underwent a total of 104 GKS procedures for treatment of 314 tumors. Eighteen patients received repeated GKS. Follow-up magnetic resonance (MR) imaging was used at a mean of 7.1 months after GKS to evaluate the change in 132 tumors after treatment. The mean prescription dose at the tumor margin was 21.8 Gy. The tumor growth control rate was 82.6%. Tumor volume and the delivered peripheral dose were significantly correlated with tumor growth control on univariate and multivariate analyses. Sixty (45.5%) of the 132 tumors assessed with MR imaging were associated with apparent peritumoral edema at the time of GKS. After treatment, peritumoral edema disappeared in 27 tumors, decreased in 13, was unchanged in 16, and progressed in four. Newly developed peritumoral edema after GKS was rare. The delivered peripheral dose was significantly correlated with control of peritumoral edema. The overall median survival time after GKS was 9.5 months. In this study, 34 patients died of systemic disease and 10 died of progressive brain metastases. Multivariate analysis showed that the number of lesions at the first GKS, the Karnofsky Performance Scale score at the first GKS, the recursive partitioning analysis classification, and the interval from diagnosis of RCC to brain metastasis were significantly correlated with survival time.

Conclusions

Gamma Knife surgery is effective for metastatic brain tumors from RCC. The disappearance rate of tumors is relatively low, but growth control is high. The delivered dose to the tumor margin is significantly correlated with the control of peritumoral edema. Gamma Knife surgery should be used as the initial treatment modality, if possible, even in patients with multiple metastases. Repeated GKS is recommended for newly developed brain metastases because of the low sensitivity of RCC to conventional radiation therapy.
Microhemorrhage, a possible mechanism for cyst formation in vestibular schwannomas
Authors: Park Chul-Kee , Kim Dong-Chul , Park Sung-Hye , Kim Jeong Eun , Paek Sun Ha , Kim Dong Gyu , Jung Hee-Won
Published: January 2008

Object

Cystic vestibular schwannoma (VS) is a unique subgroup of VSs characterized by unpredictable expansion of the cyst component. Little is known, however, about the mechanism of cyst formation. In this study the authors compared neuroimaging and histological characteristics of cystic with solid VS to determine the pathogenesis of the cystic subgroup.

Methods

Two cohorts, one comprising 10 patients with cystic VS and the other comprising 10 patients with solid VS, were studied. Surgery was chosen as the primary treatment in all patients, with no other modality applied. Preoperative magnetic resonance images and histological characteristics of the tumor in patients with cystic VSs were evaluated and compared with those in the group with solid VSs. Differences between the two groups were assessed using the chi-square test. Neuroimaging findings revealed that either fluid-fluid level or hemosiderin deposit was present in all cystic VSs. Histological evidence of microhemorrhage, such as hemosiderinladen macrophages (p = 0.069), hemosiderin deposits (p = 0.019), thrombotic vessels (p = 0.008), and abnormal vessel proliferation (p = 0.006) were more prominent in cystic VSs compared with solid ones. There was no difference in Antoni type dominance and Ki-67 proliferative index between the two groups.

Conclusions

Intratumoral microhemorrhage is a possible mechanism of pathogenesis in cystic VS.
Preclinical evaluation of the neuroprotective effect of soluble complement receptor Type 1 in a nonhuman primate model of reperfused stroke
Authors: Mocco J , Mack William J. , Ducruet Andrew F. , King Ryan G. , Sughrue Michael E. , Coon Alexander L. , Sosunov Sergei A. , Sciacca Robert R. , Zhang Yuan , Marsh Henry C. , Pinsky David J. , Connolly E. Sander
Published: January 2008

Object

Postischemic cerebral inflammatory injury has been extensively investigated in an effort to develop effective neuroprotective agents. The complement cascade has emerged as an important contributor to postischemic neuronal injury. Soluble complement receptor Type 1 (sCR1), a potent inhibitor of complement activation, has been shown to reduce infarct volume and improve functional outcome after murine stroke. Given numerous high-profile failures to translate promising antiinflammatory strategies from the laboratory to the clinic and given the known species-specificity of the complement cascade, the authors sought to evaluate the neuroprotective effect of sCR1 in a nonhuman primate model of stroke.

Methods

A total of 48 adult male baboons (Papio anubis) were randomly assigned to receive 15 mg/kg of sCR1 or vehicle. The animals were subjected to 75 minutes of middle cerebral artery occlusion/reperfusion. Perioperative blood samples were analyzed for total complement activity by using a CH50 assay. Infarct volume and neurological scores were assessed at the time the animals were killed, and immunohistochemistry was used to determine cerebral drug penetration and C1q deposition. An interim futility analysis led to termination of the trial after study of 12 animals. Total serum complement activity was significantly depressed in the sCR1-treated animals compared with the controls. Immunostaining also demonstrated sCR1 deposition in the ischemic hemispheres of treated animals. Despite these findings, there were no significant differences in infarct volume or neurological score between the sCR1- and vehicle-treated cohorts.

Conclusions

A preischemic bolus infusion of sCR1, the most effective means of administration in mice, was not neuroprotective in a primate model. This study illustrates the utility of a translational primate model of stroke in the assessment of promising antiischemic agents prior to implementation of large-scale clinical trials.
Commercial flight and patients with intracranial mass lesions: a caveat
Authors: Zrinzo Ludvic U. , Crocker Matthew , Zrinzo Laurence V. , Thomas David G. T. , Watkins Laurence
Published: January 2008

✓The authors report two cases of neurological deterioration following long commercial flights. Both individuals harbored intracranial space-occupying lesions. The authors assert that preexisting reduced intracranial compliance diminishes an individual’s reserve to accommodate the physiological changes resulting from a commercial flight. Airline passengers are exposed to a mild degree of hypercapnia as well as conditions that simulate those of high-altitude ascents. High-altitude cerebral edema following an ascent to great heights is one facet of acute mountain sickness and can be life threatening in conditions similar to those present on commercial flights. Comparable reports documenting neurological deterioration at high altitudes in patients with coexisting space-occupying lesions were also reviewed.
Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience
Authors: McGirt Matthew J. , Blessing Robert , Alexander Michael J. , Nimjee Shahid M. , Woodworth Graeme F. , Friedman Allan H. , Graffagnino Carmelo , Laskowitz Daniel T. , Lynch John R.
Published: January 2008

Object

Impairment of endothelial nitric oxide synthase (eNOS), endothelium-dependent relaxation, and cerebrovascular autoregulation all occur in vasospastic cerebral arteries following subarachnoid hemorrhage (SAH). The 3-hy-droxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, both improve endothelial function and increase eNOS messenger RNA, protein, and enzymatic activity threefold. Increasing experimental evidence in animal models of SAH suggests that statins may ameliorate cerebral vasospasm. The authors hypothesized that patients chronically treated with statins would have a decreased risk of symptomatic vasospasm after SAH.

Methods

The authors retrospectively reviewed the charts of 115 patients with SAH who were consecutively admitted to the Neuroscience Intensive Care Unit of Duke University between 1998 and 2001. The independent association of statin therapy to symptomatic vasospasm was assessed using multivariate logistic regression analysis. Fifteen patients (13%) admitted with SAH were receiving statin therapy for at least 1 month before admission. Forty-nine patients (43%) experienced symptomatic vasospasm a mean of 5.8 ± 3 days after onset of SAH. Current statin therapy on admission (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01–0.77) was independently associated with an 11-fold reduction in the risk of symptomatic vasospasm. Fisher Grade 3 SAH (OR 2.82, 95% CI 1.50–5.71) and rupture of anterior cerebral or internal carotid artery aneurysm (OR 3.77, 95% CI 1.29–10.91) were independently associated with an increased risk of symptomatic vasospasm.

Conclusions

In this retrospective case series, patients who received statin therapy for at least 1 month demonstrated an 11-fold decrease in the risk of developing symptomatic vasospasm after SAH.
Radiosurgical treatment for rolandic arteriovenous malformations
Authors: Andrade-Souza Yuri M. , Ramani Meera , Scora Daryl , Tsao May N. , terBrugge Karel , Schwartz Michael L.
Published: January 2008

Object

The authors reviewed the radiosurgical outcomes in patients with arteriovenous malformations (AVMs) located in the rolandic area, including the primary motor and sensory gyri.

Methods

The study population consisted of 38 patients with rolandic-area AVMs who underwent linear accelerator radiosurgery at the University of Toronto between 1989 and 2000. Obliteration rate, risk of hemorrhage during the latency period, radiation-induced complications, seizure control, and functional status were evaluated. Patients were also divided into two subgroups according to AVM volume (< 3 cm3 and ≥ 3 cm3).

Patients were followed up for a median of 42.4 months (range 30–103 months), and the median age of the patients was 40 years (range 12–67 years). The median AVM volume was 8.1 cm3 (range 0.32–21, mean 8.32 cm3), and the median dose at the tumor margin was 15 Gy (range 15–22, mean 16.8 Gy). The risk of hemorrhage after radiosurgery was 5.3% for the 1st year, 2.6% for the 2nd, and 0% for the 3rd. Two patients (5.3%) sustained adverse effects related to radiation for more than 6 months. Complete nidus obliteration after a single radiosurgical treatment was achieved in 23 patients (60.5%). The obliteration rate for AVMs smaller than 3 cm3 was 83.3% (10 of 12) and that for AVMs larger than or equal to 3 cm3 was 50% (13 of 26). Among the patients who had seizures as the initial presentation, 51.8% were free of seizures after radiosurgery and the seizure pattern improved in 40.7% during the 3rd and last year of follow up. Overall, excellent results (obliteration and no new or worsening neurological deficit) can be achieved in approximately 60% of patients. This percentage varies according to the AVM size and can reach 83% in patients with AVMs smaller than 3 cm3.

Conclusions

Radiosurgery is a safe and effective treatment for people with rolandic AVMs. The low rate of morbidity associated with radiosurgery, compared with other treatments, indicates that this method may be the first choice for patients with AVMs located in this area.
Does dose rate affect efficacy? The outcomes of 256 Gamma Knife surgery procedures for trigeminal neuralgia and other types of facial pain as they relate to the half-life of cobalt
Authors: Balamucki Christopher J. , Stieber Volker W. , Ellis Thomas L. , Tatter Stephen B. , DeGuzman Allan F. , McMullen Kevin P. , Lovato James , Shaw Edward G. , Ekstrand Kenneth E. , Bourland J. Daniel , Munley Michael T. , Robbins Michael , Branch Charles
Published: January 2008

Object

Gamma Knife surgery (GKS) is a treatment option for patients with refractory typical trigeminal neuralgia (TN), TN with atypical features, and atypical types of facial pain. The Gamma Knife’s 201 60Co sources decay with a half-life of 5.26 years. The authors examined whether the decrease in dose rate over 4.6 years between Co source replacements affected the control rates of facial pain in patients undergoing GKS.

Methods

The authors collected complete follow-up data on 239 of 326 GKS procedures performed in patients with facial pain. Patients were classified by their type of pain. The isocenter of a 4-mm collimator helmet was targeted at the proximal trigeminal nerve root, and the dose (80–90 Gy) was prescribed at the 100% isodose line. Patients reported the amount of pain control following radiosurgery by answering a standardized questionnaire.

Eighty percent of patients experienced greater than 50% pain relief, and 56% of patients experienced complete pain relief after GKS. Neither dose rate nor treatment time was significantly associated with either the control rate or degree of pain relief. A significant association between the type of facial pain and the pain control rate after GKS was observed (p < 0.001; Pearson chi-square test).

In their statistical analysis, the authors accounted for changes in prescription dose over time to prevent the dose rate from being a confounding variable. There was no observable effect of the dose rate or of the treatment duration within the typical period to source replacement.

Conclusions

Patients with facial pain appear to receive consistent treatment with GKS at any time during the first half-life of the Co sources.
Genetic profiling of a distant second glioblastoma multiforme after radiotherapy: recurrence or second primary tumor?
Authors: van Nifterik Krista A. , Elkhuizen Paula H. M. , van Andel Rob J. , Stalpers Lukas J. A. , Leenstra Sieger , Lafleur M. Vincent M. , Vandertop W. Peter , Slotman Ben J. , Hulsebos Theo J. M. , Sminia Peter
Published: January 2008

Object

In nearly all patients with glioblastoma multiforme (GBM) a local recurrence develops within a short period of time. In this paper the authors describe two patients in whom a second GBM developed after a relatively long time interval at a site remote from the primary tumor. The genetic profiles of the tumors were compared to discriminate between distant recurrence and a second primary tumor.

Methods

Both patients harboring a supratentorial GBM were treated with surgery and local high-dose radiotherapy. Local control of the disease at the primary tumor site was achieved. Within 2 years, a second GBM developed in both patients, not only outside the previously irradiated target areas but infratentorially in one patient and in the opposite hemisphere in the other. The tumors were examined for the presence of several genetic alterations that are frequently found in GBMs—a loss of heterozygosity at chromosome regions 1p36, 10p15, 19q13, and 22q13, and at the CDKN2A, PTEN, DMBT1, and TP53 gene regions; a TP53 mutation; and EGFR amplification.

In the first patient, genetic profiling revealed that the primary tumor had an allelic imbalance for markers in several chromosome regions for which the second tumor displayed a complete loss. In the second patient, genetic profiling demonstrated the presence of genetic changes in the second tumor that were identical with and additional to those found in the primary tumor.

Conclusions

Based on the similarities between the genetic profiles of the primary and the second tumors in these patients, the authors decided that in each case the second distant GBM was a distant recurrence rather than a second independent primary tumor.
Photophobia in a blind patient: an alternate visual pathway
Authors: Amini Amin , Digre Kathleen , Couldwell William T.
Published: January 2008

✓ Photophobia is a common neurological and ophthalmological symptom that has been associated with a growing number of neurosurgical conditions, especially compressive lesions. The exact signaling pathways and neurophysiological features of the disorder are not well understood; however, data from multiple studies have shown the significance of the trigeminal system and the pretectal nuclei in its pathophysiology. The authors report on a rare case of a blind patient who presented with photophobia without evidence of light perception. They also review the literature and early experimental data in an effort to understand the possible neuronal pathways and structures involved in photophobia.
Spontaneous resolution of syringomyelia and Chiari malformation Type I in a patient with cerebrospinal fluid otorrhea
Authors: Coppa Nicholas D. , Kim H. Jeffrey , McGrail Kevin M.
Published: January 2008

✓ The spontaneous resolution of syringomyelia in the setting of a Chiari malformation Type I (CM-I) has been reported infrequently. Several theories about the pathogenesis and spontaneous resolution of syringomyelia associated with CM-I have been proposed. The authors present the case of a patient with spontaneous resolution of a CM-I and syringomyelia coinciding with the development of cerebrospinal fluid (CSF) otorrhea. Although cases of spontaneous resolution of syringomyelia have been reported, this is the first reported case of spontaneous resolution of syringomyelia and a CM-I associated with the simultaneous development of CSF otorrhea.
Physiological and clinical advantages of median nerve fascicle transfer to the musculocutaneous nerve following brachial plexus root avulsion injury
Authors: Nath Rahul K. , Lyons Andrew B. , Bietz Gabriel
Published: January 2008

Object

Loss of biceps muscle function is a significant disability after brachial plexus root avulsion injuries. Nerve grafting techniques to reestablish anatomical and functional continuity between the spinal cord and the avulsed root have not proven successful. Using nerve transfers for functional restoration of root avulsion injuries appears to be effective and has physiological advantages for reducing regeneration distances. Since the early 1990s, the Oberlin technique of transferring ulnar nerve fascicles to the motor branch of the musculocutaneous nerve has been the preferred operative technique for reinnervation and restoration of biceps muscle function. In the current study the authors examine the efficacy of an alternative technique using median nerve fascicles transferred to the musculocutaneous nerve to reinnervate the biceps muscle.

Methods

Forty consecutive patients with combined C5–6 brachial plexus root avulsions were evaluated pre- and postoperatively according to the British Medical Research Council Motor Grading Scale. Personal interviews concerning quality of life (QOL) after surgery were conducted and scored based on standards set by the World Health Organization. All patients showed some degree of improvement in biceps muscle function. Thirty-six (90%) of the 40 patients regained movement against gravity. The patients had a 77% improvement in overall QOL after the surgery; most notably, 92% of the patients reported their lack of need for medication and 75% a significant lessening of postoperative pain. Redirection of part of the healthy median nerve resulted in no measurable functional deficits, and only 28 patients reported minor sensory disturbances in the first web space for an average of 3 months after surgery.

Conclusions

Median nerve fascicle transfer resulted in a significant improvement in biceps muscle function with an acceptable level of morbidity and should be considered an effective, and in many cases preferable, alternative to ulnar nerve fascicle transfer.
Resection of benign sciatic notch dumbbell-shaped tumors
Authors: Spinner Robert J. , Endo Toshiki , Amrami Kimberly K. , Dozois Eric J. , Babovic-Vuksanovic Dusica , Sim Franklin H.
Published: January 2008

Object

The operative management of combined intrapelvic and extrapelvic sciatic notch dumbbell-shaped tumors is challenging. The relatively rare occurrence of these tumors and the varied extent of disease have made it difficult for surgeons to establish definitive surgical indications or predict favorable neurological outcomes based on preoperative imaging data.

Methods

In the past 3 years, the authors treated five patients presenting with radiating leg pain as a result of benign sciatic notch dumbbell-shaped tumors. These tumors in three patients with unilateral leg symptoms were considered unresectable by other neurosurgeons because of presumed direct intrinsic neural involvement. After high-resolution magnetic resonance (MR) imaging demonstrated that the extensive tumors were separate from the sciatic nerve and the lumbosacral plexus, however, these patients underwent a combined one-stage transabdominal and posterior transgluteal complete resection. Normal neurological status was maintained postoperatively in these three patients, and after more than 1 year of postoperative follow up, there were no tumor recurrences.

In two patients with bilateral symptoms and extensive tumor burden, serial MR images showed that innumerable tumors directly involved the entire cross-sectional area of the sciatic nerves and extended longitudinally to the lumbosacral plexuses. Tumor debulking or resection in these patients would have resulted in neurological deficits and would not have addressed their neuropathic pain, and therefore no surgery was performed. These two patients were treated pharmacologically and advised to monitor their tumor status over the course of their lifetimes in case of malignant transformation of the tumor.

Conclusions

A combined one-stage transabdominal and transgluteal approach allows safe resection of selected benign but extensive sciatic notch tumors. High-resolution MR imaging is a useful tool in the management of these tumors because it allows the surgeon to visualize the anatomical relationships of the tumor to the sciatic nerve. The authors believe that as this imaging technology advances, it will provide surgeons with a method to predict definitively which sciatic notch tumors displace rather than directly involve the sciatic nerve, and therefore indicate which tumors can be resected safely and completely.
Effects of ethanol on limited resuscitation in a model of traumatic brain injury and hemorrhagic shock
Authors: Zink Brian J. , Stern Susan A. , McBeth Brian D. , Wang Xu , Mertz Michelle
Published: January 2008

Object

Limited resuscitation following uncontrolled hemorrhagic shock (HS) has been associated with improved outcomes in various animal models, although it has not been previously studied in the setting of traumatic brain injury (TBI) and ethanol intoxication. The aim of the present study was to determine the effects of ethanol intoxication in a model of experimental TBI and HS treated with limited resuscitation.

Methods

After induction of anesthesia and the placement of instruments, swine were subjected to a fluid-percussion injury of 3 atm. Simultaneously, hemorrhage was induced from an arterial catheter via a computerized roller pump to a mean arterial blood pressure (MABP) of 50 mm Hg, at which time uncontrolled hemorrhage was induced by the creation of an aortic tear. When the MABP decreased to 30 mm Hg, limited resuscitation to a MABP of 60 mm Hg was begun. After 60 minutes, animals were aggressively resuscitated to baseline MABP levels. Two groups of animals were studied: those receiving tap water by gastrostomy tube and those receiving ethanol (4 g/kg) by gastrostomy tube. Animals were monitored for 180 minutes after TBI. Hemorrhage volumes were significantly greater in ethanol-infused animals (mean ± standard deviation, 41 ± 34 mm Hg) compared with tap water–infused animals (17 ± 18 mm Hg; p = 0.048). Resuscitation requirements were significantly higher and metabolic parameters significantly worse in the ethanol group. Survival time was also significantly decreased in the animals infused with ethanol (81 ± 60 minutes) compared with those infused with tap water (130 ± 51 minutes; p = 0.035).

Conclusions

Ethanol intoxication led to increased hemorrhage volume and worsened hemodynamic and metabolic profiles in this model of limited resuscitation after TBI and HS. Ethanol-exposed animals had increased resuscitation requirements and decreased survival times.