bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant G protein signaling in nervous system tumors
Authors: Woods Stacey A. , Marmor Eric , Feldkamp Matthias , LAU NELSON , Apicelli Anthony J. , Boss Gerry , Gutmann David H. , Guha Abhijit 
Published: May 2009

Object. Guanosine triphosphate (GTP)—binding proteins, also known as G proteins, play important roles in the regulation of cell growth and differentiation by transmitting intracellular signals from cell surface receptors. In this paper, the authors review G protein signaling in general and its aberrations in four human nervous system tumors.
Methods. In the nervous system, four tumor types have been associated with aberrant G protein signaling. The first tumor type includes astrocytomas, which have increased levels of the activated form of the small G protein, p21-ras, without primary oncogenic p21-ras mutations. The likely source for increased p21-ras activity in sporadically occurring astrocytomas is overexpressed or constitutively activated growth factor receptors, whereas in neurofibromatosis Type 1 (NF1)—associated astrocytomas, the source is a loss of expression of neurofibromin, a major inactivator of p21-ras (ras—GTPase activating protein [GAP]). The second type of tumor associated with aberrant G protein signaling includes sporadic and NF1-associated neurofibromas and malignant peripheral nerve sheath tumors, which also have increased p21-ras activity due to a loss of neurofibromin expression. The third tumor type includes subependymal giant cell astrocytomas as part of the tuberous sclerosis complex (TSC). These tumors display a loss of tuberin expression due to germline mutations in the TSC2 gene. Tuberin functions as an inactivator of the small G protein rap1B (rap1-GAP) and, hence, loss of its expression could lead to increased rap1B activity. In addition to TSC-associated tumors, the authors demonstrate that the majority of sporadically occurring astrocytomas display either loss of tuberin or overexpression of rap1B. This suggests that increased rap1B activity, which can augment p21-ras—mediated signals, also contributes to G protein—mediated aberrant signaling in sporadically occurring astrocytomas. The fourth tumor type includes a significant subset of pituitary adenomas that show constitutive activation of the Gα subunit of the large heterotrimeric Gs protein, which is involved in hormone receptor signaling. The net result of this aberrant activation is increased cyclic adenosine monophosphate and mitogenic tumor-promoting signals.
Conclusions. The authors' review of G protein signaling and aberrations in this process is made with the long-term view that increased understanding of relevant signaling pathways will eventually lead to novel biological targeted therapies against these tumors.
Cerebral metabolism after fluid-percussion injury and hypoxia in a feline model
Authors: Zauner Alois , Clausen Tobias , Alves Oscar L. , Rice Ann , Levasseur Joseph , Young Harold F. , Bullock Ross 
Published: May 2009

Object. Currently, there are no good clinical tools to identify the onset of secondary brain injury and/or hypoxia after traumatic brain injury (TBI). The aim of this study was to evaluate simultaneously early changes of cerebral metabolism, acid—base homeostasis, and oxygenation, as well as their interrelationship after TBI and arterial hypoxia.
Methods. Cerebral biochemistry and O2 supply were measured simultaneously in a feline model of fluid-percussion injury (FPI) and secondary hypoxic injury. After FPI, brain tissue PO2 decreased from 33 ± 5 mm Hg to 10 ± 4 mm Hg and brain tissue PCO2 increased from 55 ± 2 mm Hg to 81 ± 9 mm Hg, whereas cerebral pH fell from 7.1 ± 0.06 to 6.84 ± 0.14 (p < 0.05 for all three measures). After 40 minutes of hypoxia, brain tissue PO2 and pH decreased further to 0 mm Hg and 6.48 ± 0.28, respectively (p < 0.05), whereas brain tissue PCO2 remained high at 83 ± 13 mm Hg. Secondary hypoxic injury caused a drastic increase in cerebral lactate from 513 ± 69 µM/L to 3219 ± 490 µM/L (p < 0.05). The lactate/glucose ratio increased from 0.7 ± 0.1 to 9.1 ± 2 after hypoxia was introduced. The O2 consumption decreased significantly from 18.5 ± 1.1 µl/mg/hr to 13.2 ± 2.1 µl/mg/hr after hypoxia was induced.
Conclusions. Cerebral metabolism, O2 supply, and acid—base balance were severely compromised ultra-early after TBI, and they declined further if arterial hypoxia was present. The complexity of pathophysiological changes and their interactions after TBI might explain why specific therapeutic attempts that are aimed at the normalization of only one component have failed to improve outcome in severely head injured patients.
Characteristics of hypothermic preconditioning influencing the induction of delayed ischemic tolerance
Authors: Yunoki Masatoshi , Nishio Shinsaku , Ukita Naoya , Anzivino Matthew J. , Lee Kevin S. 
Published: May 2009

Object. A brief period of hypothermia has recently been shown to induce delayed tolerance to ischemic brain injury. This form of tolerance is initiated several hours after hypothermic preconditioning (HPC) and persists for a few days. Hypothermia-induced tolerance could provide a means for limiting cellular injury during predictable periods of ischemia, such as those that occur during many surgical procedures. The purpose of this study was to characterize the parameters of HPC that regulate the induction of delayed tolerance.
Methods. The general design of the experiments was to perform HPC or a sham procedure on adult Sprague-Dawley rats. Twenty-four hours later, the animals were subjected to a transient period of ischemia induced by a 1-hour period of three-vessel occlusion. Infarct volume was assessed 24 hours postischemia. In the first series of experiments, the depth of global (that is, whole-body) HPC was set at 25.5, 28.5, or 31.5°C, and the duration of HPC was fixed at 20 minutes. In the second series of experiments, the duration of global HPC was set at 20, 60, 120, or 180 minutes, and the depth of HPC was set at 33 or 34.5°C. In the third series of experiments, focal HPC was administered by selectively cooling the head to achieve a cortical temperature of 28.5 or 31.5°C for 20 minutes, with the duration of HPC fixed at 20 minutes.
The magnitude of tolerance induced by HPC was dependent on the depth and duration of the hypothermic stimulus. The parameters of hypothermia that are capable of inducing tolerance are similar to, or less severe than, those already in clinical use during intraoperative procedures. Focal cooling was as effective as global cooling for eliciting tolerance, indicating that it is possible to establish tolerance while limiting the potential complications of systemic hypothermia.
Conclusions. The results of these experiments indicate that HPC may provide an effective and safe means for limiting cellular injury resulting from predictable periods of central nervous system ischemia.
Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis
Authors: Kumar Krishna , Hunter Gary , Demeria Denny D. 
Published: May 2009

Object. The object of this study was to compare the cost-effectiveness of intrathecal drug therapy (IDT) with that of conventional pain therapy (CPT) in patients suffering from chronic low back pain caused by failed back syndrome. In this study, the authors tabulated actual costs, in Canadian dollars, in a consecutive series of patients undergoing IDT within the Canadian health care system and have compared them with costs in a control group in the same environment. The influence of these treatments on the quality of life (QOL) was also analyzed.
Methods. The authors report on a series of 67 patients suffering from failed back syndrome, 23 of whom underwent implantation of a programmable drug delivery pump and 44 of whom acted as controls. Patients were followed for a 5-year period during which the investigators tabulated the actual costs incurred for diagnostic imaging, professional fees, implantation costs including hardware, nursing visits for maintenance of the pumps, alternative therapies, and hospitalization costs for breakthrough pain. From this data, cumulative costs for each group were calculated for a 5-year period. Patient responses on the Oswestry Pain Questionnaire were analyzed to assess the impact of treatment on QOL. The actual cumulative costs for IDT during a 5-year period were $29,410, as opposed to $38,000 for CPT. High initial costs of equipment required for IDT were recovered by 28 months. After this time point, managing patients with CPT became the more expensive treatment option for the remainder of the follow-up period. The Oswestry Disability Index showed a 27% improvement for patients in the IDT group, compared with a 12% improvement in the control group.
Conclusions. In patients who respond to this treatment, IDT is cost effective in the long term despite high initial costs of implantable devices.
Thalamic deep brain stimulation for the treatment of tremor due to multiple sclerosis: a prospective study of tremor and quality of life
Authors: Berk Caglar , Carr Jason , Sinden Marci , Martzke Jeff , Honey Christopher R. 
Published: May 2009

Object. In several studies a significant reduction in tremor after thalamic deep brain stimulation (DBS) has been reported among patients with multiple sclerosis (MS). It has not been determined if this results in an improved quality of life. In this study the authors prospectively evaluated the effects of thalamic DBS on tremor and quality of life.
Methods. Videotapes of the patients' tremor were made preoperatively and 2 and 12 months postoperatively, and tremor was scored by a neurologist blinded to the treatment. Patients were tested pre- and postoperatively to measure any changes in their reported ability to perform selected activities of daily living and in their health-related quality of life. Patients were asked to complete a questionnaire about their satisfaction with the surgery. Postoperative changes were examined using paired t-tests.
There were significant reductions in postural, action, and overall tremor at 2 and 12 months postoperatively. The patients' reported ability to feed themselves was significantly improved 2 months after surgery (p = 0.01). There were short-term trends toward improvement in reported dressing ability, personal hygiene, and writing. There were no significant changes in the SF-36 subscales or total score.
Conclusions. In this cohort of patients with MS who suffered from tremor, thalamic DBS significantly improved their tremor and ability to feed themselves. Patient satisfaction with the procedure, however, was variable. Preoperative patient education about what functions might (and might not) be improved is crucial to avoid unrealistic expectations. Our results indicate that younger patients with MS tremor who had a shorter disease duration and no superimposed ataxia benefited most from this surgery.
Surgical procedures for posterior fossa tumors in children: does craniotomy lead to fewer complications than craniectomy?
Authors: Gnanalingham Kanna K. , Lafuente Jesus , Thompson Dominic , Harkness William , Hayward Richard 
Published: May 2009

Object. Traditionally, access to the posterior fossa involved a suboccipital craniectomy. More recently, posterior fossa craniotomies have been described, although the long-term benefits of this procedure are not clear. The authors compared the postoperative complications of craniectomies and craniotomies in children with posterior fossa tumors.
Methods. From a total of 110 children undergoing surgery for posterior fossa tumors, 56 underwent craniectomy and 54 had a craniotomy. The mean duration of the hospital stay was longer in the craniectomy group (17.5 compared with 14 days). At operation, similar numbers of patients in both groups had total macroscopic clearance of the tumor, complete dural closure, and duraplasty.
Postoperatively, more patients in the craniectomy group were noted to have cerebrospinal fluid (CSF) leakage (27 compared with 4%; p < 0.01) and pseudomeningoceles (23 compared with 9%; p < 0.05). There was no significant difference between the two groups in the numbers of patients with CSF infections, wound infections, or hydrocephalus requiring permanent CSF drainage. Patients with CSF leaks had a longer duration of hospital stay (20.7 compared with 14.9 days; p < 0.01), and were more likely to have CSF infections (35 compared with 12%; p < 0.01) and wound infections (24 compared with 1%; p < 0.01) than patients without CSF leaks. Postoperatively, wound exploration and reclosures for CSF leakage were more likely in the craniectomy group (11 compared with 0%; p < 0.01). Multivariate analysis revealed that the only predictor of CSF leakage postoperatively was the type of surgery (that is, craniotomy compared with craniectomy; odds ratio 10.8; p = 0.03).
Conclusions. Craniectomy was associated with postoperative CSF leaks, pseudomeningocele, increased wound reclosures, and thus prolonged hospital stays. In turn, CSF leakage was associated with infections of the CSF and wound. The authors propose mechanisms that may explain why CSF leakage is less likely if the bone flap is replaced.
Trigeminal neuralgia caused by microarteriovenous malformations of the trigeminal nerve root entry zone: symptomatic relief following complete excision of the lesion with nerve root preservation
Authors: Edwards Richard J. , Clarke Yvonne , Renowden Shelley A. , Coakham Hugh B. 
Published: May 2009

Object. Within a series of 341 consecutive patients who underwent posterior fossa surgery for trigeminal neuralgia (TN), in five the cause was found to be a microarteriovenous malformation (micro-AVM) located in the region of the trigeminal nerve root entry zone (REZ). The surgical management and clinical outcomes of these cases are presented.
Methods. Patients were identified from a prospectively collected database of all cases of TN treated at one institution between 1980 and 2000. Presentation was clinically indistinguishable from TN caused by vascular compression. Preoperative imaging, including computerized tomography scanning (two cases) and magnetic resonance (MR) imaging and MR angiography (three cases), failed to demonstrate an AVM except for one case in which multiple abnormal vessels were identified in the trigeminal REZ on an MR image obtained using a 1.5-tesla magnet. All patients underwent a standard retromastoid craniotomy. In all cases a small AVM embedded in the trigeminal REZ was identified and completely excised, with preservation of the trigeminal nerve. All patients experienced immediate relief of pain following surgery. Postoperatively, in one patient a small pontine hematoma developed, resulting in permanent trigeminal nerve anesthesia in the V2 and V3 divisions. All patients were free from pain at a mean follow-up period of 30 months.
Conclusions. These rare lesions are usually angiographically occult, but may sometimes be identifiable on high-resolution MR images. Total microsurgical resection with nerve preservation is possible, although operative complications are relatively common, reflecting the intimate association between these lesions and the pons. Complete resection is advised not only for symptom relief, but also to eliminate the theoretical risk of pontine hemorrhage.
A mixture of ethylene vinyl alcohol copolymer and ethanol yielding a nonadhesive liquid embolic agent to treat cerebral arteriovenous malformations: initial clinical experience
Authors: Hamada Jun-Ichiro , Kai Yutaka , Morioka Motohiro , Kazekawa Kiyoshi , Ishimaru Yasuji , Iwata Hiroo , Ushio Yukitaka 
Published: May 2009

Object. The authors report their clinical experience with their new nonadhesive liquid embolic agent, an ethylene vinyl alcohol copolymer (EVAL)/ethanol mixture, to treat arteriovenous malformations (AVMs).
Methods. Between June 1995 and April 2001, 57 patients with confirmed AVMs underwent embolization of their lesions with the EVAL/ethanol mixture. In 87 procedures consisting of one to three stages, the authors embolized 185 feeding arteries to occlude as much of the AVM as possible. Repeated injections under fluoroscopic control could be performed smoothly without encountering cementing of the catheter to the vessel wall. Among the 87 embolizations undertaken in 57 patients, seven procedures (8%) in six patients produced new postembolization symptoms. Resolution of these symptoms occurred within hours or days after four of the seven procedures; permanent neurological deficits remained after the other three procedures (3.4%). Of the 57 patients, three underwent postembolization radiosurgery, and 54 underwent radical treatment with microsurgical extirpation. Histopathological examination of the 54 specimens disclosed mild inflammation within the embolized lumen without inflammatory reactions in the media or adventitia. Follow-up angiograms obtained 3 years after radiosurgery was administered showed that in all three patients treated in this fashion the nidus had completely disappeared.
Conclusions. The EVAL/ethanol mixture is handled easily and appears to be an effective and safe agent for preoperative embolization of AVMs.
A nonadhesive liquid embolic agent composed of ethylene vinyl alcohol copolymer and ethanol mixture for the treatment of cerebral arteriovenous malformations: experimental study
Authors: Hamada Jun-Ichiro , Kai Yutaka , Morioka Motohiro , Kazekawa Kiyoshi , Ishimaru Yasuji , Iwata Hiroo , Ushio Yukitaka 
Published: May 2009

Object. The authors have developed a mixture of ethylene vinyl alcohol copolymer (EVAL) and iopamidol, which is dissolved in ethanol, as an alternative solvent to provide a safe means of embolizing arteriovenous malformations (AVMs).
Methods. A two-stage delivery technique is required to prevent premature precipitation in the catheter when using this material: the catheter is first infused with 30% ethanol and this is followed by the delivery of the EVAL—ethanol mixture. Acute angiographic changes were analyzed after superselective delivery of dimethyl sulfoxide (DMSO) and 30% ethanol into the renal artery of rabbits. Histological changes following the embolization of the renal artery achieved using the EVAL—ethanol mixture were recorded at 1 hour and at 2 and 16 weeks after the procedure. Although DMSO always produced severe, rapidly progressive vasospasm in the renal artery during a 1- to 60-minute postinfusion, 30% ethanol did not. Microscopically, the lumens of embolized vessels examined 1 hour after embolization with EVAL—ethanol appeared to be filled with EVAL sponges, leaving almost no open spaces. The space between the EVAL sponges and the inner surface of the vessels was filled with fresh thrombus. In the vessel walls of specimens examined 2 weeks after embolization there was no or a slight inflammatory reaction. Scattered in the EVAL sponges were almost equal numbers of neutrophilic granulocytes and mononuclear cells, indicative of a mild inflammatory response. In specimens examined 16 weeks postembolization, the changes noted at 2 weeks were intensified. There was no definite histopathological evidence of mural hemorrhage, perivascular extravasation of the mixture, or perivascular hemorrhage in any specimen that was examined.
Conclusions. Although the degree of permanence of this embolization material is yet unknown, the mixture was easy to handle, and appeared safe and effective for AVM embolization. Its nonadhesive characteristic and its ability to be infused by repeated injections make it an attractive alternative to currently available materials. The good results obtained in this study led us to undertake a clinical trial, the results of which are contained in a companion article in this issue of the Journal of Neurosurgery.
Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion
Authors: Lonser Russell R. , Walbridge Stuart , Garmestani Kayhan , Butman John A. , Walters Hugh A. , Vortmeyer Alexander O. , Morrison Paul F. , Brechbiel Martin W. , Oldfield Edward H. 
Published: May 2009

Object. Intrinsic disease processes of the brainstem (gliomas, neurodegenerative disease, and others) have remained difficult or impossible to treat effectively because of limited drug penetration across the blood—brainstem barrier with conventional delivery methods. The authors used convection-enhanced delivery (CED) of a macromolecular tracer visible on magnetic resonance (MR) imaging to examine the utility of CED for safe perfusion of the brainstem.
Methods. Three primates (Macaca mulatta) underwent CED of various volumes of infusion ([Vis]; 85, 110, and 120 µl) of Gd-bound albumin (72 kD) in the pontine region of the brainstem during serial MR imaging. Infusate volume of distribution (Vd), homogeneity, and anatomical distribution were visualized and quantified using MR imaging. Neurological function was observed and recorded up to 35 days postinfusion. Histological analysis was performed in all animals. Large regions of the pons and midbrain were successfully and safely perfused with the macromolecular protein. The Vd was linearly proportional to the Vi (R2 = 0.94), with a Vd/Vi ratio of 8.7 ± 1.2 (mean ± standard deviation). Furthermore, the concentration across the perfused region was homogeneous. The Vd increased slightly at 24 hours after completion of the infusion, and remained larger until the intensity of infusion faded (by Day 7). No animal exhibited a neurological deficit after infusion. Histological analysis revealed normal tissue architecture and minimal gliosis that was limited to the region immediately surrounding the cannula track.
Conclusions. First, CED can be used to perfuse the brainstem safely and effectively with macromolecules. Second, a large-molecular-weight imaging tracer can be used successfully to deliver, monitor in vivo, and control the distribution of small- and large-molecular-weight putative therapeutic agents for treatment of intrinsic brainstem processes.
Temporal pattern of cochlear nerve degeneration following compression injury: a quantitative experimental observation
Authors: Shimamura Norihito , Sekiya Tetsuji , Yagihashi Akinori , Suzuki Shigeharu 
Published: May 2009

Object. It has been empirically recognized that the cochlear nerve is highly vulnerable to traumatic stress resulting from surgical procedures; therefore, careful manipulation of the cochlear nerve is mandatory in preventing trauma-induced hearing loss during cerebellopontine angle (CPA) surgery. There is, however, no precise knowledge about the temporal pattern of cochlear nerve degeneration following trauma. This study was performed to determine the temporal pattern of injury that occurs after cochlear nerve trauma, knowledge of which is indispensable not only to neurosurgeons but also to all those who manage lesions involving the cochlear nerve.
Methods. Right suboccipital craniectomies were performed in groups of rats with the aid of a surgical microscope, and the seventh and eighth cranial nerve trunks were identified at the internal auditory meatus. The cochlear nerve was quantifiably compressed while compound action potentials of the cochlear nerve were monitored and recorded. Following injury, one group of rats was killed for histological examination at the end of each week for 4 weeks. Data from this study disclosed that the degeneration of the compressed cochlear nerve progressed in a relatively rapid manner and was complete within 1 week after the insult. The main pathophysiological mechanisms responsible for cochlear neuronal death in this experimental setting appeared to be necrosis, and an apoptotic mechanism seemed to play a subsidiary role.
Conclusions. Accurate knowledge about the temporal profile of trauma-induced cochlear nerve degeneration is closely linked with the problem of the therapeutic time window. The results of the present study indicated that any measures to ameliorate cochlear nerve degeneration following trauma should be started as early as possible (within 1 week) after an injury.