bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats
Authors: Degen Jeffrey W. , Walbridge Stuart , Vortmeyer Alexander O. , Oldfield Edward H. , Lonser Russell R.
Published: May 2009

Object. Convection-enhanced delivery (CED) can be used safely to perfuse regions of the central nervous system (CNS) with therapeutic agents in a manner that bypasses the blood—brain barrier (BBB). These features make CED a potentially ideal method for the distribution of potent chemotherapeutic agents with certain pharmacokinetic properties to tumors of the CNS. To determine the safety and efficacy of the CED of two chemotherapeutic agents (with properties ideal for this method of delivery) into the CNS, the authors perfused naive rats and those harboring 9L gliomas with carboplatin or gemcitabine.

Methods. Dose-escalation toxicity studies were performed by perfusing the striatum (10 µl, 24 rats) and brainstem (10 µl, 16 rats) of naive rats with carboplatin (0.1, 1, and 10 mg/ml) or gemcitabine (0.4, 4, and 40 mg/ml) via CED. Efficacy trials involved the intracranial implantation of 9L tumor cells in 20 Fischer 344 rats. The tumor and surrounding regions were perfused with 40 µl of saline (control group, four rats), 1 mg/ml of carboplatin (four rats), or 4 mg/ml of gemcitabine (four rats) 7 days after implantation. Eight rats harboring the 9L glioma were treated with the systemic administration of 60 mg/kg of carboplatin (four rats) or 150 mg/kg of gemcitabine (four rats) 7 days postimplantation. Clinical, gross, and histological analyses were used to determine toxicity and efficacy.

Toxicity occurred in rats that had received only the highest dose of the CED of carboplatin or gemcitabine. Among rats with 9L gliomas, all control and systemically treated animals died within 26 days of tumor implantation. Long-term survival (120 days) and eradication of the tumor occurred in both CED-treated groups (75% of rats in the carboplatin group and 50% of rats in the gemcitabine group). Furthermore, animals harboring the 9L glioma and treated with intratumoral CED of carboplatin or gemcitabine survived significantly longer than controls treated with intratumoral saline (p < 0.01) or systemic chemotherapy (p < 0.01).

Conclusions. The perfusion of sensitive regions of the rat brain can be accomplished without toxicity by using therapeutic concentrations of carboplatin or gemcitabine. In addition, CED of carboplatin or gemcitabine to tumors in this glioma model is safe and has potent antitumor effects. These findings indicate that similar treatment paradigms may be useful in the treatment of glial neoplasms in humans.
Effects of delayed, prolonged hypothermia on the pial vascular response after traumatic brain injury in rats
Authors: Ueda Yuji , Wei Enoch P. , Kontos Hermes A. , Suehiro Eiichi , Povlishock John T.
Published: May 2009

Object. In the experimental setting, hypothermia has been demonstrated to attenuate the damaging consequences of stroke and traumatic brain injury (TBI). Laboratory studies of TBI have focused primarily on the use of early hypothermic intervention, with little consideration of the potential efficacy of more delayed but prolonged hypothermia, which would constitute a more clinically relevant approach. In this investigation, the authors evaluated whether delayed, prolonged hypothermia after TBI protected the cerebral microcirculation.

Methods. Male Sprague—Dawley rats were equipped with cranial windows for direct visualization of the pial arterial circulation and then subjected to impact-acceleration brain injury. The rats were randomly divided into four experimental groups: Group 1 consisted of normothermic animals; in Group 2 the rats received a 1-hour period of hypothermia (32°C) 30 minutes posttrauma, followed by slow rewarming (32–37°C/90 minutes); and in Groups 3 and 4 the rats received a more delayed induction (at 1 hour postinjury) of either 1 hour (Group 3) or 2 hours (Group 4) of hypothermia, followed by the slow rewarming. The pial arteriolar responses to acetylcholine (ACh) or hypercapnia were measured until up to 6 hours postinjury. With this approach the authors found that the normothermic group demonstrated severely impaired vasoreactivity in terms of ACh-dependent dilation and CO2 reactivity in comparison to baseline values (p < 0.001). In contrast, hypothermia of short duration that was initiated early (30 minutes postinjury) conferred significant cerebrovascular protection (p < 0.001), yet this protection was reduced when the onset of this 1-hour hypothermic period was postponed to 1 hour postinjury. Nevertheless, reduced protection could be significantly improved (p < 0.001) with prolongation of the hypothermic period to 2 hours.

Conclusions. The results of this study show that early as well as delayed but prolonged hypothermia attenuate the impaired vascular responsiveness seen after TBI, indicating the potential clinical usefulness of this treatment.
Interleukin-1β and adverse effects on cerebral blood flow during long-term global hypoperfusion
Authors: Maher Cormac O. , Anderson Robert E. , Martin Heidi S. , McClelland Robyn L. , Meyer Fredric B.
Published: May 2009

Object. The effects of interleukin (IL)-1β on the cerebral vasculature are complex and incompletely understood. Many pathophysiological states in which inflammatory cascades have been implicated also have varying degrees of cerebral hypoperfusion. The purpose of this investigation was to examine the long-term effects of this proinflammatory cytokine and its antagonist on cerebral blood flow (CBF) following global cerebral hypoperfusion.

Methods. Sprague—Dawley rats were randomly assigned to 12 groups and given continuous intracerebroventricular (ICV) infusions of IL-1β, the IL-1 receptor antagonist (IL-1ra), or saline vehicle (control). Global cerebral hypoperfusion was produced by occlusion of both carotid arteries and one vertebral artery. Cerebral blood flow was measured at baseline and again after initiation of the infusions by performing a 133Xe clearance study.

Prolonged ICV administration of IL-1β resulted in a significant decrease in CBF compared with that in controls. Prolonged administration of the antagonist IL-1ra resulted in significant increases in CBF compared with that in both IL-1β—treated animals and controls.

Conclusions. This experiment demonstrates that long-term treatment with the proinflammatory cytokine IL-1β adversely affects CBF.
Facial neuropathy due to axonal degeneration and microvasculitis following gamma knife surgery for vestibular schwannoma: a histological analysis
Authors: Watanabe Takashi , Saito Nobuhito , Hirato Junko , Shimaguchi Hidetoshi , Fujimaki Hiroya , Sasaki Tomio
Published: May 2009

✓ Complete facial palsy (House—Brackmann Grade VI) developed in a 63-year-old man with a vestibular schwannoma 25 months after he had undergone two gamma knife surgeries performed 33 months apart and involving a cumulative dose of 24 Gy directed to the tumor margin at the 50% isodose line. Magnetic resonance imaging demonstrated tumor enlargement with central nonenhancement, which initially had been recognized 21 months after the second radiosurgery. Microsurgery was performed to achieve total removal of the tumor. Histological and immunohistochemical examinations of the facial nerve specimen removed from the edge of the tumor revealed a loss of axons, proliferation of Schwann cells, and microvasculitis. In this case, microvasculitis and axonal degeneration were probably the major causes of the radiation-induced facial neuropathy.
Use of an anteromedial subdural strip electrode in the evaluation of medial temporal lobe epilepsy
Authors: Cohen-Gadol Aaron A. , Spencer Dennis D.
Published: May 2009

✓ The temporal lobe is the most common site of partial epilepsy that is amenable to surgical therapy, and therefore ictal localization in this region is important. The authors describe the application of an anteromedial subdural strip electrode for the evaluation of epilepsy originating from the medial temporal lobe. This strip is advanced around the temporal pole and underneath the lesser wing of the sphenoid bone as it follows the medial temporal lobe contour. The advantages of this method of placement are the consistent path and reliable final position of the strip along the medial basal temporal lobe surface. This method allows adequate coverage of the parahippocampal gyrus along its long axis extending posterior to the level of the collicular plate. This technique has been used with no complications during intracranial monitoring of more than 100 patients with presumed temporal lobe epilepsy.
Clip wrapping for partial avulsion of the aneurysm neck
Authors: Lanzino Giuseppe , Spetzler Robert F.
Published: May 2009

✓ An intraoperative aneurysm rupture due to a tear at the aneurysm neck can be a tricky complication to manage. The authors describe a simple technique found to be useful in such a case.
No effect of enoxaparin on outcome of aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled clinical trial
Authors: Siironen Jari , Juvela Seppo , Varis Joona , Porras Matti , Poussa Kristiina , Ilveskero Sorella , Hernesniemi Juha , Lassila Riitta
Published: May 2009

Object. From the moment an intracranial aneurysm ruptures, cerebral blood flow is impaired, and this impairment mainly determines the outcome in patients who survive after the initial bleeding. The exact mechanism of impairment is unknown, but activation of coagulation and fibrinolysis correlate with clinical condition and outcome after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether enoxaparin, a low-molecular-weight heparin, which is a well-known anticoagulating agent, has any effect on the outcome of aneurysmal SAH postoperatively.

Methods. In this randomized, double-blind, single-center clinical trial, 170 patients (85 per group) with aneurysmal SAH were randomly assigned to receive either enoxaparin (40 mg subcutaneously once daily) or a placebo, starting within 24 hours after occlusion of the aneurysm and continuing for 10 days. Analysis was done on an intention-to-treat basis. Outcome was assessed at 3 months on both the Glasgow Outcome and modified Rankin Scales. Patients were eligible for the study if surgery was performed within 48 hours post-SAH, and no intracerebral hemorrhage was larger than 20 mm in diameter on the first postoperative computerized tomography scan.

At 3 months, there were no significant differences in outcome by treatment group. Of the 170 patients, 11 (6%) died, and only 95 (56%) had a good outcome. Principal causes of unfavorable outcome were poor initial condition, delayed cerebral ischemia, and surgical complications. There were four patients with additional intracranial bleeding in the group receiving enoxaparin. The bleeding was not necessarily associated with the treatment itself, nor did it require treatment, and there were no such patients in the placebo group.

Conclusions. Enoxaparin seemed to have no effect on the outcome of aneurysmal SAH in patients who had already received routine nimodipine and who had received triple-H therapy when needed. Routine use of low-molecular-weight heparin should be avoided during the early postoperative period in patients with SAH, because this agent seems to increase intracranial bleeding complications slightly, with no beneficial effect on neurological outcome.
Characterization of perioperative seizures and epilepsy following aneurysmal subarachnoid hemorrhage
Authors: Lin Chih-Lung , Dumont Aaron S. , Lieu Ann-Shung , Yen Chen-Po , Hwang Shiuh-Lin , Kwan Aij-Lie , Kassell Neal F. , Howng Shen-Long
Published: May 2009

Object. The reported incidence, timing, and predictive factors of perioperative seizures and epilepsy after subarachnoid hemorrhage (SAH) have differed considerably because of a lack of uniform definitions and variable follow-up periods. In this study the authors evaluate the incidence, temporal course, and predictive factors of perioperative seizures and epilepsy during long-term follow up of patients with SAH who underwent surgical treatment.

Methods. Two hundred seventeen patients who survived more than 2 years after surgery for ruptured intracranial aneurysms were enrolled and retrospectively studied. Episodes were categorized into onset seizures (≤ 12 hours of initial hemorrhage), preoperative seizures, postoperative seizures, and late epilepsy, according to their timing.

The mean follow-up time was 78.7 months (range 24–157 months). Forty-six patients (21.2%) had at least one seizure post-SAH. Seventeen patients (7.8%) had onset seizures, five (2.3%) had preoperative seizures, four (1.8%) had postoperative seizures, 21 (9.7%) had at least one seizure episode after the 1st week postoperatively, and late epilepsy developed in 15 (6.9%). One (3.8%) of 26 patients with perioperative seizures (onset, preoperative, or postoperative seizure) had late epilepsy at follow up. The mean latency between the operation and the onset of late epilepsy was 8.3 months (range 0.3–19 months). Younger age (< 40 years old), loss of consciousness of more than 1 hour at ictus, and Fisher Grade 3 or greater on computerized tomography scans proved to be significantly related to onset seizures. Onset seizure was also a significant predictor of persistent neurological deficits (Glasgow Outcome Scale Scores 2–4) at follow up. Factors associated with the development of late epilepsy were loss of consciousness of more than 1 hour at ictus and persistent postoperative neurological deficit.

Conclusions. Although up to one fifth of patients experienced seizure(s) after SAH, more than half had seizure(s) during the perioperative period. The frequency of late epilepsy in patients with perioperative seizures (7.8%) was not significantly higher than those without such seizures (6.8%). Perioperative seizures did not recur frequently and were not a significant predictor for late epilepsy.
Enhanced stability of somatosensory evoked potentials attained in the median nerve by using temporal electrodes for intraoperative recording in patients in the semisitting position
Authors: Wiedemayer Helmut , Sandalcioglu Ibrahim Erol , Regel Jens , Armbruster Wolf , Schaefer Heike , Stolke Dietmar
Published: May 2009

Object. Findings published in case reports indicate that monitoring of median nerve somatosensory evoked potentials (MN-SSEPs) is unreliable in patients who undergo surgery while in the semisitting position due to the occurrence of changes in the potentials that are unrelated to neurological damage. The present study was designed to test the hypothesis that in these patients MN-SSEPs are more stable when recording electrodes are placed over the temporal region.

Methods. In 30 patients who underwent surgery in the semisitting position, MN-SSEPs were recorded intraoperatively by using electrodes placed over the temporal region as well as those placed at conventional recording sites. The authors analyzed MN-SSEP amplitudes and latencies at different recording sites and at distinct steps of the monitoring procedure.

In 10 of the 30 patients a clinically significant attenuation (>50%) of MN-SSEP amplitude was observed at conventional recording sites and this was obviously not related to neurological damage. In contrast, no significant changes were observed in MN-SSEPs recorded from electrodes located over the temporal region.

Conclusions. In patients who undergo surgery in the semisitting position, the use of additional recording electrodes placed over the temporal region makes intraoperative MN-SSEP monitoring less prone to false-positive alarms and thus enhances the reliability of intraoperative MN-SSEP monitoring.
Analysis of taste disturbance before and after surgery in patients with vestibular schwannoma
Authors: Watanabe Katsushige , Saito Nobuhito , Taniguchi Makoto , Kirino Takaaki , Sasaki Tomio
Published: May 2009

Object. The frequency, nature, and history of subjective taste disturbance before and after vestibular schwannoma (VS) surgery was investigated.

Methods. Personal interviews were conducted in 108 patients with unilateral VS. Abnormalities in taste perception, either a significant reduction or a change in character, were experienced by 31 patients (28.7%) before surgery and by 37 (34.3%) after tumor removal. Preoperative taste disturbance worsened after surgery in five (16.1%) of the 31 patients, remained unchanged in eight (25.8%), improved in two (6.5%), and became normal in 16 (51.6%). Taste disturbance occurred postoperatively in 22 (28.6%) of 77 patients who had experienced no preoperative taste disturbance. The mean onset of the abnormality after resection was 1.1 ± 1.7 months. Postoperative taste disturbance resolved in 24 of the 37 patients (64.9%) within 1 year after onset.

Conclusions. Subjective taste disturbance was common before and after VS removal, and the natural history of this condition was very variable in the pre- and postoperative periods. All patients who undergo surgery for VS should receive appropriate counseling about the likelihood and course of postoperative complications, including dysfunction of the sensory component of the facial nerve.
A prospective controlled study of sleep respiratory events in patients with craniovertebral junction malformation
Authors: Botelho Ricardo Vieira , Bittencourt Lia Rita Azeredo , Rotta José Marcos , Tufik Sergio
Published: May 2009

Object. Craniovertebral junction malformation (CVJM) or Chiari malformation in adults, with or without syringomyelia and basilar invagination, produces neuronal dysfunction of the brainstem, cerebellum, cranial nerves, and upper spinal cord. The respiratory center and some of its afferent and efferent components can be altered in these diseases. The authors studied patients with and without CVJM to determine whether this physical feature contributed to sleep disturbances.

Methods. Respiratory manifestations during sleep were studied prospectively, by using whole-night polysomnography, in 32 symptomatic patients (CVJM group) and 16 healthy volunteers (control group). Patients with CVJM presented with more sleep disturbances (reports of snoring and apnea) than those in the control group. The apnea/hypopnea index values were higher in patients with CVJMs than in the control group (13 ± 15 compared with 3 ± 6; p = 0.007) and the rate of central sleep apneas was higher in the CVJM than in the control group (22 ± 30 compared with 4 ± 8%; p = 0.009). The apnea/hypopnea index was highest in the subgroup with basilar invagination than in the other subgroups. The central apneic episodes were more frequent in the patients with basilar invagination (35 ± 40%; p = 0.001) and in those with syringomyelia (17.6 ± 24.6%; p = 0.003) than in the control group (4 ± 8%). Patients with symptomatic CVJM, especially those with basilar invagination, presented with more sleep respiratory compromise than did those in the control group.

Conclusions. The incidence of sleep apnea/hypopnea syndrome is significantly higher in patients with CVJM.
Increased invasive capacity of connexin43-overexpressing malignant glioma cells
Authors: Zhang Wei , Nwagwu Chiedozie , Le Duc Minh , Yong V. Wee , Song Hua , Couldwell William T.
Published: May 2009

Object. Malignant glioma cells, similar to astrocytes, express connexin43 (Cx43) universally but at widely varied levels. Data from previous studies have demonstrated that malignant glioma cells form functional gap junction channels among themselves as well as with astrocytes and that such a communication has the potential to modulate the phenotypic characteristics of astrocytes. Recently, gap junctions have been demonstrated to play a role in the invasive phenotype of malignant gliomas. In this study, the authors have further investigated the motility and invasion ability of Cx43-overexpressing and Cx43-deficient malignant glioma cells.

Methods. Using a standard invasion system of a Matrigel transwell invasion chamber, the authors found that the number of Cx43-transfected C6 glioma cells (C6-Cx43 cells) migrating through the Matrigel-coated membrane was similar to that of mock-transfected control cells (C6-mock cells) during the first 24 hours, but increased significantly thereafter. When these cells were cocultured with astrocytes, the number of invading C6-Cx43 cells was more than threefold greater than the number of invading C6-mock cells. Results of an in vitro cell motility assay also demonstrated that C6-Cx43 cells were more motile and scatter-active than C6-mock cells. Furthermore, zymographic analysis of MMPs, an important determinant in glioma invasion, demonstrated that the amounts of MMP-2 and MMP-9 in culture medium collected from C6-Cx43 cells were orders of magnitude higher than those from C6-mock cells. In addition, BB-94, a synthetic MMP inhibitor, significantly inhibited C6-Cx43 cell invasion.

Conclusions. The overexpression of gap junction proteins in glioma cells and the intercellular communication between tumor and nontumor glia cells may play important roles in the facilitation of glioma cell invasion.
Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor—secreting cells in a model of middle cerebral artery occlusion in rats
Authors: Fujiwara Kenjiro , Date Isao , Shingo Tetsuro , Yoshida Hideyuki , Kobayashi Kazuki , Takeuchi Akira , Yano Akimasa , Tamiya Takashi , Ohmoto Takashi
Published: May 2009

Object. This study was conducted to evaluate the effects of grafting encapsulated basic fibroblast growth factor (bFGF)—secreting cells in rat brains subjected to ischemic injury.

Methods. Two cell lines were used for encapsulated grafting in this experiment, namely, a bFGF-secreting cell line established by genetic manipulation of baby hamster kidney (BHK) cells, and a naive BHK cell line. Forty-seven Sprague—Dawley rats were used in this experiment. The animals were divided into the following three groups: those receiving grafts of encapsulated bFGF-secreting cells (BHK-bFGF group); those with grafts of encapsulated naive BHK cells (naive BHK group); and those with no grafts (control group). The authors implanted encapsulated cells into the right striatum of host rats in the BHK-bFGF and naive BHK groups. Six days after grafting, the host and control animals underwent permanent right middle cerebral artery occlusion (MCAO) with an intraluminal suture procedure. The infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride staining and computerized image analysis 24 hours after MCAO. Fragmentations of DNA in the host brains were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling 12 hours after MCAO.

The authors found that the infarct volume in the BHK-bFGF group was reduced by approximately 30% compared with that in the naive BHK and control groups. In the ischemic penumbral area, the number of apoptotic cells in the BHK-bFGF group was significantly decreased compared with that in the other groups.

Conclusions. The grafting of encapsulated BHK bFGF-secreting cells protected the brain from ischemic injury. Encapsulation and grafting of genetically engineered cells such as bFGF-secreting cells is thus thought to be a useful method for protection against cerebral ischemia.
Evaluation of a novel propylene oxide—treated collagen material as a dural substitute
Authors: Maher Cormac O. , Anderson Robert E. , McClelland Robyn L. , Link Michael J.
Published: May 2009

Object. The authors evaluated a new non—cross-linked, propylene oxide—treated, acellular collagen matrix for use as a dural substitute in rabbits. They then compared this material to a commonly used dural substitute as well as to native dura mater used during primary closure.

Methods. Forty-six rabbits were randomly assigned to eight groups of five or six rabbits each. These groups differed according to the type of closure material that was used during surgery (native dura, control dural substitute, or experimental dural substitute) and the duration of convalescence. At the end of the experiment, the tightness of the duraplasty was assessed in each live rabbit by continuous infusion of fluid into the cisterna magna until leakage was detected. The animals were killed and each specimen was sectioned and studied histologically. The authors found that the experimental dural substitute was safe in animals for this application, that it held sutures well, and that a watertight closure was usually achieved. There were fewer adhesions between the experimental material and neural tissue was less likely to adhere to the cranium than the control graft. Histological examination showed that the experimental material had slightly more spindle cells and vascularity than the control graft.

Conclusions. The experimental graft material has several features that make it an attractive candidate for use as a dural substitute.
Successful stent placement for cervical artery dissection associated with the Ehlers—Danlos syndrome
Authors: Kurata Akira , Oka Hidehiro , Ohmomo Taketomo , Ozawa Hitoshi , Suzuki Sachio , Fujii Kiyotaka , Kan Shinichi , Miyasaka Yoshio , Arai Harue
Published: May 2009

✓ This 44-year-old man with Ehlers—Danlos syndrome (EDS) Type IV presented with hemiparesis and the Gerstmann syndrome. Left carotid artery (CA) angiography revealed a dissecting aneurysm with severe stenosis located in the common CA; the lesion was successfully treated with a stent graft. The patient's clinical course after endovascular surgery was uneventful, without occurrence of megacolon. The literature for spontaneous CA dissection in EDS Type IV cases is reviewed and points for investigation and treatment are discussed.
Volume of residual disease as a predictor of outcome in adult patients with recurrent supratentorial glioblastomas multiforme who are undergoing chemotherapy
Authors: Keles G. Evren , Lamborn Kathleen R. , Chang Susan M. , Prados Michael D. , Berger Mitchel S.
Published: May 2009

Object. For patients with recurrent glioblastomas multiforme (GBMs) the prognosis is poor. Although chemotherapy may provide a survival advantage, the role of the extent of tumor resection, or the volume of the residual tumor at the time of recurrence, before instituting chemotherapy, is unclear. This study was designed to assess the response to chemotherapy based on the volume of residual disease (VRD) at the start of treatment in patients with recurrent GBMs. To accomplish this, the authors evaluated a homogeneous group of patients with recurrent GBMs who received the same chemotherapeutic agent.

Methods. One hundred nineteen adult patients with recurrent supratentorial GBMs received temozolomide chemotherapy at the time of tumor recurrence. In this cohort the authors analyzed the prognostic significance of volumetrically assessed tumor mass on time to tumor progression (TTP) and survival time (ST).

Multivariate analysis demonstrated that the VRD at the beginning of chemotherapy was a statistically significant predictor of both TTP (p < 0.0001) and ST (p < 0.006) when adjusted for the patient's age, performance score, and time from the initial diagnosis. Patients in whom the VRD was less than 10 cm3 at the start of chemotherapy had a 6-month progression-free survival rate of 32% compared with 8% for patients with a VRD between 10 and 15 cm3 and 3% for patients with a VRD larger than 15 cm3. Patients in whom the VRD was smaller than 10 cm3 had a 1-year survival rate of 37% compared with 9% for patients with a VRD between 10 and 15 cm3 and 18% for patients with a VRD larger than 15 cm3.

Conclusions. These data indicate that patients with recurrent GBMs who start chemotherapy with a smaller volume (< 10 cm3) of residual disease may have a more favorable response to chemotherapy and a more favorable outcome.
Transcranial echo-guided transsphenoidal surgical approach for the removal of large macroadenomas
Authors: Suzuki Ryuta , Asai Jun-ichiro , Nagashima Goro , Itokawa Hiroshi , Chang Chih-Wei , Noda Masayuki , Fujimoto Michio , Fujimoto Tsukasa
Published: May 2009

Object. Transsphenoidal surgery for the removal of macroadenomas has some disadvantages, including the risk of performing procedures without adequate visualization, difficulties in estimating the amount of residual tumor, and the risk of injuring major vessels. To overcome these disadvantages, the authors have developed transcranial echo-guided transsphenoidal surgery.

Methods. Three patients with large macroadenomas and two patients with irregularly shaped macroadenomas were selected for this operation. In addition to standard preparations for transsphenoidal surgery, in each case the right frontal bone was trephined and an echo probe was inserted transdurally through the trephination hole. During tumor removal, brightness-mode echo images and Doppler color flow images were obtained. The echo images allowed for real-time visualization of the tumor and surrounding brain structures including major arteries and the cisterns; histological heterogeneities of the tumor could also be appreciated. The tumors were removed safely and maximal tumor removal was achieved.

Conclusions. Transcranial echo-guided transsphenoidal surgery provides real-time visualization of tumor removal. The method enhances the safety of this surgery, maximizes the removal of the tumor, and is inexpensive.
What we research: survey of American Association of Neurological Surgeons and Congress of Neurological Surgeons member publications
Authors: Burnett Mark G. , Stein Sherman C. , Grady M. Sean
Published: May 2009

Object. The goal of this study was to create a searchable database of research manuscripts authored by members of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS) to describe the nature and character of the research currently being undertaken by neurosurgeons.

Methods. Manuscripts published by all physician members listed in the 2001 AANS/CNS Membership Directory (6921 physicians) were gathered into a database through individual literature searches of the author name for the calendar year 2001. Duplicate publications were purged and the database was reviewed for accuracy. An internal verification of the database revealed a 4% underreporting rate. Statistics from the database were compiled and displayed with information about AANS/CNS members and their clinical activities.

The AANS/CNS members published a total of 2748 research the manuscripts in 479 different journals during 2001. Thirty-eight percent of the manuscripts (1042 of 2748) were authored by US members and 62% (1706 of 2748) by non-US members. The focus of the majority of manuscripts included the areas of brain tumor (26%; 707 of 2748), vascular disease (20%; 558 of 2748), spine (10%; 282 of 2748), and trauma (8%; 233 of 2748). Sixty-nine percent of manuscripts (1897 of 2748) were retrospective and technical clinical studies, and of these 39% (744 of 1897) were case reports. Laboratory investigations made up 15% (414 of 2748) of all manuscripts, whereas prospective randomized clinical trials represented 1% (34 of 2748).

Conclusions. The majority of AANS/CNS member manuscripts are authored by non—US members despite their small AANS/CNS representation. Most research is clinical, based on retrospective data, and includes a large number of case reports. A disparity exists between what neurosurgeons do clinically and both the quantity and subject of their research.
Prevention of apoptotic but not necrotic cell death following neuronal injury by neurotrophins signaling through the tyrosine kinase receptor
Authors: Kim Dong H. , Zhao Xiurong , Tu Christina H. , Casaccia-Bonnefil Patrizia , Chao Moses V.
Published: May 2009

Object.Neurotrophins prevent the death of neurons during embryonal development and have potential as therapeutic agents. During development, neuronal death occurs only by apoptosis and not by necrosis. Following injury, however, neurons can die by both processes. Data from prior studies have not clearly indicated whether neurotrophins can decrease apoptosis compared with necrosis. The goal of this study was to determine the effect of neurotrophin treatment on each of these processes following injury and to characterize the receptor(s) required.

Methods.The authors used an in vitro model of injury with the aid of primary cortical neurons obtained from rat embryos. After 9 days in culture and the elimination of glia, homogeneous and mature neurons were available for experimentation. Noxious stimuli were applied, including radiation, hypoxia, and ischemia. Subsequent cell death by apoptosis or necrosis was noted based on morphological and enzymatic assessments (such as lactate dehydrogenase [LDH] release) and assays for DNA fragmentation. The effect of treatment with nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 was determined. Finally, Western blot analyses were performed to note the neurotrophin receptor status in the neurons (tyrosine kinase receptors [Trks] and p75).

The authors studied different stimuli-induced cell death by using different processes. With the application of radiation, cells died primarily by apoptosis, as evidenced by cell shrinkage, the presence of apoptotic bodies, and specific DNA fragmentation. This was a delayed process (> 6 hours) that could be reduced by gene transcription or protein synthesis inhibitors. With ischemia, cells died immediately by necrosis, showing cell enlargement and rupture. Ischemic cell death was not affected by the inhibition of macromolecular synthesis. Hypoxia produced a mixture of the two cell death processes.

Both BDNF and neurotrophin-3 demonstrated protection against apoptotic cell death only. Statistically significant decreases of both LDH release and apoptosis-specific DNA fragmentation were noted following radiation and hypoxia, but not for ischemia. Nerve growth factor, unlike the other neurotrophins, did not affect apoptosis because a functional receptor, Trk A, was not expressed by the cortical neurons. There was expression of both Trk B and Trk C, which bind BDNF and neurotrophin-3.

Conclusions.These findings have significant clinical implications. Neurotrophins may only be effective in disorders in which apoptosis, and not necrosis, is the major process. Furthermore, the Trk signaling cascade must be activated for this response to occur. Because the expression of these receptors diminishes in adulthood, neurotrophin application may be most appropriate in the pediatric population.
Magnesium and experimental vasospasm
Authors: Macdonald R. Loch , Curry Daniel J. , Aihara Yasuo , Zhang Zhen-Du , Jahromi Babak S. , Yassari Reza
Published: May 2009

Object. Interest has developed in the use of magnesium (Mg++) as a neuroprotectant and antivasospastic agent. Magnesium may increase cerebral blood flow (CBF) and reduce the contraction of cerebral arteries caused by various stimuli. In this study the authors tested the hypothesis that a continuous intravenous infusion of Mg++ reduces cerebral vasospasm after experimental subarachnoid hemorrhage (SAH).

Methods. A dose-finding study was conducted in five monkeys (Macaca fascicularis) to determine what doses of intravenous MgSO4 elevate the cerebrospinal fluid (CSF) concentrations of Mg++ to vasoactive levels and to determine what effects these doses have on the diameters of cerebral arteries, as shown angiographically. After a standard dose of MgSO4 had been selected it was then administered in a randomized, controlled, blinded study to 10 monkeys (five animals/group) with SAH, beginning on Day 0 and continuing for 7 days, at which time angiography was repeated. A 0.086-g/kg bolus of MgSO4 followed by an infusion of 0.028 g/kg/day MgSO4 significantly elevated serum and CSF levels of Mg++ (five monkeys). Magnesium sulfate significantly elevated the serum level of total Mg++ from a control value of 0.83 ± 0.04 mmol/L to 2.42 ± 1.01 mmol/L on Day 7 and raised the CSF level from 1.3 ± 0.04 mmol/L to 1.76 ± 0.14 mmol/L. There was no angiographic evidence of any effect of MgSO4 on normal cerebral arteries. After SAH, the vasospasm in the middle cerebral artery was not significantly reduced (46 ± 8% in the MgSO4-treated group compared with 35 ± 6% in the placebo [vehicle]-treated group, p > 0.05, unpaired t-test).

Conclusions. Magnesium sulfate did not significantly reduce cerebral vasospasm after SAH in the doses tested. An investigation of SAH is warranted mainly to test whether a benefit can be achieved by neuroprotection or by augmentation of CBF by dilation of small vessels and/or collateral pathways.
Tensile strength of cranial pia mater: preliminary results
Authors: Aimedieu Patrick , Grebe Reinhard
Published: May 2009

Object. The goal of this study was to determine the tensile strength of cranial pia mater.

Methods. Samples of isolated bovine cranial pia mater were subjected to quasistatic traction to evaluate its tensile strength. The experimental curves of physiological deformation that were obtained can be subdivided into three parts that represent different mechanical properties: the nonlinear initial part of the curve demonstrates increasing stiffness, followed by a quasilinear pattern of elastic behavior, and finally a negative relationship (slope) between force and elongation, which characterizes a progressive deterioration. These three steps precede final sample rupture. The stiffness of the pia mater was calculated for both the initial and the linear (elastic) parts of the mean curve. The initial part and the elastic part of the curve show a typical stiffness value of 0.024 N/mm and 0.19 N/mm, respectively. The maximal mean force and corresponding maximal deformation that were attained were 1.1 N and 0.19, respectively.

Conclusions. Although very thin and apparently fragile, pia mater exhibits an unexpectedly high level of stiffness and should have a significant influence on total brain mechanical properties in response to loading.
Superior semicircular canal dehiscence: a new indication for middle fossa craniotomy
Authors: Martin Jonathan E. , Neal Christopher J. , Monacci William T. , Eisenman David J.
Published: May 2009

✓ Superior semicircular canal dehiscence is a recently described condition resulting in pressure-induced vertigo in affected patients. The diagnosis is established with the appearance of characteristic electronystagmographic and neuroimaging findings. This condition is amenable to surgical treatment by resurfacing of the dehiscence in the defect in the middle cranial fossa floor with preservation of superior semicircular canal function. The authors report on the treatment of a 35-year-old man with superior semicircular canal dehiscence by a joint neurosurgical and otolaryngological team.
Performance of bipolar forceps during coagulation and its dependence on the tip material: a quantitative experimental assay
Authors: Mikami Takeshi , Takahashi Akira , Hashi Kazuo , Gasa Shinsei , Houkin Kiyohiro
Published: May 2009

✓ The aim of this study was to measure objectively the adherence of burned tissue to bipolar forceps to evaluate the coagulation performance of forceps made of different types of metals. Coagulation performance of bipolar forceps made of gold, titanium, and stainless steel was determined by comparing the amount of protein in the adhered coagulum on the tips. The amount of adhered coagulum was significantly less on the gold-plated bipolar forceps than on those made of the other two materials. The ease with which coagulum could be removed was compared using the cleaning cycle of an ultrasonic rinsing device. This ease of removal was also significant with the gold-plated forceps. Electron microscopy observations of the surface of the forceps tips revealed a significant difference in roughness among these materials, and there were also significant differences in wetting tensions. Measuring adherence based on three different types of roughness and wetting tensions of forceps made from the same metal (titanium) also demonstrated a significant difference in the cleaning cycle. Histological examination of an artery coagulated with the gold-plated bipolar forceps showed that the structure had been completely collapsed without destruction of the layers, whereas arteries coagulated with the other materials revealed severely damaged structures. Adherence to bipolar forceps was dependent on both the material in the tips and the roughness of this material. The gold-plated bipolar forceps demonstrated the best performance.
Double-stent method: therapeutic alternative for small wide-necked aneurysms
Authors: Doerfler Arnd , Wanke Isabel , Egelhof Thomas , Stolke Dietmar , Forsting Michael
Published: May 2009

✓ The authors present two cases of patients with small, acutely ruptured, wide-necked aneurysms of the distal vertebral artery that were not amenable to conventional coil embolization and were instead treated by means of a double-stent method in which one stent was placed inside another. Angiography performed immediately after the procedure revealed a significant reduction in aneurysm filling; total occlusion of the lesion was observed after 7 days and confirmed 6 months later in both aneurysms. By placing one stent inside the other, stent permeability can be reduced, which may result in significant hemodynamic changes with accelerated aneurysm thrombosis. This double-stent method may represent a therapeutic alternative, especially in cases of small, wide-necked aneurysms in which conventional endovascular techniques or stent-supported coil embolization is not considered feasible or is believed to be too dangerous, and surgical treatment is contraindicated.
Novel closure technique for the endonasal transsphenoidal approach
Authors: Liu James K. , Orlandi Richard R. , Apfelbaum Ronald I. , Couldwell William T.
Published: May 2009

✓ Transsphenoidal microsurgery has been the standard approach to sellar lesions since the repopularization of the technique with modifications by Dott, Guiot, and Hardy. The endonasal transseptal transsphenoidal approach, as introduced by Hirsch, is still commonly used by pituitary surgeons to remove lesions of the sellar and parasellar region. One disadvantage of this approach is that the submucosal dissection requires postoperative nasal packing, which is a source of discomfort in patients who undergo transsphenoidal surgery. The authors describe a novel closure technique for the unilateral endonasal transsphenoidal approach that eliminates the need for full nasal packing, minimizing postoperative rhinological morbidity. This technique has been performed in 67 patients harboring sellar and parasellar lesions. All patients recovered rapidly without significant rhinological sequelae.
Ruptured distal middle cerebral artery aneurysm
Authors: Horiuchi Tetsuyoshi , Tanaka Yuichiro , Takasawa Hisayoshi , Murata Takahiro , Yako Takehiro , Hongo Kazuhiro
Published: May 2009

Object. Ruptured distal middle cerebral artery (MCA) aneurysms are uncommon, and their clinical and radiological features are poorly understood. To clarify characteristics of these lesions, the authors undertook a retrospective analysis of nine patients with ruptured distal MCA aneurysms.

Methods. The medical records of patients who underwent surgical repair of ruptured intracranial aneurysms between 1988 and 2002 at Shinshu University Hospital and its affiliated hospitals were retrospectively evaluated. The authors found only nine patients with a ruptured distal MCA aneurysm, and their clinical, neuroimaging, and intraoperative findings were evaluated.

Conclusions. This study of nine patients with distal MCA aneurysms is the largest series to date. Eight lesions were saccular aneurysms that were clipped and the remaining one was a mycotic aneurysm that was trapped. Eight of the nine patients suffered cerebral hematomas with subarachnoid hemorrhage. All patients had good outcomes after obliteration of their aneurysm, although their preoperative condition was not good.
Poor-grade aneurysmal subarachnoid hemorrhage: relationship of cerebral metabolism to outcome
Authors: Sarrafzadeh Asita , Haux Daniel , Küchler Ingeborg , Lanksch Wolfgang R. , Unterberg Andreas W.
Published: May 2009

Object. The majority of patients with poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies (WFNS) Grades IV and V, have high morbidity and mortality rates. The objective of this study was to investigate cerebral metabolism in patients with low-compared with high-grade SAH by using bedside microdialysis and to evaluate whether microdialysis parameters are of prognostic value for outcome in SAH.

Methods. A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 ± 12.9 years); these patients were studied for 162 ± 84 hours (mean ± standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I–III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed.

In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03).

Conclusions. Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future.