bluuebunny/crossref_metadata_2025 huggingface dataset:
Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study
Authors: Kovacs Kalman , Horvath Eva , Stefaneanu Lucia , Bilbao Juan , Singer William , Muller Paul J. , Thapar Kamal , Stone Elaine
Published: June 2009

✓ The authors report on the morphological features of a pituitary adenoma that produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone combination produced by a single adenoma is extremely rare; a review of the available literature showed that only one previous case has been published. The tumor, which was removed from a 62-year-old man with acromegaly, was studied by histological and immunocytochemical analyses, transmission electron microscopy, immunoelectron microscopy, and in situ hybridization. When the authors used light microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma composed of two separate cell types: one cell population synthesized GH and the other ACTH.

The cytogenesis of pituitary adenomas that produce more than one hormone is obscure. It may be that two separate cells—one somatotroph and one corticotroph—transformed into neoplastic cells, or that the adenoma arose in a common stem cell that differentiated into two separate cell types. In this case immunoelectron microscopy conclusively demonstrated ACTH in the secretory granules of several somatotrophs. This was associated with a change in the morphological characteristics of secretory granules. Thus it is possible that the tumor was originally a somatotropic adenoma that began to produce ACTH as a result of mutations that occurred during tumor progression.
Management and results of sciatic nerve injuries: a 24-year experience
Authors: Kline David G. , Kim Daniel , Midha Rajiv , Harsh Carter , Tiel Robert
Published: June 2009

Object.The purpose of this retrospective clinical study was to present results and provide management guidelines for various types of sciatic injuries.

Methods.Over a 24-year period, 380 patients with sciatic nerve injuries were managed. In 230 patients (60%), the injury was at the buttock level, with injection injuries comprising more than half of these cases. Thigh-level sciatic injury was evaluated in 150 cases (40%) and was usually secondary to one of four main causes: 1) gunshot wound; 2) femur fracture; 3) laceration; or 4) contusion. Patients with partial deficits uncomplicated by severe pain or with significant spontaneous recovery or late referral were managed medically. Surgical exploration was not indicated in 23% of injuries at the thigh level and almost 50% of those at the buttock level. Most of these patients achieved partial but good spontaneous recovery, especially in the tibial division distribution. Surgical intervention was required for more complete and persistent deficits in either the tibial or peroneal distribution. Divisions of the sciatic nerve were split apart and evaluated independently. Management was guided by nerve action potential (NAP) recordings, which indicated whether neurolysis or resection of the lesion was required. Repair was then made by using sutures or more frequently by graft placement.

In most cases in which neurolysis was performed because a positive NAP was recorded distal to the lesion, useful function was found in the peroneal distribution. Unfortunately, significant recovery occurred in only 36% of patients who received suture or graft repairs of the peroneal division. Good-to-excellent outcome was common for the tibial division, even in cases in which repair was proximal and required lengthy grafts. The relatively favorable recovery of tibial as opposed to peroneal divisions of the sciatic nerve occurred regardless of the level or mechanism of injury.

Conclusions.Surgical exploration and, when necessary, repair of sciatic nerve injuries is worthwhile in selected cases.
Systemic T cell adoptive immunotherapy of malignant gliomas
Authors: Plautz Gregory E. , Barnett Gene H. , Miller David W. , Cohen Bruce H. , Prayson Richard A. , Krauss John C. , Luciano Mark , Kangisser Debra B. , Shu Suyu
Published: June 2009

Object.To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells.

Methods.In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 × 108to 1.5 × 1011. There were no Grade 3 or 4 toxicities associated with the treatment. Following T-cell transfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient demonstrated stable disease that has lasted for more than 17 months. The remaining patients had progressive disease; however, four of the eight patients with recurrent tumor remain alive more than 1 year after surgery for recurrence. Three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer.

Conclusions.These intriguing clinical observations warrant further trials to determine whether this approach can provide therapeutic benefits and improve survival.
Causes and management of aneurysmal hemorrhage occurring during embolization with Guglielmi detachable coils
Authors: McDougall Cameron G. , Halbach Van V. , Dowd Christopher F. , Higashida Randall T. , Larsen Donald W. , Hieshima Grant B.
Published: June 2009

Object. The purpose of this review is to describe the incidence, causes, management, and outcome of aneurysmal hemorrhage that occurred in patients during endovascular treatment with the Guglielmi detachable coil (GDC) system.

Methods. At the authors' institution between September 1991 and August 1995, more than 200 patients were treated using GDCs for intracranial aneurysms. The first 200 patients treated in this fashion were reviewed and all who experienced new subarachnoid hemorrhage (SAH) during the procedure were identified. Angiographic studies were also reviewed and patients were contacted for longer-term follow up when possible.

Four patients who experienced intraprocedural SAH were identified. The causes of hemorrhage were believed to be perforation of the aneurysm by the guidewire in one patient, perforation by the microcatheter in a second, and perforation by the delivery wire in a third. The fourth patient had a hemorrhage during injection of contrast material for control angiographic studies after placement of the final coil. One patient died, but the other three experienced no neurological symptoms or recovered without acquiring additional deficits. Overall a procedural hemorrhage rate of 2% was seen, with permanent morbidity and mortality rates of 0% and 0.5%, respectively.

Conclusions. Although SAH during endovascular treatment of intracranial aneurysms remains a significant risk, its incidence is low and a majority of patients can survive without serious sequelae.
Analysis of treatment failure after radiosurgery for arteriovenous malformations
Authors: Ellis Thomas L. , Friedman William A. , Bova Frank J. , Kubilis Paul S. , Buatti John M.
Published: June 2009

Object. The aim of this study was to evaluate the causes of treatment failure in patients with arteriovenous malformations (AVMs) who underwent radiosurgery, which is increasingly used as a treatment method for selected, surgically high-risk AVMs. Unfortunately, radiosurgical treatment fails in a small but significant percentage of patients. In the time period covered in this study, 72 patients attained angiographically confirmed cures after radiosurgery and 36 were retreated after the initial radiosurgical treatment failed.

Methods. Using a computerized image fusion technique, the initial radiosurgical dosimetry plan was superimposed on the remaining AVM nidus at the time of retreatment. Twenty-six percent of the retreated cases were found to have AVM niduses outside the original treatment isodose line, which means that targeting error was a factor. The retreated group was also statistically compared with the cured group.

Conclusions. Multivariate analysis revealed that the following factors were statistically significant predictors of treatment failure: increasing AVM size, decreasing treatment dose, and increasing Spetzler—Martin grade.
Delayed aneurysm regrowth and recanalization after Guglielmi detachable coil treatment
Authors: Mericle Robert A. , Wakhloo Ajay K. , Lopes Demetrius K. , Lanzino Giuseppe , Guterman Lee R. , Hopkins L. Nelson
Published: June 2009

✓ Guglielmi detachable coil (GDC) treatment for complicated cerebral aneurysms is an attractive option that has become widely accepted in recent years. This technique is usually considered only if the patient harbors an aneurysm that is not a good candidate for surgical clipping. However, the definition of “surgical candidate” varies among institutions, and many patients worldwide are being treated with GDCs as primary therapy. Although most centers currently perform follow-up angiography at 6 months to 1 year, others do not routinely perform it after an initially good result. The authors present a case that indicates longer follow up may be necessary and illustrates some of the pitfalls of GDC treatment.

This 56-year-old man presented to the emergency room with a Hunt and Hess Grade II subarachnoid hemorrhage and was found to have a wide-necked basilar apex aneurysm. Because of associated medical comorbidities, it was decided to treat the aneurysm with endovascular techniques. The patient did well on follow-up angiography at 1 year postprocedure. However, at approximately 2 years follow up, the aneurysm was demonstrated to have dramatically recanalized and regrown, requiring open surgical intervention.

Endovascular coiling was insufficient to treat this aneurysm and complicated definitive surgical management because a large coil mass had been placed in the operative field. It can be inferred from this case that angiographic follow up of these types of lesions may be beneficial up to 2 years after GDC treatment.
Acute postoperative seizures following anterior temporal lobectomy for intractable partial epilepsy
Authors: Malla Bhaskara Rao , O'Brien Terence J. , Cascino Gregory D. , So Elson L. , Radhakrishnan Kurupath , Silbert Peter , Marsh W. Richard
Published: June 2009

Object. Recurrence of seizures immediately following epilepsy surgery can be emotionally devastating, and raises concerns about the chances of successfully attaining long-term seizure control. The goals of this study were to investigate the frequency of acute postoperative seizures (APOS) occurring in the 1st postoperative week following anterior temporal lobectomy (ATL) to identify potential risk factors and to determine their prognostic significance.

Methods. One hundred sixty consecutive patients who underwent an ATL for intractable nonlesional temporal lobe epilepsy were retrospectively studied. Acute postoperative seizures occurred in 32 patients (20%). None of the following factors were shown to be significantly associated with the occurrence of APOS: age at surgery, duration of epilepsy, side of surgery, extent of neocortical resection, electrocorticography findings, presence of mesial temporal sclerosis, and hippocampal volume measurements (p > 0.05). Patients who suffered from APOS overall had a lower rate of favorable outcome with respect to seizure control at the last follow-up examination than patients without APOS (62.5% compared with 83.6%, p < 0.05). The type of APOS was of prognostic importance, with patients whose APOS were similar to their preoperative habitual seizures having a significantly worse outcome than those whose APOS were auras or were focal motor and/or generalized tonic—clonic seizures (excellent outcome: 14.3%, 77.8%, and 75%, respectively, p < 0.05). Only patients who had APOS similar to preoperative habitual seizures were less likely to have an excellent outcome than patients without APOS (14.3% compared with 75%, p < 0.05). Timing of the APOS and identification of a precipitating factor were of no prognostic importance.

Conclusions. The findings of this study may be useful in counseling patients who suffer from APOS following ATL for temporal lobe epilepsy.
Posteroventral medial pallidotomy for treatment of Parkinson's disease: preoperative magnetic resonance imaging features and clinical outcome
Authors: Desaloms J. Michael , Krauss Joachim K. , Lai Eugene C. , Jankovic Joseph , Grossman Robert G.
Published: June 2009

Object. The goal of this study was to investigate the impact of mild or moderate degrees of degenerative or ischemic encephalopathy on predicting clinical outcome following unilateral posteroventral medial pallidotomy for treatment of advanced Parkinson's disease (PD).

Methods. Thirty-five patients with PD were studied prospectively. The presence and degree of cortical atrophy, ventriculomegaly, deep white matter lesions (DWML), periventricular lucencies (PVL), and the presence of lacunes and status cribriformis (multiple and bilateral enlarged Virchow—Robin spaces) were determined by magnetic resonance (MR) imaging before the patients underwent stereotactic pallidotomy performed according to a standard protocol. Clinical outcome was measured using a standard battery of tests including application of the Unified Parkinson's Disease Rating Scale (UPDRS). The preoperative MR imaging features were correlated with UPDRS subscores such as motor “off” score, the activities of daily living (ADL) off score, the off subscore for bradykinesia, the percentage of “on” time dyskinesias, and a global outcome rating. The MR findings were also correlated with the occurrence of side effects. Global outcome was rated as markedly improved in 22 patients (63%) and as moderately improved in 12 patients (34%) 6 months postoperatively. At the 1-year follow-up examination, global outcome in 31 patients was rated as markedly improved in 14 patients (45%), as moderately improved in another 14 (45%), as slightly improved in two (6%), and as worse in one patient (3%). The mean UPDRS motor off score changed from 58.7 preoperatively to 33.2 at 6 months and 33.4 at 1 year (p < 0.0001), the ADL off score from 31.8 to 18.2 at 6 months and 18.6 at 1 year (p < 0.0001), the off score from contralateral bradykinesia from 11.6 to 5.6 at 6 months and 4.1 at 1 year (p < 0.0001), and the percentage of awake time with dyskinesias from 37.4 to 17.4% at 6 months and 21.1% at 1 year (p < 0.0001). The presence of mild or moderate degrees of cortical atrophy, PVL, and DWML had no effect on clinical outcome. Patients with status cribriformis and those with lacunes tended to show comparatively less improvement in the UPDRS ADL off score (p = 0.014 and p = 0.016, respectively) at 6 months. This tendency was also present in patients with status cribriformis 1 year postoperatively (p = 0.046). Patients with both status cribriformis and lacunes had a higher incidence of transient altered mental status immediately postoperatively (p = 0.05).

Conclusions. Mild-to-moderate degrees of cortical atrophy, ventriculomegaly, and ischemic encephalopathy do not predispose patients to less favorable outcomes following unilateral pallidotomy. Patients with both status cribriformis and lacunes have a higher risk of transient side effects; however, with regard to clinical outcome, these patients should not be denied surgical treatment.
Selection of severely head injured patients for mild hypothermia therapy
Authors: Shiozaki Tadahiko , Sugimoto Hisashi , Taneda Mamoru , Oda Jun , Tanaka Hiroshi , Hiraide Atsushi , Shimazu Takeshi
Published: June 2009

Object. The authors have analyzed the efficacy of inducing mild hypothermia (34°C) in 62 severely head injured patients to control fulminant intracranial hypertension.

Methods. All 62 patients fulfilled the following criteria: 1) persistent intracranial pressure (ICP) greater than 20 mm Hg despite fluid restriction, hyperventilation, and high-dose barbiturate therapy; 2) an ICP lower than the mean arterial pressure; and 3) a Glasgow Coma Scale (GCS) score of 8 or less on admission. The patients were divided into three groups based on computerized tomography findings: extracerebral hematoma (34 patients with subdural and/or epidural hematoma), focal cerebral lesion (20 patients with localized brain contusion and/or intracerebral hematoma), and diffuse swelling (eight patients with no focal mass lesion). Mild hypothermia prevented ICP elevation in 35 (56.5%) of the 62 patients whose ICP was greater than 20 mm Hg despite conventional therapies. Among those 35 patients whose ICP was controlled by mild hypothermia, 12 (34.3%) achieved functional recovery (good outcome or moderate disability). However, functional recovery was observed in only five (10.9%) of the 46 patients whose ICP was greater than 40 mm Hg after conventional therapies. Of 40 patients with an admission GCS score of 5 to 8, there were 11 (27.5%) who achieved functional recovery. On the contrary, mild hypothermia was not effective in 22 patients with an admission GCS score of 3 or 4. In the patients with focal cerebral lesions, ICP was controlled by mild hypothermia in 17 patients (85%) and patient outcome was intimately related to the extent of the damage. Among 18 patients with extracerebral hematoma who had a midline shift of 9 to 12 mm, raised ICP could be successfully controlled by mild hypothermia in 16 patients (88.9%) and three (16.7%) achieved functional recovery. However, ICP could not be controlled in patients with extracerebral hematoma who had a midline shift of 13 mm or more. In patients with diffuse swelling, ICP elevation could not be prevented at all by mild hypothermia.

Conclusions. The authors conclude that mild hypothermia is effective for preventing ICP elevation in patients without diffuse brain swelling in whom ICP remains higher than 20 mm Hg but less than 40 mm Hg after conventional therapies.
The resolution of syringohydromyelia without hindbrain herniation after posterior fossa decompression
Authors: Iskandar Bermans J. , Hedlund Gary L. , Grabb Paul A. , Oakes W. Jerry
Published: June 2009

Object.To provide more information about this rare condition, the authors describe five cases of syringohydromyelia without hindbrain herniation. Preoperative magnetic resonance imaging with and without gadolinium—diethylenetriamine pentaacetic acid revealed no evidence of spinal cord tumor, arachnoiditis, or spinal dysraphism.

Methods.Craniocervical decompression was performed in all patients, after which there was resolution of the symptoms in the four symptomatic patients, and all five showed marked reduction in the size of the syrinx.

Conclusions.The authors hypothesize the rare occurrence of syringohydromyelia resulting from a Chiari-like pathophysiological condition but lacking a hindbrain hernia. Patients with this condition may benefit from craniocervical decompression.
Expression of the basic fibroblast growth factor gene in mild and more severe head injury in the rat
Authors: Yang Shu-Yuan , Cui Jian-Zhong
Published: June 2009

Object. The goal of this study was to investigate the relationship between basic fibroblast growth factor (bFGF) gene expression and neuropathological changes in the hippocampus after varying degrees of brain injury.

Methods. Mild and severe brain injury in rats was produced by using Marmarou's method. There were 25 animals in each brain injury group and 25 additional animals served as controls. Basic fibroblast growth factor gene expression was investigated by means of RNA hybridization, in situ hybridization, immunohistochemical analysis, and histological analysis using hematoxylin and eosin staining.

A 3.7-kb bFGF messenger (m)RNA was detected in the rat hippocampus in both control and injured rats. In the mild injury group its expression was increased at 12 hours after injury and peaked on the 3rd day. Neuronal degeneration in the hippocampal CA2 and CA3 sectors was maximum on that day. In the severe injury group, the expression of the bFGF gene was the same as that in the mild injury group at corresponding times, but the number of surviving neurons in the CA2 and CA3 sectors was much lower than in the mild injury group. In situ hybridization showed that the main cells that expressed bFGF mRNA were pyramidal and granulocytic neurons in all three experimental groups. The number of neurons expressing bFGF mRNA in the severe injury group was less than that in the mild injury group, but the intensity of expression was greater. Immunohistochemical staining showed that the number of neurons expressing the bFGF protein was less in the severe injury group than in the mild injury group.

Conclusions. It is concluded that after mild injury there is a close relationship between the expression of the bFGF gene and the degree of histological change in the hippocampus; this indicates that as one of the growth factors, bFGF may participate in the protection and repair processes of neurons following brain injury. In severe injury there is a reduced expression of bFGF. The reason for this appears to be that more of the cells that have the potential to express bFGF have died, reducing the ability to express the bFGF gene. Conversely, it is possible that there may be an intrinsic insufficiency of expression of the gene, compatible with the known vulnerability of the hippocampus to many pathological conditions. Consideration should be given to supplying exogenous bFGF to protect the brain, particularly the hippocampus, after injury.
Stereotactically guided thalamotomy for treatment of parkinsonian tremor isolated to the lower extremity
Authors: Keller Thomas M. , Tcheng Thomas K. , Burkhard Pierre R. , Richard Héléne , Tamas Laszlo B.
Published: June 2009

✓ The authors present a case of tremor isolated to the lower extremity that was treated with stereotactically guided thalamotomy in a patient with Parkinson's disease. The technology that makes this procedure effective for this particular manifestation of parkinsonism is discussed.
Blood blisterlike aneurysms of the internal carotid artery
Authors: Abe Masamitsu , Tabuchi Kazuo , Yokoyama Hiroaki , Uchino Akira
Published: June 2009

Object. An aneurysm arising from the anterior wall of the internal carotid artery (ICA) is a poorly understood entity. A small hemispherical bulge from the anterior wall of the ICA, which is called a “blood blisterlike aneurysm” (BBA), may be confused with a tiny berry aneurysm although the clinical features are distinctly different. This paper summarizes the clinical course of patients with this lesion to clarify the nature of the BBA.

Methods. Six patients with BBAs who presented with subarachnoid hemorrhage (SAH) are described. In all patients, the initial angiogram obtained soon after SAH showed only a small bulge from the anterior wall of the ICA. In three of the six patients this bulge had progressed to a saccular appearance within a few weeks. The wall of the lesion was so thin and fragile that the aneurysm ruptured at the base during clipping or within a few hours after clipping in two patients.

Conclusions. From the authors' experience, as well as a review of the literature, which includes an autopsy study of similar cases, it is inferred that these lesions are focal wall defects covered only with thin fibrous tissue and that they are therefore not true aneurysms. Direct clipping often causes laceration of the lesion, whereas complete wrapping or clipping after wrapping is effective, but may fail to prevent growth of the aneurysm. Endovascular occlusion of the cervical ICA with or without bypass surgery, which is less risky than direct surgery, is another option.
Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results
Authors: Galanis Evanthia , Buckner Jan C. , Dinapoli Robert P. , Scheithauer Bernd W. , Jenkins Robert B. , Wang Chiao Hua , O'Fallon Judith R. , Farr Gist
Published: June 2009

Object. Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM.

Methods. The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31–81 years). The median tumor size was 5 cm (range 2–8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy.

The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components.

Conclusions. The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.
Vascular extracellular matrix remodeling in cerebral aneurysms
Authors: Bruno Gerard , Todor Roxanne , Lewis Isabel , Chyatte Douglas
Published: June 2009

Object.The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms.

Methods.Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)—plasminogen activator (PA), urokinase-type (u)—PA, membranetype (MT1)—matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin.

Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present.

Conclusions.Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.
Dynamic determination of human glioma invasion in vitro
Authors: Nygaard Svein J. T. , Haugland Hans K. R. , Laerum Ole Didrik , Lund-Johansen Morten , Bjerkvig Rolf , Tysnes Ole-Björn
Published: June 2009

Object. The goal of this study was to evaluate whether there is any relationship between survival of patients with brain tumor and tumor proliferation or tumor invasion in vitro.

Methods. Samples of freshly resected brain tumors from 14 patients with glioblastoma multiforme (GBM) were directly grown as three-dimensional multicellular spheroids. The tumor spheroids were cocultured with fetal rat brain cell aggregates (BCAs), used to represent an organotypical normal brain tissue model. Before the coculture, the tumor spheroids and the BCAs were stained with two different carbocyanine dyes, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) and 3,3′-dioctadecycloxacarbocyanine perchlorate (DiO), respectively. During the coculture, confocal laser scanning microscopy allowed a sequential analysis of tumor cell invasion by visualizing dynamic aspects of the invasive process. Single cocultures were examined at three different time points (24, 48, and 96 hours). During the observation period there was a change in the structural morphology of the cocultures, with a progressive decrease in BCA volume. Furthermore, the scanning confocal micrographs revealed a bidirectional movement of tumor cells and normal cells into brain and tumor tissue, respectively. It is also shown that there is a considerable variation in the rate of BCA destruction in cocultures of glioma spheroids generated directly from biopsy specimens. This variation is seen both between spheroids generated from the same biopsy as well as between spheroids that are grown from different biopsy specimens.

Cell proliferation measured by Ki-67 immunohistochemical analysis of biopsy samples obtained in the same patients revealed a correlation between tumor cell proliferation and tissue destruction of the BCAs, as determined by a reduction in BCA volume (p = 0.0338). No correlation was found when survival was related to the same parameters (p > 0.05).

Conclusions. The present work provides a model for quick and efficient assessment of dynamic interactions between tumor and normal brain tissue shortly after surgery.
Cervical bone spur presenting with spontaneous intracranial hypotension
Authors: Vishteh A. Giancarlo , Schievink Wouter I. , Baskin Jonathan J. , Sonntag Volker K. H.
Published: June 2009

✓ Spontaneous intracranial hypotension due to a spinal cerebrospinal fluid (CSF) leak is a rare but increasingly recognized cause of postural headaches. The exact cause of these CSF leaks often remains unknown. The authors treated a 32-year-old man with a unique cause of spontaneous intracranial hypotension. He suffered an excruciating headache that was exacerbated by his being in an upright position. The results of four-vessel cerebral angiography were negative; however, magnetic resonance (MR) imaging of the brain revealed pachymeningeal enhancement and hindbrain herniation. A presumptive diagnosis of spontaneous intracranial hypotension was made. Myelography revealed extrathecal contrast material ventral to the cervical spinal cord as well as an unusual midline bone spur at C5–6. The patient's symptoms did not resolve with the application of epidural blood patches, and he subsequently underwent an anterior approach to the C5–6 spur. After discectomy, a slender bone spur that had pierced the thecal sac was found. After its removal, the dural rent was closed using two interrupted prolene sutures. The patient was discharged home 2 days later. On follow up his symptoms had resolved, and on MR imaging the pachymeningeal enhancement had resolved and the cerebellar herniation had improved slightly.
Vascular decompression of a vertebral artery loop producing cervical radiculopathy
Authors: Detwiler Paul W. , Porter Randall W. , Harrington Timothy R. , Sonntag Volker K. H. , Spetzler Robert F.
Published: June 2009

✓ Vertebral artery tortuosity and loop formation are rare causes of cervical radiculopathy. The authors present the case of a 70-year-old man with 9 years of progressive right-sided cervical and scapular pain but no history of trauma. Computerized tomography myelography and magnetic resonance imaging revealed an ovoid mass in the right C3–4 intervertebral foramen. The patient underwent a right C-3 and C-4 hemilaminectomy and a complete C3–4 facetectomy. A pulsatile vascular structure was found compressing the right C-4 nerve root. The bone overlying the vascular structure was removed, producing decompression of the nerve root. Immediate postoperative angiography showed that this lesion was a focal vertebral artery loop. The patient's symptoms resolved after surgery, supporting the use of vascular decompression of a cervical nerve root compressed by a vertebral artery loop for the relief of radicular symptoms.
High-resolution T2-reversed magnetic resonance imaging on a high magnetic field system
Authors: Fujii Yukihiko , Nakayama Naoki , Nakada Tsutomu
Published: June 2009

Because of the high signal-to-noise (S/N) ratio, T2-weighted images obtained using high-field magnetic resonance (MR) imaging systems can be expected to provide high anatomical and contrast resolution. Furthermore, the improved structural and contrast resolution of these high S/N T2-weighted images can be processed for optimum perceptual resolution through the application of gray-scale reversal and expansion of the gray-scale window, known as T2-reversed (T2R) imaging. In this study, the authors investigated high-resolution T2R MR imaging performed on a high-field (3-tesla) system for its clinical utility in detecting various physiological and pathological conditions.
A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury
Authors: Marshall Lawrence F. , Maas Andrew I. R. , Marshall Sharon Bowers , Bricolo Albino , Fearnside Michael , Iannotti Fausto , Klauber Melville R. , Lagarrigue Jacques , Lobato Ramiro , Persson Lennart , Pickard John D. , Piek Jürgen , Servadei Franco , Wellis Georgios N. , Morris Gabrielle F. , Means Eugene D. , Musch Bruno
Published: June 2009

Object. The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries.

Methods. A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4–8) and 15% (163) had sustained a moderate head injury (GCS score 9–12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p = 0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p = 0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p = 0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups.

Conclusions. Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents.
Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage
Authors: Polin Richard S. , Bavbek Murad , Shaffrey Mark E. , Billups Kevin , Bogaev Christopher A. , Kassell Neal F. , Lee Kevin S.
Published: June 2009

Object.The goal of this study was to explore whether the levels of soluble adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). This association was suggested by the known inflammatory response in vasospasm and the role of vascular adhesion molecules in regulating leukocytic adhesion to, and migration across, vascular endothelium.

Methods.A prospective analysis was performed on CSF samples obtained in 17 patients who had suffered a recent aneurysmal SAH and in 16 control patients by using quantitative enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion molecule—1 (ICAM—1), vascular adhesion molecule—1 (VCAM-1), and L-selectin.

Levels of soluble forms of E-selectin (p = 0.0013), ICAM-1 (p = 0.0001), and VCAM-1 (p = 0.048) were found to be elevated in the CSF of patients after SAH compared with levels in the CSF of normal controls, patients with unruptured aneurysms, and patients tested months after SAH occurred. In addition, individual patients tested at the time of their initial ictus demonstrated a fall in adhesion molecule levels over time. Levels of E-selectin (p = 0.044) were highest in patients who later developed moderate or severe vasospasm.

Conclusions.Adhesion molecules are known to be involved in white cell adherence to the endothelium and subsequent diapedesis and migration in which a role in initiation of tissue damage is postulated. The authors have demonstrated the elevation of three adhesion molecules, with severely elevated levels of E-selectin seen in patients who later develop vasospasm. A correlation with a role of vascular adhesion molecules in the pathogenesis of cerebral vasospasm is suggested.
Transthoracic vertebrectomy for metastatic spinal tumors
Authors: Gokaslan Ziya L. , York Julie E. , Walsh Garrett L. , McCutcheon Ian E. , Lang Frederick F. , Putnam Joe B. , Wildrick David M. , Swisher Stephen G. , Abi-Said Dima , Sawaya Raymond
Published: June 2009

Object. Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region.

Methods. Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%.

Conclusions. These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.
Direct convective delivery of macromolecules to peripheral nerves
Authors: Lonser Russell R. , Weil Robert J. , Morrison Paul F. , Governale Lance S. , Oldfield Edward H.
Published: June 2009

Object. Although many macromolecules have treatment potential for peripheral nerve disease, clinical use of these agents has been restricted because of limitations of delivery including systemic toxicity, heterogeneous dispersion, and inadequate distribution. In an effort to overcome these obstacles, the authors examined the use of convection to deliver and distribute macromolecules into peripheral nerves.

Methods. For convective delivery, the authors used a gas-tight, noncompliant system that provided continuous flow through a small silica cannula (inner diameter 100 µm, outer diameter 170 µm) inserted into a peripheral nerve. Increases in the volume of infusion (Vi) (10, 20, 30, 40, and 80 µl) of 14C-labeled (nine nerves) or gadolinium-labeled (two nerves) albumin were infused unilaterally or bilaterally into the tibial nerves of six primates (Macaca mulatta) at 0.5 µl/minute. The volume of distribution (Vd), percentage recovery, and delivery homogeneity were determined using quantitative autoradiography, an imaging program developed by the National Institutes of Health, magnetic resonance (MR) imaging, scintillation counting, and kurtosis (K) analysis. One animal that was infused bilaterally with gadolinium-bound albumin (40 µl to each nerve) underwent MR imaging and was observed for 16 weeks after infusion.

The Vd increased with the Vi in a logarithmic fashion. The mean Vd/Vi ratio over all Vi was 3.7 ± 0.8 (mean ± standard deviation). The concentration across the perfused region was homogeneous (K = −1.07). The infusate, which was limited circumferentially by the epineurium, followed the parallel arrangement of axonal fibers and filled long segments of nerve (up to 6.8 cm). Recovery of radioactivity was 75.8 ± 9%. No neurological deficits arose from infusion.

Conclusions. Convective delivery of macromolecules to peripheral nerves is safe and reliable. It overcomes obstacles associated with current delivery methods and allows selective regional delivery of putative therapeutic agents to long sections of nerve. This technique should permit the development of new treatments for numerous types of peripheral nerve lesions.
Subsidence of seizure induced by stereotactic radiation in a patient with a hypothalamic hamartoma
Authors: Arita Kazunori , Kurisu Kaoru , Iida Koji , Hanaya Ryosuke , Akimitsu Tomohide , Hibino Seiichiro , Pant Basant , Hamasaki Masatake , Shinagawa Shoji
Published: June 2009

✓ The authors report on a patient who exhibited intractable epilepsy due to an inaccessible hypothalamic hamartoma and subsequently underwent stereotactic radiosurgery. This 25-year-old man had a 24-year history of intractable gelastic and tonic—clonic seizures. Magnetic resonance (MR) imaging performed at examination as well as that performed 30 months earlier demonstrated a nonenhancing and nonprogressive spherical mass, approximately 10 mm in diameter, located on the patient's right side at the floor of the third ventricle. Focal radiation treatment performed with a gamma knife unit administered 36 Gy to the center and 18 Gy to the periphery of the lesion. This treatment resulted in an improvement in seizure control. Before the patient underwent radiosurgery, he suffered from three to six generalized seizures per month in spite of attentive compliance with an anticonvulsant medication regimen. After irradiation of the harmatoma, the frequency of the seizures transiently increased and then subsided 3 months posttreatment. The patient has been free of seizures for the last 21 months, with no neurological or endocrinological complications. Magnetic resonance imaging performed 12 months posttreatment demonstrated complete disappearance of the lesion.
Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up
Authors: Bracken Michael B. , Shepard Mary Jo , Holford Theodore R. , Leo-Summers Linda , Aldrich E. Francois , Fazl Mahmood , Fehlings Michael G. , Herr Daniel L. , Hitchon Patrick W. , Marshall Lawrence F. , Nockels Russ P. , Pascale Valentine , Perot Phanor L. , Piepmeier Joseph , Sonntag Volker K. H. , Wagner Franklin , Wilberger Jack E. , Winn H. Richard , Young Wise
Published: June 2009

Object. A randomized double-blind clinical trial was conducted to compare neurological and functional recovery and morbidity and mortality rates 1 year after acute spinal cord injury in patients who had received a standard 24-hour methylprednisolone regimen (24MP) with those in whom an identical MP regimen had been delivered for 48 hours (48MP) or those who had received a 48-hour tirilazad mesylate (48TM) regimen.

Methods. Patients for whom treatment was initiated within 3 hours of injury showed equal neurological and functional recovery in all three treatment groups. Patients for whom treatment was delayed more than 3 hours experienced diminished motor function recovery in the 24MP group, but those in the 48MP group showed greater 1-year motor recovery (recovery scores of 13.7 and 19, respectively, p = 0.053). A greater percentage of patients improving three or more neurological grades was also observed in the 48MP group (p = 0.073). In general, patients treated with 48TM recovered equally when compared with those who received 24MP treatments. A corresponding recovery in self care and sphincter control was seen but was not statistically significant. Mortality and morbidity rates at 1 year were similar in all groups.

Conclusions. For patients in whom MP therapy is initiated within 3 hours of injury, 24-hour maintenance is appropriate. Patients starting therapy 3 to 8 hours after injury should be maintained on the regimen for 48 hours unless there are complicating medical factors.