bluuebunny/crossref_metadata_2025 huggingface dataset:
Addition of intravenous N-methyl-D-aspartate receptor antagonists to local fibrinolytic therapy for the optimal treatment of experimental intracerebral hemorrhages
Authors: Thiex Ruth , Weis Joachim , Krings Timo , Barreiro Sonia , Yakisikli-Alemi Funda , Gilsbach Joachim M. , Rohde Veit
Published: January 2008

Object

Fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) is considered a treatment option in patients with deep-seated intracerebral hemorrhage (ICH). Nevertheless, the results of animal experiments have shown that tPA exerts pleiotropic actions in the brain, including regulation of vasoactivity, amplification of calcium conductance by cleavage of the N-methyl-D-aspartate (NMDA) receptor subunit, and activation of metalloproteinases, which increase excitotoxicity, damage the blood–brain barrier, and worsen edema. The authors investigated whether the noncompetitive NMDA receptor antagonist MK801 can be used as an adjuvant therapy in combination with rtPA to attenuate the unfavorable delayed edema formation and inflammation observed following rtPA therapy in an experimental porcine model of ICH.

Methods

Twenty pigs were used in this study; MK801 (0.3 mg/kg) was administered to each pig intravenously immediately after hematoma induction and on the 1st and 3rd day after hematoma induction. Ten of the 20 pigs were randomly assigned to fibrinolytic therapy with rtPA (MK801–tPA group), whereas in the remaining 10 control animals (MK801 group) the hematomas were allowed to follow their natural courses of resorption. The extent of edema formation was evaluated using magnetic resonance (MR) imaging volumetry on Days 0, 4, and 10 after hematoma induction and was compared with histopathological changes found at necropsy. The mean edema volumes in these two groups were also compared with that in the group of nine pigs examined in a preceding experimental series, in which the animals’ hematomas were only treated with rtPA (tPA group).

In the 10 animals in the MK801–tPA group, the mean perihematoma edema volume on MR images had not significantly increased by Day 4 (p < 0.08) or Day 10 (p < 0.35) after hematoma induction. In the 10 animals in the MK801 group, the increase in mean perifocal edema size was significant after 4 days (p < 0.001) and nonsignificant after 10 days (p < 0.09). In the nine animals in the tPA group, the mean edema volume significantly increased by Days 4 (p < 0.002) and 10 (p < 0.03).

Conclusions

As suggested by the reduction in delayed edema volume and the inflammatory response, MK801 modifies the neurotoxic properties of rtPA but not those of blood degradation products. Possibly, fibrinolytic therapy of ICH is more beneficial if combined with agents such as MK801.
Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor
Authors: Sehba Fatima A. , Friedrich Victor , Makonnen Girma , Bederson Joshua B.
Published: January 2008

Object

Structural changes in brain parenchymal vessels occur within minutes after subarachnoid hemorrhage (SAH). These changes include platelet aggregation, activation of vascular collagenases, and destruction of perivascular collagen IV. Because collagen IV is an important component of the basal lamina, the authors attempted to further define changes in vascular structure (length and luminal diameter) and their relationship to vascular permeability immediately after SAH. In addition, the authors explored whether such alterations were attenuated by administration of a nitric oxide (NO) donor.

Methods

Endovascular perforation was used to induce SAH in rats. Two sets of experiments were performed. The first established changes in vascular structure and permeability (collagen IV and endothelial barrier antigen [EBA] dual immunofluorescence) during the first 24 hours after SAH. In the second, the investigators examined the effects of an NO donor on vascular structure, permeability, and collagenase activity (in situ zymography). In this second study, animals received intravenous infusion of the NO donor S-nitrosoglutathione (GSNO, 1 μM/8 μl/min) 15 minutes after induction of SAH and were killed 3 hours after SAH onset. Controls were naive unoperated animals for the first study and saline-infused SAH animals for the second.

The authors found a time-dependent decrease in area fraction, length, and luminal diameter of collagen IV– and EBA-immunofluorescent vessels after SAH. The greatest change occurred at 3 hours after onset of SAH. Administration of GSNO was associated with striking preservation of collagen IV and EBA immunofluorescence compared with saline treatment. Zymography indicated decreased collagenase activity in GSNO-treated SAH animals compared with saline-treated SAH animals.

Conclusions

These results demonstrate changes in the structure and permeability of brain parenchymal microvessels after SAH and their reversal by treatment with an NO donor.
Survival and invasiveness of astrocytomas promoted by erythropoietin
Authors: Mohyeldin Ahmed , Dalgard Clifton L. , Lu Huasheng , Mcfate Thomas , Tait A. Sasha , Patel Viral C. , Wong Kondi , Rushing Elizabeth , Roy Subhojit , Acs Geza , Verma Ajay
Published: January 2008

Object

The hypoxia-inducible pleiotropic hormone, erythropoietin (EPO), has recently been found to promote the development and survival of neurons and astrocytes. Since hypoxia has been implicated in the malignant progression of some human cancers, the authors investigated whether EPO signaling influenced the malignant properties of human astrocytoma cells.

Methods

Reverse transcriptase–polymerase chain reaction, Western blot analysis, and immunohistochemical studies were used to measure EPO and its receptor (EPOR). Cell viability, Matrigel invasion assays, metalloprotease assays, EPO neutralizing antibodies, and EPOR overexpression were used to study the biological actions of EPO.

Expression of both EPO and EPOR was observed in the hypoxic regions and invasive margins of glioma specimens obtained at biopsy, and expression of EPOR correlated with the stage of the tumor. The EPOR was also functionally upregulated by hypoxia in cultured glioblastoma multiforme (GBM) cells. Both hypoxia and EPO protected cultured GBM cells from cisplatin cytotoxicity and promoted the invasiveness of GBM cells through Matrigel by potentiating metalloprotease activity. Hypoxia-enhanced cell invasion was attenuated in cells that overexpressed a nonfunctional EPOR.

Conclusions

Hypoxia-inducible autocrine and paracrine EPO signaling participates in the malignant progression of GBMs.
Image-guided convection-enhanced delivery of gemcitabine to the brainstem
Authors: Murad Gregory J. A. , Walbridge Stuart , Morrison Paul F. , Szerlip Nicholas , Butman John A. , Oldfield Edward H. , Lonser Russell R.
Published: January 2008

Object

To determine if the potent antiglioma chemotherapeutic agent gemcitabine could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution using a surrogate magnetic resonance (MR) imaging tracer, the authors used convection-enhanced delivery to perfuse the primate brainstem with gemcitabine and Gd–diethylenetriamine pentaacetic acid (DTPA).

Methods

Six primates underwent convective brainstem perfusion with gemcitabine (0.4 mg/ml; two animals), Gd-DTPA (5 mM; two animals), or a coinfusion of gemcitabine (0.4 mg/ml) and Gd-DTPA (5 mM; two animals), and were killed 28 days afterward. These primates were observed over time clinically (six animals), and with MR imaging (five animals), quantitative autoradiography (one animal), and histological analysis (all animals). In an additional primate, 3H-gemcitabine and Gd-DTPA were coinfused and the animal was killed immediately afterward.

In the primates there was no histological evidence of infusate-related tissue toxicity. Magnetic resonance images obtained during infusate delivery demonstrated that the anatomical region infused with Gd-DTPA was clearly distinguishable from surrounding noninfused tissue. Quantitative autoradiography confirmed that Gd-DTPA tracked the distribution of 3H-gemcitabine and closely approximated its volume of distribution (mean volume of distribution difference 13.5%).

Conclusions

Gemcitabine can be delivered safely and effectively to the primate brainstem at therapeutic concentrations and at volumes that are higher than those considered clinically relevant. Moreover, MR imaging can be used to track the distribution of gemcitabine by adding Gd-DTPA to the infusate. This delivery paradigm should allow for direct therapeutic application of gemcitabine to brainstem gliomas while monitoring its distribution to ensure effective tumor coverage and to maximize safety.
External ventricular drain infections are independent of drain duration: an argument against elective revision
Authors: Lo Cheng H. , Spelman Denis , Bailey Michael , Cooper D. James , Rosenfeld Jeffrey V. , Brecknell John E.
Published: January 2008

Object

The authors explored the relationship among the duration of external ventricular drainage, revision of external ventricular drains (EVDs), and cerebrospinal fluid (CSF) infection to shed light on the practice of electively revising these drains.

Methods

In a retrospective study of 199 patients with 269 EVDs in the intensive care unit at a major trauma center in Australasia, the authors found 21 CSF infections. Acinetobacter accounted for 10 (48%) of these infections. Whereas the duration of drainage was not an independent predictor of infection, multiple insertions of EVDs was a significant risk factor. Second and third EVDs in previously uninfected patients were more likely to become infected than first EVDs. An EVD infection was initially identified a mean of 5.5 ± 0.7 days postinsertion (standard error of the mean); these data—that is, the number of days—were normally distributed.

Conclusions

This pattern of infection is best explained by EVD-associated CSF infections being acquired by the introduction of bacteria on insertion of the drain rather than by subsequent retrograde colonization. Elective EVD revision would be expected to increase infection rates in light of these results, and thus the practice has been abandoned by the authors' institution.
Prognostic value of the lateral spread response for intraoperative electromyography monitoring of the facial musculature during microvascular decompression for hemifacial spasm
Authors: Kong Doo-Sik , Park Kwan , Shin Byoung-gook , Lee Jeong Ah , Eum Dong-Ok
Published: January 2008

Object

The authors conducted a large retrospective study in which they evaluated the efficacy of intraoperative electromyography (EMG) monitoring of facial musculature during microvascular decompression (MVD) and assessed the predictive value of the lateral spread response (LSR) as a prognostic indicator for the treatment outcome of hemifacial spasm (HFS).

Methods

The authors undertook intraoperative monitoring during MVD in 300 consecutive patients with HFS. The patients were divided into two groups based on whether the LSR disappeared or persisted following decompression. The mean follow-up period was 35.8 months (range 12–55 months). In 263 (87.7%) of the 300 patients, the LSR was observed during intraoperative facial EMG monitoring. In 230 (87.4%) of these 263 patients, the LSR disappeared following decompression (Group I), and in the remaining 33 patients (12.5%) the LSR persisted despite decompression (Group II). At the postoperative 1-year follow-up visit, there was a significant difference in clinical outcomes between both groups (p < 0.05).

Conclusions

Facial EMG monitoring of the LSR is an effective tool to use when performing complete decompression, and it may be helpful in predicting outcomes.
Endoscopic, endonasal extended transsphenoidal, transplanum transtuberculum approach for resection of suprasellar lesions
Authors: Laufer Ilya , Anand Vijay K. , Schwartz Theodore H.
Published: January 2008

Object

The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision and a microscope and have reported a significant risk of cerebrospinal fluid (CSF) leakage. The authors report on a series of purely endoscopic endonasal surgeries for resection of suprasellar supradiaphragmatic lesions above a normal-sized sella turcica with a low risk of CSF leakage.

Methods

A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (three tuberculum sellae and two planum sphenoidale meningiomas) and five were post-chiasmal (four craniopharyngiomas and one Rathke cleft cyst). The floor of the planum sphenoidale and the sella turcica was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was performed in only five cases. Complete resection of the lesions was achieved in all but one patient. The pituitary stalk was preserved in all but one patient, whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus (DI). Vision improved postoperatively in all patients with preoperative impairment. Six patients had temporary DI; in five, the DI became permanent. Four patients with craniopharyngiomas required cortisone and thyroid replacement. After a mean follow up of 10 months, there was only one transient CSF leak when a lumbar drain was clamped prematurely on postoperative Day 5.

Conclusions

A purely endoscopic endonasal approach to suprasellar supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leakage is low and lumbar drainage can be avoided. A larger series will be required to validate this approach.
Contribution of Notch signaling activation to human glioblastoma multiforme
Authors: Kanamori Masayuki , Kawaguchi Tomohiro , Nigro Janice M. , Feuerstein Burt G. , Berger Mitchel S. , Miele Lucio , Pieper Russell O.
Published: January 2008

Object

Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth.

Methods

Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation.

Conclusions

Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy.
Attenuation of experimental subarachnoid hemorrhage–induced cerebral vasospasm by the adenosine A2A receptor agonist CGS 21680
Authors: Lin Chih-Lung , Shih Huei-Chuan , Lieu Ann-Shung , Lee Kung-Shing , Dumont Aaron S. , Kassell Neal F. , Howng Shen-Long , Kwan Aij-Lie
Published: January 2008

Object

Impaired endothelium-dependent relaxation is present in vasospastic cerebral vessels after subarachnoid hemorrhage (SAH) and may result from deficient production of endothelial nitric oxide synthase (eNOS) or increased production and/or activity of inducible NOS (iNOS). Accumulating evidence demonstrates that adenosine A2A receptors increase the production of NO by human and porcine arterial endothelial cells, which in turn leads to vasodilation. This study was designed to examine the effects of an adenosine A2A receptor agonist, (2(4-[2-carboxyethyl]phenyl)ethylamino)-5′-N-ethylcarboxamidoadenosine (CGS 21680), in the prevention of SAH-induced vasospasm.

Methods

Experimental SAH was induced in Sprague–Dawley rats by injecting 0.3 ml of autologous blood into the cisterna magna of each animal. Intraperitoneal injections of CGS 21680 or vehicle were administered 5 minutes and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging measurements of cross-sectional areas of the basilar artery (BA) 48 hours after SAH. Expression of eNOS and iNOS in the BA was also evaluated.

Prior to perfusion–fixation, there were no significant differences among animals in the control and treated groups in any physiological parameter that was recorded. The CGS 21680 treatment significantly attenuated SAH-induced vasospasm. Induction of iNOS mRNA and protein in the BA by the SAH was significantly diminished by administration of CGS 21680. The SAH-induced suppression of eNOS mRNA and protein was also relieved by the CGS 21680 treatment.

Conclusions

This is the first evidence that adenosine A2A receptor agonism is effective in preventing SAH-induced vasospasm without significant complications. The beneficial effect of adenosine A2A receptor agonists may be, at least in part, related to the prevention of augmented expression of iNOS and the preservation of normal eNOS expression following SAH. Adenosine A2A receptor agonism holds promise in the treatment of cerebral vasospasm following SAH and merits further investigation.
Attenuation of experimental subarachnoid hemorrhage–induced increases in circulating intercellular adhesion molecule–1 and cerebral vasospasm by the endothelin-converting enzyme inhibitor CGS 26303
Authors: Lin Chih-Lung , Kwan Aij-Lie , Dumont Aaron S. , Su Yu-Feng , Kassell Neal F. , Wang Chih-Jen , Wu Shu-Chuan , Kuo Ching-Ling , Huang Ching-Shan , Jeng Arco Y. , Liu Chin-San
Published: January 2008

Object

Adhesion molecules, including intercellular adhesion molecule–1 (ICAM-1), vascular cell adhesion molecule–1 (VCAM-1), and E-selectin, are important mediators of inflammation, and their levels are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The investigators previously found that CGS 26303 is effective in preventing and reversing arterial narrowing in a rabbit model of SAH. The purpose of the present study was to examine whether levels of adhesion molecules are altered after treatment with CGS 26303 in this animal model.

Methods

New Zealand White rabbits were each injected with 3 ml of autologous blood in the cisterna magna, and intravenous treatment with CGS 26303 (30 mg/kg) was initiated 1 hour later. The compound was subsequently administered at 12, 24, and 36 hours post-SAH. Blood samples were collected at 48 hours post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. After the rabbits had been killed by perfusion–fixation, the basilar arteries (BAs) were removed and sliced, and their cross-sectional areas were measured.

Treatment with CGS 26303 attenuated arterial narrowing after SAH. Morphologically, corrugation of the internal elastic lamina of BAs was prominently observed in the SAH only and vehicle-treated SAH groups, but not in the CGS 26303–treated SAH group or in healthy controls. There were no significant differences in the levels of VCAM-1 among the four groups. The levels of E-selectin were increased in all animals subjected to SAH (those in the SAH only, SAH plus vehicle, and SAH plus CGS 26303 groups) compared with healthy controls (no SAH); however, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and treatment with CGS 26303 reduced ICAM-1 to control levels following SAH.

Conclusions

These results show that ICAM-1 may play a role in mediating SAH-induced vasospasm and that a reduction of ICAM-1 levels after SAH may partly contribute to the antispastic effect of CGS 26303.
Growth and regression of arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia
Authors: Du Rose , Hashimoto Tomoki , Tihan Tarik , Young William L. , Perry Victor , Lawton Michael T.
Published: January 2008

✓ Data on the growth, regression, and de novo formation of arteriovenous malformations (AVMs) suggest that some of these lesions are not formed and developed only during embryogenesis. Patients with hereditary hemorrhagic telangiectasia (HHT) have a genetic propensity to form AVMs. The authors report on the growth and regression of AVMs in a single patient with HHT. This 26-day-old boy with a family history of HHT1 and a mutation in ENG on chromosome 9 presented with a generalized seizure. Results of computed tomography revealed a left frontoparietal intra-parenchymal hemorrhage. Cerebral angiography revealed multiple AVMs. Follow-up angiograms obtained 5 months later showed both growth and regression of the AVMs. A craniotomy was performed for complete resection of the left parietal AVM. Histopathological features of the surgical specimen were examined. Active angiogenesis, as indicated by increased endothelial proliferation, might be a part of the underlying pathophysiology of the growth and regression of AVMs.
Effect of hyperoxia on cerebral metabolic rate for oxygen measured using positron emission tomography in patients with acute severe head injury
Authors: Diringer Michael N. , Aiyagari Venkatesh , Zazulia Allyson R. , Videen Tom O. , Powers William J.
Published: January 2008

Object

Recent observations indicate that traumatic brain injury (TBI) may be associated with mitochondrial dysfunction. This, along with growing use of brain tissue PO2 monitors, has led to considerable interest in the potential use of ventilation with 100% oxygen to treat patients who have suffered a TBI. To date, the impact of normobaric hyperoxia has only been evaluated using indirect measures of its impact on brain metabolism. To determine if normobaric hyperoxia improves brain oxygen metabolism following acute TBI, the authors directly measured the cerebral metabolic rate for oxygen (CMRO2) with positron emission tomography before and after ventilation with 100% oxygen.

Methods

Baseline measurements of arterial and jugular venous blood gases, mean arterial blood pressure, intracranial pressure, cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction, and CMRO2 were made at baseline while the patients underwent ventilation with a fraction of inspired oxygen (FiO2) of 0.3 to 0.5. The FiO2 was then increased to 1.0, and 1 hour later all measurements were repeated.

Five patients were studied a mean of 17.9 ±5.8 hours (range 12–23 hours) after trauma. The median admission Glasgow Coma Scale score was 7 (range 3–9). During ventilation with 100% oxygen, there was a marked rise in PaO2 (from 117 ± 31 to 371 ± 99 mm Hg, p < 0.0001) and a small rise in arterial oxygen content (12.7 ± 4.0 to 13.3 ± 4.6 vol %, p = 0.03). There were no significant changes in systemic hemodynamic or other blood gas measurements. At the baseline evaluation, bihemispheric CBF was 39 ± 12 ml/100 g/min and bihemispheric CMRO2 was 1.9 ± 0.6 ml/100 g/min. During hyperoxia there was no significant change in either of these measurements. (Values are given as the mean ± standard deviation throughout.)

Conclusions

Normobaric hyperoxia did not improve brain oxygen metabolism. In the absence of outcome data from clinical trials, these preliminary data do not support the use of 100% oxygen in patients with acute TBI, although larger confirmatory studies are needed.
Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging: intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for visualization and assessment, and implications for surgical intervention
Authors: Kuhn Matthew J. , Picozzi Piero , Maldjian Joseph A. , Schmalfuss Ilona M. , Maravilla Kenneth R. , Bowen Brian C. , Wippold Franz J. , Runge Val M. , Knopp Michael V. , Wolansky Leo J. , Gustafsson Lars , Essig Marco , Anzalone Nicoletta
Published: January 2008

Object

The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors.

Methods

Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics.

Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (κ > 0.4).

Conclusions

Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.
Clinical impact of integrated functional neuronavigation and subcortical electrical stimulation to preserve motor function during resection of brain tumors
Authors: Mikuni Nobuhiro , Okada Tsutomu , Enatsu Rei , Miki Yukio , Hanakawa Takashi , Urayama Shin-ichi , Kikuta Kenichiro , Takahashi Jun A. , Nozaki Kazuhiko , Fukuyama Hidenao , Hashimoto Nobuo
Published: January 2008

Object

The authors evaluated the clinical impact of combining functional neuronavigation with subcortical electrical stimulation to preserve motor function following the removal of brain tumors.

Methods

Forty patients underwent surgery for treatment of brain tumors located near pyramidal tracts that had been identified by fiber tracking. The distances between the electrically stimulated white matter and the pyramidal tracts were measured intraoperatively with tractography-integrated functional neuronavigation, and correlated with subcortical motor evoked potentials (MEPs) and clinical symptoms during and after resection of the tumors.

Motor function was preserved after appropriate tumor resection in all cases. In 18 of 20 patients, MEPs were elicited from the subcortex within 1 cm of the pyramidal tracts as measured using intraoperative neuronavigation. During resection, improvement of motor weakness was observed in two patients, whereas transient mild motor weakness occurred in two other patients. In 20 patients, the distances between the stimulated subcortex and the estimated pyramidal tracts were more than 1 cm, and MEPs were detected in only three of these patients following stimulation.

Conclusions

Intraoperative functional neuronavigation and subcortical electrical stimulation are complementary techniques that may facilitate the preservation of pyramidal tracts around 1 cm of resected tumors.
Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders
Authors: Kenney Christopher , Simpson Richard , Hunter Christine , Ondo William , Almaguer Michael , Davidson Anthony , Jankovic Joseph
Published: January 2008

Object

The object of this study was to assess the long-term safety of deep brain stimulation (DBS) in a large population of patients with a variety of movement disorders.

Methods

All patients treated with DBS at the authors' center between 1995 and 2005 were assessed for intraoperative, perioperative, and long-term adverse events (AEs).

A total of 319 patients underwent DBS device implantation. Of these 319, 182 suffered from medically refractory Parkinson disease; the other patients had essential tremor (112 patients), dystonia (19 patients), and other hyperkinetic movement disorders (six patients). Intraoperative AEs were rare and included vasovagal response in eight patients (2.5%), syncope in four (1.2%), severe cough in three (0.9%), transient ischemic attack in one (0.3%), arrhythmia in one (0.3%), and confusion in one (0.3%). Perioperative AEs included headache in 48 patients (15.0%), confusion in 16 (5.0%), and hallucinations in nine (2.8%). Serious intraoperative/perioperative AEs included isolated seizure in four patients (1.2%), intracerebral hemorrhage in two patients (0.6%), intraventricular hemorrhage in two patients (0.6%), and a large subdural hematoma in one patient (0.3%). Persistent long-term complications of DBS surgery included dysarthria (4.0%), worsening gait (3.8%), cognitive dysfunction (4.0%), and infection (4.4%). Revisions were completed in 25 patients (7.8%) for the following reasons: loss of effect, lack of efficacy, infection, lead fracture, and lead migration. Hardware-related complications included 12 lead fractuxres and 10 lead migrations.

Conclusions

The authors conclude that in their 10-year experience, DBS has proven to be safe for the treatment of medically refractory movement disorders.
Antitumor effects of vaccination with dendritic cells transfected with modified receptor for hyaluronan-mediated motility mRNA in a mouse glioma model
Authors: Amano Takayuki , Kajiwara Koji , Yoshikawa Koichi , Morioka Jun , Nomura Sadahiro , Fujisawa Hirosuke , Kato Shoichi , Fujii Masami , Fukui Mikiko , Hinoda Yuji , Suzuki Michiyasu
Published: January 2008

Object

The receptor for hyaluronan-mediated motility (RHAMM) is frequently overexpressed in brain tumors and was recently identified as an immunogenic antigen by using serological screening of cDNA expression libraries. In this study, which was conducted using a mouse glioma model, the authors tested the hypothesis that vaccination with dendritic cells transfected with RHAMM mRNA induces strong immunological antitumor effects.

Methods

The authors constructed a plasmid for transduction of the mRNAs transcribed in vitro into dendritic cells, which were then used to transport the intracellular protein RHAMM efficiently into major histocompatibility complex class II compartments by adding a late endosomal–lysosomal sorting signal to the RHAMM gene. The dendritic cells transfected with this RHAMM mRNA were injected intraperitoneally into the mouse glioma model 3 and 10 days after tumor cell implantation. The antitumor effects of the vaccine were estimated by the survival rate, histological analysis, and immunohistochemical findings for immune cells.

Mice in the group treated by vaccination therapy with dendritic cells transfected with RHAMM mRNA survived significantly longer than those in the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing T cells activated by CD4+, CD8+, and CD25+ were found in the group vaccinated with dendritic cells transfected with RHAMM mRNA.

Conclusions

These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with RHAMM mRNA for the treatment of malignant glioma.
Motor cortex stimulation: mild transient benefit in a primate model of Parkinson disease
Authors: Wu Alex K. , McCairn Kevin W. , Zada Gabriel , Wu Tiffany , Turner Robert S.
Published: January 2008

Object

The authors sought to examine the therapeutic efficacy of motor cortex stimulation (MCS) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–treated macaques and to characterize therapeutic differences with varying modes, frequencies, and durations of stimulation.

Methods

Motor cortex stimulation was delivered at currents below motor threshold and at frequencies between 5 and 150 Hz through epidural electrodes over the primary motor cortex. The animals were studied during and without MCS using video analysis, activity logging, and food retrieval tasks. Animals were examined using two different stimulation protocols. The first protocol consisted of 1 hour of MCS therapy daily. The second protocol exposed the animal to continuous MCS for more than 24 hours with at least 2 weeks between MCS treatments.

Conclusions

Daily MCS yielded no consistent change in symptoms, but MCS at 2-week intervals resulted in significant increases in activity. Effects of biweekly MCS disappeared, however, within 24 hours of the onset of continuous MCS. In this study, MCS only temporarily reduced the severity of MPTP-induced parkinsonism.
Comparison of laser surface scanning and fiducial marker–based registration in frameless stereotaxy
Authors: Schicho Kurt , Figl Michael , Seemann Rudolf , Donat Markus , Pretterklieber Michael L. , Birkfellner Wolfgang , Reichwein Astrid , Wanschitz Felix , Kainberger Franz , Bergmann Helmar , Wagner Arne , Ewers Rolf
Published: January 2008

✓The authors compared the accuracy of laser surface scanning patient registration using the commercially available Fazer (Medtronic, Inc.) with the conventional registration procedure based on fiducial markers (FMs) in computer-assisted surgery.

Four anatomical head specimens were prepared with 10 titanium microscrews placed at defined locations and scanned with a 16-slice spiral computed tomography unit. To compare the two registration methods, each method was applied five times for each cadaveric specimen; thus data were obtained from 40 registrations. Five microscrews (selected following a randomization protocol) were used for each FM-based registration; the other five FMs were selected for coordinate measurements by touching with a point measurement stylus. Coordinates of these points were also measured manually on the screen of the navigation computer. Coordinates were measured in the same manner after laser surface registration.

The root mean square error as calculated by the navigation system ranged from 1.3 to 3.2 mm (mean 1.8 mm) with the Fazer and from 0.3 to 1.8 mm (mean 1.0 mm) with FM-based registration. The overall mean deviations (the arithmetic mean of the mean deviations of measurements on the four specimens) were 3.0 mm (standard deviation [SD] range 1.4–2.6 mm) with the Fazer and 1.4 mm (SD range 0.4–0.9 mm) with the FMs. The Fazer registration scans 300 surface points. Statistical tests showed the difference in the accuracy of these methods to be highly significant.

In accordance with the findings of other groups, the authors concluded that the inclusion of a larger number of registration points might improve the accuracy of Fazer registration.
Arteriovenous Malformation
Authors: Young William L. , Kwok Pui-Yan , Pawlikowska Ludmila , Lawton Michael T. , Kim Helen , Hysi Pirro G. , Marchuk Douglas A.
Published: January 2008

Object.

Important central nervous system (CNS) manifestations in patients with hereditary hemorrhagic telangiectasia (HHT) include arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Hereditary hemorrhagic telangiectasia is caused by germline mutations of two genes: ENG (HHT Type 1) and ACVRL1 (HHT Type 2). The ENG gene variations have been associated with the formation of intracranial aneurysms. The authors studied whether sequence variations in ACVRL1 or ENG are associated with the development of clinically sporadic arteriovenous dysplasias and aneurysms of the CNS.

Methods.

The coding sequence (in 44 patients with AVMs and 27 with aneurysms) and the 5′ end and the polyA site (in 53 patients with AVMs) of the ACVRL1 gene were analyzed for sequence variations using direct sequencing and single-strand conformational polymorphism analysis. One ENG and three ACVRL1 gene polymorphisms were genotyped using restriction enzyme–based analysis in 101 patients with sporadic AVMs and DAVFs of the CNS, 79 patients treated for intracranial aneurysms, and 202 control volunteers.

The authors identified a statistically significant association between the IVS3 −35A/T polymorphism in intron 3 of the ACVRL1 gene and the development of AVMs and DAVFs (p = 0.004; odds ratio [OR] 1.73; 95% confidence interval [CI] 1.19–2.51; after adjustments for age and sex), but not aneurysms (crude OR 0.82; 95% CI 0.55–1.18).

Conclusions.

The results of this study link ACVRL1 (HHT Type 2 gene) to the formation of the clinically sporadic variants of vascular malformations of the CNS most commonly seen in patients with HHT, that is, AVMs and DAVFs.
Train time as a quantitative electromyographic parameter for facial nerve function in patients undergoing surgery for vestibular schwannoma
Authors: Prell Julian , Rampp Stefan , Romstöck Johann , Fahlbusch Rudolf , Strauss Christian
Published: January 2008

Object

The authors describe a quantitative electromyographic (EMG) parameter for intraoperative monitoring of facial nerve function during vestibular schwannoma removal. This parameter is based on the automated detection of A trains, an EMG pattern that is known to be associated with postoperative facial nerve paresis.

Methods

For this study, 40 patients were examined. During the entire operative procedure, free-running EMG signals were recorded in muscles targeted by the facial nerve. A software program specifically designed for this purpose was used to analyze these continuous recordings offline. By automatically adding up time intervals during which A trains occurred, a quantitative parameter was calculated, which was named “train time.”

A strong correlation between the length of train time (measured in seconds) and deterioration of postoperative facial nerve function was demonstrated. Certain consecutive safety thresholds at 0.5 and 10 seconds were defined. Their transgression reliably indicated postoperative facial nerve paresis. At less than a 10-second train time, discrete worsening, and at more than 10 seconds, profound deterioration of facial nerve function can be anticipated.

Conclusions

Train time as a quantitative parameter was shown to be a reliable indicator of facial nerve paresis after surgery for vestibular schwannoma.
Radiosurgery of growth hormone–producing pituitary adenomas: factors associated with biochemical remission
Authors: Pollock Bruce E. , Jacob Jeffrey T. , Brown Paul D. , Nippoldt Todd B.
Published: January 2008

Object

The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission.

Methods

Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)–producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor–I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22–168 months).

Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6–63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2–6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4–13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years.

Conclusions

Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH–producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.
Stereotactic radiation treatment for recurrent nonbenign meningiomas
Authors: Mattozo Carlos A. , De Salles Antonio A. F. , Klement Ivan A. , Gorgulho Alessandra , McArthur David , Ford Judith M. , Agazaryan Nzhde , Kelly Daniel F. , Selch Michael T.
Published: January 2008

Object

The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign).

Methods

Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months.

Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%).

Conclusions

Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.
Medial plantar nerve compression by a tibial artery schwannoma
Authors: Spinner Robert J. , Scheithauer Bernd W. , Amrami Kimberly K.
Published: January 2008

✓ The authors describe the case of a patient with a novel cause of medial plantar symptoms due to extrinsic compression by a schwannoma arising within the adventitia of the tibial artery in the ankle region. Additionally they provide the operative, histological, and imaging findings.
Epstein–Barr virus infection as a complication of transplantation of a nerve allograft from a living related donor
Authors: Larsen Mikko , Habermann Thomas M. , Bishop Allen T. , Shin Alexander Y. , Spinner Robert J.
Published: January 2008

✓Reconstruction of extensive nerve defects is hampered by the amount of autogenous nerve tissue available for transplantation and by donor site morbidity. Nerve allografts, being of foreign origin and potentially unlimited in supply, provide a solution to these problems. Studies have shown that nerve allotransplants require immunosuppression only until end-organ connections are made and that immunosuppressant therapy may be subsequently discontinued with no negative effect on functional outcome. Also, recent experimental and clinical focus has been on shorter periods of immunosuppression in order to reduce risk, even stopping immunosuppression after regeneration has reached the distal suture line rather than before recovery of end-organ connections. In the pediatric population, the increased disease burden and increased potential for nerve regeneration as well as the frequent availability of a living related donor make allografts all the more attractive as solutions to nerve reconstructive problems. Nevertheless, the risks of immunosuppression must not be underemphasized, and they deserve more attention in the current nerve transplantation literature.

The authors report on a child who, at the age of 1 year, received a nerve allograft from a living related donor who was positive for Epstein–Barr virus (EBV). The child quickly developed a symptomatic EBV infection concurrent with immunosuppressant drug therapy. The immunosuppression regimen was stopped prematurely, and the patient suffered only a short illness, but the EBV infection could have developed into a life-threatening posttransplant lymphoproliferative disorder (PTLD). The patient is consequently predisposed to develop PTLD and will have to be monitored for the rest of his life. This case highlights the importance of considering the potentially fatal risks associated with this elective procedure. Future studies are needed to quantify and minimize this complication. Nevertheless, it should be weighed against the potential functional benefit from using nerve allografts.
Use of fenestrated aneurysm clips in microvascular decompression surgery
Authors: Attabib Najmedden , Kaufmann Anthony M.
Published: January 2008

✓The standard techniques of microvascular decompression (MVD) surgery in which implant materials such as shredded Teflon felt are used may be inadequate in some complex cases. The authors evaluated the use of fenestrated aneurysm clips to maintain transposition of culprit vessels in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS).

The authors conducted a retrospective review of MVD operations in which the culprit vessel was transposed and then maintained in position with a fenestrated aneurysm clip secured in position by suturing it to the dura mater.

Among a consecutive series of more than 450 MVD surgeries, the fenestrated aneurysm clip sling was used in eight of the last 100 cases: six for HFS and two for TN. The follow-up period ranged from 1 to 13 months, and complete symptom resolution was noted in seven of the eight patients. No patient exhibited evidence of any surgical complications.

This approach can be safely performed in complicated MVD cases such as reoperations and transpositions of long ectatic arteries. To the best of the authors' knowledge this is the first report in which the use of fenestrated aneurysm clips in MVD surgery is described.