bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral metabolism after fluid-percussion injury and hypoxia in a feline model
Authors: Zauner Alois , Clausen Tobias , Alves Oscar L. , Rice Ann , Levasseur Joseph , Young Harold F. , Bullock Ross
Published: May 2009

Object. Currently, there are no good clinical tools to identify the onset of secondary brain injury and/or hypoxia after traumatic brain injury (TBI). The aim of this study was to evaluate simultaneously early changes of cerebral metabolism, acid—base homeostasis, and oxygenation, as well as their interrelationship after TBI and arterial hypoxia.

Methods. Cerebral biochemistry and O2 supply were measured simultaneously in a feline model of fluid-percussion injury (FPI) and secondary hypoxic injury. After FPI, brain tissue PO2 decreased from 33 ± 5 mm Hg to 10 ± 4 mm Hg and brain tissue PCO2 increased from 55 ± 2 mm Hg to 81 ± 9 mm Hg, whereas cerebral pH fell from 7.1 ± 0.06 to 6.84 ± 0.14 (p < 0.05 for all three measures). After 40 minutes of hypoxia, brain tissue PO2 and pH decreased further to 0 mm Hg and 6.48 ± 0.28, respectively (p < 0.05), whereas brain tissue PCO2 remained high at 83 ± 13 mm Hg. Secondary hypoxic injury caused a drastic increase in cerebral lactate from 513 ± 69 µM/L to 3219 ± 490 µM/L (p < 0.05). The lactate/glucose ratio increased from 0.7 ± 0.1 to 9.1 ± 2 after hypoxia was introduced. The O2 consumption decreased significantly from 18.5 ± 1.1 µl/mg/hr to 13.2 ± 2.1 µl/mg/hr after hypoxia was induced.

Conclusions. Cerebral metabolism, O2 supply, and acid—base balance were severely compromised ultra-early after TBI, and they declined further if arterial hypoxia was present. The complexity of pathophysiological changes and their interactions after TBI might explain why specific therapeutic attempts that are aimed at the normalization of only one component have failed to improve outcome in severely head injured patients.
Characteristics of hypothermic preconditioning influencing the induction of delayed ischemic tolerance
Authors: Yunoki Masatoshi , Nishio Shinsaku , Ukita Naoya , Anzivino Matthew J. , Lee Kevin S.
Published: May 2009

Object. A brief period of hypothermia has recently been shown to induce delayed tolerance to ischemic brain injury. This form of tolerance is initiated several hours after hypothermic preconditioning (HPC) and persists for a few days. Hypothermia-induced tolerance could provide a means for limiting cellular injury during predictable periods of ischemia, such as those that occur during many surgical procedures. The purpose of this study was to characterize the parameters of HPC that regulate the induction of delayed tolerance.

Methods. The general design of the experiments was to perform HPC or a sham procedure on adult Sprague-Dawley rats. Twenty-four hours later, the animals were subjected to a transient period of ischemia induced by a 1-hour period of three-vessel occlusion. Infarct volume was assessed 24 hours postischemia. In the first series of experiments, the depth of global (that is, whole-body) HPC was set at 25.5, 28.5, or 31.5°C, and the duration of HPC was fixed at 20 minutes. In the second series of experiments, the duration of global HPC was set at 20, 60, 120, or 180 minutes, and the depth of HPC was set at 33 or 34.5°C. In the third series of experiments, focal HPC was administered by selectively cooling the head to achieve a cortical temperature of 28.5 or 31.5°C for 20 minutes, with the duration of HPC fixed at 20 minutes.

The magnitude of tolerance induced by HPC was dependent on the depth and duration of the hypothermic stimulus. The parameters of hypothermia that are capable of inducing tolerance are similar to, or less severe than, those already in clinical use during intraoperative procedures. Focal cooling was as effective as global cooling for eliciting tolerance, indicating that it is possible to establish tolerance while limiting the potential complications of systemic hypothermia.

Conclusions. The results of these experiments indicate that HPC may provide an effective and safe means for limiting cellular injury resulting from predictable periods of central nervous system ischemia.
De novo dissecting aneurysm in a patient with a ruptured saccular lesion
Authors: Ikeda Toshiki , Kurita Hiroki , Konishi Yoshifumi , Fujitsuka Mitsuyuki , Hino Ken , Shiokawa Yoshiaki , Saito Isamu
Published: May 2009

✓ Formation of a new saccular aneurysm after successful treatment of ruptured aneurysm has recently raised significant clinical concerns; however, de novo formation and rupture of a dissecting aneurysm has not been discussed. The authors report on a 42-year-old man who initially sought treatment for a ruptured saccular aneurysm of the right middle cerebral artery, which was successfully eliminated by surgical clipping of the aneurysm neck. Two years later, the patient presented with another subarachnoid hemorrhage and was found to have a dissecting aneurysm of the right vertebral artery, which arose from a previously angiographically documented normal artery. This rare association sheds light on the causes and growth of two distinct types of aneurysms, both clinically and pathologically.
Continuous somatosensory evoked potential monitoring during brain tumor resection
Authors: Grant Gerald A. , Farrell Donald , Silbergeld Daniel L.
Published: May 2009

✓ The neurosurgical management of intrinsic brain tumors and brain metastases mandates maximum resection with preservation of functional cortex. There have been previous reports on the use of cortical somatosensory evoked potentials (SSEPs) for localization of functional cortex prior to resection. The identification of rolandic cortex with the use of intraoperative SSEP monitoring enables the neurosurgeon to tailor the surgery to achieve a greater extent of resection while minimizing the risk of morbidity. The use of continuous SSEP monitoring during resection to provide an ongoing functional assessment of somatosensory cortex has not been reported. This powerful technique is illustrated using four case examples.
Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis
Authors: Kumar Krishna , Hunter Gary , Demeria Denny D.
Published: May 2009

Object. The object of this study was to compare the cost-effectiveness of intrathecal drug therapy (IDT) with that of conventional pain therapy (CPT) in patients suffering from chronic low back pain caused by failed back syndrome. In this study, the authors tabulated actual costs, in Canadian dollars, in a consecutive series of patients undergoing IDT within the Canadian health care system and have compared them with costs in a control group in the same environment. The influence of these treatments on the quality of life (QOL) was also analyzed.

Methods. The authors report on a series of 67 patients suffering from failed back syndrome, 23 of whom underwent implantation of a programmable drug delivery pump and 44 of whom acted as controls. Patients were followed for a 5-year period during which the investigators tabulated the actual costs incurred for diagnostic imaging, professional fees, implantation costs including hardware, nursing visits for maintenance of the pumps, alternative therapies, and hospitalization costs for breakthrough pain. From this data, cumulative costs for each group were calculated for a 5-year period. Patient responses on the Oswestry Pain Questionnaire were analyzed to assess the impact of treatment on QOL. The actual cumulative costs for IDT during a 5-year period were $29,410, as opposed to $38,000 for CPT. High initial costs of equipment required for IDT were recovered by 28 months. After this time point, managing patients with CPT became the more expensive treatment option for the remainder of the follow-up period. The Oswestry Disability Index showed a 27% improvement for patients in the IDT group, compared with a 12% improvement in the control group.

Conclusions. In patients who respond to this treatment, IDT is cost effective in the long term despite high initial costs of implantable devices.
Thalamic deep brain stimulation for the treatment of tremor due to multiple sclerosis: a prospective study of tremor and quality of life
Authors: Berk Caglar , Carr Jason , Sinden Marci , Martzke Jeff , Honey Christopher R.
Published: May 2009

Object. In several studies a significant reduction in tremor after thalamic deep brain stimulation (DBS) has been reported among patients with multiple sclerosis (MS). It has not been determined if this results in an improved quality of life. In this study the authors prospectively evaluated the effects of thalamic DBS on tremor and quality of life.

Methods. Videotapes of the patients' tremor were made preoperatively and 2 and 12 months postoperatively, and tremor was scored by a neurologist blinded to the treatment. Patients were tested pre- and postoperatively to measure any changes in their reported ability to perform selected activities of daily living and in their health-related quality of life. Patients were asked to complete a questionnaire about their satisfaction with the surgery. Postoperative changes were examined using paired t-tests.

There were significant reductions in postural, action, and overall tremor at 2 and 12 months postoperatively. The patients' reported ability to feed themselves was significantly improved 2 months after surgery (p = 0.01). There were short-term trends toward improvement in reported dressing ability, personal hygiene, and writing. There were no significant changes in the SF-36 subscales or total score.

Conclusions. In this cohort of patients with MS who suffered from tremor, thalamic DBS significantly improved their tremor and ability to feed themselves. Patient satisfaction with the procedure, however, was variable. Preoperative patient education about what functions might (and might not) be improved is crucial to avoid unrealistic expectations. Our results indicate that younger patients with MS tremor who had a shorter disease duration and no superimposed ataxia benefited most from this surgery.
Surgical procedures for posterior fossa tumors in children: does craniotomy lead to fewer complications than craniectomy?
Authors: Gnanalingham Kanna K. , Lafuente Jesus , Thompson Dominic , Harkness William , Hayward Richard
Published: May 2009

Object. Traditionally, access to the posterior fossa involved a suboccipital craniectomy. More recently, posterior fossa craniotomies have been described, although the long-term benefits of this procedure are not clear. The authors compared the postoperative complications of craniectomies and craniotomies in children with posterior fossa tumors.

Methods. From a total of 110 children undergoing surgery for posterior fossa tumors, 56 underwent craniectomy and 54 had a craniotomy. The mean duration of the hospital stay was longer in the craniectomy group (17.5 compared with 14 days). At operation, similar numbers of patients in both groups had total macroscopic clearance of the tumor, complete dural closure, and duraplasty.

Postoperatively, more patients in the craniectomy group were noted to have cerebrospinal fluid (CSF) leakage (27 compared with 4%; p < 0.01) and pseudomeningoceles (23 compared with 9%; p < 0.05). There was no significant difference between the two groups in the numbers of patients with CSF infections, wound infections, or hydrocephalus requiring permanent CSF drainage. Patients with CSF leaks had a longer duration of hospital stay (20.7 compared with 14.9 days; p < 0.01), and were more likely to have CSF infections (35 compared with 12%; p < 0.01) and wound infections (24 compared with 1%; p < 0.01) than patients without CSF leaks. Postoperatively, wound exploration and reclosures for CSF leakage were more likely in the craniectomy group (11 compared with 0%; p < 0.01). Multivariate analysis revealed that the only predictor of CSF leakage postoperatively was the type of surgery (that is, craniotomy compared with craniectomy; odds ratio 10.8; p = 0.03).

Conclusions. Craniectomy was associated with postoperative CSF leaks, pseudomeningocele, increased wound reclosures, and thus prolonged hospital stays. In turn, CSF leakage was associated with infections of the CSF and wound. The authors propose mechanisms that may explain why CSF leakage is less likely if the bone flap is replaced.
Trigeminal neuralgia caused by microarteriovenous malformations of the trigeminal nerve root entry zone: symptomatic relief following complete excision of the lesion with nerve root preservation
Authors: Edwards Richard J. , Clarke Yvonne , Renowden Shelley A. , Coakham Hugh B.
Published: May 2009

Object. Within a series of 341 consecutive patients who underwent posterior fossa surgery for trigeminal neuralgia (TN), in five the cause was found to be a microarteriovenous malformation (micro-AVM) located in the region of the trigeminal nerve root entry zone (REZ). The surgical management and clinical outcomes of these cases are presented.

Methods. Patients were identified from a prospectively collected database of all cases of TN treated at one institution between 1980 and 2000. Presentation was clinically indistinguishable from TN caused by vascular compression. Preoperative imaging, including computerized tomography scanning (two cases) and magnetic resonance (MR) imaging and MR angiography (three cases), failed to demonstrate an AVM except for one case in which multiple abnormal vessels were identified in the trigeminal REZ on an MR image obtained using a 1.5-tesla magnet. All patients underwent a standard retromastoid craniotomy. In all cases a small AVM embedded in the trigeminal REZ was identified and completely excised, with preservation of the trigeminal nerve. All patients experienced immediate relief of pain following surgery. Postoperatively, in one patient a small pontine hematoma developed, resulting in permanent trigeminal nerve anesthesia in the V2 and V3 divisions. All patients were free from pain at a mean follow-up period of 30 months.

Conclusions. These rare lesions are usually angiographically occult, but may sometimes be identifiable on high-resolution MR images. Total microsurgical resection with nerve preservation is possible, although operative complications are relatively common, reflecting the intimate association between these lesions and the pons. Complete resection is advised not only for symptom relief, but also to eliminate the theoretical risk of pontine hemorrhage.
A mixture of ethylene vinyl alcohol copolymer and ethanol yielding a nonadhesive liquid embolic agent to treat cerebral arteriovenous malformations: initial clinical experience
Authors: Hamada Jun-Ichiro , Kai Yutaka , Morioka Motohiro , Kazekawa Kiyoshi , Ishimaru Yasuji , Iwata Hiroo , Ushio Yukitaka
Published: May 2009

Object. The authors report their clinical experience with their new nonadhesive liquid embolic agent, an ethylene vinyl alcohol copolymer (EVAL)/ethanol mixture, to treat arteriovenous malformations (AVMs).

Methods. Between June 1995 and April 2001, 57 patients with confirmed AVMs underwent embolization of their lesions with the EVAL/ethanol mixture. In 87 procedures consisting of one to three stages, the authors embolized 185 feeding arteries to occlude as much of the AVM as possible. Repeated injections under fluoroscopic control could be performed smoothly without encountering cementing of the catheter to the vessel wall. Among the 87 embolizations undertaken in 57 patients, seven procedures (8%) in six patients produced new postembolization symptoms. Resolution of these symptoms occurred within hours or days after four of the seven procedures; permanent neurological deficits remained after the other three procedures (3.4%). Of the 57 patients, three underwent postembolization radiosurgery, and 54 underwent radical treatment with microsurgical extirpation. Histopathological examination of the 54 specimens disclosed mild inflammation within the embolized lumen without inflammatory reactions in the media or adventitia. Follow-up angiograms obtained 3 years after radiosurgery was administered showed that in all three patients treated in this fashion the nidus had completely disappeared.

Conclusions. The EVAL/ethanol mixture is handled easily and appears to be an effective and safe agent for preoperative embolization of AVMs.
A nonadhesive liquid embolic agent composed of ethylene vinyl alcohol copolymer and ethanol mixture for the treatment of cerebral arteriovenous malformations: experimental study
Authors: Hamada Jun-Ichiro , Kai Yutaka , Morioka Motohiro , Kazekawa Kiyoshi , Ishimaru Yasuji , Iwata Hiroo , Ushio Yukitaka
Published: May 2009

Object. The authors have developed a mixture of ethylene vinyl alcohol copolymer (EVAL) and iopamidol, which is dissolved in ethanol, as an alternative solvent to provide a safe means of embolizing arteriovenous malformations (AVMs).

Methods. A two-stage delivery technique is required to prevent premature precipitation in the catheter when using this material: the catheter is first infused with 30% ethanol and this is followed by the delivery of the EVAL—ethanol mixture. Acute angiographic changes were analyzed after superselective delivery of dimethyl sulfoxide (DMSO) and 30% ethanol into the renal artery of rabbits. Histological changes following the embolization of the renal artery achieved using the EVAL—ethanol mixture were recorded at 1 hour and at 2 and 16 weeks after the procedure. Although DMSO always produced severe, rapidly progressive vasospasm in the renal artery during a 1- to 60-minute postinfusion, 30% ethanol did not. Microscopically, the lumens of embolized vessels examined 1 hour after embolization with EVAL—ethanol appeared to be filled with EVAL sponges, leaving almost no open spaces. The space between the EVAL sponges and the inner surface of the vessels was filled with fresh thrombus. In the vessel walls of specimens examined 2 weeks after embolization there was no or a slight inflammatory reaction. Scattered in the EVAL sponges were almost equal numbers of neutrophilic granulocytes and mononuclear cells, indicative of a mild inflammatory response. In specimens examined 16 weeks postembolization, the changes noted at 2 weeks were intensified. There was no definite histopathological evidence of mural hemorrhage, perivascular extravasation of the mixture, or perivascular hemorrhage in any specimen that was examined.

Conclusions. Although the degree of permanence of this embolization material is yet unknown, the mixture was easy to handle, and appeared safe and effective for AVM embolization. Its nonadhesive characteristic and its ability to be infused by repeated injections make it an attractive alternative to currently available materials. The good results obtained in this study led us to undertake a clinical trial, the results of which are contained in a companion article in this issue of the Journal of Neurosurgery.
Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion
Authors: Lonser Russell R. , Walbridge Stuart , Garmestani Kayhan , Butman John A. , Walters Hugh A. , Vortmeyer Alexander O. , Morrison Paul F. , Brechbiel Martin W. , Oldfield Edward H.
Published: May 2009

Object. Intrinsic disease processes of the brainstem (gliomas, neurodegenerative disease, and others) have remained difficult or impossible to treat effectively because of limited drug penetration across the blood—brainstem barrier with conventional delivery methods. The authors used convection-enhanced delivery (CED) of a macromolecular tracer visible on magnetic resonance (MR) imaging to examine the utility of CED for safe perfusion of the brainstem.

Methods. Three primates (Macaca mulatta) underwent CED of various volumes of infusion ([Vis]; 85, 110, and 120 µl) of Gd-bound albumin (72 kD) in the pontine region of the brainstem during serial MR imaging. Infusate volume of distribution (Vd), homogeneity, and anatomical distribution were visualized and quantified using MR imaging. Neurological function was observed and recorded up to 35 days postinfusion. Histological analysis was performed in all animals. Large regions of the pons and midbrain were successfully and safely perfused with the macromolecular protein. The Vd was linearly proportional to the Vi (R2 = 0.94), with a Vd/Vi ratio of 8.7 ± 1.2 (mean ± standard deviation). Furthermore, the concentration across the perfused region was homogeneous. The Vd increased slightly at 24 hours after completion of the infusion, and remained larger until the intensity of infusion faded (by Day 7). No animal exhibited a neurological deficit after infusion. Histological analysis revealed normal tissue architecture and minimal gliosis that was limited to the region immediately surrounding the cannula track.

Conclusions. First, CED can be used to perfuse the brainstem safely and effectively with macromolecules. Second, a large-molecular-weight imaging tracer can be used successfully to deliver, monitor in vivo, and control the distribution of small- and large-molecular-weight putative therapeutic agents for treatment of intrinsic brainstem processes.
Temporal pattern of cochlear nerve degeneration following compression injury: a quantitative experimental observation
Authors: Shimamura Norihito , Sekiya Tetsuji , Yagihashi Akinori , Suzuki Shigeharu
Published: May 2009

Object. It has been empirically recognized that the cochlear nerve is highly vulnerable to traumatic stress resulting from surgical procedures; therefore, careful manipulation of the cochlear nerve is mandatory in preventing trauma-induced hearing loss during cerebellopontine angle (CPA) surgery. There is, however, no precise knowledge about the temporal pattern of cochlear nerve degeneration following trauma. This study was performed to determine the temporal pattern of injury that occurs after cochlear nerve trauma, knowledge of which is indispensable not only to neurosurgeons but also to all those who manage lesions involving the cochlear nerve.

Methods. Right suboccipital craniectomies were performed in groups of rats with the aid of a surgical microscope, and the seventh and eighth cranial nerve trunks were identified at the internal auditory meatus. The cochlear nerve was quantifiably compressed while compound action potentials of the cochlear nerve were monitored and recorded. Following injury, one group of rats was killed for histological examination at the end of each week for 4 weeks. Data from this study disclosed that the degeneration of the compressed cochlear nerve progressed in a relatively rapid manner and was complete within 1 week after the insult. The main pathophysiological mechanisms responsible for cochlear neuronal death in this experimental setting appeared to be necrosis, and an apoptotic mechanism seemed to play a subsidiary role.

Conclusions. Accurate knowledge about the temporal profile of trauma-induced cochlear nerve degeneration is closely linked with the problem of the therapeutic time window. The results of the present study indicated that any measures to ameliorate cochlear nerve degeneration following trauma should be started as early as possible (within 1 week) after an injury.
The effect of brain temperature on hemoglobin extravasation after traumatic brain injury
Authors: Kinoshita Kosaku , Chatzipanteli Katina , Alonso Ofelia F. , Howard Mackenzie , Dietrich W. Dalton
Published: May 2009

Object. Although the benefits of posttraumatic hypothermia have been reported in experimental studies, the potential for therapeutic hypothermia to increase intracerebral hemorrhage remains a clinical concern. The purpose of this study was to quantify the amount of extravasated hemoglobin after traumatic brain injury (TBI) and to assess the changes in intracerebral hemoglobin concentrations under posttraumatic hypothermic and hyperthermic conditions.

Methods. Intubated and anesthetized rats were subjected to fluid-percussion injury (FPI). In the first experiment, rats were divided into moderate (1.8–2.2 atm) and severe (2.4–2.7 atm) TBI groups. In the second experiment, the effects of 3 hours of posttraumatic hypothermia (33 or 30°C), hyperthermia (39°C), or normothermia (37°C) on hemoglobin levels following moderate trauma were assessed. The rats were perfused with saline at 24 hours postinjury, and then the traumatized and contralateral hemispheres, including the cerebellum, were dissected from whole brain. The hemoglobin level in each brain was quantified using a spectrophotometric hemoglobin assay. The results of these assays indicate that moderate and severe FPI induce increased levels of hemoglobin in the ipsilateral hemisphere (p < 0.0001). After severe TBI, the hemoglobin concentration was also significantly increased in the contralateral hemisphere (p < 0.05) and cerebellum (p < 0.005). Posttraumatic hypothermia (30°C) attenuated hemoglobin levels (p < 0.005) in the ipsilateral hemisphere, whereas hyperthermia had a marked adverse effect on the hemoglobin concentration in the contralateral hemisphere (p < 0.05) and cerebellum (p < 0.005).

Conclusions. Injury severity is an important determinant of the degree of hemoglobin extravasation after TBI. Posttraumatic hypothermia reduced hemoglobin extravasation, whereas hyperthermia increased hemoglobin levels compared with normothermia. These findings are consistent with previous data reporting that posttraumatic temperature manipulations alter the cerebrovascular and inflammatory consequences of TBI.
Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation
Authors: Rohde Veit , Rohde Ina , Thiex Ruth , Ince Azize , Jung Axel , Dückers Gregor , Gröschel Klaus , Röttger Carina , Küker Wilhelm , Müller Harald D. , Gilsbach Joachim M.
Published: May 2009

Object. Fibrinolysis therapy accomplished using tissue plasminogen activator (tPA) and aspiration is considered to be a viable alternative to microsurgery and medical therapy for the treatment of deep-seated spontaneous intracerebral hematomas (SICHs). Tissue plasminogen activator is a mediator of thrombin- and ischemia-related delayed edema. Because both thrombin release and ischemia occur after SICH, the authors planned to investigate the effect of fibrinolytic therapy on hematoma and delayed edema volume.

Methods. A spherical hematoma was created in the frontal white matter of 18 pigs. In the tPA-treated group (nine pigs), a mean of 1.55 ml tPA was injected into the clot and the resulting liquefied blood was aspirated. Magnetic resonance (MR) imaging was performed on Days 0 (after surgery), 4, and 10, and the volumes of hematoma and edema were determined. In the animals not treated with tPA (untreated group; nine pigs), the volume of hematoma dropped from 1.43 ± 0.42 ml on Day 0 to 0.85 ± 0.28 ml on Day 10. In the tPA-treated group, the volume of hematoma was reduced from 1.51 ± 0.28 ml on Day 0 to 0.52 ± 0.39 ml on Day 10. In comparison with the untreated group, the reduction in hematoma volume was significantly accelerated (p = 0.02). In the untreated group, perihematomal edema increased from 0.32 ± 0.61 ml to 1.73 ± 0.73 ml on Day 4, before dropping to 1.17 ± 0.92 ml on Day 10. In the tPA-treated group, the volume of the edema increased from 0.09 ± 0.21 ml on Day 0 to 1.93 ± 0.79 ml on Day 4, and further to 3.34 ± 3.21 ml on Day 10. The increase in edema volume was significantly more pronounced in the tPA-treated group (p = 0.04).

Conclusions. Despite a significantly accelerated reduction in hematoma volume, the development of delayed perifocal edema was intensified by fibrinolytic therapy, which is probably related to the function of tPA as a mediator of edema formation after thrombin release and ischemia. Further experimental and clinical investigations are required to establish the future role of fibrinolysis in the management of SICH.
Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid
Authors: Olzowy Bernhard , Hundt Cornelia S. , Stocker Susanne , Bise Karl , Reulen Hans Jürgen , Stummer Walter
Published: May 2009

Object. Accumulation of protoporphyrin IX (PPIX) in malignant gliomas is induced by 5-aminolevulinic acid (5-ALA). Because PPIX is a potent photosensitizer, the authors sought to discover whether its accumulation might be exploited for use in photoirradiation therapy of experimental brain tumors, without injuring normal or edematous brain.

Methods. Thirty rats underwent craniotomy and were randomized to the following groups: 1) photoirradiation of cortex (200 J/cm2, 635-nm argon-dye laser); 2) photoirradiation of cortex (200 J/cm2) 6 hours after intravenous administration of 5-ALA (100 mg/kg body weight); 3) cortical cold injury for edema induction; 4) cortical cold injury with simultaneous administration of 5-ALA (100 mg/kg body weight) and photoirradiation of cortex (200 J/cm2) 6 hours later; or 5) irradiation of cortex (200 J/cm2) 6 hours after intravenous administration of Photofrin II (5 mg/kg body weight). Tumors were induced by cortical inoculation of C6 cells and 9 days later, magnetic resonance (MR) images were obtained. On Day 10, animals were given 5-ALA (100 mg/kg body weight) and their brains were irradiated (100 J/cm2) 3 or 6 hours later. Seventy-two hours after irradiation, the brains were removed for histological examination.

Irradiation of brains after administration of 5-ALA resulted in superficial cortical damage, the effects of which were not different from those of the irradiation alone. Induction of cold injury in combination with 5-ALA and irradiation slightly increased the depth of damage. In the group that received irradiation after intravenous administration of Photofrin II the depth of damage inflicted was significantly greater. The extent of damage in response to 5-ALA and irradiation in brains harboring C6 tumors corresponded to the extent of tumor determined from pretreatment MR images.

Conclusions. Photoirradiation therapy in combination with 5-ALA appears to damage experimental brain tumors selectively, with negligible damage to normal or perifocal edematous tissue.
Analysis of von Hippel—Lindau mutations with comparative genomic hybridization in sporadic and hereditary hemangioblastomas: possible genetic heterogeneity
Authors: Gijtenbeek Johanna M. M. , Jacobs Bram , Sprenger Sandra H. E. , Eleveld Marc J. , van Kessel Ad Geurts , Kros Johan M. , Sciot Raf , van Calenbergh Frank , Wesseling Pieter , Jeuken Judith W. M.
Published: May 2009

Object. Hemangioblastomas (HBs) occur sporadically or as a manifestation of von Hippel—Lindau (VHL) disease. In the majority of VHL-related HBs, inactivation of the VHL tumor suppressor gene (TSG), which is located on chromosome 3p25–26, is found. The VHL gene is assumed to be involved also in the development of sporadic HBs. In a previous study of chromosomal aberrations of sporadic HBs, multiple chromosomal imbalances were found in the majority of tumors. The aim of this study was to analyze further both sporadic HBs and VHL-related HBs to determine if these histopathologically identical tumors have a different genetic background.

Methods. Sixteen sporadic HBs and seven VHL-related HBs were identified by clinical criteria and analyzed. Comparative genomic hybridization was used to screen for chromosomal imbalances throughout the entire HB genome. Additionally, mutation analysis of the VHL gene was performed using direct sequencing.

Loss of chromosome 3 and multiple other chromosomal imbalances were found in the sporadic HBs, although only one imbalance, a loss of chromosome 3, was detected in the seven VHL-related HBs. Somatic VHL gene mutations were found in one third of sporadic HBs, whereas a mutation of the VHL gene was detected in all VHL-related HBs.

Conclusions. These results indicate that the molecular mechanisms underlying sporadic HBs and VHL-related HBs are different. Inactivation of the VHL gene is probably not the most important event in the tumorigenesis of sporadic HBs. Other mechanisms of inhibition of VHL protein function, or inactivation of other TSGs, on chromosome 3p or on other chromosomes, might be important in the development of sporadic HBs.
Large cerebral arteriovenous malformation presenting with venous ischemia in the contralateral hemisphere
Authors: Kurozumi Kazuhiko , Onoda Keisuke , Tsuchimoto Shoji
Published: May 2009

✓ The authors report a rare case in which a large cerebral arteriovenous malformation (AVM) located in the left parietooccipital region presented with venous ischemia in the contralateral hemisphere. A 74-year-old man was admitted to the hospital because he was experiencing a loss of appetite, disorientation, and left hemiparesis. Computerized tomography scans revealed a low-density area in the right temporal lobe. Angiography demonstrated a large AVM in the left parietooccipital lobe and dilation, stagnation, and meanders of cortical veins in the contralateral hemisphere. The authors speculated that the elevated sinus pressure caused by a huge venous return of blood from the AVM produced venous ischemia in the contralateral hemisphere.
Preoperative ventriculostomy and rebleeding after aneurysmal subarachnoid hemorrhage
Authors: McIver Jon I. , Friedman Jonathan A. , Wijdicks Eelco F. M. , Piepgras David G. , Pichelmann Mark A. , Toussaint L. Gerard , McClelland Robyn L. , Nichols Douglas A. , Atkinson John L. D.
Published: May 2009

Object. Despite the widespread use of ventriculostomy in the treatment of acute hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH), there is no consensus regarding the risk of rebleeding associated with ventriculostomy before aneurysm repair. This present study was conducted to assess the risk of rebleeding after preoperative ventriculostomy in patients with aneurysmal SAH.

Methods. The authors reviewed the records of all patients with acute SAH who were treated at a single institution between 1990 and 1997. Thus, the records of 304 consecutive patients in whom an aneurysmal SAH source was documented on angiographic studies and who had presented to the authors' institution within 7 days of ictus were analyzed. Rebleeding was confirmed by evidence of recurrent hemorrhage on computerized tomography scans in all cases.

Forty-five patients underwent ventriculostomy for acute hydrocephalus after aneurysmal SAH at least 24 hours before aneurysm repair. Ventriculostomy was performed within 24 hours of SAH in 38 patients, within 24 to 48 hours in three patients, and more than 48 hours after SAH in four patients. The mean time interval between SAH and surgery in patients who did not undergo ventriculostomy was no different from the mean interval between ventriculostomy and surgery in patients who underwent preoperative ventriculostomy (3.6 compared with 3.8 days, p = 0.81). Fourteen (5.4%) of the 259 patients who did not undergo ventriculostomy suffered preoperative aneurysm rebleeding, whereas two (4.4%) of the 45 patients who underwent preoperative ventriculostomy had aneurysm rebleeding.

Conclusions. No evidence was found that preoperative ventriculostomy performed after aneurysmal SAH is associated with an increased risk of aneurysm rebleeding when early aneurysm surgery is performed.
Radiation-induced meningioma: a descriptive study of 253 cases
Authors: Sadetzki Siegal , Flint-Richter Pazit , Ben-Tal Tehila , Nass Dvora
Published: May 2009

Object. Ionizing radiation is the only established risk factor recognized today in the causation of meningioma. The aim of the present report is to describe the demographic and clinical characteristics of a large series of 253 patients with radiation-induced meningiomas (RIMs). These parameters were compared with those of 41 patients with meningiomas in whom there was no previous history of irradiation (non-RIM group) and with other series of patients presented in the literature.

Methods. The cases of RIM were recruited from a cohort of appproximately 11,000 individuals who had been treated with ionizing radiation during childhood for tinea capitis and from a group of individuals who, as adults, applied for compensation because of that treatment. The non-RIM group was identified through the Israeli Cancer Registry. Exposure to radiation was carefully validated among all cases of RIM and absence of previous irradiation was verified for all patients in the non-RIM group.

Significantly, a lower patient age at diagnosis, higher prevalence of calvarial tumors, higher proportion of multiple meningiomas, and a nonsignificant higher recurrence rate were observed among patients with RIM compared with the non-RIM group. The mean latency period from date of radiation exposure to development of a meningioma among the RIM group was approximately 36 years.

Conclusions. The findings of this study agree with those of other studies indicating the demographic, clinical, and even genetic variability between RIM and non-RIM cases. The existence of two different subtypes of meningiomas may have profound implications for screening, early diagnosis, and therapy of meningiomas.
Extravascular collagen in the human epileptic brain: a potential substrate for aberrant cell migration in cases of temporal lobe epilepsy
Authors: Veznedaroglu Erol , Bockstaele Elisabeth J. Van , O'Connor Michael J.
Published: May 2009

Object. Several lines of evidence have demonstrated a number of cellular changes that occur within the hippocampus in patients with temporal lobe epilepsy (TLE). These include aberrant migration of granule cells and sprouting of mossy fibers, processes that have been linked to the hyperexcitability phenomenon observed in cases of TLE. In the present study the authors examined brain tissues obtained in patients undergoing temporal lobectomy surgery and in patients at autopsy (normal human control specimens), and compared the subcellular composition of regions of the hippocampus containing dispersed granule cells.

Methods. Six human hippocampi were obtained in patients undergoing temporal lobectomies for intractable seizures. The patients ranged in age from 24 to 50 years. Two of the six patients had a history of head trauma and one had experienced a febrile seizure during childhood. Immediately following excision from the brain, the tissue was placed in an acrolein—paraformaldehyde fixative. The hippocampi were processed along with six human brain control specimens obtained at autopsy for light and electron microscopic evaluation. The tissues were then labeled for collagen types I through IV. Positive collagen labeling was identified, with the aid of both light and electron microscopy, in the parenchyma of all patients with TLE but not in the control tissues.

Conclusions. The authors report the first localization of collagen outside of the vasculature and meninges in the brains of patients with TLE. Recent evidence of collagen's chemoattractant properties and its role in epileptogenesis in animal models suggests that collagen may play a role in cellular migration and seizure activity in a subset of patients. Further studies with a larger series of patients are warranted.
Prognostic factors and outcome after different types of resection for temporal lobe epilepsy
Authors: Clusmann Hans , Schramm Johannes , Kral Thomas , Helmstaedter Christoph , Ostertun Burkhard , Fimmers Rolf , Haun Dorothee , Elger Christian E.
Published: May 2009

Object. It is unknown whether different resection strategies for temporal lobe epilepsy (TLE) produce alterations in seizure control or neuropsychological performance.

Methods. A series of 321 patients who underwent surgery for TLE between 1989 and 1997 was submitted to a uniand multifactorial analysis of clinical, electrophysiological, neuroimaging, neuropsychological, and surgical factors to determine independent predictors of outcome. Until 1993, most patients with TLE underwent standard anterior temporal lobectomy (ATL); beginning in 1993, surgical procedures were increasingly restricted to lesions detected on magnetic resonance (MR) imaging and the presumed epileptogenic foci: for example, amygdalohippocampectomy (AH) or lesionectomy/corticectomy began to be used more often.

The mean follow-up duration in this study was 38 months. Two hundred twenty-seven patients were classified as seizure free (70.7%), and 36 patients had rare and nondisabling seizures (11.2%); these groups were summarized as having good seizure control (81.9%). Twenty-four patients attained more than 75% improvement (7.5%), and no worthwhile improvement was seen in 34 cases (10.6%); these groups were summarized as having unsatisfactory seizure control (18.1%).

On unifactorial analysis the following preoperative factors were associated with good seizure control (p < 0.05): single and concordant lateralizing focus on electroencephalography studies, low seizure frequency, absence of status epilepticus, concordant lateralizing memory deficit, clear abnormality on MR images, suspected ganglioglioma or dysembryoplastic neuroepithelial tumor (DNT), and absence of dysplasia on MR images. Stepwise logistic regression revealed a model containing five factors that were predictive for good seizure control (p < 0.1): 1) clear abnormality on MR images; 2) absence of status epilepticus; 3) MR imaging—confirmed ganglioglioma or DNT; 4) concordant lateralizing memory deficit; and 5) absence of dysplasia on MR images. Seizure outcome was mainly correlated with diagnosis and clinical factors. No significant differences were found regarding different resection types performed for comparable tumors. Neuropsychological testing revealed better postoperative results after limited resections compared with standard ATL, especially with regard to attention level, verbal memory, and calculated total neuropsychological performance.

Conclusions. Different strategies for surgical approaches in TLE result in equally good outcomes. Seizure outcome is mainly dependent on the diagnosis and clinical factors, whereas the neuropsychological results are more beneficial after resections limited to an epileptogenic lesion and focus.
Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging
Authors: Saint-Cyr Jean A. , Hoque Tasnuva , Pereira Luiz C. M. , Dostrovsky Jonathan O. , Hutchison William D. , Mikulis David J. , Abosch Aviva , Sime Elspeth , Lang Anthony E. , Lozano Andres M.
Published: May 2009

Object. The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD).

Methods. Fifty-four DBS electrodes were localized in and adjacent to the subthalamic nucleus (STN) postoperatively by using magnetic resonance (MR) imaging in a series of 29 patients in whom electrodes were implanted for the treatment of medically refractory PD, and for whom quantitative clinical assessments were available both pre- and postoperatively. A novel MR imaging sequence was developed that optimized visualization of the STN. The coordinates of the tips of these electrodes were calculated three dimensionally and the results were normalized and corrected for individual differences by using intraoperative neurophysiological data (mean 5.13 mm caudal to the midcommissural point [MCP], 8.46 mm inferior to the anterior commissure—posterior commissure [AC—PC], and 10.2 mm lateral to the midline).

Despite reported concerns about distortion on the MR image, reconstructions provided consistent data for the localization of electrodes. The neurosurgical procedures used, which were guided by combined neuroimaging and neurophysiological methods, resulted in the consistent placement of DBS electrodes in the subthalamus and mesencephalon such that the electrode contacts passed through the STN and dorsally adjacent fields of Forel (FF) and zona incerta (ZI). The mean location of the clinically effective contacts was in the anterodorsal STN (mean 1.62 mm posterior to the MCP, 2.47 mm inferior to the AC—PC, and 11.72 mm lateral to the midline). Clinically effective stimulation was most commonly directed at the anterodorsal STN, with the current spreading into the dorsally adjacent FF and ZI.

Conclusions. The anatomical localization of clinically effective electrode contacts provided in this study yields useful information for the postoperative programming of DBS electrodes.
Local delivery of mitoxantrone for the treatment of malignant brain tumors in rats
Authors: DiMeco Francesco , Li Khan W. , Tyler Betty M. , Wolf Ariel S. , Brem Henry , Olivi Alessandro
Published: May 2009

Object. Mitoxantrone is a drug with potent in vitro activity against malignant brain tumor cell lines; however, its effectiveness as a systemic agent has been hampered by poor central nervous system penetration and dose-limiting myelosuppression. To avoid these problems, we incorporated mitoxantrone into biodegradable polymeric wafers to be used for intracranial implantation, a strategy that has been shown to be safe and successful in the treatment of malignant gliomas. The authors investigated the release kinetics, toxicity, distribution, and efficacy of mitoxantrone delivered from intracranially implanted biodegradable wafers in the treatment of 9L gliosarcoma in Fischer 344 rats.

Methods. Mitoxantrone released from the biodegradable wafer matrix reached therapeutic drug concentrations in the brain for at least 35 days. Only animals with implanted wafers of the highest drug loading dose (20% mitoxantrone by weight) showed signs of significant toxicity. In three separate efficacy experiments, animals treated with mitoxantrone-loaded biodegradable wafers had significantly improved survival compared with control animals. The combined median survival for each treatment group was the following: 0% mitoxantrone wafers, 19 days; 1%, 30 days, p < 0.0001; 5%, 34 days, p < 0.0001; and 10%, 50 days, p < 0.0001.

Conclusions. These findings establish that mitoxantrone delivered from intracranially implanted biodegradable wafers is effective in the treatment of malignant gliomas in rodents and should be considered for future clinical application in humans.
Transcorneal stimulation of trigeminal nerve afferents to increase cerebral blood flow in rats with cerebral vasospasm: a noninvasive method to activate the trigeminovascular reflex
Authors: Atalay Basar , Bolay Hayrunnisa , Dalkara Turgay , Soylemezoglu Figen , Oge Kamil , Ozcan Osman Ekin
Published: May 2009

Object. The goal of this study was to investigate whether stimulation of trigeminal afferents in the cornea could enhance cerebral blood flow (CBF) in rats after they have been subjected to experimental subarachnoid hemorrhage (SAH). Cerebral vasospasm following SAH may compromise CBF and increase the risks of morbidity and mortality. Currently, there is no effective treatment for SAH-induced vasospasm. Direct stimulation of the trigeminal nerve has been shown to dilate constricted cerebral arteries after SAH; however, a noninvasive method to activate this nerve would be preferable for human applications. The authors hypothesized that stimulation of free nerve endings of trigeminal sensory fibers in the face might be as effective as direct stimulation of the trigeminal nerve.

Methods. Autologous blood obtained from the tail artery was injected into the cisterna magna of 10 rats. Forty-eight and 96 hours later (five rats each) trigeminal afferents were stimulated selectively by applying transcorneal biphasic pulses (1 msec, 3 mA, and 30 Hz), and CBF enhancements were detected using laser Doppler flowmetry in the territory of the middle cerebral artery. Stimulation-induced changes in cerebrovascular parameters were compared with similar parameters in sham-operated controls (six rats). Development of vasospasm was histologically verified in every rat with SAH. Corneal stimulation caused an increase in CBF and blood pressure and a net decrease in cerebrovascular resistance. There were no significant differences between groups for these changes.

Conclusions. Data from the present study demonstrate that transcorneal stimulation of trigeminal nerve endings induces vasodilation and a robust increase in CBF. The vasodilatory response of cerebral vessels to trigeminal activation is retained after SAH-induced vasospasm.